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Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence
Chao Yang, Shan-ze Wang, Sheng Chen, Shuo Du, Guan-qun Wang, Wei Guo, Xiao-long Xie, Bi-hui Peng, Shi-hao Du, Ji-ping Zhao
Journal of Integrative Medicine    2024, 22 (3): 258-269.   DOI: 10.1016/j.joim.2024.03.011
Accepted: 07 March 2024
Online available: 07 March 2024

Abstract403)   HTML    PDF      
Urinary incontinence (UI) is a common problem worldwide. It has a major impact on the physical and social activities and interpersonal relationships. UI is common in women, but is under-reported and under-treated. It affects the quality of life in female patients severely and is known as a “nonlethally social cancer.” Acupuncture and moxibustion has been proposed as a potentially effective intervention for female UI. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI. The CPG was developed according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPGs, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method. The CPGs contain ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions, which include nine conditional recommendations for the intervention, one conditional recommendations for either the intervention or the comparison. The CPG also provide one conventional filiform needle therapy protocol, two deep puncturing stimulation on lumbosacral acupoints therapy protocols, and four moxibustion therapy protocols, based on the protocols presented in RCTs reviews by the GDG.
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Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis
Shi-hao Du, Sheng Chen, Shan-ze Wang, Guan-qun Wang, Shuo Du, Wei Guo, Xiao-long Xie, Bi-hui Peng, Chao Yang, Ji-ping Zhao
Journal of Integrative Medicine    2024, 22 (3): 245-257.   DOI: 10.1016/j.joim.2024.03.009
Accepted: 25 December 2023
Online available: 01 March 2024

Abstract318)   HTML    PDF      
Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPGs for the use of acupuncture and moxibustion to treat AR. The CPGs were developed according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPGs, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPGs contain recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPGs also provide one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized clinical trials (RCTs) reviewed by the GDG.

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Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer
Zhengting Deng, Shufang Liang, Guokai Huang, Yuqian Wang, Xiaoyu Tu, Yani Zhang, Shu Li, Tao Liu, Binbin Cheng
Journal of Integrative Medicine    2024, 22 (3): 295-302.  
Accepted: 18 November 2023
Online available: 23 November 2023

Abstract310)   HTML    PDF      
Objective: Effects of arsenic trioxide (As2O3) on hepatocellular carcinoma (HCC) has been documented widely. In addition, autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3 -induced apoptosis in liver cancer cells.
Methods: The viability of hepatoma cells was determined with MTT assay. The apoptosis of As2O3-induced liver cancer cells was evaluated by flow cytometry, Hoechst 33258 staining and TUNEL assays. The autophagy of liver cancer cell was detected by immunofluorescence, western blot assay and transmission electron microscopy.
Results: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cells increased with the concentration of As2O3 as determined by Flow cytometry. Apoptosis in liver cancer cells induced by As2O3 was also demonstrated by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, we also found that As2O3 treatment induced liver cancer cells autophagy, which was demonstrated by western blot, immunofluorescence of LC3-II and Beclin 1 expression and transmission electron microscopy observation. In liver cancer cells, As2O3 inhibited the PI3K/AKT/mTOR signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator, SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-MA partially reversed As2O3-induced cell viability inhibition, and enhanced autophagy with serum starvation facilitated As2O3-induced cell death.
Conclusion: As2O3 is able to induce liver cancer cells apoptosis and autophagy. Autophagy induced by As2O3 may play a proapoptotic effect in the anti-liver cancer effects. Our present study provides novel insights into the anti-liver cancer effects of As2O3.
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A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment
Chinmayee Priyadarsani Mandhata, Chita Ranjan Sahoo, Rabindra Nath Padhy
Journal of Integrative Medicine    2023, 21 (4): 332-353.   DOI: 10.1016/j.joim.2023.05.001
Accepted: 21 March 2023
Online available: 22 May 2023

Abstract275)   HTML    PDF      
Acquired immune deficiency syndrome (AIDS) is a worldwide epidemic caused by human immunodeficiency virus (HIV) infection. Newer medicines for eliminating the viral reservoir and eradicating the virus are urgently needed. Attempts to locate relatively safe and non-toxic medications from natural resources are ongoing now. Natural-product-based antiviral candidates have been exploited to a limited extent. However, antiviral research is inadequate to counteract for the resistant patterns. Plant-derived bioactive compounds hold promise as powerful pharmacophore scaffolds, which have shown anti-HIV potential. This review focuses on a consideration of the virus, various possible HIV-controlling methods and the recent progress in alternative natural compounds with anti-HIV activity, with a particular emphasis on recent results from natural sources of anti-HIV agents.
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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency
Jing-shun Meng, Yun He, Heng-bin Yang, Li-ping Zhou, Si-yuan Wang, Xi-lin Feng, Omar Yahya Al-shargi, Xiao-min Yu, Li-qing Zhu, Chang-quan Ling
Journal of Integrative Medicine    2024, 22 (1): 72-82.   DOI: 10.1016/j.joim.2023.10.030
Accepted: 22 May 2023
Online available: 12 November 2023

Abstract274)   HTML    PDF      

Objective

Melittin and its derivatives have been characterized to establish effective gene delivery systems. Their capability of facilitating endosomal release enhances the nanoparticles-based gene delivery. Nevertheless, little investigation has been conducted to explore its potential application in the context of viral vectors.

Methods

Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus vectors. These vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene delivery. In addition, the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice. Finally, the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle.

Results

A total of 76 melittin-related peptides were compiled from existing literature. Among them, cMA2, Melt13, p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 vectors. The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV. Mechanistically, bafilomycin A1, a vacuolar endosome acidification inhibitor, completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors. Most importantly, p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 mice.

Conclusion

The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression. While further modifications remain an area of interest, our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

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Jiedu Recipe inhibits hypoxia-induced stemness in hepatocellular carcinoma via Wnt/β-catenin pathway
Bing-jie Guo, Yi Ruan, Ya-jing Wang, Chu-lan Xiao, Zhi-peng Zhong, Bin-bin Cheng, Juan Du, Bai Li, Wei Gu, Zi-fei Yin
Journal of Integrative Medicine    2023, 21 (5): 474-486.  
Accepted: 12 May 2023
Online available: 28 May 2023

Abstract254)   HTML    PDF      

Objective

In the management of hepatocellular carcinoma (HCC), traditional Chinese medicine represents as a significant complementary and alternative therapy. Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease HCC recurrence and metastasis rates. This study aimed to uncover the mechanism of JR in HCC treatment.

Methods

The components of JR were detected by liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was first screened by network pharmacology and microarray messenger ribonucleic acid (mRNA) chip assays, followed by experimental validation on human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, thiazolyl blue tetrazolium bromide, wound healing, along with transwell assays were applied respectively to assess HCC cell characteristics of proliferation, migration and invasion under hypoxic setting. Image-iT? Hypoxia Reagent was added to reveal hypoxic conditions. A stem cell sphere formation assay was used to detect stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin, α-smooth muscle actin and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, sex determining region Y box protein 2 were analyzed by Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involves the Wnt/β-catenin pathway.

Results

According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. Our findings showed that JR strongly decreased hypoxia, and obviously suppressed HCC cell features of proliferation, migration and invasion. Moreover, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Further results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed hypoxia-induced cancer stem-like properties in HCC by blocking the Wnt/β-catenin pathway.

Conclusion

JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions.

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Clinical evidence of three traditional Chinese medicine drugs and three herbal formulas for COVID-19: A systematic review and meta-analysis of the Chinese population
Liang-zhen You, Qian-qian Dai, Xiao-ying Zhong, Dong-dong Yu, He-rong Cui, Yi-fan Kong, Meng-zhu Zhao, Xin-yi Zhang, Qian-qian Xu, Zhi-yue Guan, Xu-xu Wei, Xue-cheng Zhang, Song-jie Han, Wen-jing Liu, Zhao Chen, Xiao-yu Zhang, Chen Zhao, Ying-hui Jin, Hong-cai Shang
Journal of Integrative Medicine    2023, 21 (5): 441-454.   DOI: 10.1016/j.joim.2023.08.001
Accepted: 21 February 2023
Online available: 05 August 2023

Abstract242)   HTML    PDF      
Background
The coronavirus disease 2019 (COVID-19) continues to spread worldwide. Integrated Chinese and Western medicine have had some successes in treating COVID-19.

Objective
This study aims to evaluate the efficacy and safety of three traditional Chinese medicine drugs and three herbal formulas (3-drugs-3-formulas) in patients with COVID-19.

Search strategy

Relevant studies were identified from 12 electronic databases searched from their establishment to April 7, 2022.


Inclusion criteria

Randomized controlled trials (RCTs), non-RCTs and cohort studies that evaluated the effects of 3-drugs-3-formulas for COVID-19. The treatment group was treated with one of the 3-drugs-3-formulas plus conventional treatment. The control group was treated with conventional treatment.


Data extraction and analysis

Two evaluators screened and selected literature independently, then extracted basic information and assessed risk of bias. The treatment outcome measures were duration of main symptoms, hospitalization time, aggravation rate and mortality. RevMan 5.4 was used to analyze the pooled results reported as mean difference (MD) with 95% confidence interval (CI) for continuous data and risk ratio (RR) with 95% CI for dichotomous data.


Results
Forty-one studies with a total of 13,260 participants were identified. Our analysis suggests that compared with conventional treatment, the combination of 3-drugs-3-formulas might shorten duration of fever (MD = –1.39; 95% CI: –2.19 to –0.59; P < 0.05), cough (MD = –1.57; 95% CI: –2.16 to –0.98; P < 0.05) and fatigue (MD = –1.36; 95% CI: –2.21 to –0.51; P < 0.05), decrease length of hospital stay (MD = –2.62; 95% CI –3.52 to –1.72; P < 0.05), the time for nucleic acid conversion (MD = –2.92; 95% CI: –4.26 to –1.59; P < 0.05), aggravation rate (RR = 0.49; 95% CI: 0.38 to 0.64; P < 0.05) and mortality (RR = 0.34; 95% CI: 0.19 to 0.62; P < 0.05), and increase the recovery rate of chest CT manifestations (RR = 1.22; 95% CI: 1.14 to 1.3; P < 0.05) and total effectiveness (RR = 1.24; 95% CI: 1.09 to 1.42; P < 0.05).

Conclusion
The 3-drugs-3-formulas can play an active role in treating all stages of COVID-19. No severe adverse events related to 3-drugs-3-formulas were observed. Hence, 3-drugs-3-formulas combined with conventional therapies have effective therapeutic value for COVID-19 patients. Further long-term high-quality studies are essential to demonstrate the clinical benefits of each formula.
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Electro-acupuncture promotes gut motility and alleviates functional constipation by regulating gut microbiota and increasing butyric acid generation in mice
Ming-min Xu, Yu Guo, Ying Chen, Wei Zhang, Lu Wang, Ying Li
Journal of Integrative Medicine    2023, 21 (4): 397-406.   DOI: 10.1016/j.joim.2023.05.003
Accepted: 17 March 2023
Online available: 01 June 2023

Abstract239)   HTML    PDF      

Objective

Abnormalities in the gut microbiota and intestinal short-chain fatty acid (SCFA) levels are implicated in the pathogenesis of functional constipation (FC). Electro-acupuncture (EA) has been shown to improve constipation-related symptoms and rebalance the gut microbiota. However, it is currently unknown whether the gut microbiota is a key mechanistic target for EA or how EA promotes gut motility by regulating the gut microbiota and SCFAs. Therefore, we assessed the effects of EA in FC mice and pseudo-germfree (PGF) mice to address these questions.

Methods

Forty female Kunming mice were randomly separated into a normal control group (n = 8), an FC group (n = 8), an FC + EA group (n = 8), a PGF group (n = 8) and a PGF + EA group (n = 8). The FC group and FC + EA group were treated with diphenoxylate to establish the FC model; the PGF group and PGF + EA group were given an antibiotic cocktail to initiate the PGF model. After maintaining the model for 14 d, mice in the FC + EA and PGF + EA groups received EA stimulation at the ST25 and ST37 acupoints, once a day, 5 times per week, for 2 weeks. Fecal parameters and intestinal transit rate were calculated to assess the efficacy of EA on constipation and gastrointestinal motility. Colonic contents were used to quantify gut microbial diversity using 16S rRNA sequencing, and measure SCFA concentrations using gas chromatography-mass spectrometry.

Results

EA significantly shortened the first black stool defecation time (P < 0.05) and increased the intestinal transit rate (P < 0.01), and fecal pellet number (P < 0.05), wet weight (P < 0.05) and water content (P < 0.01) over 8 h, compared with the FC group, showing that EA promoted gut motility and alleviated constipation. However, EA treatment did not reverse slow-transit colonic motility in PGF mice (P > 0.05), demonstrating that the gut microbiota may play a mechanistic role in the EA treatment of constipation. In addition, EA treatment restored the Firmicutes to Bacteroidetes ratio and significantly increased butyric acid generation in FC mice (P < 0.05), most likely due to the upregulation of Staphylococcaceae microorganisms (P < 0.01).

Conclusion

EA-mediated resolution of constipation occurs through rebalancing the gut microbiota and promoting butyric acid generation.

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Xiaotan Sanjie Recipe Inhibits Gastric Cancer Metastasis by Regulating GnT-V-Mediated E-Cadherin Glycosylation
Nian Huang, Haiwei He, Yuyu He, Wei Gu, Mingjuan Xu, Long Liu
Journal of Integrative Medicine    2023, 21 (6): 561-574.   DOI: 10.1016-j.joim.2023.06.029
Accepted: 02 May 2023
Online available: 30 July 2023

Abstract221)      PDF(pc) (1367KB)(146)    PDF(mobile) (1367KB)(12)   
Objective: Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound, exerts a significant inhibitory effect on the GC metastasis. Nevertheless, the mechanism underlying the XTSJ-mediated inhibition of GC metastasis is unknown. Our study demonstrated the regulation of XTSJ on the GnT-V-mediated addition of β1,6 GlcNAc branches to E-cadherin and affected GC metastasis in vitro and in vivo.
Methods: The effect (and associated mechanism) of XTSJ on GC metastasis was evaluated in vitro (using GC cell lines) and in vivo (using a GC mouse model) by focusing on the expression of GnT-V (encoded by MGAT5).
Results: We demonstrated that the migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. Moreover, we showed that XTSJ increased the accumulation of E-cadherins at junctions between GC cells, an effect which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5+XTSJ mice than in those of BGC-823-MGAT5+solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.
Conclusion: Our study confirmed that XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting E-cadherin accumulation at cell-cell junctions.
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Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity
Yan-qiong Zhang, Chun-xia Shi, Dan-mei Zhang, Lu-yi Zhang, Lu-wen Wang, Zuo-jiong Gong
Journal of Integrative Medicine    2023, 21 (5): 464-473.   DOI: 10.1016/j.joim.2023.08.002
Accepted: 01 June 2023
Online available: 21 August 2023

Abstract213)      PDF      

Objective

Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.

Methods

Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.

Results

Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.

Conclusion

SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.


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Efficacy of acupuncture on cancer pain: A systematic review and meta-analysis
Miguel Faria, Mónica Teixeira, Maria João Pinto, Paulo Sargento
Journal of Integrative Medicine    2024, 22 (3): 235-244.   DOI: 10.1016/j.joim.2024.03.002
Accepted: 13 March 2024
Online available: 13 March 2024

Abstract205)   HTML    PDF      

Background

Pain associated with cancer is one of the greatest causes of reduced quality of life in patients. Acupuncture is one of the treatments used to address this issue, with the great advantage of having little or no side effects, especially when compared with pharmacological pain-killers.

Objective

The aim of this systematic review and meta-analysis was to evaluate the current evidence regarding the efficacy of acupuncture for cancer pain.

Search strategy

Six electronic databases (PubMed, EBSCO, Cochrane Library, Scielo, b-On and Scopus) were searched for relevant articles about pain relief in cancer patients from their beginning until 2022 using MeSH terms such as “acupuncture,” “electroacupuncture,” “ear acupuncture,” “acupuncture analgesia,” ‘‘oncological pain,” and “cancer pain.”

Inclusion criteria

Studies included were randomized controlled trials (RCTs) where acupuncture was compared with no treatment, placebo acupuncture or usual care.

Data extraction and analysis

Three independent reviewers participated in data extraction and evaluation of risk of bias, and a meta-analysis was conducted. The primary outcome was pain intensity, measured with the visual analog scale, numeric rating scale, or brief pain inventory. Secondary outcomes also assessed were quality of life, functionality, xerostomia, pain interference, and analgesic consumption. Results were expressed as standardized mean difference (SMD) with 95% confidence interval (CI). 

Results

Sixteen RCTs with a total of 1124 participants were included in the meta-analysis, with the majority of the studies presenting a low or unclear risk of bias. Acupuncture was more effective in reducing pain than no treatment (SMD = –0.90, 95% CI [–1.68, –0.12]), sham acupuncture (SMD = –1.10, 95% CI [–1.59, –0.61]) or usual care (SMD = –1.16, 95% CI [–1.38, –0.93]).

Conclusion

The results of this study suggest that acupuncture may be an effective intervention to reduce pain associated with cancer. Despite some limitations due to the low quality and small sample size of some included studies, as well as the different types and stages of cancer, acupuncture might provide an effective and safe treatment to reduce cancer pain.

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Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol
Xiao-cong Wang, Xiao-yu Liu, Kang-le Shi, Qing-gang Meng, Yue-fan Yu, Shi-yao Wang, Juan Wang, Chang Qu, Cong Lei, Xin-ping Yu
Journal of Integrative Medicine    2023, 21 (6): 528-536.   DOI: 10.1016/j.joim.2023.10.003
Accepted: 11 September 2023
Online available: 29 October 2023

Abstract201)   HTML    PDF      
As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials.
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Phytochemical interventions for post-traumatic stress disorder: A cluster co-occurrence network analysis using CiteSpace
Biao Gao, Yi-cui Qu, Meng-yu Cai, Yin-yin Zhang, Hong-tao Lu, Hong-xia Li, Yu-xiao Tang, Hui Shen
Journal of Integrative Medicine    2023, 21 (4): 385-396.   DOI: 10.1016/j.joim.2023.06.006
Accepted: 16 March 2023
Online available: 15 June 2023

Abstract200)   HTML    PDF      
Objective
This study investigated trends in the study of phytochemical treatment of post-traumatic stress disorder (PTSD).

Methods
The Web of Science database (2007–2022) was searched using the search terms “phytochemicals” and “PTSD,” and relevant literature was compiled. Network clustering co-occurrence analysis and qualitative narrative review were conducted.

Results
Three hundred and one articles were included in the analysis of published research, which has surged since 2015 with nearly half of all relevant articles coming from North America. The category is dominated by neuroscience and neurology, with two journals, Addictive Behaviors and Drug and Alcohol Dependence, publishing the greatest number of papers on these topics. Most studies focused on psychedelic intervention for PTSD. Three timelines show an “ebb and flow” phenomenon between “substance use/marijuana abuse” and “psychedelic medicine/medicinal cannabis.” Other phytochemicals account for a small proportion of the research and focus on topics like neurosteroid turnover, serotonin levels, and brain-derived neurotrophic factor expression.

Conclusion
Research on phytochemicals and PTSD is unevenly distributed across countries/regions, disciplines, and journals. Since 2015, the research paradigm shifted to constitute the mainstream of psychedelic research thus far, leading to the exploration of botanical active ingredients and molecular mechanisms. Other studies focus on anti-oxidative stress and anti-inflammation.
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A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China
Dong-jue Wei, Hui-juan Li, Zi-pan Lyu, Ai-ping Lyu, Zhao-xiang Bian, Linda LD Zhong
Journal of Integrative Medicine    2023, 21 (6): 550-560.   DOI: 10.1016/j.joim.2023.11.002
Accepted: 03 August 2023
Online available: 07 November 2023

Abstract198)   HTML    PDF      
Objective
Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients.

Methods
A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process.

Results
We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs.

Conclusion
This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC.
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Efficacy and safety of Huzhang Granule, a compound Chinse herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial
Hao Wang, Si-ting Chen, Xiao-jie Ding, Le Kuai, Liang Hua, Xin Li, Yi-fei Wang, Ming Zhang, Bin Li, Rui-ping Wang, Mi Zhou
Journal of Integrative Medicine    2024, 22 (3): 270-278.   DOI: 10.1016/j.joim.2024.03.008
Accepted: 22 February 2024
Online available: 26 March 2024

Abstract189)   HTML    PDF      

Background

Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinse herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown.

Objective

The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients.

Design, setting, participants and interventions

The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1).

Main outcome measures

The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient’s and investigator’s global evaluations of therapeutic response.

Results

The mean reduction in pain was –51.22 mm (95% confidence interval [CI], [–53.42, –49.03] mm) for the HZG and –52.00 mm (95% CI, [–54.06, –49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [–2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05).

Conclusion

HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2000036970).


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Short-term effects of cupping and scraping therapy for chronic nonspecific low-back pain: A prospective, multicenter randomized trial
Jun-yan He, Xiao-yu Tu, Zi-fei Yin, Hui Mu, Ming-jun Luo, Xing-yu Chen, Wei-bin Cai, Xue Zhao, Can Peng, Fan-fu Fang, Can Lü, Bai Li
Journal of Integrative Medicine    2024, 22 (1): 39-45.   DOI: 10.1016/j.joim.2024.01.004
Accepted: 04 May 2023
Online available: 24 January 2024

Abstract181)   HTML    PDF      
Background
As one of the most common musculoskeletal ailments, chronic nonspecific low-back pain (CNLBP) causes persistent disability and substantial medical expenses. Epidemiological evidence shows that the incidence rate of CNLBP in young and middle-aged people who are demanded rapidly recovery and social contribution is rising. Recent guidelines indicate a reduced role for medicines in the management of CNLBP.

Objective
The present study investigates the short-term effects of cupping and scraping therapy using a medicated balm, compared to nonsteroidal anti-inflammatory drug (NSAID) with a capsaicin plaster, in the treatment of CNLBP.

Design, setting, participants and interventions
We designed a prospective multicenter randomized clinical trial enrolling patients from January 1, 2022 to December 31, 2022. A total of 156 patients with CNLBP were randomized into two parallel groups. Diclofenac sodium-sustained release tablets were administered orally to participants in the control group for one week while a capsaicin plaster was applied externally. Patients in the test group were treated with cupping and scraping using a medical device and medicated balm.

Main outcome measures
Primary outcome was pain recorded using the visual analogue scale (VAS). Two secondary outcomes were recorded using the Japanese Orthopedic Association low-back pain scale (JOA) and the traditional Chinese medicine (TCM) syndrome integral scale (TCMS) as assessment tools.

Results
Between baseline and postintervention, all changes in outcome metric scales were statistically significant (P < 0.001). Compared to the control group, patients in the test group had a significantly greater treatment effect in all outcome variables, as indicated by lower VAS and TCMS scores and higher JOA scores, after the one-week intervention period (P < 0.001). Further, according to the findings of multivariate linear regression analysis, the participants’ pain (VAS score) was related to their marital status, age, smoking habits and body mass index. No adverse reactions were reported for any participants in this trial.

Conclusion
The effectiveness of TCM combined with the new physiotherapy tool is superior to that of NSAID combined with topical plasters, regarding to pain intensity, TCM symptoms and quality of life. The TCM plus physiotherapy also showed more stable and long-lasting therapeutic effects.


Trial registration

This study was registered at Chinese Clinical Trial Registry (ChiCTR2200055655).

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Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis
Han-yu Xu, Lin-na Wu, Yuan Zhang, Te Ba, Xiao-feng Zhao
Journal of Integrative Medicine    2024, 22 (4): 459-472.   DOI: 10.1016/j.joim.2024.05.005
Accepted: 10 April 2024
Online available: 31 May 2024

Abstract176)   HTML    PDF      

Background

Electroacupuncture is often used to treat insomnia.

Objective

To evaluate the efficacy and safety of electroacupuncture for insomnia.

Search strategy

Databases including PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data and VIP Full-text e-Journals Database were searched up to January 15, 2023.

Inclusion criteria

Randomized clinical trials were included if they compared the clinical efficacy and safety of electroacupuncture with sham acupuncture, no treatment or usual care (UC) and general acupuncture.

Data extraction and analysis

The full texts of the studies were reviewed to remove ineligible literature. The extracted data included authors, publication year, diagnostic criteria, sample size, population characteristics, interventions and outcomes. The above steps were performed independently by two reviewers and the data were cross-checked. Stata15.0 software was used to analyze the extracted outcome data. For continuous data (Pittsburgh Sleep Quality Index [PSQI] score and Insomnia Severity Index score), weighted mean difference (WMD) was calculated and 95% confidence interval (CI) was reported when the same scale was applied. For dichotomous variables (clinical response rate and adverse events), a meta-analysis was performed using risk ratio (RR) as the effect indicator.

Results

Thirty-one trials with 2226 subjects were included. The meta-analysis suggested that electroacupuncture was more effective in improving insomnia compared with the control group (sham acupuncture, no treatment, UC and general acupuncture) (RR = 1.21; 95% CI: [1.16, 1.27]), significantly reducing the PSQI score in insomnia patients after treatment and at follow-up (WMD = ?3.23; 95% CI: [?4.29, ?2.17]; P < 0.001). There was no significant difference in the incidence of adverse events between the EA and control groups (sham acupuncture and no treatment or UC. RR = 1.48; 95% CI: [0.91, 2.40]; P = 0.117). In addition, the regression results revealed that receiving electroacupuncture for seven to nine weeks provided the best efficacy (P < 0.05).

Conclusion

Electroacupuncture can significantly promote better sleep quality in insomnia patients and is suitable for the treatment of various types of insomnia. However, the articles included were single-center trials with small sample sizes, and some articles were of poor quality. Therefore, further research is still needed to confirm these findings.

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The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19
Ming Huang, Yao-yuan Liu, Ke Xiong, Feng-wen Yang, Xin-yao Jin, Zhao-qi Wang, Jun-hua Zhang, Bo-li Zhang
Journal of Integrative Medicine    2023, 21 (5): 407-412.   DOI: 10.1016/j.joim.2023.08.003
Accepted: 04 May 2023
Online available: 09 August 2023

Abstract173)   HTML    PDF      
The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies.
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Efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension: A systematic review and meta-analysis
Zheng-gang Zhu, Jian-ru Wang, Xiao-yan Pan
Journal of Integrative Medicine    2024, 22 (1): 12-21.   DOI: 10.1016/j.joim.2023.11.006
Accepted: 11 September 2023
Online available: 25 November 2023

Abstract165)   HTML    PDF      
Background
Scraping therapy is widely used in treating stage I and II essential hypertension in China. However, there has been no systematic evaluation of the efficacy of scraping therapy on blood pressure and sleep quality in stage I and II essential hypertension.

Search strategy
Seven electronic databases (PubMed, Scopus, Cochrane Library, Web of Science, EBSCO, China National Knowledge Infrastructure and Wanfang Data electronic databases) were searched from inception to December 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for “scraping therapy,” “scraping,” “Guasha,” “Gua sha,” “hypertension,” and “high blood pressure” during the database searches.

Inclusion criteria
Randomized controlled trials (RCTs) were included if they recruited patients with stage I and II essential hypertension and included a scraping therapy intervention. The intervention group received antihypertensive drugs and scraping therapy, while the control group only took antihypertensive drugs.

Data extraction and analysis
Review Manager 5.4.0 and STATA 15.1 were used to enter all the relevant outcome variables to conduct the meta-analysis. The quality of the selected RCTs was assessed using the PEDro scale. The sensitivity analysis was carried out by iteratively excluding individual studies and repeating the analysis to determine the stability of the findings and identify any studies with greater influence on the outcome. Subgroup analysis was performed to find the source of heterogeneity. Funnel plots were used to evaluate the publication bias of included studies.

Results
Nine RCTs including 765 participants were selected. Meta-analysis showed that scraping therapy combined with medication had an advantage over the use of medication alone in lowering systolic blood pressure (mean difference [MD] = ?5.09, 95% confidence interval [CI] = ?6.50 to ?3.67, P < 0.001) and diastolic blood pressure (MD = ?2.66, 95% CI = ?3.17 to ?2.14, P < 0.001). Subgroup analysis showed that scraping therapy improved sleep quality in middle-aged patients with hypertension, but the efficacy was better in elderly patients (MD = ?7.91, 95% CI = ?8.65 to ?7.16, P < 0.001) than in middle-aged patients (MD = ?2.67, 95% CI = ?4.12 to ?1.21, P = 0.0003).

Conclusion
The available evidence indicates that scraping therapy has significant effects on patients with stage I and II hypertension, and it improves sleep quality for elderly patients with hypertension better than for middle-aged ones. Scraping therapy can be an adjunctive treatment for stage I and II essential hypertension. However, further high-quality studies are needed to verify its effectiveness and the best therapeutic strategies.
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Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study
Jian-bo Song, Li-qin Zhao, Hong-ping Wen, Yuan-ping Li
Journal of Integrative Medicine    2023, 21 (6): 593-604.   DOI: 10.1016/j.joim.2023.09.001
Accepted: 13 May 2023
Online available: 26 September 2023

Abstract164)   HTML    PDF      
Objective
The aim of this study is to identify molecules from traditional Chinese medicine (TCM) with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants.

Methods
We applied the Apriori algorithm to identify important combinations of herbs in the TCM prescriptions for the treatment of coronavirus disease 2019 (COVID-19). Then, we explored the active components and core targets using network pharmacology. In addition, the molecular docking approach was performed to investigate the interaction of these components with the main structural and non-structural proteins, as well as the mutants. Furthermore, their stability in the binding pockets was further evaluated with the molecular dynamics approach.

Results
A combination of Amygdalus Communis Vas., Ephedra Herba and Scutellaria baicalensis Georgi was selected as the important herbal combination, and 11 main components and 20 core targets against COVID-19 were obtained. These components, including luteolin, naringenin, stigmasterol, baicalein, and so on, were the potentially active compounds against COVID-19. The binding affinity of these compounds with the potential targets was as high as the positive controls. Among them, baicalein could interfere with multiple targets simultaneously, and it also interfered with the interaction between spike protein and angiotensin-converting enzyme 2 receptor. Additionally, almost all the systems reached stability during dynamics simulation.

Conclusion
The combination of Amygdalus Communis Vas., Ephedra Herba and Scutellaria baicalensis Georgi was the most important herbal combination for the treatment of COVID-19. Baicalein may be a potential candidate against SARS-CoV-2 and its variants.
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Similarities and differences between kaiy in Persian medicine and moxibustion in Chinese medicine
Amir Mohammad Jaladat, Mahdi Alizadeh Vaghasloo, Fatemeh Atarzadeh, Mohammad Hossein Ayati, Amir Human Kazemi, Emine Akin, Mohammad Hashem Hashempur
Journal of Integrative Medicine    2023, 21 (4): 354-360.   DOI: 10.1016/j.joim.2023.05.002
Accepted: 26 December 2022
Online available: 10 May 2023

Abstract161)   HTML    PDF      
Kaiy (medieval cautery) is an ancient method of heat therapy in traditional Persian medicine (TPM). Some of its important applications have been neglected during the medical revolution. Meanwhile, different treatment modalities that incorporate heat, including moxibustion, have progressed in traditional Chinese medicine. In this study, we reviewed the main TPM textbooks that were written specifically in the field of kaiy. We consider the traditional teachings in the context of contemporary information gathered from the scientific literature about moxibustion and modern cauterization. Some surgical therapeutic indications of kaiy (e.g., debridement and coagulative procedures) have been advanced by the innovation of electro-cauterization, but those therapeutic applications that were based on the TPM humoral theory for relieving body coldness or myofascial pains—which are similar to moxibustion usages—have not received the same attention. Apart from the broad similarities of kaiy and moxibustion as thermal therapies with similar indications, there is a striking correspondence between kaiy point mapping and acupoints. Therefore, further research on different kaiy aspects is recommended.

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Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial
Dong Kee Jang, Jun Kyu Lee, Chan Yung Jung, Kyung Ho Kim, Ha Ra Kang, Yeon Sun Lee, Jong Hwa Yoon, Kwang Ro Joo, Min Kyu Chae, Yong Hyeon Baek, Byung-Kwan Seo, Sang Hyub Lee, Chiyeon Lim
Journal of Integrative Medicine    2023, 21 (6): 537-542.   DOI: 10.1016/j.joim.2023.10.004
Accepted: 07 September 2023
Online available: 02 November 2023

Abstract158)   HTML    PDF      
Background
Electroacupuncture (EA) may reduce the severity of acute pancreatitis (AP) and provide additional pain relief in patients with chronic pancreatitis. However, the ability of EA to relieve pain in patients with AP has not been well documented.

Objective
This study was undertaken to compare the pain-relieving effects of EA and conventional treatment in patients with AP.

Design, setting, participants and interventions

This study was conducted using a randomized, controlled, three-arm, parallel-group and multi-center design. Patients diagnosed with AP were randomly and equally assigned to EA1, EA2 or control groups. All participants received conventional standard-of-care therapy for AP. Local EA alone was administered in EA1, and local plus distal EA was given in EA2. Local EA included two abdominal acupoints, while distal EA included twelve peripheral acupoints. EA groups underwent one session of EA daily for 4 days (days 1–4), or until pain was resolved or discharged.


Main outcome measures

The primary outcome measure was the change in the visual analogue scale (VAS; 0–100) pain score between baseline and day 5.


Results
Eighty-nine participants were randomized into EA1, EA2 and control groups, and 88 (EA1, 30; EA2, 29; control, 29) were included in the full-analysis set. VAS score change (median [interquartile range]) on day 5 was (12.3 ± 22.5) in the EA1 group, (10.3 ± 21.5) in the EA2 group, and (8.9 ± 15.2) in the control group. There were not significant differences in the change in VAS score among treatments (P = 0.983). However, time to food intake was significantly shorter in the EA group (EA1 + EA2) than in the control group (median 2.0 days vs 3.0 days), with a hazard ratio of 0.581 (P = 0.022; 95% CI, 0.366–0.924). No significant adverse events occurred.

Conclusion
EA treatment did not significantly reduce pain after 4 days of treatment in patients with AP-associated abdominal pain but significantly reduced time to first food intake.

Trial registration: ClinicalTrials.gov identifier NCT03173222.
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The acceptance of traditional Chinese medicine among patients with Parkinson's disease: A hospital survey
Peng Wang, Jing Hong, Zhu-qian Tang, Bi-zhen Gong, Xiao-rong Qi, Han Jiang, Bo Pan, Qi Chen
Journal of Integrative Medicine    2024, 22 (2): 180-187.   DOI: 10.1016/j.joim.2024.03.005
Accepted: 08 March 2024
Online available: 08 March 2024

Abstract154)   HTML    PDF      
Objective
The efficacy of medications for Parkinson's disease (PD) tend to decline over time, which has a serious impact on patients' health and quality of life. To some extent, traditional Chinese medicine (TCM) can resolve the distressing problem of ineffective dopaminergic medication in PD patients. The purpose of this study was to investigate the attitude, acceptance, and independent predictors of TCM in PD patients admitted to the outpatient department of a tertiary hospital.

Methods
A cross-sectional study of PD patients was conducted in the outpatient department of a large tertiary hospital in Beijing from March 2022 to June 2023. A self-report questionnaire was developed to investigate PD patients' attitudes and acceptance of TCM based on the questionnaire. Multivariate logistic regression analyses were also performed to further clarify the independent predictors influencing patients' adoption of TCM therapy.

Results
A total of 397 patients completed the questionnaire, of which 78.09% were willing to be treated with TCM and 21.91% indicated that they were not willing to use TCM. Multifactorial logistic regression analysis showed that several parameters were correlated with a patient's willingness to include TCM in their therapeutic regime. These included education level of a bachelor's degree (odds ratio [OR) = 8.554; 95% confidence interval [CI]: 4.112–17.794; P < 0.001, vs junior high school education), living in an urban setting (OR = 8.022; 95% CI: 4.577–14.060; P < 0.001, vs rural), having other underlying diseases (OR = 5.126; 95% CI: 3.078–8.537; P < 0.001, vs none), having previously used TCM (OR = 3.083; 95% CI: 1.852–5.134; P < 0.001, vs not used), believing that TCM therapy is safe (OR = 3.530; 95% CI: 1.446–8.616; P = 0.006, vs not thought), believing that TCM therapy is effective (OR = 3.859; 95% CI: 1.482–10.047; P = 0.006, vs not understood), and being willing to discuss ongoing TCM therapy with an attending physician (OR = 62.468; 95% CI: 30.350–128.574; P < 0.001, vs not informed).

Conclusion
This study initially investigated the acceptance, attitude, and independent predictors of TCM use among PD patients. To expand the prevalence of TCM use among patients with PD, we recommend to broadening the public outreach for TCM via contemporary means of Internet and broadcast communication, enhancing access to TCM services in rural communities, and strengthening the communication between doctors and patients.
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Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses
Tian-tian Meng, Ya-ping You, Min Li, Jian-bo Guo, Xin-bin Song, Jing-yi Ding, Xiao-long Xie, An-qi Li, Shang-jin Li, Xiang-jun Yin, Peng Wang, Zhe Wang, Bao-liang Wang, Qing-yong He
Journal of Integrative Medicine    2024, 22 (2): 163-179.   DOI: 10.1016/j.joim.2024.03.003
Accepted: 20 March 2024
Online available: 20 March 2024

Abstract153)   HTML    PDF      

Background

Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published.

Objective

This overview aims to assess the quality of related SRs and MAs.

Search strategy

PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022.

Inclusion criteria

SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included.

Data extraction and analysis

Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted.

Results

Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores.

Conclusion

GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS.

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Delivery of acupuncture in clinical trials: Research acupuncturists’perspectives
Joyce K. Anastasi, Bernadette Capili, Jessica Neumaier, Londa Hackett
Journal of Integrative Medicine    2023, 21 (4): 315-319.   DOI: 10.1016/j.joim.2023.03.007
Accepted: 20 October 2022
Online available: 30 March 2023

Abstract152)   HTML    PDF      
Delivery of acupuncture in the setting of a clinical trial is a unique practice that diverges significantly from the delivery of acupuncture in a real-world clinical setting. Research acupuncturists, particularly those trained in traditional Chinese medicine (TCM), are often required to set aside valued precepts of traditional care, including diagnosing imbalances, individualizing treatment, and forging a therapeutic relationship with patients. TCM-trained acupuncturists express mixed feelings about participating in clinical trials. Many are eager to play a vital role in the advancement of acupuncture science and appreciate the need for strict protocol adherence to minimize bias. However, the acupuncturist(s) may also have concerns about clinical trial methodology, including but not limited to the delivery of a control condition, e.g., sham acupuncture. Investigators should anticipate certain questions and even a level of resistance to the requirements of research among acupuncturists and be prepared to address them. This manuscript presents a brief review of the subjective experience of the research acupuncturist within the available scientific literature as it pertains to the delivery of active and sham clinical research protocols. Our goals are to better understand the perspectives of acupuncturists who may participate in clinical research, so that their concerns may be addressed in study design and methodology. To that end, we suggest the creation of a novel training program specifically for clinical trial acupuncturists, intended for qualified TCM- and Western-trained practitioners, that would help to standardize the research acupuncturist’s role and help to strengthen the design and execution of acupuncture studies.
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Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study
Betty H Wang, Ya-li Lin, Yin-yan Gao, Jin-lu Song, Lang Qin, Ling-qi Li, Wen-qi Liu, Claire CW Zhong, Mary Y Jiang, Chen Mao, Xiao-bo Yang, Vincent CH Chung, Irene XY Wu
Journal of Integrative Medicine    2024, 22 (3): 223-234.   DOI: 10.1016/j.joim.2024.04.003
Accepted: 26 March 2024
Online available: 27 April 2024

Abstract151)   HTML    PDF      

Background

Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet.

Objective

To investigate trial characteristics related to treatment effect estimates on CHM RCTs.

Search strategy

This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021.

Inclusion criteria

An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis.

Data extraction and analysis

Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step method was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively.

Results

Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95% CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: –0.70; 95% CI: [–0.99, –0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: –0.33; 95% CI: [–0.61, –0.05]), not using intention-to-treat analysis (dSMD: –0.75; 95% CI: [–1.43, –0.07]), and without funding support (dSMD: –0.22; 95% CI: [–0.41, –0.02]) tended to show larger effect estimates.

Conclusion

This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs.

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Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells
Jia-jia Liu, Xue Zhang, Bang-lan Cai, Man-man Qi, Yong-bin Chi, Bin Peng, Deng-hai Zhang
Journal of Integrative Medicine    2024, 22 (3): 286-294.   DOI: 10.1016/j.joim.2024.03.007
Accepted: 27 November 2023
Online available: 16 March 2024

Abstract151)   HTML    PDF      
Objective
Research has shown that celastrol can effectively treat a variety of diseases, yet when passing a certain dosage threshold, celastrol becomes toxic, causing complications such as liver and kidney damage and erythrocytopenia, among others. With this dichotomy in mind, it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.

Methods
In this study, insulin-resistant HepG2 (IR-HepG2) cells were prepared using palmitic acid and used for in vitro experiments. IR-HepG2 cells were treated with celastrol alone or in combination with N-acetylcysteine (NAC) or ferrostatin-1 (Fer-1) for 12, 24 or 48 h, at a range of doses. Cell counting kit-8 assay, Western blotting, quantitative reverse transcription-polymerase chain reaction, glucose consumption assessment, and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.

Results
Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-HepG2 cells. Celastrol downregulated glutathione peroxidase 4 (GPX4) mRNA. Molecular docking models predicted that solute carrier family 7 member 11 (SLC7A11) and GPX4 were covalently bound by celastrol. Importantly, we found for the first time that the application of ferroptosis inhibitors (especially NAC) was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-HepG2 cells.

Conclusion
One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis, which can be alleviated by treatment with ferroptosis inhibitors. These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.
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Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway
Yuan-yuan Ding, Feng Xu, Ya-feng Wang, Lin-lin Han, Shi-qian Huang, Shuai Zhao, Lu-lin Ma, Tian-hao Zhang, Wen-jing Zhao, Xiang-dong Chen
Journal of Integrative Medicine    2023, 21 (5): 496-508.   DOI: 10.1016/j.joim.2023.07.001
Accepted: 28 June 2023
Online available: 05 July 2023

Abstract150)   HTML    PDF      
Objective
This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats.

Methods
The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA.

Results
APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05).

Conclusion
EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP.
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Anti-inflammatory mechanism of electroacupuncture involves the modulation of multiple systems, levels and targets and is not limited to “driving the vagus-adrenal axis”
Arthur Yin Fan
Journal of Integrative Medicine    2023, 21 (4): 320-323.   DOI: 10.1016/j.joim.2023.06.001
Accepted: 04 May 2023
Online available: 07 June 2023

Abstract143)   HTML    PDF      
In October 2021, an international collaborative study on the use of electroacupuncture (EA) to treat inflammation was published in the journal Nature by Dr. Qiufu Ma’s team. Based on the results of EA on inflammation in the mouse model of lipopolysaccharide inflammatory storm, the study showed that the distal effect of acupuncture can be achieved by “driving the vagus-adrenal axis (through the adrenal medulla, by releasing catecholamines).” PROKR2Cre-marked sensory neurons, which innervate the deep hindlimb fascia but not the abdominal fascia, are crucial for driving this axis. The study suggests the existence of specificity distribution of acupoints, that different EA stimulation intensities or different needle penetration depths have different therapeutic effects, that photosensitive stimulation may be a substitute for needle acupuncture, and that massage, stretching and body movements may also activate PROKR2Cre-markable dorsal root ganglion sensory neurons and elicit anti-inflammatory effects. However, results of some other studies are contrary to the conclusions of Ma’s team. For examples: low-intensity EA at GB30 point significantly reduced the inflammation in the rat model of persistent inflammation, which is more relevant to the real daily acupuncture practice, and this effect was partly related to the adrenal cortex and associated with the stimulation of corticosterone and adrenocorticotropic hormone; manual acupuncture (similar to the low-intensity EA) at KI3, Zhichuan point (an extra point), etc. was effective in a severe COVID-19 patient with sepsis; stimulating ST25 with low-intensity EA or manual acupuncture was effective against gastrointestinal inflammations; the above mentioned points are not in an area enriched with PROKR2Cre-marked sensory nerve endings. Evidence shows that the mechanism of EA against inflammation includes modulating multi-systems, multi-levels and multi-targets, which does not limit to “driving the vagus-adrenal axis.”
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Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial
Li-ying Liu, Yang Su, Rong-rong Wang, Yuan-yuan Lai, Lei Huang, Yi-ting Li, Xin-yue Tao, Meng-hua Su, Xiao-yan Zheng, Shi-chen Huang, Yong-na Wu, Si-yi Yu, Fan-rong Liang, Jie Yang
Journal of Integrative Medicine    2024, 22 (1): 32-38.   DOI: 10.1016/j.joim.2024.01.005
Accepted: 16 December 2023
Online available: 24 January 2024

Abstract140)   HTML    PDF      
Background
Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea.

Objective
This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval.

Design, setting, participants and interventions

Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval.


Main outcome measures

The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms.


Results
The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05).

Conclusion
TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval.

Trial registration number

ChiCTR2100050153.

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Effects of acupuncture on hypothalamic–pituitary–adrenal axis: Current status and future perspectives
Jia-yuan Zheng, Jing Zhu, Yu Wang, Zhan-zhuang Tian
Journal of Integrative Medicine    2024, 22 (4): 445-458.   DOI: 10.1016/j.joim.2024.06.004
Accepted: 08 May 2024
Online available: 24 June 2024

Abstract139)   HTML    PDF      
The hypothalamic–pituitary–adrenal (HPA) axis is a critical component of the neuroendocrine system, playing a central role in regulating the body’s stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus, hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis. This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.
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A review of whole-medical systems and holistic care approach for type 2 diabetes and associated metabolic syndrome
Loveness Makoni, Idah T. Manduna, Alaisa L. Mbiriri
Journal of Integrative Medicine    2024, 22 (3): 199-209.   DOI: 10.1016/j.joim.2024.04.001
Accepted: 17 July 2023
Online available: 24 May 2024

Abstract137)   HTML    PDF      
Whole-person care and holistic care approach has been proposed for complementary and integrative health care for type 2 diabetes mellitus. However, some doubts still exist on the feasibility of replicating processes followed in clinical trials and observational studies in real-world settings. This narrative literature review summarized and assessed existing clinical evidence (clinical trials, observational studies, and case reports) describing holistic and integrated care approach in adult and adolescent individuals with type 2 diabetes mellitus in clinical practice. The goal was to highlight existing evidence for implementation and outcomes of whole-medical systems and holistic integrated care approach for type 2 diabetes mellitus. A nonsystematic literature search was performed on Google Scholar, PubMed, Web of Science, ProQuest and ScienceDirect to identify clinical evidence from different parts of the world, evaluating the use of whole-medical systems and/or holistic care interventions in clinical practice for management of type 2 diabetes mellitus. Relevant keywords were used in the search. Data were analyzed using content analysis and simple descriptive statistics (percentages). Most of the studies (64%) were mainly conducted in Eastern countries (India, China and Israel) while 36% of the studies were conducted in the Western countries (USA, Netherlands, Canada and Mexico). Lifestyle medicine and integrated naturopathy were shown to be the commonly used whole-medical systems for type 2 diabetes mellitus management. Significant improvements in type 2 diabetes parameters, medication use, other symptoms, and overall feeling of wellness were observed in all studies. This review study revealed limited utilization and/or documentation of whole-medical systems or holistic care treatments for type 2 diabetes mellitus in regions of the world other than eastern countries. Lifestyle medicine, naturopathy, yoga, Ayurveda and traditional Chinese medicine were shown to be effective for type 2 diabetes mellitus, either as an alternative or as a complementary therapy.
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Abstracts for SAR/RCMI PolyU International Research Conference
Journal of Integrative Medicine    2024, 22 (3): 303-378.   DOI: 10.1016/S2095-4964(24)00328-5
Online available: 20 May 2024

Abstract136)      PDF(pc) (1776KB)(246)      
May 23–25, 2024, the Hong Kong Polytechnic University, Hong Kong, China
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From ancient wisdom to modern science: Gut microbiota sheds light on property theory of traditional Chinese medicine
Ya-nan Yang, Jia-guo Zhan, Ying Cao, Chong-ming Wu
Journal of Integrative Medicine    2024, 22 (4): 413-444.   DOI: 10.1016/j.joim.2024.06.001
Accepted: 14 May 2024
Online available: 24 June 2024

Abstract134)   HTML    PDF      
The property theory of traditional Chinese medicine (TCM) has been practiced for thousands of years, playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism, chemical composition analysis, machine learning, ion current modeling, and supercritical fluid technology have provided valuable insight into how aspects of TCM property theory may be measured, these studies only capture specific aspects of TCM property theory in isolation, overlooking the holistic perspective inherent in TCM. To systematically investigate the modern interpretation of the TCM property theory from multidimensional perspectives, we consulted the Chinese Pharmacopoeia (2020 edition) to compile a list of Chinese materia medica (CMM). Then, using the Latin names of each CMM and gut microbiota as keywords, we searched the PubMed database for relevant research on gut microbiota and CMM. The regulatory patterns of different herbs on gut microbiota were then summarized from the perspectives of the four natures, the five flavors and the meridian tropism. In terms of the four natures, we found that warm-natured medicines promoted the colonization of specific beneficial bacteria, while cold-natured medicines boosted populations of some beneficial bacteria while suppressing pathogenic bacteria. Analysis of the five flavors revealed that sweet-flavored and bitter-flavored CMMs positively influenced beneficial bacteria while inhibiting harmful bacteria. CMMs with different meridian tropism exhibited complex modulative patterns on gut microbiota, with Jueyin (Liver) and Taiyin (Lung) meridian CMMs generally exerting a stronger effect. The gut microbiota may be a biological indicator for characterizing the TCM property theory, which not only enhances our understanding of classic TCM theory but also contributes to its scientific advancement and application in healthcare.

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Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer: A systematic review
Bizhar Ahmed Tayeb, Ikhwan Yuda Kusuma, Alaa A.M. Osman, Renáta Minorics
Journal of Integrative Medicine    2024, 22 (2): 137-162.   DOI: 10.1016/j.joim.2024.02.001
Accepted: 30 January 2024
Online available: 13 March 2024

Abstract133)   HTML    PDF      

Background

The field of personalized medicine has gained increasing attention in cancer care, with the aim of tailoring treatment strategies to individual patients for improved outcomes. Herbal medicine, with its long-standing historical use and extensive bioactive compounds, offers a rich source of potential treatments for various diseases, including cancer.

Objective

To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer diseases. Additionally, to explore the general characteristics of the studies included in the analysis, focusing on their key features and trends.

Search strategy

A comprehensive literature search was conducted from multiple online databases, including PubMed, Scopus, Web of Science, and CINAHL-EBSCO. The search strategy was designed to identify studies related to personalized cancer medicine and herbal interventions.

Inclusion criteria

Publications pertaining to cancer research conducted through in vitro, in vivo, and clinical studies, employing natural products were included in this review.

Data extraction and analysis

Two review authors independently applied inclusion and inclusion criteria, data extraction, and assessments of methodological quality. The quality assessment and biases of the studies were evaluated based on modified Jadad scales. A detailed quantitative summary of the included studies is presented, providing a comprehensive description of their key features and findings.

Results

A total of 121 studies were included in this review for analysis. Some of them were considered as comprehensive experimental investigations both in vitro and in vivo. The majority (n = 85) of the studies included in this review were conducted in vitro, with 44 of them specifically investigating the effects of herbal medicine on animal models. Additionally, 7 articles with a combined sample size of 31,271 patients, examined the impact of herbal medicine in clinical settings.

Conclusion

Personalized medication can optimize the use of herbal medicine in cancer treatment by considering individual patient factors such as genetics, medical history, and other treatments. Additionally, active phytochemicals found in herbs have shown potential for inhibiting cancer cell growth and inducing apoptosis, making them a promising area of research in preclinical and clinical investigations.


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Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling
Lu-lu Han, Xin Zhang, Hui Zhang, Ting Li, Yi-chen Zhao, Ming-hui Tian, Feng-lei Sun, Bo Feng
Journal of Integrative Medicine    2024, 22 (1): 83-92.   DOI: 10.1016/j.joim.2024.01.003
Accepted: 10 January 2024
Online available: 24 January 2024

Abstract132)   HTML    PDF      
Objective
Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD).

Methods
An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.

Results
AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 μmol/L and 1 μg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.

Conclusion
AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity.
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Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson’s disease: A randomized double-blind placebo-controlled trial
Yu Zhang, Xiao-bo Zhu, Yang Zhao, Gui-yun Cui, Wen-tao Li, Can-xing Yuan, Jian-ping Huang, Ying Wan, Na Wu, Lu Song, Jia-hao Zhao, Yan Liang, Chuan-ying Xu, Mei-juan Liu, Chen Gao, Xin-xin Chen, Zhen-guo Liu
Journal of Integrative Medicine    2024, 22 (5): 545-551.   DOI: 10.1016/j.joim.2024.07.002 Get rights and content
Accepted: 15 April 2024
Online available: 09 July 2024

Abstract131)   HTML    PDF      
Background
Patients with Parkinson’s disease (PD) undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia (LID). Amantadine is the main drug recommended for the treatment of LID by current guidelines, but it is far from meeting clinical needs. Tianqi Pingchan Granule (TPG), a compound Chinese herbal medicine, has been developed to relieve symptom of LID.
Objective
This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID.
Design, setting, participants and interventions
This is a randomized double-blind placebo-controlled trial, conducted from January 2020 to August 2021 at 6 sites in Jiangsu, Zhejiang and Shanghai, China. One hundred PD patients with ≥ 0.5 h of LID were randomly assigned to either the TPG plus amantadine group (TPG group) or the placebo plus amantadine group (placebo group), and treated for a period of 12 weeks. To ensure unbiased results, all study participants, investigators and sponsors were unaware of group allocations. Additionally, the data analysts remained blinded until the analysis was finalized.
Main outcome measures
The primary outcome was assessed using the Unified Dyskinesia Rating Scale (UDysRS) (Range 0–104). The key secondary end point was improvement of motor and non-motor symptoms. Safety analyses included all enrolled patients.
Results
One hundred patients were enrolled and randomized into the two treatment groups. The changes in UDysRS at week 12 were –11.02 for the TPG group and –4.19 for the placebo group (treatment difference –6.83 [–10.53 to –3.12]; P = 0.0004). Adverse events were reported for 2 of 50 patients (4.0%) in each of the groups.
Conclusion
This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated, demonstrating the efficacy and safety of TPG for the treatment of LID in PD.
Trial registration: 
ClinicalTrials.gov
 identifier: NCT04173832.
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Herbal medicine use in Republic of Korea to alleviate side effects of COVID-19 vaccines: A cross-sectional study
Hae-Chang Yoon
Journal of Integrative Medicine    2023, 21 (4): 361-368.   DOI: 10.1016/j.joim.2023.06.002
Accepted: 02 February 2023
Online available: 08 June 2023

Abstract127)   HTML    PDF      
Objective
Coronavirus disease 2019 (COVID-19) has spread worldwide, and several virus variants have emerged. Vaccines are administered to help prevent the infection. In Republic of Korea, most people take herbal medicine. This study investigated the use of herbal medicine to counter the side effects of COVID-19 vaccines.

Methods
This cross-sectional study was conducted using an online survey. Chi-square tests were used to determine differences in the use of herbal medication according to sociodemographic characteristics. Independent two-sample and paired t-tests were performed to examine the effect and satisfaction of herbal medicine use for countering the side effects of COVID-19 vaccines. One-way analysis of variance was used to determine vaccine-related differences.

Results
A total of 233 and 181 participants received the first and second doses of COVID-19 vaccines, respectively. The majority of herbal medicine users were in their thirties, had a bachelor’s degree, suffered from side effects of vaccination, and received Vaxzevria for their first COVID-19 vaccine dose and Comirnaty for their second dose. The herbal medicine group had a higher satisfaction level of post-vaccination side effects than the non-herbal medicine group (P < 0.0001). The numeric rating scale scores for vaccination side effects were lower among participants who took herbal medication to alleviate those symptoms (P < 0.0001). The most commonly used herbal formula was Shuanghetang.

Conclusion
A third of participants receiving COVID-19 vaccines used herbal medication to counter the side effects of vaccination. The use of herbal medicine was associated with age, education level, vaccine brand, and whether side effects of vaccination occurred. Herbal medication use was associated with greater satisfaction compared to vaccine recipients not using herbal medication.
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Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration
Kang-di Yang, Xu Zhang, Ming-cong Shao, Li-na Wang
Journal of Integrative Medicine    2023, 21 (6): 575-583.   DOI: 10.1016/j.joim.2023.10.002
Accepted: 19 December 2022
Online available: 29 October 2023

Abstract126)   HTML    PDF      
Objective
Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC).

Methods
An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method.

Results
We demonstrated that the ability of AAE to induce overexpression of the cytokine C–C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38.

Conclusion
Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments.
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Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress
Qian-zhuo Liu, Hui Han, Xin-ru Fang, Lu-yao Wang, Dan Zhao, Miao-zhu Yin, Nian Zhang, Peng-yu Jiang, Zhi-hui Ji, Li-min Wu
Journal of Integrative Medicine    2024, 22 (4): 493-502.   DOI: 10.1016/j.joim.2024.05.003
Accepted: 15 April 2024
Online available: 23 May 2024

Abstract125)   HTML    PDF      
Objective
Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD.

Methods
Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress.

Results
Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway.

Conclusion
Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.
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Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease
Lin-hong Jiang, Pei-jun Li, Ying-qi Wang, Mei-ling Jiang, Xiao-yu Han, Yi-die Bao, Xin-liao Deng, Wei-bing Wu, Xiao-dan Liu
Journal of Integrative Medicine    2023, 21 (6): 518-527.   DOI: 10.1016/j.joim.2023.11.005
Accepted: 16 October 2023
Online available: 14 November 2023

Abstract124)   HTML    PDF      
Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation.
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Unlocking the potential: How acupuncture reshapes the liver-centered lipid metabolism pattern to fight obesity
Shu-rui Yang, Li Chen, Dan Luo, Ya-yuan Wang, Feng-xia Liang
Journal of Integrative Medicine    2024, 22 (5): 523-532.   DOI: 10.1016/j.joim.2024.08.004
Accepted: 18 July 2024
Online available: 20 August 2024

Abstract124)   HTML    PDF      
Obesity, a widespread global health issue, is frequently linked to disrupted lipid metabolism, resulting in excessive accumulation of adipose tissue and associated health complications. Acupuncture, a traditional Chinese medical modality, has exhibited potential as a viable intervention for addressing obesity. The underlying mechanism proposed involves the stimulation of specific acupoints to exert a regulatory influence on hepatic function. The liver has a central role in lipid metabolism, including processes such as lipid synthesis, storage and distribution. Acupuncture is believed to enhance the liver’s efficiency in processing lipids, thereby reducing lipid accumulation and improving metabolic functions. Research indicates that acupuncture can influence the expression of certain genes and proteins involved in lipid metabolism in the liver. This includes upregulating genes that promote lipid breakdown and oxidation, and downregulating those involved in lipid synthesis. Additionally, acupuncture has been shown to improve insulin sensitivity, which is crucial for the regulation of lipid metabolism. Furthermore, the potential anti-inflammatory effects of acupuncture may play a significant role in its efficacy for the treatment of obesity. The presence of chronic inflammation has been strongly associated with metabolic disorders such as obesity. Through its ability to mitigate inflammation, acupuncture can potentially aid in the restoration of lipid metabolism and the reduction of body weight. Moreover, the amelioration of hepatic oxidative stress represents another mechanism by which acupuncture may contribute to the reduction of lipid deposition. Notably, the liver, being the primary site of lipid metabolism, maintains communication with various organs including the brain, adipose tissue, skeletal muscle and intestines. This perspective opens new avenues for the treatment of obesity, emphasizing the importance of holistic approaches in managing complex metabolic disorders.
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Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives
Mei Zhang, Rui Zheng, Wen-jing Liu, Jun-ling Hou, Yu-lei Yang, Hong-cai Shang
Journal of Integrative Medicine    2023, 21 (5): 413-422.   DOI: 10.1016/j.joim.2023.08.004
Accepted: 30 April 2023
Online available: 11 August 2023

Abstract123)   HTML    PDF      
Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient’s immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ’s anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia.
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Promoting whole person health: Exploring the role of traditional Chinese medicine in Polish healthcare
Monika Rybicka, Jing Zhao, Karolina Piotrowicz, Sara Ptasnik, Kamila Mitka, Magdalena Kocot-Kępska, Ka-Kit Hui
Journal of Integrative Medicine    2023, 21 (6): 509-517.   DOI: 10.1016-j.joim.2023.10.001
Accepted: 08 October 2023
Online available: 30 October 2023

Abstract121)   HTML    PDF      
Poland has a unique history of traditional Chinese medicine (TCM) dating back to the 17th century when Polish missionary Michael (Micha?) Boym was a pioneer in the field. In the 20th century, his successor, Professor Zbigniew Garnuszewski, reintroduced acupuncture to medical practice in Poland. However, other methods of TCM and its holistic approach to patient care have not found their place in modern medicine in Poland. At present, the legal status of TCM in Poland remains unregulated, with TCM included in the broad spectrum of complementary and alternative medicine (CAM) practices. Few reports are available on the use of TCM methods among the Polish population. Integrative medicine combines conventional medicine with evidence-based CAM interventions and considers all aspects of a patient’s health, including physical, emotional, mental, social and environmental factors. An integrative healthcare model that incorporates TCM modalities and lifestyle recommendations as well as a whole person approach may provide a more sustainable solution for the constantly underfinanced Polish healthcare system, which faces challenges of multimorbidity in an aging society and limited access to care. The coronavirus disease 2019 pandemic, war in Ukraine, and ongoing climate crisis have underscored the need to strengthen the resilience of the Polish healthcare system and search for new solutions. A model of care that blends the best of biomedicine and TCM healing approaches may be a better option for both patients and the healthcare system in Poland.
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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines
Li-hua Zhu, Yu-pei Liang, Lian Yang, Feng Zhu, Li-jun Jia, He-gen Li
Journal of Integrative Medicine    2024, 22 (4): 503-514.   DOI: 10.1016-j.joim.2024.05.004
Accepted: 16 May 2024
Online available: 24 May 2024

Abstract121)   HTML    PDF      
Objective
Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer (NSCLC) and elucidates the underlying molecular mechanisms.

Methods
The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays. Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots. Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology, were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.

Results
Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1 (NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.

Conclusion
Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.
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Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: A multicenter, double-blind, placebo-controlled, randomized trial
Jia-jia Wu, Tian-yi Zhang, Ying-hui Qi, Min-yan Zhu, Yan Fang, Chao-jun Qi, Li-ou Cao, Ji-fang Lu, Bo-han Lu, Lu-min Tang, Jian-xiao Shen, Shan Mou
Journal of Integrative Medicine    2024, 22 (3): 279-285.   DOI: 10.1016/j.joim.2024.04.004
Accepted: 04 November 2022
Online available: 23 April 2024

Abstract121)   HTML    PDF      
Background
Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy.

Objective
This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI.

Design, setting, participants and interventions
This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules.

Main outcome measures
The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria.

Results
Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively.

Conclusion
The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI.

Trial Registration
Chinese Clinical Trial Registry ChiCTR2100051723.
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Mechanisms of acupuncture at Zusanli (ST36) and its combinational acupoints for stress gastric ulcer based on the correlation between Zang-fu and acupoints
Mu He, Xue Yee Lim, Jing Li, Ling Li, Tong Zhang
Journal of Integrative Medicine    2025, 23 (1): 1-11.   DOI: 10.1016/j.joim.2024.12.003
Accepted: 12 August 2024
Online available: 10 December 2024

Abstract121)   HTML    PDF      
Gastric ulcer (GU) is a common digestive system disease. Acupuncture, as one of the external treatments of traditional Chinese medicine (TCM), has the characteristics of multi-target, multi-pathway and multi-level action in the treatment of GU. The relationship between meridian points and Zang-fu is an important part of the theory of TCM, which is crucial for the diagnosis and treatment of diseases. There is an external and internal link between acupoints and Zang-fu. The pathological reaction of Zang-fu can manifest as acupoint sensitization, while stimulation of acupoints can play a therapeutic role in the internal Zang-fu. Therefore, the acupoint has the functions of reflecting and treating diseases. This review explores the tender points on the body surface of patients with GU and the rules of acupoint selection. In addition, Zusanli (ST36), as one of the most used acupoints of the stomach meridian, was selected to show the mechanisms behind acupoint stimulation in the treatment of GU in greater detail, specifically in the well-studied model of the stress-induced GU (SGU). Hence, the mechanisms of acupuncture at ST36 and points commonly used in combination with ST36 to treat SGU are discussed further. Treatment effects can be achieved through anti-inflammatory and antioxidant activities, gastric mucosal injury repair, and interaction with the brain-gut axis. In summary, this review provides evidence for a comprehensive understanding of the phenomena and mechanism of acupoint functions for GU.
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Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial
Jian-sheng Li, Hai-long Zhang, Wen Guo, Lu Wang, Dong Zhang, Li-min Zhao, Miao Zhou
Journal of Integrative Medicine    2023, 21 (6): 543-549.   DOI: 10.1016/j.joim.2023.11.003
Accepted: 12 May 2023
Online available: 08 November 2023

Abstract119)   HTML    PDF      
Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear.

Objective: The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF.

Design, setting, participants and interventions: We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment.

Main outcome measures: The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George’s Respiratory Questionnaire for IPF (SGRQ-I) score.

Results: The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: –3.30 days; 95% CI, –6.300 to –0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: –0.67; 95% CI: –0.89 to –0.44; P < 0.001) and SGRQ-I score (between-group difference: –10.36; 95% CI: –16.483 to –4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: –0.67; 95% CI: –0.91 to –0.43; P < 0.001) and SGRQ-I (between-group difference: –10.28; 95% CI, –15.838 to –4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant.

Conclusion: KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research.

Trial registration: Chinese Clinical Trial Registry (ChiCTR1900026289).
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Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China
Shun-xian Zhang, Xiao-xu Chen, Yong Zheng, Bing-hua Cai, Wei Shi, Ming Ru, Hui Li, Dan-dan Zhang, Yu Tian, Yue-lai Chen
Journal of Integrative Medicine    2023, 21 (4): 369-376.   DOI: 10.1016/j.joim.2023.06.005
Accepted: 04 May 2023
Online available: 14 June 2023

Abstract118)           
Objective
Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19).

Methods
This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis.

Results
Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.

Conclusion
Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding.
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Distribution of licensed acupuncturists and educational institutions in the United States at the start of 2023, during the late stage of the COVID-19 pandemic
Arthur Yin Fan, De-guang He, Anu Sangraula, Sarah Faggert Alemi, Amy Matecki
Journal of Integrative Medicine    2024, 22 (4): 379-384.   DOI: 10.1016/j.joim.2024.06.002
Accepted: 16 May 2024
Online available: 24 June 2024

Abstract118)   HTML    PDF      
This study was conducted to identify the number and density of active licensed acupuncturists (LAcs), as well as the number of accredited schools in acupuncture and Oriental medicine (AOM), as of January 1, 2023, in the United States (U.S.). The number of active LAcs as of January 1, 2023 was 34,524, potentially 33,364 after removing license duplication in multiple states, among which the largest three states were California (with 7317 LAcs [21.19% of the total]), New York (5024 [14.55%]) and Florida (2644 [7.66%]). The total number of LAcs decreased by 8.87% from 2018, and fell short of our projected number of LAcs in 2023 by 9037, or 20.75%. The overall LAc density in the U.S.—measured as the number of LAcs per 100,000 population—was 10.36, less than in 2018. There were 56 active, accredited AOM schools which offered a total of 147 programs (121 at the level necessary for licensing [entry-level], 12 for an advanced practicing degree [advanced-level], and 14 for certifications). Broken down further, offerings included 50 master’s degrees in acupuncture, 40 master’s degrees in Oriental medicine, 31 entry-level doctorate degrees (10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine), and 12 advanced-level doctorate degrees in AOM. The certification programs included one in East-Asian Medical Bodywork and 13 in CHM. Among these schools in 2023, institutions in the West and East Coast states comprised 67.86% (decreased from 77.42% in 2018) of the national total. California, Florida and Illinois represented 39.29%. There were 48 jurisdictions with acupuncture practice laws in place. The data suggests that the acupuncture profession in the U.S. has been significantly impacted during the coronavirus disease 2019 pandemic.
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ISSN 2095-4964
CN 31-2083/R

Editors-in-Chief:
Chang-quan Ling, Shanghai, China
Guang Ji, Shanghai, China
Frequency: 6 issues per year
Publisher: Science Press, China

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