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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

Abstract104)      PDF(pc) (1367KB)(89)    PDF(mobile) (1367KB)(9)   
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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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

Abstract124)   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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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

Abstract203)   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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Muscle energy technique for chronic obstructive pulmonary disease: A feasibility study
Danielle A. Baxter, Meaghan E. Coyle, Catherine J Hill, Christopher Worsnop, Johannah L. Shergis
Journal of Integrative Medicine    2023, 21 (3): 245-253.   DOI: 10.1016/j.joim.2023.03.006
Accepted: 28 October 2022
Online available: 14 April 2023

Abstract94)   HTML    PDF      

Objective

This study aimed to investigate the feasibility of implementing a manual therapy technique (muscle energy technique, MET) protocol in a hospital pulmonary rehabilitation (PR) program for patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Methods

Participants aged 40 years and over, with moderate to severe COPD, were recruited into this 12-week study. The primary outcome measures were feasibility (acceptability of the intervention and attendance/adherence to the trial) and safety (adverse events, AEs). All participants received the MET and PR therapies. Participants and assessors were unblinded. Semi-standardized MET was delivered on 6 occasions (a maximum of once per week) at the hospital directly before a PR session. Participants undertook PR sessions as per the hospital program at a frequency of two days per week for 8 weeks. Participants were contacted 4 weeks after their final MET treatment via a telephone call to assess acceptability of the intervention.

Results

Thirty-three participants were enrolled, with a median age of 74 years (range 45–89 years). The median number of MET sessions that participants attended was 5 (range 0–6) out of a possible 6 sessions (83% attendance). At follow-up, participants overwhelmingly enjoyed the MET treatment with some subjectively reporting improved breathing. There were no major AEs related to the intervention, with the majority of AEs classified as expected events related to COPD exacerbations.

Conclusion

It is feasible to implement a manual therapy protocol using MET as an adjunct to PR in a hospital setting. Recruitment rates were satisfactory and there were no AEs related to the MET component of the intervention.

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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

Abstract79)   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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A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications
Anusree DasNandy, Rajashri Virge, Harsha V. Hegde, Debprasad Chattopadhyay
Journal of Integrative Medicine    2023, 21 (3): 226-235.   DOI: 10.1016/j.joim.2023.02.003
Accepted: 28 September 2022
Online available: 28 February 2023

Abstract83)   HTML    PDF      
Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications.
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Lipidomic investigation of the protective effects of Polygonum perfoliatum against chemical liver injury in mice
Lei Peng, Hua-guo Chen, Xin Zhou
Journal of Integrative Medicine    2023, 21 (3): 289-301.   DOI: 10.1016/j.joim.2023.03.002
Accepted: 07 November 2022
Online available: 09 March 2023

Abstract76)   HTML    PDF      
Objective: Recent investigations have demonstrated that Polygonum perfoliatum L. can protect against chemical liver injury, but the mechanism behind its efficacy is still unclear. Therefore, we studied the pharmacological mechanism at work in P. perfoliatum protection against chemical liver injury.
Methods: To evaluate the activity of P. perfoliatum against chemical liver injury, levels of alanine transaminase, lactic dehydrogenase, aspartate transaminase, superoxide dismutase, glutathione peroxidase and malondialdehyde were measured, alongside histological assessments of the liver, heart and kidney tissue. A nontargeted lipidomics strategy based on ultra-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry method was used to obtain the lipid profiles of mice with chemical liver injury and following treatment with P. perfoliatum; these profiles were used to understand the possible mechanisms behind P. perfoliatum’s protective activity.
Results: Lipidomic studies indicated that P. perfoliatum protected against chemical liver injury, and the results were consistent between histological and physiological analyses. By comparing the profiles of liver lipids in model and control mice, we found that the levels of 89 lipids were significantly changed. In animals receiving P. perfoliatum treatment, the levels of 8 lipids were significantly improved, relative to the model animals. The results showed that P. perfoliatum extract could effectively reverse the chemical liver injury and significantly improve the abnormal liver lipid metabolism of mice with chemical liver injury, especially glycerophospholipid metabolism.
Conclusion: Regulation of enzyme activity related to the glycerophospholipid metabolism pathway may be involved in the mechanism of P. perfoliatum’s protection against liver injury.
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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

Abstract100)      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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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

Abstract169)   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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Understanding health literacy from a traditional Chinese medicine perspective
Zhiyi Qian, Grace Y. Wang, Marcus Henning, Yan Chen
Journal of Integrative Medicine    2023, 21 (3): 215-220.   DOI: 10.1016/j.joim.2023.03.001
Accepted: 19 January 2023
Online available: 04 March 2023

Abstract93)   HTML    PDF      
Health literacy is critical to improving individual and public health. However, indigenous perceptions of health are largely absent from Western-derived measurements, contributing to disparities in health outcomes between indigenous and non-indigenous populations. China is the country with the world’s largest population and only officially introduced the term “health literacy” in 2008. Current measures of health literacy in China are primarily based on Western-derived constructs, which have been shown to have poor comparability to the unique dual medical system in China. Given its significant importance to health management globally, understanding health perceptions from a traditional Chinese medicine perspective is essential. This review explores the concept and core elements of indigenous health literacy, evaluates the existing definitions and measurement tools as applied to the concept, and proposes a new model of traditional Chinese medicine health literacy.
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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

Abstract123)   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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Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9
Ya Zhong, Bo-wen Zhang, Jin-tao Li, Xin Zeng, Jun-xia Pei, Ya-mei Zhang, Yi-xi Yang, Fu-lun Li, Yu Deng, Qi Zhao
Journal of Integrative Medicine    2023, 21 (6): 584-592.   DOI: 10.1016/j.joim.2023.11.004
Accepted: 25 October 2023
Online available: 11 November 2023

Abstract37)   HTML    PDF      
Objective
To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation.

Methods
Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.

Results
EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin–proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.

Conclusion
Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.
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The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro
Tong Liu, Qing-qing Shao, Wen-jia Wang, Tian-li Liu, Xi-ming Jin, Li-jun Xu, Guang-ying Huang, Zhuo Chen
Journal of Integrative Medicine    2023, 21 (3): 277-288.   DOI: 10.1016/j.joim.2023.03.003
Accepted: 19 October 2022
Online available: 21 March 2023

Abstract241)   HTML    PDF      

Objective

JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.

Methods

HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125–50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.

Results

HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).

Conclusion

JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1.

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Cultural stress: The undiagnosed epidemic of our time
Howard Murad
Journal of Integrative Medicine    2023, 21 (3): 221-225.   DOI: 10.1016/j.joim.2023.03.008
Accepted: 06 January 2023
Online available: 30 March 2023

Abstract60)   HTML    PDF      
Global technologies that have made the world more interconnected have also, inadvertently, amplified the forces of stress that are now with us 24 hours a day, seven days a week. The accumulated impact of this stress I call cultural stress anxiety syndrome and call on integrative medicine practitioners to recognize that it is exacerbating whatever acute stressors are also present in our patients’ lives. In this Commentary, I outline seven major components of cultural stress (time pressure, digital intrusion, digital dependency, isolation, sedentary lifestyle, poor sleep, and uncertainty), describe their health consequences, and finally, offer cultural stress-specific remedies I have utilized in my own practice, along with studies that affirm their efficacy. My hope is that we, as integrative medicine practitioners who are cognizant of the role that stress plays in disease development, will more fully appreciate the added impact of cultural stress, and advise our patients on the importance of proactive stress management.
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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

Abstract61)   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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Effects of hyperbaric oxygen therapy on human psychomotor performance: A review
Dorota Olex-Zarychta
Journal of Integrative Medicine    2023, 21 (5): 430-440.   DOI: 10.1016/j.joim.2023.08.006
Accepted: 19 June 2023
Online available: 20 August 2023

Abstract26)   HTML    PDF      
Psychomotor performance is the coordination of a sensory or ideational (cognitive) process and a motor activity. All sensorimotor processes involved in planning and execution of voluntary movements need oxygen supply and seem to be significantly disrupted in states of hypoxia. Hyperbaric oxygen therapy has become a widely used treatment in routine medicine and sport medicine due to its beneficial effects on different aspects of human physiology and performance. This paper presents state-of-the-art data on the effects of hyperbaric oxygen therapy on different aspects of human psychomotor function. The therapy’s influence on musculoskeletal properties and motor abilities as well as the effects of hyperbaric oxygenation on cognitive, myocardial and pulmonary functions are presented. In this review the molecular and physiological processes related to human psychomotor performance in response to hyperbaric oxygen are discussed to contribute to this fast-growing field of research in integrative medicine.
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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

Abstract56)   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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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

Abstract97)   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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A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases
Jianjun Sun
Journal of Integrative Medicine    2023, 21 (4): 324-331.   DOI: 10.1016/j.joim.2023.06.004
Accepted: 12 May 2023
Online available: 08 June 2023

Abstract57)   HTML    PDF      
The prognosis of infectious diseases is determined by host-pathogen interactions. Control of pathogens has been the central dogma of treating infectious diseases in modern medicine, but the pathogen-directed medicine is facing significant challenges, including a lack of effective antimicrobials for newly emerging pathogens, pathogen drug resistance, and drug side effects. Here, a mathematic equation (termed equation of host-pathogen interactions, HPI-Equation) is developed to dissect the key variables of host-pathogen interactions. It shows that control of pathogens does not necessarily lead to host recovery. Instead, a combination of promoting a host's power of self-healing and balancing immune responses provides the best benefit for host. Moreover, the HPI-Equation elucidates the scientific basis of traditional Chinese medicine (TCM), a host-based medicine that treats infectious diseases by promoting self-healing power and balancing immune responses. The importance of self-healing power elucidated in the HPI-Equation is confirmed by recent studies that the tolerance mechanism, which is discovered in plants and animals and conceptually similar to self-healing power, improves host survival without directly attacking pathogens. In summary, the HPI-Equation describes host-pathogen interactions with mathematical logic and precision; it translates the ancient wisdoms of TCM into apprehensible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine.

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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

Abstract42)   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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Chrononutrition in traditional European medicine—ideal meal timing for cardiometabolic health promotion
Nora Selena Eberli, Ludivine Colas, Anne Gimalac
Journal of Integrative Medicine    DOI: 10.1016/j.joim.2024.02.002
Accepted: 01 February 2024
Online available: 01 March 2024

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    DOI: 10.1016/j.joim.2024.03.005
Accepted: 08 March 2024
Online available: 08 March 2024

Acupuncture and moxibustion for irritable bowel syndrome: An umbrella systematic review
Yue-ying Ma, Zhou Hao, Zi-yi Chen, Yan-xi Shen, Hui-rong Liu, Huan-gan Wu, Chun-hui Bao
Journal of Integrative Medicine    2024, 22 (1): 22-31.   DOI: 10.1016/j.joim.2023.12.001
Accepted: 09 November 2023
Online available: 23 December 2023

Abstract29)   HTML    PDF      
Background
Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with altered bowel habits. Several clinical studies have demonstrated the effectiveness of acupuncture and moxibustion for IBS. Many systematic reviews of acupuncture and moxibustion for IBS have been published in recent years, but their results are not entirely consistent.

Objective
To evaluate the methodological, reporting, and evidence quality of systematic reviews of acupuncture and moxibustion for IBS.

Search strategy
Systematic reviews of acupuncture and moxibustion for IBS published before February 20, 2023 were searched in eight databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, and China Biology Medicine. The keywords used for literature search were acupuncture, moxibustion, systematic review, meta-analysis, and irritable bowel syndrome.

Inclusion criteria
Systematic reviews and meta-analyses of randomized controlled trials of acupuncture and moxibustion for IBS were included.

Data extraction and analysis
Relevant information was independently extracted by two investigators. The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to evaluate the methodological quality, reporting quality and evidence quality, respectively.

Results
A total of 342 studies were retrieved and 15 systematic reviews were included. The results of AMSTAR 2 showed low methodological quality in 2 studies and very low methodological quality in the remaining 13 studies, with main issues being failure to register a protocol, incomplete search strategy, not providing a list of excluded studies, incomplete consideration of the risk of bias in the included studies, and a failure to assess the publication bias. The results of PRISMA 2020 showed seriously deficient reporting quality of 2 studies, somewhat deficient reporting quality of 12 studies, and relatively complete reporting quality of 1 study, with the main problems being lack of a complete search strategy, non-availability of a list of excluded studies with justification for their exclusion, not conducting heterogeneity and sensitivity analyses, not evaluating the credibility of the evidence, and not registering the protocol. The results of GRADE showed that the quality of the evidence is low or very low.

Conclusion
Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence.
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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    DOI: 10.1016/j.joim.2024.03.009
Accepted: 25 December 2023
Online available: 01 March 2024

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    DOI: 10.1016/j.joim.2024.03.011
Accepted: 07 March 2024
Online available: 07 March 2024

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

Abstract91)   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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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

Abstract72)   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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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

Abstract95)   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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Mechanical effects of needle texture on acupoint tissue
Ming-zhu Sun, Xin Wang, Ying-chen Li, Wei Yao, Wei Gu
Journal of Integrative Medicine    2023, 21 (3): 254-267.   DOI: 10.1016/j.joim.2023.03.005
Accepted: 14 November 2022
Online available: 23 March 2023

Abstract111)   HTML    PDF      
Objective
This study aims to clarify how the stimulation of acupuncture points is achieved by needles with different surface texture during acupuncture; it also seeks to lessen injury at the insertion site and increase the therapeutic efficacy of acupuncture, by simulating the mechanical effects of various needle surface patterns on Zusanli (ST36) without changing the radius of acupuncture needles.

Methods
Five acupuncture needle models with different surface patterns, including the smooth needle, the lined needle, the ringed needle, the left-hand threaded needle and the right-hand threaded needle, and a layered model of the Zusanli acupoint were used to investigate how to reduce tissue damage and increase stimulation during acupuncture treatment. Puncturing of the skin as well as lifting-inserting and twisting needle manipulations were simulated using these models, and the degree of damage and force of stimulation caused by the acupuncture needles with different surface patterns during acupuncture were compared.

Results
The smooth needle and the lined needle caused the least tissue damage during insertion, while the left-hand threaded and the right-hand threaded needles caused the most damage. The ringed needle, the left-hand threaded needle and the right-hand threaded needle stimulated the acupoint tissue more during lifting-inserting manipulations, while the lined needle and the smooth needle produced less stimulation. The stimulation of the lined needle on the acupoint tissue was the largest during twisting manipulation, whereas the left-hand threaded needle and the right-hand threaded needle had smaller effects. In lifting-inserting and twisting manipulations, both the left-hand threaded needle and right-hand threaded needle provided more stimulation, but the torsion direction in which they produced better stimulation was the opposite.

Conclusion
According to the simulation results, the ringed pattern enhances stimulation best in the lifting-inserting manipulation, whereas the lined pattern enhances stimulation best in the twisting manipulation. Both the right-hand and left-hand thread patterns have certain enhancing effects in these two operations. Taking the geometric properties of the pattern into account, the left-hand thread pattern and the right-hand thread pattern have the geometric characteristics of both the lined pattern and the ringed pattern. To conclude, a pattern perpendicular to the movement direction during the acupuncture manipulation creates more stimulation. These results have significance for future needle design.
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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

Abstract62)           
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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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

Abstract90)   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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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

Abstract48)   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

Abstract48)   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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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

Abstract59)   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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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   
Accepted: 18 November 2023
Online available: 23 November 2023

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

Abstract50)   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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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

Abstract75)   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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Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis
Chong-yang Sun a, Zhi-yi Xiong, Cheng-yi Sun, Pei-hong Ma, Xiao-yu Liu, Chi-yun Sun, Ze-yin Xin, Bao-yan Liu, Cun-zhi Liu, Shi-yan Yan
Journal of Integrative Medicine    2023, 21 (5): 455-463.   DOI: 10.1016/j.joim.2023.08.005
Accepted: 16 May 2023
Online available: 11 August 2023

Abstract39)   HTML    PDF      
Background
The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.

Objective
This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.

Search strategy
PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.

Inclusion criteria
Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.

Data extraction and analysis
Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.

Results
Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = ?0.99; 95% confidence interval [CI], ?1.31 to ?0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = ?0.20; 95% CI, ?0.80 to ?0.39. Average severity score: SMD = ?0.35; 95% CI, ?0.90 to ?0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, ?0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.

Conclusion
Strong placebo response and some relative factors were found in patients with primary dysmenorrhea.

PROSPERO registration number: CRD42022304215.
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From talk to action: Developing a model to foster effective integration of traditional medicine into the Ghanaian healthcare system
Irene G. Ampomah, Bunmi S. Malau-Aduli, Aduli E.O. Malau-Aduli, Theophilus I. Emeto
Journal of Integrative Medicine    2023, 21 (5): 423-429.   DOI: 10.1016/j.joim.2023.06.007
Accepted: 18 April 2023
Online available: 22 June 2023

Abstract36)   HTML    PDF      
This research assessed the experience of stakeholders and the efficacy of integrating traditional medicine into the Ghanaian health system using the Ashanti Region as the focal point. Elements of an integrative healthcare delivery model including philosophies/values, structure, process and outcome were used to conduct a quality assessment of the integrated health system in Ghana. Each element clearly showed that Ghana is currently not running a coordinated health practice model, thus making it a tolerant, rather than an inclusive, health system. Therefore, the primary purpose of this research is to discuss the development of a new and appropriately customised model that could enhance the practice of integrated healthcare in Ghana. The model we present has flexibility and far-reaching applicability in other African countries because such countries share similar socio-cultural and economic characteristics. As such, governments and health practitioners could adapt this model to improve the practice of integrated healthcare in their specific settings. Hospital administrators and health system researchers could also adapt the model to investigate or to monitor the progress and efficacy of integrated healthcare practices within their settings. This might help to understand the relationships between the integration of traditional medicine and health outcomes for a given population.
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Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine
Yu-jie Wang, Yan Wang, Pei Tao
Journal of Integrative Medicine    2023, 21 (3): 302-314.   DOI: 10.1016/j.joim.2023.04.001
Accepted: 27 June 2022
Online available: 27 April 2023

Abstract58)   HTML    PDF      
Objective
The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.

Methods
The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.

Results
Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.

Conclusion
Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines.
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Neuroprotective potential of cannabidiol: Molecular mechanisms and clinical implications
Srushti M. Tambe, Suraj Mali, Purnima D. Amin, Mozaniel Oliveira
Journal of Integrative Medicine    2023, 21 (3): 236-244.   DOI: 10.1016/j.joim.2023.03.004
Accepted: 10 March 2023
Online available: 18 March 2023

Abstract76)   HTML    PDF      
Cannabidiol (CBD), a nonpsychotropic phytocannabinoid that was once largely disregarded, is currently the subject of significant medicinal study. CBD is found in Cannabis sativa, and has a myriad of neuropharmacological impacts on the central nervous system, including the capacity to reduce neuroinflammation, protein misfolding and oxidative stress. On the other hand, it is well established that CBD generates its biological effects without exerting a large amount of intrinsic activity upon cannabinoid receptors. Because of this, CBD does not produce undesirable psychotropic effects that are typical of marijuana derivatives. Nonetheless, CBD displays the exceptional potential to become a supplementary medicine in various neurological diseases. Currently, many clinical trials are being conducted to investigate this possibility. This review focuses on the therapeutic effects of CBD in managing neurological disorders like Alzheimer’s disease, Parkinson’s disease and epilepsy. Overall, this review aims to build a stronger understanding of CBD and provide guidance for future fundamental scientific and clinical investigations, opening a new therapeutic window for neuroprotection.
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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

Abstract63)   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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Mapping the clinical practice of traditional, complementary and integrative medicine in oncology in Western countries: A multinational cross-sectional survey
Matthias Huemer, Sandro Graca, Sarah Bitsche, Guenter Hofmann, Mike Armour, Martin Pichler
Journal of Integrative Medicine    2024, 22 (1): 64-71.   DOI: 10.1016/j.joim.2023.12.002
Accepted: 14 December 2023
Online available: 08 January 2024

Abstract15)   HTML    PDF      

Background

Many cancer patients seek adjunctive therapies to biomedical cancer treatments at some point of their disease trajectory. While acupuncture is increasingly recommended by leading oncological associations, limited evidence exists concerning the evidence-informed practice and adherence to current guidelines of traditional complementary and integrative medicine (TCIM) practitioners treating cancer patients.

Methods

An international online-survey assessed the demographical data, clinical practice, and sources of information used by TCIM practitioners in Austria, Germany, United States of America, Australia, and New Zealand. 

Results

 In total, 404 respondents completed the survey, of which 254 (62.9%) treated cancer patients. Most practitioners were acupuncturists and herbalists (57.1%), had (16.8 ± 9.9) years of clinical experience and see a median of 2 (1, 4) cancer patients per week. Breast cancer (61.8%) is the most common cancer type seen in TCIM clinics. Adjunctive TCIM treatments are frequently concurrent with the patient’s cancer specific treatment (39.9%), which is also reflected by the main goal of a TCIM treatment to alleviate side effects (52.4%). However, only 28.0% of the respondents are in contact with the treating oncologist. According to the respondents, pain is most effectively treated using acupuncture, while herbal medicine is best for cancer-related fatigue. TCIM practitioners mostly use certified courses (33.1%) or online databases (28.3%) but often believe that experts are more reliable to inform their practice (37.0%) than research publications (32.7%).

Conclusion

Acupuncturists and herbalists commonly treat cancer patients. Most practitioners use TCIM as an adjunct to biomedicine as supportive care and use it largely in accordance with current oncological guidelines.

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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

Abstract30)   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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Identifying behavioral determinants and stage of readiness for performing knee massage among individuals with knee osteoarthritis: An observational study
Donya Nemati, Niki Munk, Navin Kaushal
Journal of Integrative Medicine    2024, 22 (1): 54-53.   DOI: 10.1016/j.joim.2024.01.006
Accepted: 02 November 2023
Online available: 24 January 2024

Abstract20)   HTML    PDF      
Objective
Patients who experience knee osteoarthritis or chronic knee pain can alleviate their symptoms by performing self-knee massage. Understanding the readiness and types of determinants needed to facilitate self-knee massage is needed to design effective, theory-informed interventions. The primary objective of this study was to apply the transtheoretical model of behavior change to identify how factors, which include the type of knee condition and pain level, predict an individual’s readiness to adopt self-knee massage. The secondary objective employed the capability, opportunity and motivation-behavior (COM-B) model to identify relevant determinants that are predictive of an individual’s readiness to undertake self-knee massage.

Methods
An observational study design was used to recruit individuals with knee osteoarthritis (n = 270) and chronic knee pain (n = 130). Participants completed an online survey that assessed the transtheoretical model of behavior change stages, COM-B determinants (capability, opportunity and motivation), along with self-administered massage behavior. Multivariate analysis of covariance and structural equation modeling were used to test the primary and secondary objective, respectively.

Results
Participants who had knee osteoarthritis scored higher on the action stage compared to those with chronic pain (P = 0.003), and those who experienced greater level of pain scored higher in the contemplation (P < 0.001) and action phases (P < 0.001) of performing knee massage compared to those with milder pain. The COM-B structural equation model revealed self-administered knee massage to be predicted by capability (β = 0.31, P = 0.004) and motivation (β = 0.29, P < 0.001), but not opportunity (β = –0.10, P = 0.39). Pain level predicted motivation (β = 0.27, P < 0.001), but not capability (β = 0.09, P = 0.07) or opportunity (β = 0.01, P = 0.83). Tests for mediating effects found that determinants of COM-B (motivation and capability) mediate between pain level and self-administered massage behavior (β = 0.10, P = 0.002).

Conclusion
Clinicians and researchers can expect that patients diagnosed with knee osteoarthritis or who have chronic knee pain are ready (action stage) or are considering the behavior (contemplation stage) of self-knee massage. Individuals who report having knee osteoarthritis or chronic knee pain should be coached to develop the skills to perform self-knee massage and helped to develop the motivation to carry out the therapy.
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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression
Rosemary Arnold, Jenifer Murphy-Smith, Chee H. Ng, David Mischoulon, Gerard J. Byrne, Chad A. Bousman, Con Stough, Michael Berk, Jerome Sarris
Journal of Integrative Medicine    2024, 22 (1): 46-53.   DOI: 10.1016/j.joim.2024.01.007
Accepted: 10 August 2023
Online available: 24 January 2024

Abstract13)   HTML    PDF      
Objective
The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment. Many well-designed randomized controlled trials (RCTs) of depression have a high proportion of placebo responders, with little understanding as to why. The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders.

Methods
This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo (n = 69 in placebo group). We investigated participant characteristics such as socio-demographics, clinical features, and recruitment methods, and their association with the placebo response. Monoaminergic genetic polymorphisms were also assessed. Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score. The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models.

Results
Greater levels of education, particularly pursuing post-high school education, better self-reported general health, marriage/de facto, greater improvement in the first trial week, and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response. An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy. Single nucleotide polymorphisms from the tryptophan hydroxylase 1 (TPH1) gene (A779C and A218C) were weakly associated with greater placebo response, although the evidence was attenuated after accounting for multiple comparisons.

Conclusion
This is, to our knowledge, the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response. Several variables appeared to predict the placebo response. Such findings may encourage future trial designs which could dampen placebo response, improve assay sensitivity, and allow for treatment effects to be potentially more detectable.
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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation
Meng Li, Yang Zhou, Hui Zhu, Lie-ming Xu, Jian Ping
Journal of Integrative Medicine    DOI: 10.1016/j.joim.2024.03.006
Accepted: 17 February 2024
Online available: 07 March 2024

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

Abstract33)   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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Tocotrienol isoforms: The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials
Maria Younes, Ghady Loubnane, Christopher Sleiman, Sandra Rizk
Journal of Integrative Medicine    2024, 22 (1): 1-11.   DOI: 10.1016/j.joim.2024.01.002
Accepted: 19 July 2023
Online available: 18 January 2024

Abstract42)   HTML    PDF      
Tocotrienols are found in a variety of natural sources, like rice bran, annatto seeds and palm oil, and have been shown to have several health-promoting properties, particularly against chronic diseases such as cancer. The incidence of cancer is rapidly increasing around the world, not only a result of continued aging and population growth, but also due to the adoption of aspects of the Western lifestyle, such as high-fat diets and low-physical activity. The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers, including breast, lung, ovarian, prostate, liver, brain, colon, myeloma and pancreatic cancers. These findings, along with the reported safety profile of tocotrienols in healthy human volunteers, encourage further research into these compounds’ potential use in cancer prevention and treatment. The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks, such as cellular proliferation, apoptosis, angiogenesis and metastasis. MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits. Following an overview of pre-clinical studies, we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.
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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

Abstract39)   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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ISSN 2095-4964
CN 31-2083/R

Editors-in-Chief:
Changquan Ling, Shanghai, China
Lixing Lao, Virginia, USA
Frequency: 6 issues per year
Publisher: Science Press, China

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