Urinary incontinence (UI) is a common problem worldwide. It has a major impact on the physical and social activities and interpersonal relationships. UI is common in women, but is under-reported and under-treated. It affects the quality of life in female patients severely and is known as a “nonlethally social cancer.” Acupuncture and moxibustion has been proposed as a potentially effective intervention for female UI. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI. The CPG was developed according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPGs, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method. The CPGs contain ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions, which include nine conditional recommendations for the intervention, one conditional recommendations for either the intervention or the comparison. The CPG also provide one conventional filiform needle therapy protocol, two deep puncturing stimulation on lumbosacral acupoints therapy protocols, and four moxibustion therapy protocols, based on the protocols presented in RCTs reviews by the GDG.

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

Objective: Effects of arsenic trioxide (As2O3) on hepatocellular carcinoma (HCC) has been documented widely. In addition, autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3 -induced apoptosis in liver cancer cells.
Methods: The viability of hepatoma cells was determined with MTT assay. The apoptosis of As2O3-induced liver cancer cells was evaluated by flow cytometry, Hoechst 33258 staining and TUNEL assays. The autophagy of liver cancer cell was detected by immunofluorescence, western blot assay and transmission electron microscopy.
Results: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cells increased with the concentration of As2O3 as determined by Flow cytometry. Apoptosis in liver cancer cells induced by As2O3 was also demonstrated by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, we also found that As2O3 treatment induced liver cancer cells autophagy, which was demonstrated by western blot, immunofluorescence of LC3-II and Beclin 1 expression and transmission electron microscopy observation. In liver cancer cells, As2O3 inhibited the PI3K/AKT/mTOR signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator, SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-MA partially reversed As2O3-induced cell viability inhibition, and enhanced autophagy with serum starvation facilitated As2O3-induced cell death.
Conclusion: As2O3 is able to induce liver cancer cells apoptosis and autophagy. Autophagy induced by As2O3 may play a proapoptotic effect in the anti-liver cancer effects. Our present study provides novel insights into the anti-liver cancer effects of As2O3.

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.

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

Background

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

Objective

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

Design, setting, participants and interventions

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

Main outcome measures

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

Results

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

Conclusion

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

Trial registration

Chinese Clinical Trial Registry (ChiCTR2000036970).

Background

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

Objective

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

Search strategy

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

Inclusion criteria

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

Data extraction and analysis

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

Results

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

Conclusion

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

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.

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.

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.

Gastric ulcer (GU) is a common digestive system disease. Acupuncture, as one of the external treatments of traditional Chinese medicine (TCM), has the characteristics of multi-target, multi-pathway and multi-level action in the treatment of GU. The relationship between meridian points and Zang-fu is an important part of the theory of TCM, which is crucial for the diagnosis and treatment of diseases. There is an external and internal link between acupoints and Zang-fu. The pathological reaction of Zang-fu can manifest as acupoint sensitization, while stimulation of acupoints can play a therapeutic role in the internal Zang-fu. Therefore, the acupoint has the functions of reflecting and treating diseases. This review explores the tender points on the body surface of patients with GU and the rules of acupoint selection. In addition, Zusanli (ST36), as one of the most used acupoints of the stomach meridian, was selected to show the mechanisms behind acupoint stimulation in the treatment of GU in greater detail, specifically in the well-studied model of the stress-induced GU (SGU). Hence, the mechanisms of acupuncture at ST36 and points commonly used in combination with ST36 to treat SGU are discussed further. Treatment effects can be achieved through anti-inflammatory and antioxidant activities, gastric mucosal injury repair, and interaction with the brain-gut axis. In summary, this review provides evidence for a comprehensive understanding of the phenomena and mechanism of acupoint functions for GU.

Background
Moderate to severe breast pain has major effects on the quality of life for patients. Patent Chinese medicines are widely used in the treatment of breast pain due to their stable dosage form and good efficacy.

Objective
To evaluate the beneficial effects and safety of Hongjin Xiaojie Capsule (HJXJC), a Chinese patent medicine, for the treatment of cyclical breast pain.

Design, setting, participants and intervention
This is a multicenter, single-blind randomized controlled trial conducted in 3 medical centers in China from 2019 to 2021. Patients with moderate to severe cyclic breast pain were randomly divided into the intervention group (who took HJXJC, four capsules per dose, three times a day for 12 weeks) and the control group (waiting for the treatment) in a 1:1 ratio.

Main outcome measures
The primary outcome was pain duration, and the patients recorded measurements at baseline and at the end of weeks 4, 8, 12 and 16 on a patient log card.

Results
The full analysis set (FAS) population included 298 participants (intervention group, n = 150; control group, n = 148), while the per-protocol analysis set (PPS) included 274 participants. After 12 weeks, the duration of breast pain was significantly shorter in the intervention group (FAS: mean difference, –6.69; 95% CI, –7.58 to –5.80; P < 0.01, vs control. PPS: mean difference, –7.09; 95% CI, –8.01 to –6.16; P < 0.01, vs control). The Short-form McGill Pain Questionnaire (SF-MPQ) scores were significantly lower in the intervention group (FAS: mean difference, –12.55; 95% CI, –13.90 to –11.21; P < 0.01, vs control. PPS: mean difference, –13.07; 95% CI, –14.48 to –11.66; P < 0.01, vs control). The above indicators continued to be significantly different through week 16. Moreover, in the intervention group, breast lumps shrank after 12 weeks and the size of breast lumps was statistically smaller than that in the control group (P < 0.05), whereas the sizes of breast nodules and uterine fibroid showed no statistically significant difference compared with the control group (P > 0.05). At weeks 8 and 12, the dysmenorrhea scores in the intervention group were lower than those in the control group (P < 0.05). No obvious adverse reactions were observed in any group.

Conclusion

HJXJC can significantly shorten the duration of breast pain, reduce breast pain, reduce the size of breast lumps, and relieve dysmenorrhea. However, it has no significant effect on the size of breast nodules or uterine fibroid.

Trial registration

This trial has been registered at the ISRCTN Registry. Number: ISRCTN44184398.

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

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

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

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

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

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

Trial registration

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

Background

Electroacupuncture is often used to treat insomnia.

Objective

To evaluate the efficacy and safety of electroacupuncture for insomnia.

Search strategy

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

Inclusion criteria

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

Data extraction and analysis

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

Results

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

Conclusion

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

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.

Background
Chronic obstructive pulmonary disease (COPD), a common respiratory disease, can be effectively treated by traditional Chinese medicine (TCM). Qingfei Huatan, a TCM formula, has been reported to effectively alleviate the clinical symptoms of COPD patients. However, there is a lack of multi-centre, randomised, double-blind, controlled clinical trials documenting the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD (AECOPD).
Objective
This study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD, thereby providing high-quality clinical evidence.
Design, setting, participants and interventions
A total of 276 patients with AECOPD were included in this multi-centre, randomised, double-blind, placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:1. Patients in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day, for 14 days, in addition to Western medicine treatment. All patients were followed up for 3 months.
Main outcome measures
The primary outcome was time taken to symptom stabilisation. The secondary outcomes included duration of antibiotic use, clinical symptom and sign score, TCM syndrome score, dyspnoea score, and quality of life (QOL) score. Meanwhile, the safety of the formula was assessed through routine urine and stool tests, electrocardiograms, liver and kidney function tests, and the observation of adverse events throughout the trial.
Results
The time taken for effective stabilisation (P < 0.05) and obvious stabilisation (P < 0.01), and the duration of antibiotic use (P < 0.05) were significantly shorter in the treatment group than in the control group. On days 6, 9, 12 and 14 of treatment, clinical symptom and sign score decreased in both groups, particularly in the treatment group (P < 0.01). On days 9, 12 and 14 of treatment, the TCM syndrome scores of both groups were reduced (P < 0.01), with more significant reductions in the treatment group. At 3 months after the end of treatment, the treatment group continued to have lower clinical symptom and sign score and TCM syndrome score than the control group (P < 0.01). On days 6, 9, 12 and 14 of treatment, dyspnoea and QOL scores were markedly reduced in the two groups (P < 0.05 and P < 0.01, respectively), especially in the treatment group. At 3 months after the end of treatment, dyspnoea and QOL scores were lower in the treatment group than those in the control group (P < 0.01). No serious adverse events were observed in either group.
Conclusion
The Qingfei Huatan formula can effectively shorten the duration of AECOPD and antibiotic use, significantly relieve clinical symptoms, and increase QOL for AECOPD patients, with a favourable safety profile. These results suggest that this formula can be used as a complementary treatment for AECOPD patients.
Trial registration: The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1900026576).

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

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

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

Conclusion
This study initially investigated the acceptance, attitude, and independent predictors of TCM use among PD patients. To expand the prevalence of TCM use among patients with PD, we recommend to broadening the public outreach for TCM via contemporary means of Internet and broadcast communication, enhancing access to TCM services in rural communities, and strengthening the communication between doctors and patients.

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

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

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

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

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

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

Trial Registration
Chinese Clinical Trial Registry ChiCTR2100051723.

Background

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

Objective

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

Search strategy

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

Inclusion criteria

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

Data extraction and analysis

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

Results

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

Conclusion

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

Background

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

Objective

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

Search strategy

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

Inclusion criteria

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

Data extraction and analysis

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

Results

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

Conclusion

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

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.

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

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

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

Conclusion
One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis, which can be alleviated by treatment with ferroptosis inhibitors. These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.

Objective

Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. 

Methods

HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting analysis were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes.

Results

Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy.

Conclusion

Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis.

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.

The hypothalamic–pituitary–adrenal (HPA) axis is a critical component of the neuroendocrine system, playing a central role in regulating the body’s stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus, hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis. This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.

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.

Background

Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years.

Objective

This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm.

Design, setting, participants and interventions

A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18–80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks.

Main outcome measures

The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]).

Results

HQQR’s primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). 

Conclusion

This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension.

Trial registration

ChiCTR2000035092 (http://www.chictr.org.cn/).

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

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

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

Conclusion
Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

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

Background

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

Objective

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

Search strategy

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

Inclusion criteria

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

Data extraction and analysis

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

Results

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

Conclusion

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

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.

May 23–25, 2024, the Hong Kong Polytechnic University, Hong Kong, China

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

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).

Obesity, a widespread global health issue, is frequently linked to disrupted lipid metabolism, resulting in excessive accumulation of adipose tissue and associated health complications. Acupuncture, a traditional Chinese medical modality, has exhibited potential as a viable intervention for addressing obesity. The underlying mechanism proposed involves the stimulation of specific acupoints to exert a regulatory influence on hepatic function. The liver has a central role in lipid metabolism, including processes such as lipid synthesis, storage and distribution. Acupuncture is believed to enhance the liver’s efficiency in processing lipids, thereby reducing lipid accumulation and improving metabolic functions. Research indicates that acupuncture can influence the expression of certain genes and proteins involved in lipid metabolism in the liver. This includes upregulating genes that promote lipid breakdown and oxidation, and downregulating those involved in lipid synthesis. Additionally, acupuncture has been shown to improve insulin sensitivity, which is crucial for the regulation of lipid metabolism. Furthermore, the potential anti-inflammatory effects of acupuncture may play a significant role in its efficacy for the treatment of obesity. The presence of chronic inflammation has been strongly associated with metabolic disorders such as obesity. Through its ability to mitigate inflammation, acupuncture can potentially aid in the restoration of lipid metabolism and the reduction of body weight. Moreover, the amelioration of hepatic oxidative stress represents another mechanism by which acupuncture may contribute to the reduction of lipid deposition. Notably, the liver, being the primary site of lipid metabolism, maintains communication with various organs including the brain, adipose tissue, skeletal muscle and intestines. This perspective opens new avenues for the treatment of obesity, emphasizing the importance of holistic approaches in managing complex metabolic disorders.

Objective

Traditional Chinese medicine (TCM) incorporates traditional diagnostic methods and several major treatment modalities including Chinese herbal medicine, Chinese patent medicine, and non-pharmacological methods such as acupuncture and tuina. Even though TCM is used daily by more than 70,000 healthcare facilities and over 700,000 clinical practitioners in China, there is a poor understanding of the extent to which TCM diagnostic methods are used, how different treatment modalities are deployed in general, and what major factors may affect the integration of TCM and Western medicine. This study aimed to fill this void in the literature.

Methods

In the 2021 National Healthcare Improvement Evaluation Survey, we included three questions gauging the perception and practices of TCM amongst physicians working in TCM-related facilities, investigating the frequency of their deployment of TCM diagnostic methods, and predominant TCM treatment methods. Our empirical analysis included descriptive statistics, intergroup chi-square analysis, and binary logistic regression to examine the association between different types of facilities and individual characteristics and TCM utilization patterns.

Results

A total of 7618 clinical physicians comprised our study sample. Among them, 84.27% have integrated TCM and Western medicine in their clinical practice, and 80.77% of TCM practitioners used the 4 diagnostic methods as a tool in their clinical practice. Chinese herbal medicine was the most widely utilized modality by Chinese TCM physicians (used by 88.49% of respondents), compared with the Chinese patent medicine and non-pharmacological TCM methods, which were used by 73.14%, and 69.39%, respectively. Herbal tea as an out-of-pocket health-maintenance intervention is also a notable practice, recommended by 29.43% of physicians. Significant variations exist across certain institutions, departments, and individual practitioners.

Conclusion

Given that most of the surveyed physicians integrated TCM with Western medicine in their clinical practices, the practice of “pure TCM” appears to be obsolete in China’s tertiary healthcare institutions. Notably, remarkable variation exists in the use of different TCM modalities across institutions and among individuals, which might be related to and thus limited by the practitioners’ experience. Future research focusing on the efficacy and safety of TCM interventions for specific diseases, the development of standardized clinical guidelines, and the enhancement of TCM education and training are called for to optimize TCM-Western medicine integration.

Objective

The concept of constitution in traditional Chinese medicine (TCM) has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia. However, rigorous statistical evidence on the correlation between TCM constitutions—particularly mixed constitutions—and insomnia disorder remains limited. This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.

Methods

A cross-sectional study was conducted at the Department of Preventive Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, from November 2022 to December 2023. TCM constitutions were assessed using the Constitution in Chinese Medicine Questionnaire. Insomnia disorder was diagnosed by experienced internal medicine physicians according to the criteria of the International Classification of Sleep Disorders, Third Edition. A total of 1065 eligible participants (242 with insomnia disorder and 823 controls) were included in the final analysis.

Results

Among the participants, 862 (80.94%) exhibited biased constitutions, with 75.30% of these having mixed constitutions. Logistic regression analysis revealed a negative association between the gentleness constitution and insomnia disorder, whereas qi-deficiency, yang-deficiency, phlegm-dampness and qi-depression constitutions were positively associated with insomnia disorder. These associations remained significant after adjusting for potential confounders and were further validated through sensitivity analysis using propensity score matching.

Conclusion

Significant associations between TCM constitutions and insomnia disorder were demonstrated. Future research should further investigate these relationships and explore the underlying mechanisms through rigorous longitudinal and interventional studies to improve understanding and clinical applications.

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

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

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

Conclusion
Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

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

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

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

Conclusion
AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity.

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.

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with “stopping” and “continuation” criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation.

Phytosomes (phytophospholipid complex) are dosage forms that have recently been introduced to increase the stability and therapeutic effect of herbal medicine. Currently, bioactive herbs and the phytochemicals they contain are considered to be the best remedies for chronic diseases. One promising approach to increase the efficacy of plant-based therapies is to improve the stability and bioavailability of their bio-active ingredients. Phytosomes employ phospholipids as their active ingredients, and use their amphiphilic properties to solubilize and protect herbal extracts. The unique properties of phospholipids in drug delivery and their use in herbal medicines to improve bioavailability results in significantly enhanced health benefits. The introduction of phytosome nanotechnology can alter and revolutionize the current state of drug delivery. The goal of this review is to explain the application of phytosomes, their future prospects in drug delivery, and their advantages over conventional formulations.

Background

China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy.

Objective

This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach.

Design, setting, participants and interventions

This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment.

Main outcome measures

The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12.

Results

Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05).

Conclusion

Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL.

Trial registration

Chinese Clinical Trial Registry ChiCTR2200056216.

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

Background
Sleep disturbance is commonly seen in fibromyalgia syndrome (FMS); however, high quality studies involving manual therapies that target FMS-linked poor sleep quality are lacking for the Indian population.

Objective
Craniosacral therapy (CST), Bowen therapy and exercises have been found to influence the autonomic nervous system, which plays a crucial role in sleep physiology. Given the paucity of evidence concerning these effects in individuals with FMS, our study tests the effectiveness of CST, Bowen therapy and a standard exercise program against static touch (the manual placebo group) on sleep quality in FMS.

Design, setting, participants and intervention
A placebo-controlled randomized trial was conducted on 132 FMS participants with poor sleep at a hospital in Bangalore. The participants were randomly allocated to one of the four study groups, including CST, Bowen therapy, standard exercise program, and a manual placebo control group that received static touch. CST, Bowen therapy and static touch treatments were administered in once-weekly 45-minute sessions for 12 weeks; the standard exercise group received weekly supervised exercises for 6 weeks with home exercises until 12 weeks. After 12 weeks, all study participants performed the standard exercises at home for another 12 weeks.

Main outcome measures
Sleep quality, pressure pain threshold (PPT), quality of life and fibromyalgia impact, physical function, fatigue, pain catastrophizing, kinesiophobia, and positive–negative affect were recorded at baseline, and at weeks 12 and 24 of the intervention.

Results
At the end of 12 weeks, the sleep quality improved significantly in the CST group (P = 0.037) and Bowen therapy group (P = 0.023), and the PPT improved significantly in the Bowen therapy group (P = 0.002) and the standard exercise group (P < 0.001), compared to the static touch group. These improvements were maintained at 24 weeks. No between-group differences were observed for other secondary outcomes.

Conclusion
CST and Bowen therapy improved sleep quality, and Bowen therapy and standard exercises improved pain threshold in the short term. These improvements were retained within the groups in the long term by adding exercises. CST and Bowen therapy are treatment options to improve sleep and reduce pain in FMS.

Trial registration number
Registered at Clinical Trials Registry of India with the number of CTRI/2020/04/024551.

Objective
Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.
Methods
Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism.
Results
Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin‐α demonstrated a similar therapeutic effect in the MIRI mice.
Conclusion
Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.

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.

Traditional Chinese medicine (TCM) is a treasure of the Chinese culture, with a long history of use, while Western medicine, characterized by empirical evidence and linear methods, is an established global medical system. The integration of these two systems provides a synergistic strategy capable of tackling medical issues inadequately treated by each system independently. The history of integrated Chinese and Western medicine in China dates back to the 19th century and has evolved significantly, particularly with support from the Chinese government in recent decades. This commentary outlines the necessary conditions for successful integration of the two systems, including mutual respect, collaboration, and innovation within TCM, while also accessing modern information technologies such as artificial intelligence and high-throughput-omics techniques. Meanwhile, flexible hospital management systems and guidelines for evaluating quality of service are needed to support integrative work and need attention. The ultimate goal of constructing top-tier public medical institutions in China that integrate TCM and Western medicine will lead to more capable and accessible clinical services and improved healthcare outcomes.

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.

Epigallocatechin-3-gallate (EGCG), a prominent plant-based catechin predominantly derived from Camellia sinensis and widely available on the market as a health supplement, has garnered significant attention for its potential therapeutic benefits, particularly in the context of type 2 diabetes mellitus (T2DM). This review explores the multifaceted role of EGCG in addressing the “ominous octet”—the 8 core pathophysiological defects associated with T2DM. The literature search was carried out using key terms “EGCG” OR “epigallocatechin-3-gallate” OR “epigallocatechin gallate” AND “diabetes” OR “insulin resistance” OR “hyperglycemia” in the PubMed and Scopus databases. The search was constrained to articles published between January 2018 and April 2024, focusing on the document type. Full-text articles published in English and relevant to EGCG that featured a single active ingredient, included clearly explained diabetes relief mechanism, and included ominous octet aspects were included in the final review. The outcomes of the included studies were reviewed and categorized based on 8 core pathophysiological defects, collectively referred to as the ominous octet in T2DM. This review concludes that EGCG is a potent hypoglycemic agent that has beneficial effects against the ominous octet in addition to its pharmacological activities in modulating gut microbiota dysbiosis, carbohydrate digestion and metabolism, glucose transporter-mediated intestinal glucose-uptake, endothelial dysfunction, and renal damage that are significantly associated with pathogenesis of T2DM. This extensive scientific evidence suggests that EGCG may offer a novel approach to traditional antidiabetic therapies, potentially improving glycemic control and mitigating complications associated with T2DM. The inhibitory effects of EGCG on sodium-glucose transport proteins and their role in reducing renal glucose reabsorption remain unexplored, highlighting a significant research gap. Future research should also aim to broaden the scope by investigating the “egregious eleven”, which comprise a more comprehensive range of diabetic pathophysiological features. This review underscores the therapeutic promise of EGCG for managing T2DM and encourages ongoing research to fully elucidate its clinical applications.