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

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).

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.

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.

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

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.

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

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.

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.

Objective
Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.
Methods
To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.
Results
We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.
Conclusion
We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual’s prognosis, guide precision treatments, and assist clinical decision making for HCC patients.

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.

Objective: This study explores the mechanism of action of Danhongqing formula (DHQ), a compound-based Chinese medicine formula, in the treatment of cholestatic liver fibrosis.
Methods: In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout (Mdr2^-/-) mice as an animal model of cholestatic liver fibrosis. DHQ was administered orally for 8 weeks, and its impact on cholestatic liver fibrosis was evaluated by assessing liver function, liver histopathology, and the expression of liver fibrosis-related proteins. Real-time polymerase chain reaction, Western blot, immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19 (H19) and signal transducer and activator of transcription 3 (STAT3) phosphorylation in the liver tissue of Mdr2^-/- mice. In addition, cholangiocytes and hepatic stellate cells (HSCs) were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression. Cholangiocytes overexpressing H19 were constructed, and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation. The intervention effect of DHQ on these processes was also investigated. HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.
Results: DHQ alleviated liver injury, ductular reaction, and fibrosis in Mdr2^-/- mice, and inhibited H19 expression, STAT3 expression and STAT3 phosphorylation. This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19, inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium, and decreased the expression of activation markers in HSCs. The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation, and DHQ was able to successfully inhibit these effects.
Conclusion: DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2^-/- mice by inhibiting H19 upregulation in cholangiocytes and preventing the inhibition of STAT3 phosphorylation in HSC, thereby suppressing cell activation.

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

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

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

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

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

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

Conclusion
Most included systematic reviews interpreted findings to suggest that acupuncture and moxibustion have benefits for IBS. However, there is a need to improve the methodological, reporting and evidence quality of the systematic reviews. Larger, multicenter, rigorously designed randomized controlled trials and high-quality systematic reviews are required to obtain more robust evidence.

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

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

Methods

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

Results

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

Conclusion

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

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.

Objective
Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome. Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events, but its underlying mechanism is not completely understood. The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.
Methods
AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse. Acupuncture was done at the Gok-Ji (LI11) acupoints. AD-like symptoms were assessed by lesion scores, scratching behavior, and histopathological changes; intestinal barrier function was measured by fecal output, serum lipopolysaccharide levels, histopathological changes, and mRNA expression of markers involved in intestinal permeability and inflammation. Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.
Results
Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening, and also significantly altered gut microbiota structure as revealed by β-diversity indices and analysis of similarities. These beneficial effects were eliminated by antibiotic depletion of gut microbiota, but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice. Interestingly, AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability, atrophy of the mucosal structure (reduced villus height and crypt depth), decreased expression of tight junctions and mucus synthesis genes, and increased expression of inflammatory mediators in the ileum. Acupuncture attenuated these abnormalities, which was gut microbiota-dependent.
Conclusion
Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier, providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant, which is used to cure various ailments. Many investigations into the bioactive properties of visnagin have been studied to date. The literature on visnagin demonstrates its biological properties, including anti-inflammatory, anti-diabetic, and beneficial effects in cardiovascular and renal diseases. Moreover, visnagin improves sperm quality parameters, stimulates steroidogenesis, and increases serum gonadotropins and testosterone levels, while decreasing pro-inflammatory cytokines, oxidative damage, genomic instability, and it modulates apoptosis. Thus, visnagin has emerged as an exciting lead for further research, owing to its potential in various unmet clinical needs. The current review summarized its basic structure, pharmacokinetics, and pharmacological effects, focusing on its mechanisms of action. The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

Objective
Acupuncture has demonstrated efficacy as a treatment for fibromyalgia; however, predictors of short- and long-term analgesic response in this population are not well understood.
Methods
This manuscript describes a secondary analysis of a single-center, blinded, sham-controlled, randomized longitudinal acupuncture clinical trial in fibromyalgia. Baseline characterization included pressure pain threshold and pain interference, while residualized change in pain intensity from baseline to follow-up served as the primary outcome measure. Participants were randomized into groups that received verum (n = 36) or sham (n = 29) acupuncture treatment over a 12-week period (18 treatments) and were followed for 37 weeks from the initiation of treatment.
Results
Lower pressure pain thresholds at baseline were associated with greater analgesia only in the sham treatment group immediately following treatment, while those with higher pressure pain thresholds had greater analgesia with verum treatment (B = –13.43, P = 0.001). Additionally, greater perceived impact of pain at baseline was predictive of greater short-term analgesia irrespective of treatment. Pressure pain threshold was not found to be predictive of long-term differential treatment response (B= –1.71, P = 0.66). There was a significant difference in the relationship between perceived impact of pain at baseline and subsequent long-term analgesia between groups where those with greater perceived impact of pain displayed improved long-term analgesia for verum acupuncture compared to the sham group (B = –11.37, P = 0.004).
Conclusions
Our results support the use of a self-reported pain outcome in predicting long-term analgesia following acupuncture in fibromyalgia.

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

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

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

Conclusion
Clinicians and researchers can expect that patients diagnosed with knee osteoarthritis or who have chronic knee pain are ready (action stage) or are considering the behavior (contemplation stage) of self-knee massage. Individuals who report having knee osteoarthritis or chronic knee pain should be coached to develop the skills to perform self-knee massage and helped to develop the motivation to carry out the therapy.

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

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

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

Conclusion
This is, to our knowledge, the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response. Several variables appeared to predict the placebo response. Such findings may encourage future trial designs which could dampen placebo response, improve assay sensitivity, and allow for treatment effects to be potentially more detectable.

Atherosclerosis is a leading cause of mortality and morbidity worldwide. Despite the challenges in managing atherosclerosis, researchers continue to investigate new treatments and complementary therapies. Cordyceps is a traditional Chinese medicine that has recently gained attention as a potential therapeutic agent for atherosclerosis. Numerous studies have demonstrated the effectiveness of cordyceps in treating atherosclerosis through various pharmacological actions, including anti-inflammatory and antioxidant activities, lowering cholesterol, inhibiting platelet aggregation, and modulating apoptosis or autophagy in vascular endothelial cells. Notably, the current misuse of the terms cordyceps and Ophiocordyceps sinensis has caused confusion among researchers, and complicated the current academic research on cordyceps. This review focuses on the chemical composition, pharmacological actions, and underlying mechanisms contributing to the anti-atherosclerotic effects of cordyceps and the mycelium of Ophiocordyceps spp. This review provides a resource for the research on the development of new drugs for atherosclerosis from cordyceps.

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.

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.

Meal timing plays a crucial role for cardiometabolic health, given the circadian regulation of cardiometabolic function. However, to the best of our knowledge, no concept of meal timing exists in traditional European medicine (TEM). Therefore, in this narrative review, we aim to define the optimal time slot for energy intake and optimal energy distribution throughout the day in a context of TEM and explore further implications. By reviewing literature published between 2002 and 2022, we found that optimal timing for energy intake may be between 06:00 and 09:00, 12:00 and 14:00, and between 15:00 and 18:00, with high energy breakfast, medium energy lunch and low energy dinner and possibly further adjustments according to one’s chronotype and genetics. Also, timing and distribution of energy intake may serve as a novel therapeutic strategy to optimize coction, a concept describing digestion and metabolism in TEM.

Background
Red yeast rice (RYR), a natural lipid-lowering agent, is widely used in clinical practice. However, the existing meta-analyses concerning the safety of RYR preparations have yielded inconsistent results, and the credibility of the evidence has not been quantified.

Objective
This study was designed to evaluate the existing evidence and offer a comprehensive understanding of the associations between the use of RYR preparations and various adverse health outcomes.

Search strategy
Seven literature databases were searched from inception to May 5, 2023, using medical subject headings and free-text terms (e.g., “red yeast rice,” “Xuezhikang,” and “Zhibitai”).

Inclusion criteria
Meta-analyses that investigated and quantitatively estimated associations between the use of RYR preparations and adverse health outcomes were included in this study.

Data extraction and analysis
Two researchers independently extracted data using a standardized data collection table; any disagreements were resolved by consulting a third researcher. Based on the participant, intervention, comparator and outcome (PICO) framework in each eligible meta-analysis, a series of unique associations between the use of RYR preparations and adverse health outcomes were determined. The associations’ effect estimates were re-evaluated using random-effect models.

Results
Fifteen meta-analyses, comprising 186 (164 unique) randomized controlled trials, were identified. Based on A MeaSurement Tool to Assess Systematic Reviews version 2, 3 (20%) and 12 (80%) of these meta-analyses had low and critically low confidence, respectively. A total of 61 unique associations between the use of RYR preparations and adverse health outcomes were extracted from eligible meta-analyses. Based on the random-effect models, 10 (16.4%) associations indicated a significant protective effect of RYR preparations against adverse health outcomes, while 5 (8.2%) indicated an increased risk of adverse health outcomes related to uric acid, alanine transaminase and aspartate transaminase levels. The other 46 (75.4%) associations showed no significant difference between the use of RYR preparations and control treatments. Regarding the credibility of the evidence, 21 (34.4%), 34 (55.7%) and 6 (9.8%) associations showed moderate, low and very low credibility, respectively.

Conclusion
The evidence examined in this study suggests that RYR preparations are safe; however, the credibility of the evidence was not high. Further high-quality evidence is required.

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.

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.

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

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.

Objective
Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism.
Methods
We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.
Results
Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo.
Conclusion
This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.

Numerous studies from different international groups have demonstrated that sensations can be propagated along acupuncture channel pathways. The propagated sensation along the channel pathway (PSCP) can be elicited by electroacupuncture (EA), transcutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and heat applied to distal acupuncture points (acupoints). Nitric oxide (NO) levels were reported to be elevated in the gracile nucleus and skin regions near to the EA sites, with higher levels at acupoints associated with an enhanced expression of NO synthase and transient receptor potential vanilloid type 1. The stimuli, EA, MA, TENS, and heat, have been used to elicit axonal reflexes, which increase local release of NO and neuropeptides such as calcitonin gene related peptide. Furthermore, the sensation of PSCP along the body surface occurs only ipsilaterally to the stimulated acupoints in various human studies, which does not support the involvement of the spinal-thalamic pathway, which would involve cross over transmission of the signals. The gracile nucleus receives ascending input from the sciatic nerve and responds to somatosensory stimulation mainly on the ipsilateral side via the dorsal column pathway. EA at Zusanli (ST36) increases NO release and expression of NO synthase mainly in the ipsilateral side of the gracile nucleus, while the cardiovascular effects and analgesic responses to EA at ST36 are changed by influences of l-arginine-derived NO synthesis in the ipsilateral gracile nucleus in rats. The stimuli-induced release of NOergic molecules and neuropeptides exist high levels in the acupoints, which contain rich neuronal components and blood vessels. Enhanced NOergic molecules at acupoints cause axon reflexes during the stimuli, which elevate cutaneous blood flow. Elevated NOergic molecules and local blood flow may spread over acupoints one after another along the meridian lines differing from nerve pathways following the stimuli to induce PSCP. The same types of stimulation also elicit NO release in the gracile nucleus, which contributes to the somatosensory signal transduction of PSCP through the dorsal medulla-thalamic pathways. Other substances such as serotonin and catecholamines are proposed to mediate responses and certain effects of acupuncture-like stimulation but their mechanisms are poorly-understood. In this review we summarize the current understanding of the neurobiological processes of PSCP research with an emphasis on recent developments of NO mediating stimulation-evoked axon reflexes and somatosensory signal transduction for PSCP perceptions through the dorsal medulla-thalamic pathways.

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
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.

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
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.

Obesity is defined as abnormal or excessive fat accumulation that may impair health. Obesity is associated with numerous pathological changes including insulin resistance, fatty liver, hyperlipidemias, and other obesity-related diseases. These comorbidities comprise a significant public health threat. Existing anti-obesity drugs have been limited by side effects that include depression, suicidal thoughts, cardiovascular complications and stroke. Acupuncture treatment has been shown to be effective for treating obesity and obesity-related conditions, while avoiding side effects. However, the mechanisms of acupuncture in treating obesity-related diseases, especially its effect on neural circuits, are not well understood. A growing body of research has studied acupuncture’s effects on the endocrine system and other mechanisms related to the regulation of neural circuits. In this article, recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system, as well as some neural circuits involved, was summarized. Based on this, acupuncture’s potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed, leading to a deeper mechanistic understanding of acupuncture’s effects and providing insight and direction for future research about obesity.

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/).

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.

Objective
The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture.
Methods
Adult female Sprague–Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve.
Results
Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats.
Conclusion
Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract.

Objective
Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved.
Methods
A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined.
Results
EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD.
Conclusion
EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders.

Objective

Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.

Methods

Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.

Results

Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.

Conclusion

EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects.

Objective
The objective of this study was to investigate the clinical efficacy and safety of treating sepsis patients with Xuebijing injection (XBJI).
Methods
We conducted a retrospective analysis of 418 patients who experienced severe infections and were treated with XBJI from June 2018 to June 2021. Propensity score matching was used to match the patient cases. The study population included 209 pairs of cases (418 individuals), and the analysis included data from before and after a 14-day course of treatment with carbapenem alone, or carbapenem with XBJI.
Results
There were no significant differences in the 14-day mortality or length of hospital stay (P > 0.05) between the two groups. The combined treatment group had more patients with C-reactive protein that returned to normal levels (compared to baseline) than the non-combined treatment group (14.4% vs 8.1%; odds ratio [OR]: 0.528; 95% confidence interval [CI]: 0.282–0.991; P = 0.026). Similarly, the combined treatment group had higher procalcitonin attainment rate (55.0% vs 39.7%; OR: 0.513; 95% CI: 0.346–0.759; P = 0.001) than the non-combined treatment group. Further, more patients in the combined treatment group achieved normal creatinine levels than in the non-combined treatment group (64.1% vs 54.1%; OR: 0.659; 95% CI: 0.445–0.975; P = 0.037).
Conclusion
The combination of XBJI with carbapenem did not reduce the 14-day mortality rate of patients with severe infection, but it was able to reduce the level of inflammatory factors in patients with sepsis, and had a protective effect on liver and kidney function.

Objective

Prunella vulgaris L. has long been used for liver protection according to traditional Chinese medicine theory and has been proven by modern pharmacological research to have multiple potential liver-protective effects. However, its effects on non-alcoholic steatohepatitis (NASH) are currently uncertain. Our study explores the effects of P. vulgaris polysaccharides on NASH and intestinal homeostasis.

Methods

An aqueous extract of the dried fruit spikes of P. vulgaris was precipitated in an 85% ethanol solution (PVE85) to extract crude polysaccharides from the herb. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was administrated to male C57BL/6 mice to establish a NASH animal model. After 4 weeks, the PVE85 group was orally administered PVE85 (200 mg/[kg·d]), while the control group and CDAHFD group were orally administered vehicle for 6 weeks. Quantitative real-time polymerase chain reaction analysis, Western blotting, immunohistochemistry and other methods were used to assess the impact of PVE85 on the liver in mice with NASH. 16S rRNA gene amplicon analysis was employed to evaluate the gut microbiota abundance and diversity in each group to examine alterations at various taxonomic levels.

Results

PVE85 significantly reversed the course of NASH in mice. mRNA levels of inflammatory mediators associated with NASH and protein expression of hepatic nucleotide-binding leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) were significantly reduced after PVE85 treatment. Moreover, PVE85 attenuated the thickening and cross-linking of collagen fibres and inhibited the expression of fibrosis-related mRNAs in the livers of NASH mice. Intriguingly, PVE85 restored changes in the gut microbiota and improved intestinal barrier dysfunction induced by NASH by increasing the abundance of Actinobacteria and reducing the abundance of Proteobacteria at the phylum level. PVE85 had significant activity in reducing the relative abundance of Clostridiaceae at the family levels. PVE85 markedly enhanced the abundance of some beneficial micro-organisms at various taxonomic levels as well. Additionally, the physicochemical environment of the intestine was effectively improved, involving an increase in the density of intestinal villi, normalization of the intestinal pH, and improvement of intestinal permeability.

Conclusion

PVE85 can reduce hepatic lipid overaccumulation, inflammation, and fibrosis in an animal model of CDAHFD-induced NASH and improve the intestinal microbial composition and intestinal structure.

Objective
Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied.
Methods
A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels.
Results
Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein–protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds.
Conclusion
Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration.

Background

A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain.

Objective

This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment.

Search strategy

We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025.

Inclusion criteria

(1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs).

Data extraction and analysis

Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence.

Results

Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: –9.2; 95% confidence interval [CI]: [–16.0, –2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: –41.0; 95% CI: [–66.0, –16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality.

Conclusion

Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings.

Objective
This study investigated the clinical details and usage of Sa-am acupuncture in Korean medicine clinics and explored how practicing Korean medicine doctors (KMDs) think about Sa-am acupuncture.
Methods
We conducted a questionnaire-based survey of KMDs who utilize Sa-am acupuncture in their practice. The study comprehensively investigated issues related to clinical application of Sa-am acupuncture, needling techniques used during treatment, training methods, and directions for its future improvement.
Results
We analyzed 572 responses. An average of 50% of the patients visiting Korean medicine clinics were receiving Sa-am acupuncture. The most prevalent indication for Sa-am acupuncture use was digestive disorders. The patients’ appetite level and digestive function were most frequently used indicators for selecting acupuncture points. Regarding prescription compositions, Jung-Gyuk formulas were more frequently used than Seung-Gyuk formulas. Inserting the needle along the flow of the channel or against the flow of the channel was most popular. The acupuncture style most frequently used in combination with Sa-am acupuncture was Ashi point acupuncture. Strengths of Sa-am acupuncture included its versatility, easy application, and good outcomes. Limitations included the lack of rigorous education and training programs, difficulty in applying the principles for beginners, and insufficient clinical research evidence.
Conclusion
In clinics where Sa-am acupuncture is available, KMDs were providing Sa-am acupuncture to about half of their patients. Practitioners were not using all of the tonification and sedation techniques which may be due to time constraints or simply a lack of necessity. Sa-am acupuncture demonstrated high utility in clinical practice and high satisfaction based on the efficacy and safety. More training programs and high-quality research are needed to help expand the use of Sa-am acupuncture.