Chikungunya virus (CHIKV), which is primarily transmitted by Aedes aegypti and Ae. albopictus, has recently rapidly spread across the world, which poses a huge threat to public health. Chikungunya fever (CHIKF), caused by CHIKV infection, typically manifests as acute febrile illness with severe polyarthralgia that may persist for months to years. A few severe CHIKF cases may be accompanied by serious neurological complications, even resulting in death. The accelerating global expansion of CHIKV is closely associated with genetic variations of the virus, and mutated genes in CHIKV may augment the virus adaptability to Aedes vectors and transmission efficiency. Currently, the diagnosis of the CHIKV infection primarily relies on molecular and serological assays; however, there are still multiple challenges for early and differential diagnosis of CHIKV infections due to co-infections with arboviruses and nonspecific early symptoms. The first prophylactic vaccine for CHIKF has been recently approved in the United States; however, the large-scale application still awaits further validations. More importantly, there are no licensed antiviral therapies against CHIKV until now. This review describes the structure and pathogenesis of CHIKV, summarizes the latest epidemiology and advances in the diagnosis of CHIKV infections, and depicts the current status and prospects of antiviral agents and vaccine development, so as to inform evidence-based prevention and control strategies.

OBJECTIVE: To provide the experience and demonstration for the transformation of acupuncture-moxibustion techniques standards from Chinese national standards to international standards. METHODS: Questionnaire research, literature research, semi-structured interviews and expert consultation were used. RESULTS: The safety of acupuncture-moxibustion techniques was evaluated through literature research, and based on the results of the questionnaire survey, expert interviews, and expert consultation, 11 main bodies and structure of the former Chinese national standard, Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting, were adjusted and optimized in accordance with the requirements of international standard (including the language, normative references, purpose, scope, applicable environment, target population, work team, terms and definitions, general principles and basic requirements, structural elements and text structure, and compilation process); and the first international standard, World Federation of Acupuncture-Moxibustion Societis (WFAS) Technical Benchmark of Acupuncture and Moxibustion: General Rules for Drafting was formulated to specify the general rules for drafting. CONCLUSION The 3 key questions, "international compatibility", "technical operability" and "safety" should be solved technically on the basis of explicit international requirements. It is the core technical issue during transforming the national standards of technical benchmark of acupuncture and moxibustion into international standards.
Moxibustion/methods* ; Acupuncture Therapy/methods* ; Humans ; Translational Research, Biomedical/standards* ; Surveys and Questionnaires ; China ; Benchmarking/standards*

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

OBJECTIVES: To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of Buyang Huanwu Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition. METHODS: Forty normal Wistar rats were randomized into two groups (n=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting. RESULTS: Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression. CONCLUSIONS BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.
Drugs, Chinese Herbal/pharmacology* ; Arthritis, Rheumatoid/pathology* ; Animals ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Humans ; Fibroblasts/cytology* ; Rats, Wistar ; Membrane Proteins/metabolism* ; Rats ; Phosphatidylinositol 3-Kinases/metabolism* ; Mitochondria/metabolism* ; Cells, Cultured ; Proto-Oncogene Proteins/metabolism* ; Apoptosis/drug effects* ; Cell Hypoxia ; Synovial Membrane/cytology* ; Male ; Mitochondrial Proteins

BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

ObjectiveThis study conducted a "6 + 1" clinical comprehensive evaluation of the existing research on Zhichuanling oral liquid （ZOL） in the treatment of asthma，so as to clarify the clinical advantages and precise clinical positioning of ZOL in the treatment of asthma， lay a foundation for further research and academic promotion of ZOL， and provide new directions for patent cultivation. MethodAn evaluation method featuring a qualitative and quantitative combination was used， which considered the dimensions of safety，effectiveness，economy，innovation，suitability，accessibility， and traditional Chinese medicine （TCM） characteristics. According to Expert Meeting Law， relevant weights were obtained through voting. CSC_v2.0 software was used to calculate each dimension and convert it into the corresponding grade score. ResultBased on the existing materials，① ZOL instruction indicates the adverse reactions，taboo， and notes. Multiple data of clinical research before and after marketing and spontaneous reporting system shows that ZOL has controllable risk and good safety. Safety is rated as B grade. ② Multiple data of clinical research before marketing， systematic evaluation of clinical effectiveness， and Meta-analysis shows that ZOL has good effectiveness and clinical significance. Effectiveness is rated as a B grade. ③ Analysis of the cost-effectiveness of ZOL combined with conventional treatment shows that the economy of the drug is good and rated as a B grade. ④ ZOL has better innovation， which is rated as an A grade. ⑤ ZOL can basically meet the clinical drug needs based on the result of the questionnaire survey and has good suitability， which is rated as a B grade. ⑥ ZOL has better accessibility， and accessibility is rated as A grade. ⑦ ZOL involves a rich theory of TCM but insufficient experience of human usage. It is thus rated as a C grade in terms of TCM characteristics. Based on the results of "6 + 1" dimension，the clinical comprehensive evaluation of ZOL in the treatment of asthma （cold syndrome and heat syndrome）is rated as B category. ConclusionZOL has good clinical value and outstanding innovation and accessibility in the treatment of asthma （cold syndrome and heat syndrome）. It is recommended that ZOL be transformed into the relevant policy results of basic clinical drug management procedurally. At the same time，it is recommended to actively cultivate patents with TCM characteristics.

Objective: To investigate the association between frailty and type 2 diabetes mellitus (T2DM) using a bidirectional two-sample Mendelian randomization (MR) analysis, so as to provide the evidence for the prevention and control of frailty and T2DM. Methods: Frailty status was assessed using the Fried Frailty Score (FFS), with aggregated data sourced from 386 565 European samples in the UK Biobank. The T2DM data were obtained from the summary results of genome-wide analysis published by the Diabetes Genetics Replication and Meta-analysis Consortium, excluding the UK Biobank data, including 455 313 European samples. Eligible single nucleotide polymorphism site were selected from the FFS and T2DM summary data as instrumental variables. The bidirectional MR analysis was performed using the inverse-variance weighted method. The heterogeneity was assessed using the modified Cochran Q test. The horizontal pleiotropy of instrumental variables was examined using MR-Egger regression. The robustness of the results was evaluated using the leave-one-out method. The bias was tested using funnel plot. Results: The forward MR analysis revealed a statistically significant association between increased FFS and an increased risk of T2DM (OR=2.280, 95%CI: 1.169-4.447). The reverse MR analysis showed a statistically significant association between T2DM and increased FFS (β=0.026, 95%CI: 0.012-0.041). Both bidirectional MR results were robust, with no horizontal pleiotropy of the instrumental variables was found (all P>0.5); and the funnel plots did not show significant basis. Conclusion The study found a bidirectional causal association between frailty and T2DM.

This paper systematically analyzed the ancient monographs of acupuncture and moxibustion and comprehensive medical books from pre-Qin to 1911， and extracted the data according to the etiology and pathogenesis， treatment principles and methods， acupoint selection， needling and moxibustion， and taboos of needling and moxibustion. The pathogenesis of migraine in ancient books and documents is summarized as "the causes are diverse， and phlegm-dampness is the majority". For treatment， the features include "needling has a sequence， and the root and the branch should be treated separately" and "focusing on tonifying deficiency and drain excess". It is also obtained of the rich ideas of acupoints selection， extensive application records of moxibustion， unique application of bloodletting therapy and clear explanation of acupuncture and moxibustion taboos. All mentioned above is expected to enrich the ideas and methods of modern migraine treatment and improve the clinical effects.