Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus / 中西医结合学报

OBJECTIVE@#Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.@*METHODS@#An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.@*RESULTS@#XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.@*CONCLUSION@#Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses / 中西医结合学报

BACKGROUND@#Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies.@*OBJECTIVE@#This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.@*SEARCH STRATEGY@#Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used.@*INCLUSION CRITERIA@#Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.@*DATA EXTRACTION AND ANALYSIS@#A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently.@*RESULTS@#There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay.@*CONCLUSION@#Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Examining patterns of traditional Chinese medicine use in pediatric oncology: A systematic review, meta-analysis and data-mining study / 中西医结合学报

BACKGROUND@#Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.@*OBJECTIVE@#We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.@*SEARCH STRATEGY@#We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM."@*INCLUSION CRITERIA@#We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.@*DATA EXTRACTION AND ANALYSIS@#The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.@*RESULTS@#The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.@*CONCLUSION@#There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61 / 中西医结合学报

OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Trace therapeutic substances of traditional Chinese medicine: great resources of innovative drugs derived from traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.

Chinese medicine dispensing granules: history, status quo, and development prospect in "post-pilot era" / 中国中药杂志

Chinese medicine dispensing granules, the result of the efforts to transform Chinese medicinal decoction pieces in China, features portability and ease of storage. Thus, it is destined to be an indispensible dosage form in the modernization drive of Chinese medicine. The Announcement on Ending the Pilot Project of Chinese Medicine Dispensing Granules was released in February 2021 and relevant regulations went into force in November 2021, which marks the a new journey for the development of Chinese medicine dispensing granules and the beginning of the "post-pilot era". However, it faces the challenges in quality and standard. This study reviewed the history of Chinese medicine dispensing granules, analyzed the technical progress, market, and main problems in development, and proposed suggestions and prospects for its development in the "post-pilot era", which is expected to serve as a reference for its industry development and rational use.

Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients / 中国中药杂志

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

Research progress in mechanism of Chinese herbal compounds and monomers in delaying lumbar intervertebral disc degeneration / 中国中药杂志

Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/β-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.

Clinical trials and evaluation of Chinese patent medicine for chronic obstructive pulmonary disease / 中国中药杂志

The clinical randomized controlled trials(RCTs) of Chinese patent medicine in the treatment of chronic obstructive pulmonary disease(COPD) were reviewed and analyzed to provide references for clinical research, guideline development, policy formulation, and quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed, Cochrane Library, PubMed, EMbase were searched for RCTs of Chinese patent medicine for COPD as a source of clinical evidence from database inception to December 31, 2019. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. A total of 733 RCTs of Chinese patent medicine for COPD were included, among which 228 RCTs had a sample size higher than 100, accounting for 31.1% of total RCTs. Eighty-eight Chinese patent medicines were involved, including 40 oral medicines and 48 injections. A total of 327 RCTs mentioned intervention and control measures(Chinese patent medicine + conventional treatment vs conventional treatment), accounting for 43.0%. In addition, 94.40% of the RCTs reported the course of treatment, and 53.20% of the RCTs determined 8-14 d as the intervention course. The evaluation indicators adopted were numerous, among which physicochemical indicators(70.57%) and symptoms/signs(24.35%) were the most frequently employed. The operation of allocation concealment and blinding was not standard. Registration and the procedure related to ethics were mostly missing. The results indicate that there are prominent methodological problems in the clinical trials of Chinese patent medicine in the treatment of COPD, affecting the reliability and practicability of the trials. It is necessary to further standardize the design, implementation, and quality control of clinical trials of Chinese patent medicine in the treatment of COPD, highlight the clinical value of Chinese patent medicine for COPD, and improve the quality of evidence.

Clinical trials and evaluation of Chinese patent medicine for pneumonia / 中国中药杂志

The present study reviewed the clinical randomized controlled trials(RCTs) of Chinese patent medicine for pneumonia to provide references for clinical research, guideline development, and policy formulation, and promote the quality improvement of clinical evidence. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed were searched for RCTs of Chinese patent medicine for pneumonia from database inception to December 31, 2019. A total of 1 245 RCTs were included, involving 84 Chinese patent medicines, including 45 oral medicines and 39 injections. Specifically, 85.9% of RCTs had treatment course not exceeding 14 d; 43.3% of RCTs had a sample size of more than 100 cases and 6.1% of RCTs more than 200 cases; 13 types of interventions/controls were included in the RCTs, with Chinese patent medicine + western medicine vs western medicine as the top one used(32.6%). In outcome indicators, symptoms/signs(3 285) and physicochemical detection(2 066) were the most frequently applied. In the methodological evaluation, "allocation concealment" was not clearly described or mentioned in 71.2% of RCTs, and "blinding" in 23.9% of RCTs met the normative standards. Registration and research ethics were not clearly reported. There are many methodological deficiencies in terms of design and implementation in included RCTs, which may impact the reliability and practicability of the results of RCTs. Additionally, key standards were unclear(such as disease classification methods and selection of core outcome indicators). In conclusion, RCTs should give priority to the preciseness and scientificity of the protocol, strengthening quality control of the processes and accelerating the standardized research of key links.

Clinical trials and evaluation of Chinese patent medicine for influenza / 中国中药杂志

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.

Clinical trials and evaluation of Chinese patent medicine for stroke / 中国中药杂志

To systematically collect and analyze clinical randomized controlled trial(RCT) of Chinese patent medicine treatment for stroke in 2020, in order to provide basic information for clinical decision-making and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed, Cochrane Library, PubMed, EMbase were searched for RCTs of Chinese patent medicine for stroke in 2020. The publication, sample size, intervention and control measures, course of treatment, outcome indicators, methodological quality and other contents were statistically analyzed.A total of 68 RCTs studies on Chinese patent medicine for stroke were included in 2020, of which 29(42.60%) were RCTs with sample size>100 cases. A total of 41 kinds of proprietary Chinese medicines were involved, including 23 kinds of oral proprietary Chinese medicines and 18 kinds of injections. A total of 18 intervention/control cases were included in RCTs, and 19 cases(Chinese patent medicine+Western medicine vs Western medicine) were applied in RCTs, accounting for 27.90%. The duration of treatment was reported in 91.18% of the studies, and the intervention duration was 8-14 days in 50.00% of the studies. Evaluation indexes were widely used, among which physical and chemical testing indexes(49.36%) were the most widely used. According to the methodological quality evaluation, the overall methodological quality of the study is not high, especially the implementation of the allocation hidden, blind method is not accurate, and the registration, ethics and other links are often missing. In conclusion, 2020 implementation of proprietary Chinese medicine in the treatment of stroke research methodology problems is outstanding, the similar function scale large range of optional, no specification selection criteria, reliability and practicability of the impact study, need to further standardize the proprietary Chinese medicine in the treatment of stroke study design, implementation and quality control, and highlight the value of proprietary Chinese medicine in the treatment of stroke and improve the quality of the evidence.

Clinical trials and evaluation of Chinese patent medicine for heart failure / 中国中药杂志

The present study systematically collected, analyzed, and evaluated randomized controlled trial(RCT) of Chinese patent medicine in the treatment of heart failure to provide references for follow-up clinical research design, guideline update, and policy formulation, and promote the improvement of clinical evidence quality. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, VIP, Wanfang, SinoMed, PubMed, and Web of Science were searched for RCTs of Chinese patent medicine in the treatment of heart failure from database inception to December 31, 2020. The di-sease type, publication time, sample size, intervention/control setting, course of treatment, evaluation indexes, and methodological quality were analyzed and evaluated. A total of 1 631 RCTs were included, including 1 622 in Chinese and 9 in English. It was first published in 1995, with the largest number of publications in 2016. There were only 56 RCTs(3.43%) with a sample size≥200. Seventy-eight types of Chinese patent medicines were involved, including 49 types of oral drugs and 29 types of injections. There were 34 intervention/control protocols, which were dominated by Chinese patent medicine+conventional treatment vs conventional treatment, accounting for 28.51%(n=465). About 94.0% of RCTs reported the course of treatment, mainly 14-56 days. The evaluation indexes were mainly physical and chemical tests and symptoms/signs, and left ventricular ejection fraction(LVEF) was the most frequently used measurement index. In enumeration indexes, clinical efficacy(response rate) was used the most frequently. Methodologically, 92.0% of the research subjects were rated as high risk of blindness. There were only 13 RCTs(0.80%) reporting registered information. It is necessary to further standardize the design, implementation, and quality control of clinical studies in order to improve the quality of evidence and avoid research waste.

Clinical evidence analysis report of Chinese patent medicine in 2020 / 中国中药杂志

The present study collected, collated, analyzed, and evaluated randomized controlled trial(RCT) of Chinese patent medicine published in Chinese and English journals in 2020, and summarized clinical evidence of Chinese patent medicine in stages, providing references for follow-up clinical research and evidence transformation and application. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, SinoMed, Cochrane Library, PubMed, and EMbase were searched for RCTs of Chinese patent medicine published in 2020, and their research characteristics and methodological quality were analyzed and evaluated. A total of 1 285 research papers on Chinese patent medicine(1 257 in Chinese/28 in English) were included, involving 146 054 patients and 639 Chinese patent medicines, including 526 oral drugs, 68 injections, and 45 external drugs. A total of 412 diseases in 23 types were involved, which were dominated by circulatory system diseases and respiratory system diseases, specifically, cerebral infarction and angina pectoris. The sample size ranged from 20 cases to 2 673 cases, and 57.67% of RCTs had samples sizes less than 100. Single-center trials were the main ones, and multi-center trials only accounted for 4.75%(n=61). In terms of methodological quality, 52.91% of the RCTs had unclear descriptions or incorrect application of randomization methods, and the implementation of allocation concealment and blinding methods has not been paid much attention. In conclusion, compared with the conditions in 2019, the number of RCTs published in 2020 has decreased, and the research interest in respiratory diseases has increased, while the quality control in the process of research design and implementation has not been improved. Therefore, it is necessary to strengthen the methodological training of researchers and promote the output of high-quality research evidence.

Exploration and reflection on evaluation methodology of human use experience for new Chinese drug development / 中国中药杂志

The "triple combination" review system provides an opportunity for the transformation of human use experience into new Chinese drugs. However, there are some methodological and technical limitations in the assessment of human experience. Hence, the efficacy and safety evaluation methods should be established in accordance with the characteristics of Chinese herbs. This study summarized some evidence-based methodology to promote the transformation of human use experience to new Chinese drugs, mainly including the individualized pragmatic randomized controlled trial(RCT), cluster RCT, single-case RCT, single arm RCT with objective performance criteria, and partially nested RCT. As the real world data can be used to support the transformation of human experience, attention should be paid to convenient and efficient collection of data, prudent selection of design types, and adoption of appropriate ana-lysis methods to deal with confounding bias, including multi-factor regression model and propensity score. The newly proposed mixed research method can also be utilized to assess the human use experience, which is suitable for mining the theory of traditional Chinese medicine(TCM) and expert experience from different aspects. Meanwhile, considering the study design requirements and TCM cha-racteristics, this study put forward the common problems and solutions in the development of new Chinese drugs based on human use experience, including how to select the feasible outcome indicators, how to collect prescription data in the case of herb and dosage adjustment, and how to evaluate the comprehensive effectiveness of TCM from the perspective of "combination of disease and syndrome".

Mechanism and experimental verification of "Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus" combination in treatment of acute gouty arthritis based on network pharmacology / 中国中药杂志

Based on network pharmacology, the mechanism of Polygoni Cuspidati Rhizoma et Radix-Ligustri Lucidi Fructus(PL) combination against acute gouty arthritis(AGA) was explored and preliminarily verified by animal experiment. The chemical components and corresponding targets of PL were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The active components with oral bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were screened based on literature, and the related protein targets were collected. Then the protein targets were standardized with the help of UniProt database. The AGA-related targets were searched from GeneCards, NCBI, and DrugBank. The common targets of the disease and the medicinals were yielded by FunRich V3, and the protein-protein interaction(PPI) network was constructed to screen the key targets, followed by Gene Ontology(GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the key targets. Afterwards, some of the key targets were verified by sodium urate crystal-induced AGA mouse model. A total of 25 active components and 287 targets of PL, 811 targets of AGA, and 88 common targets were screened out. PPI network analysis showed that tumor necrosis factor(TNF), interleukin-6(IL-6), and interleukin-1β(IL-1β) may be the core targets of PL in the treatment of AGA. The key targets were mainly involved in 566 GO terms(P<0.05), including multiple biological processes such as inflammatory response and immune response. Moreover, they were related to 116 KEGG pathways and these pathways were involved in inflammation and immunity, mainly including NOD-like receptor signaling pathway and TNF signaling pathway. Animal experiment confirmed that PL can alleviate ankle swelling, improve abnormal gait, and down-regulate the protein expression of TNF-α, IL-6, and IL-1β in AGA mice, indicating that PL can treat AGA through TNF-α, IL-6, and IL-1β and the feasibility of network pharmacology to predict drug targets. This study preliminarily discussed the key targets and biological signaling pathways involved in the treatment of AGA with PL combination, which reflected the multi-pathway and multi-target action characteristics of Chinese medicine. Moreover, this study laid a scientific basis for research on the treatment of AGA with PL combination, as well as the mechanism of action.

Clinical comprehensive evaluation of Ginkgolide Injection in treatment of cerebral infarction / 中国中药杂志

This clinical value-oriented comprehensive evaluation of drugs was carried out in accordance with Guidelines for Management of Comprehensive Clinical Evaluation of Drugs(trial version 2021), with the qualitative and quantitative evaluation methods adopted. Based on the evidence-based medicine, epidemiology, clinical medicine, pharmacoeconomics, mathematical statistics, and health technology evaluation(HTA), the clinical value of Ginkgolide Injection was evaluated from the "6+1" dimension by giving weight to the criterion level and index level and calculating with multi-criteria decision analysis(MCDA) model and CSC v2.0. After entering the market, Ginkgolide Injection has been subjected to phase Ⅳ clinical trial, spontaneous reporting system(SRS)-based data monitoring, systematic review and Meta-analysis, acute toxicity and long-term toxicity assays, active monitoring, and RCTs, and the evidence of safety was sufficient. The results of active monitoring showed that the incidence of adverse reactions was 0.09%(rare), mainly manifested as flushing, dizziness, rash, nausea, and vomiting. According to the nested case-control study, the adverse reactions of this drug had nothing to do with the product batch, implying that the drug quality was controllable. The adverse reactions mainly resulted from the pharmacodynamic reactions. Because the drug was effective in resisting platelet aggregation, the resulting adverse reactions such as flushing, dizziness, headache, and phlebitis were caused by vasodilation. Skin rash and gastrointestinal symptoms were mainly attributed to the patients' sensitivity to drugs and their own allergic constitution. According to the sufficiency of evidence and the incidence of adverse reactions in the safety research, the safety of Ginkgolide Injection was grade A. The results of Meta-analysis showed that Ginkgolide Injection combined with conventional western medicine was superior to conventional western medicine in improving the clinical effective rate, neurological function score, and activity of daily living score of patients with cerebral infarction. The validity evidence was evaluated according to the PICO principle to be high. According to the GREAD evaluation principle, the quality of such evidence as clinical effective rate, National Institute of Health stroke scale(NIHSS), and Barthel Index(BI) was evaluated, and the results demonstrated that the evidence quality of clinical effective rate and activity of daily living score was medium. The effectiveness of Ginkgolide Injection was grade A. According to the economic report of Ginkgolide Injection, it had short-term and long-term pharmacoeconomic advantages in the treatment of ischemic stroke, and the economic evidence value was good. According to the CASP economic evaluation checklist, the overall quality evaluation results of the economic report are basically clear. To be specific, the economic evidence quality was high. Based on the comprehensive economic evidence quality and economic value, the economy of this drug was grade A. The innovation of this product was evaluated from three aspects: clinical innovation, enterprise service system innovation, and industrial innovation. Ginkgolide Injection could be used 24 h after intravenous thrombolysis for improving patients' neurological function without increasing bleeding, indicating its important clinical innovation. There were many innovations in ensuring drug supply, especially at the grass roots, drug safety, effectiveness, and reasonable price, which has provided reference for establishing enterprise philosophy, managing drug resources, developing process and technology, and determining enterprise management and marketing. Therefore, its innovation was grade A. The drug had no special medication plan in use, exhibiting good suitability for doctors, nurses, and patients. The suitability was grade B. Compared with similar drugs, its price was at a medium level, meaning good affordability, sufficient production capacity, and easy accessibility. Its accessibility was therefore grade B. This drug belonged to Chinese medicinal injection. The large-sample real-world research revealed rich human use experience, so it was grade C for the traditional Chinese medicine characteristic. According to the comprehensive evaluation, the clinical value of Ginkgolide Injection in the treatment of cerebral infarction fell into class A. It is suggested that it can be transformed into the relevant policy results of basic clinical medication management according to the procedure.

Research progress on effective components and mechanisms of anti-depressive Chinese medicine / 中国中药杂志

Since the pathogenesis of depression is complicated, the therapeutic effects of western medicine are poor accompanied by severe side effects. Chinese medicine has unique advantages in the treatment based on syndrome differentiation and contains many effective components against depression, including flavonoids, terpenes, phenylpropanoids, quinones, and alkaloids. These chemical components can delay the course of the disease, improve the curative effect, and reduce side effects of western medicine by regulating the biochemical abnormalities of monoamine neurotransmitters, brain tissue protein content, and internal environment as well as energy metabolism to make the treatment of Chinese medicine highlighted and recognized. This study systematically reviewed the effective components and mechanisms of anti-depressive Chinese medicine to inspire the rational development and utilization of new Chinese medicines against depression.

Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions" / 中国中药杂志

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Overview of systematic reviews of Shufeng Jiedu Capsules / 中国中药杂志

At present, there have been many clinical trials and systematic reviews/Meta-analysis proving the good clinical efficacy of Shufeng Jiedu Capsules in the treatment of respiratory diseases, while comprehensive discussion is still required. This article overviews and analyzes the systematic reviews/Meta-analysis of Shufeng Jiedu Capsules to provide evidence support for clinical practice. The systematic reviews/Meta-analysis of Shufeng Jiedu Capsules were searched from CBM, Wanfang, CNKI, VIP, PubMed, EMbase and Cochrane Library. The AMSTAR 2 scale and GRADE system were respectively employed for the evaluation of methodological quality and the grading of evidence quality. Finally, 8 systematic reviews/Meta-analysis published during 2018-2021 were included for analysis. The diseases involved include acute exacerbation of chronic obstructive pulmonary disease, community-acquired pneumonia, acute tonsillitis, acute exacerbation of chronic bronchitis and acute upper respiratory tract infection. The number of included RCTs studies ranged from 8 to 25. The results showed that Shufeng Jiedu Capsules combined with western medicine routine had better therapeutic effect than the latter alone in the treatment of the above five diseases. The reported adverse reactions caused by Shufeng Jiedu Capsules were mainly gastrointestinal discomforts such as mild nausea, diarrhoea and vomiting, with low incidence and mild symptoms, which can be relieved by drug withdrawal. The methodological quality of the included studies was extremely low, and the outcome indicators were mainly of low and very low grades. The efficacy and safety of Shufeng Jiedu Capsules in the clinical treatment of diseases still need to be verified based on more high-quality studies. The relevant clinical research and systematic review/Meta-analysis should pay more attention to methodological quality and reporting standards and strengthen the scientificity of research.