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Background: Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live. Compared to statins, traditional Chinese medicines are believed to be “all natural” with fewer side effects, are associated with strong patient compliance. Accordingly, a great deal of clinical studies have shown that Xuefu Zhuyu decoction (XFZYD) can significantly improve the clinical symptoms and enhance the therapeutic effect. Meanwhile, a system review and meta-analysis are conducted by us to further clarify the effectiveness and safety of XFZYD for NAFLD. Methods: We will apply to database mainly range from the English literature searches Cochrane Library, PubMed, excerpt medica database, and Web of Science to the Chinese literature China national knowledge infrastructure, Chinese biomedical literature database, VIP, and Wanfang database, randomized controlled trials (RCTs) are enrolled to evaluate the effectiveness and safety of XFZYD in the treatment of NAFLD, the enrollment of RCTs is from the establishment of the database to February 01, 2021. Simultaneously we will retrieval clinical registration tests and grey literatures. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is expressed in terms of relative risk, the continuous is represented by mean difference or standard mean difference, whether there is heterogeneity is the factor that determines the synthesis of data in fixed effect model or random effect model. Alanine aminotransferase (ALT) or Aspartic acid aminotransferase (AST) coupled with Glutamyltransferase (GGT) is considered as one of the main indicators of the NAFLD, while the pathology, imaging and diagnosis of metabolic syndrome are also auxiliary results. The last, meta-analysis was conducted by RevMan software version 5.3. Results: This study will provide evidence for treatment of NAFLD with XFZYD in terms of effectiveness and safety. Conclusion: This systematic review aims to confirm the efficacy and safety of XFZYD in the treatment of NAFLD. OSF registration number: DOI 10.17605/OSF.IO/7CWRK.

Background Chinese herbal footbaths are an external therapy of traditional Chinese medicine that has been widely used to treat dysmenorrhea. This review aims to systematically evaluate its efficacy and safety for the treatment of dysmenorrhea. Methods Databases of PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Database (VIP), Wanfang Database, China Biomedical Literature Database(CBM), and Chinese Biomedical Literature Service System (SinoMed) will be searched from the inception to September 30, 2020. The eligible randomized controlled trials (RCTs) will be identified and included. The primary outcomes include pain intensity measured by validated scales of visual analog scale, numeric rating scale, and response rate of symptom reduction. The secondary outcomes are scores on validated pain questionnaires, quality of life measured by SF-36 or other validated scales, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted by two reviewers independently. RevMan software (V.5.3.5) will be utilized to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of the evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System. Results A high-quality synthesis of current evidence of Chinese herbal footbaths for patients with dysmenorrhea will be provided in this study. Conclusion This systematic review will provide evidence of whether Chinese herbal footbaths are an effective and safe intervention for the treatment of dysmenorrhea. Systematic review registration PROSPERO CRD42020188256.

Background: Xuefu Zhuyu Tang (XFZYT), first recorded in Correction of Errors in Medical Works by Qing-ren Wang, has been proven reliable and effective for curing various diseases such as atherosclerosis, hypertension, hyperlipidemia, and angina pectoris. It consists of 11 herbs and two of them, Radix platycodonis and Radix cyathulae, have been traditionally considered as guiding herbs and deeply valued by tens of millions of Chinese medicine practitioners. Do Radix platycodonis and Radix cyathulae affect the pharmacokinetics of the effective constituent-paeoniflorin of XFZYT? If yes, in what way? This study aims to answer these questions.Materials and Methods: The medicinal solutions of XFZYT, XFZYT without Radix platycodonis (XFZYT-JG), XFZYT without Radix cyathulae (XFZYT-NX), and XFZYT without Radix platycodonis and Radix cyathulae (XFZYT-JG-NX) were prepared and administrated to rats in the normal group and the blood-stasis model group by gavage, respectively. The blood samples of rats in the normal group were obtained 5, 10, 15, 20, 30, 45, 60, 120, and 240 minutes after gavage; whereas the blood samples of rats in the blood-stasis model group were obtained 10, 15, 20, 30, 45, 90, 150, and 240 minutes after gavage. Biological samples were processed; the assays of specificity, precision, linearity, intra-day and interday precisions, recovery and stability were conducted; high performance liquid chromatography was performed to detect paeoniflorin content; and DAS software was adopted to generate pharmacokinetic parameters. Mobile phase was composed of acetonitrile and water (16:84), detection wavelength was 230 nm, and riboflavin was set as internal standard substance.Results: The pharmacokinetic parameters of the rats in the normal group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.363±0.248, 0.065±0.020, 0.099±0.033, 0.099±0.020) mg/L, Tmax = (0.276±0.084, 0.583±0.342, 0.555±0.228, 0.317±0.033)h, t1/2 = (0.501±0.241, 1.021±0.522, 0.853±0.377, 1.227±0.402) h; and AUC0-∞ = (0.381±0.415, 0.13±0.085, 0.166±0.066, 0.185±0.059) mg/L·h.; whereas the pharmacokinetic parameters for the rats in the blood-stasis model group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.315±0.153, 0.215±0.044, 0.228±0.056, 0.248±0.09) mg/L, Tmax = (0.5±0, 0.667±0.129, 0.5±0, 0.542±0.102) h, t1/2 = (0.408±0.146, 0.813±0.135, 0.708±0.383, 0.741±0.173) h, and AUC 0-∞ = (0.306±0.157, 0.408±0.136, 0.368±0.159, 0.381±0.246) mg/L·h.Conclusion: The guiding herbs, Radix platycodonis and Radix cyathulae, significantly increased the absorption amount and rate of paeoniflorin in XFZYT, and accelerated its elimination from the blood.Keywords: Xuefu Zhuyu Tang, Guiding herb, Radix platycodonis, Radix cyathulae, Paeoniflorin, Pharmacokinetics

Wenjinghuoluo prescription, a traditional Chinese medicine compound treatment of rheumatoid arthritis characterized by wind-cold-dampness arthralgia, contains five herbs, namely, C. cassia Presl., Cinnamomum cassia Presl., Paeonia lactiflora Pall., Saposhnikovia divaricate (Turcz.) Schischk., and Clematis chinensis Osbeck. We have reported that WJHL could inhibit the production of inflammatory mediators in immune cells. This study explored the effect and mechanism of WJHL on collagen-induced arthritis mice. WJHL could significantly improve clinical arthritic conditions; inhibit bone erosion and osteophyte formation in joints; decrease expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17); reduce protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3 and gene expression levels of JAK2, STAT3, IL-17A, RORγt mRNA; elevate osteoprotegerin and Foxp3 mRNA levels and lower Th17 cell proportions in splenocytes. Results suggest that WJHL, specifically regulating the JAK2/STAT3 pathway and Th17 cells, may be a promising herbal medicine candidate for the treatment of RA.

IntroductionTo date, no specific antivirus drugs or vaccines have been available to prevent or treat the COVID-19 pandemic. Mesenchymal stem cell (MSC) therapy may be a promising therapeutic approach that reduces the high mortality in critical cases. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy and safety of MSC therapy on patients with COVID-19.Methods and analysisTen databases including PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched from inception to 1 December 2020. All published randomised controlled trials, clinical controlled trials and case series that meet the prespecified eligibility criteria will be included. The primary outcomes include mortality, incidence and severity of adverse events, respiratory improvement, days from ventilator, duration of fever, progression rate from mild or moderate to severe, improvement of such serious symptoms as difficulty breathing or shortness of breath, chest pain or pressure, and loss of speech or movement, biomarkers of laboratory examination and changes in CT. The secondary outcomes include dexamethasone doses and quality of life. Two reviewers will independently perform study selection, data extraction and assessment of bias risk. Data synthesis will be conducted using RevMan software (V.5.3.5). If necessary, subgroup and sensitivity analysis will be performed. Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the strength of evidence.Ethics and disseminationEthical approval is not necessary since no individual patient or privacy data have been collected. The results of this review will be disseminated in a peer-reviewed journal or an academic conference presentation.PROSPERO registration numberCRD42020190079.

The gold standard for diagnosing asthma in children is based on clinical history of respiratory symptoms, physical examination, and respiratory function testing. Recent advances indicate that a non-invasive measure of airway inflammation, fractional exhaled nitric oxide (FeNO), provides objective data for use in asthma diagnosis. However, the diagnostic performance of FeNO in children with asthma has not been clearly defined. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of FeNO in the clinical determination of asthma in children. Databases of PubMed, the Cochrane Library, EMBASE, MEDION, and Web of Science were searched for relevant articles through March 31, 2016. A bivariate model was used for pooling estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating curves (SROC) as the main diagnostic measures. In total, eight studies met the inclusion criteria, which included 2933 subjects. The pooled estimates of sensitivity, specificity, and DOR for the detection of asthma in children were 0.79 [95 % confidence interval (CI), 0.64-0.89], 0.81 (95 % CI, 0.66-0.90), and 16.52 (95 % CI, 7.64-35.71). The SROC was 0.87 (95 % CI, 0.84-0.90). In brief, FeNO achieves a moderate diagnostic performance in the detection of asthma in children.

Background No specific anti-virus drugs or vaccines have been available for the treatment of COVID-19. Integrative traditional Chinese and western medicine has been proposed as a therapeutic option with substantial applications in China. This protocol is proposed for a systematic review and meta-analysis that aims to evaluate the efficacy of integrative traditional Chinese and western medicine treatment on patients with COVID-19. Methods Ten databases including PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang database, China Biomedical Literature Database (CBM) and Chinese Biomedical Literature Service System (SinoMed) will be searched. All published randomized controlled trials, clinical controlled trials, case-control, and case series that meet the pre-specified eligibility criteria will be included. Primary outcome measures include mortality, clinical recovery rate, duration of fever, progression rate from mild or moderate to severe, improvement of symptoms, biomarkers of laboratory examination and changes in computed tomography. Secondary outcomes include dosage of hormonotherapy, incidence and severity of adverse events and quality of life. Study selection, data extraction and assessment of bias risk will be conducted by 2 reviewers independently. RevMan software (V.5.3.5) will be used to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of evidence will be assessed by the GRADE system. Results This study will provide a well-reported and high-quality synthesis on the efficacy of integrative traditional Chinese and western medicine treatment on patients with COVID-19. Conclusion This systematic review protocol will be helpful for providing evidence of whether integrative traditional Chinese and western medicine treatment is an effective therapeutic approach for patients with COVID-19. Ethics and dissemination Ethical approval is unnecessary as no individual patient or privacy data is collected. The results of this study will be disseminated in a peer-reviewed scientific journal and/or conference presentation. Systematic review registration PROSPERO CRD42020167205.

// Xin Wu 1, * , Yaodong You 2, * , Xiaocheng Chen 3, * , Qiyang Shou 4 , Songqi Tang 5 , Jida Zhang 6 , Hao Cai 7 , Baochang Cai 7 , Dongxin Tang 8 and Gang Cao 1 1 Research Center of TCM Processing Technology, Zhejiang Chinese Medical University, Hangzhou, China 2 School of Clinical Medicine, Chengdu University of TCM, Chengdu, China 3 The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China 4 Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, China 5 College of TCM, Hainan Medical University, Haikou, China 6 College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China 7 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China 8 Guiyang University of Chinese Medicine, Guiyang, China * These authors contributed equally to this work Correspondence to: Gang Cao, email: caogang33@163.com Dongxin Tang, email: 49729065@qq.com Keywords: UHPLC-Orbitrap-MS; metabolomics; collagen-induced arthritis; wenjinghuoluo prescription; herbal formula Received: July 20, 2017 Accepted: December 06, 2017 Published: January 02, 2018 ABSTRACT Wenjinghuoluo (WJHL) prescription, the typical rheumatoid arthritis (RA) treatment compound in traditional Chinese medicine, shows favorable efficacy. The precise mechanism of WJHL on RA therapy is yet to be elucidated. This study aimed to determine the metabolic biomarkers in the early onset of RA and evaluate the regulation effect of WJHL on metabolite levels. Multivariate statistical analysis identified 93 biomarkers by precise MS/MS. These biomarkers played an important role in the regulation of key metabolic pathways associated with collagen-induced arthritis (CIA). A total of 68 biomarkers were related with the treatment of CIA by WJHL therapy. In addition, pathway analysis results showed six and three significant related pathways according to corresponding differential metabolites before and after WJHL therapy. Finally, disease and function prediction of ingenuity pathway analysis indicated that lipid metabolism, small molecule biochemistry, and carbohydrate metabolism were associated functions of WJHL therapy on CIA. Furthermore, top analysis-ready molecules of up-regulated thiamine and down-regulated arachidomic acid maybe the most related metabolites of WJHL therapy on CIA. The present work indicated that a metabolomics platform provided a new insight into understanding the mechanisms of action of natural medicines, such as WJHL.

Ethnopharmacological relevance Pien-Tze-Huang (PZH) is a famous formula of traditional Chinese medicine used to treating stroke. However, the protective effect of PZH and its mechanisms in acute ischemic stroke remain to be explored. Aim of the study To investigate the protective effect of PZH on neuronal apoptosis in acute cerebral ischemic injury rats and explore its underlying mechanisms. Materials and methods The effects of PZH were studied in acute ischemic stroke rats induced by transient middle cerebral artery occlusion, and the mitochondria-mediated apoptotic proteins including cytochrome C (Cyt C), Bax, Bcl-xl, P53, caspase-3, and caspase-9 as well as AKT and glycogen synthase kinase-3 beta (GSK-3β) were assessed. Results Four days of PZH treatment (180 mg/kg) could significantly reduce cerebral infarct volume, improve neurological deficit, attenuate inflammatory response, and inhibit neuronal apoptosis in acute ischemic stroke rats. Moreover, PZH treatment significantly decreased cytosolic Cyt C, Bax, P53, cleaved caspase-3, and cleaved caspase-9 levels, but elevated mitochondrial Cyt C and Bcl-xl levels. PZH treatment also increased phosphorylation of AKT and GSK-3β. Conclusion PZH potently protects the brain from cerebral ischemia/reperfusion injury in vivo, and inhibiting mitochondria-mediated neuronal apoptosis as well as attenuating inflammatory responses may be involved in this effect. This study provides experimental basis of PZH in treating acute cerebral ischemic stroke, which would provide some novel insights for its prevention and treatment of ischemic stroke.