A syndrome differentiation model of TCM based on multi-label deep forest using biomedical text mining.

Syndrome differentiation and treatment is the basic principle of traditional Chinese medicine (TCM) to recognize and treat diseases. Accurate syndrome differentiation can provide a reliable basis for treatment, therefore, establishing a scientific intelligent syndrome differentiation method is of great significance to the modernization of TCM. With the development of biomdical text mining technology, TCM has entered the era of intelligence that based on data, and model training increasingly relies on the large-scale labeled data. However, it is difficult to form a large standard data set in the field of TCM due to the low degree of standardization of TCM data collection and the privacy protection of patients' medical records. To solve the above problem, a multi-label deep forest model based on an improved multi-label ReliefF feature selection algorithm, ML-PRDF, is proposed to enhance the representativeness of features within the model, express the original information with fewer features, and achieve optimal classification accuracy, while alleviating the problem of high data processing cost of deep forest models and achieving effective TCM discriminative analysis under small samples. The results show that the proposed model finally outperforms other multi-label classification models in terms of multi-label evaluation criteria, and has higher accuracy in the TCM syndrome differentiation problem compared with the traditional multi-label deep forest, and the comparative study shows that the use of PCC-MLRF algorithm for feature selection can better select representative features.

Association of circulating vitamin D and omega 3 fatty acid with all-cause mortality in patients with rheumatoid arthritis: A large population-based cohort study.

OBJECTIVES: To assess the associations of both the level of circulating vitamin D and the ratio of omega-3 fatty acids to total fatty acids (omega-3 %) with mortality among participants with rheumatoid arthritis. STUDY DESIGN: This study included 4,293 and 1,157 adults with rheumatoid arthritis identified by self-report from the UK Biobank for the analysis of vitamin D and omega-3 %, respectively. MAIN OUTCOME MEASURES: Death outcomes were obtained from the National Health Service Information Centre (England and Wales) and the National Health Service Central Register Scotland (Scotland). Cox proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for mortality. RESULTS: The medians (25th-75th percentiles) of serum 25(OH)D and omega-3 % were 45.8 (31.4-62.9) nmol/L and 4.1 % (3.3 %-5.1 %), respectively. During 52,612 person-years of follow-up in the 25(OH)D group, 502 all-cause deaths occurred; and during 14,192 person-years of follow-up in the omega-3 % group, 122 all-cause deaths occurred. Rheumatoid arthritis patients with vitamin D levels of at least 20 nmol/L had an approximately 40-50 % lower risk of all-cause mortality than those with severe vitamin D deficiency (hazard ratio ranging from 0.51 to 0.62, all P values < 0.05). Each unit increase in natural log-transformed 25(OH)D was associated with a 22 % reduction in the risk of all-cause mortality, and a U-shaped association between serum 25(OH)D and all-cause mortality was found. However, the association between omega-3 % and mortality was not significant. CONCLUSIONS: Lower serum 25(OH)D concentration, but not omega-3 %, was significantly associated with higher all-cause mortality in patients with rheumatoid arthritis. Optimizing serum vitamin D levels may be an important factor in reducing mortality risk in this population.

Spatial distribution and comparative analysis of Aconitum alkaloids in Fuzi using DESI-MSI and UHPLC-QTOF-MS.

Aconitum L. poisoning is a major type of poisoning caused by herbal medicines in many countries. However, despite its toxicity, Aconitum L. is still used because of its therapeutic value. Fuzi, the lateral root of Aconitum L., is one of the most important pharmacological parts. It is necessary for rational medication to figure out the types and contents of toxic Aconitum alkaloids (AAs) in Fuzi and its processed products. The present study aims to investigate the spatial distribution of toxic AAs in Fuzi and the quantification of AAs in various processing products through mass spectrometry methods. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to directly image the sections of raw Fuzi. The results showed a high content of diester alkaloids (DAs) and a relatively uniform distribution in the sections, while the content of monoester alkaloids (MAs) was low and uneven in the sections, distributed in the cortex, epidermis, vascular column, and other parts of the tissues. The content of non-ester alkaloids (NAs) was relatively minimum, and most of the NAs were distributed in the vascular column and the tightly connected cortex of the tissue. To further investigate the difference between raw and processed Fuzi, 60 known compounds were identified using UHPLC-QTOF-MS. The total contents of alkaloids in 7 processed Fuzi were lower than that in Shengfupian (SFP). Paofupian (PFP), Paotianxiong (PTX), Paofupian (PFP*), Danfupian (DFP), and Shufupian (SFP*) were the least similar. Zhengfupian (ZFP) and Chaofupian (CFP) had significantly reduced toxicity and increased efficacy compared with other processed products because the contents of active alkaloids in other processed products were also reduced. Understanding the distribution of metabolites and the composition changes after processing can guide users and herbal manufacturers to carefully choose the relatively safe and better therapeutic species of Fuzi. The information gathered from this study can contribute towards the improved and effective management of therapeutically important, nonetheless toxic, drugs such as Aconitum L.

Modified Sijunzi granule decreases post-weaning diarrhea in Rex rabbits via promoting intestinal development.

Traditional Chinese medicine (TCM) formulas can be adjusted on the basis of TCM basic theory to achieve the best curative effect, especially for diseases with complex pathogenesis, such as post-weaning diarrhea (PWD). Shugan Jianwei Sijunzi decoction (SJ-SJZD) can be recognized as modified Sijunzi Decoction (SJZD) supplemented with Astragalus mongholicus Bunge, Bupleurum chinense DC, Citrus × aurantium L., and Crataegus pinnatifida Bunge (fruit) in a fixed dosage ratio. The inactive ingredients were subsequently added to make granule, which was Shugan Jianwei Sijunzi granule (SJ-SJZG). Previous studies have confirmed the antagonism of SJ-SJZG to PWD. However, the mechanism of SJ-SJZG protective effects on small intestine in weaned Rex rabbits remained unclear. Animals were randomly divided into negative control (NC), low dose (LD), medium dose (MD), high dose (HD), and positive control (PC). SJ-SJZG significantly increased the intestinal length and the jejunum villi length. The SIgA level was statistically increased in duodenum and jejunum with the ELISA. Immunohistochemical detection showed that SIgA protein expression was also increased significantly in jejunum. Meanwhile, the relative expression of Zo1 in duodenum and jejunum of SJ-SJZG group increased significantly. SJ-SJZG significantly increased the relative expression of occludin in duodenum and jejunum as well. Moreover, real-time PCR results showed a significant increase in GLUT2 and SGLT1 relative expression in ileum. SJ-SJZG could also obviously enhance the expression of GLUT2 in jejunum and the expression of SGLT1 in duodenum. In conclusion, SJ-SJZG had been proven to be effective in promoting the development of small intestine and improving the immunity of small intestine. Moreover, SJ-SJZG could ensure the integrity of mucosal barrier and increase the ability of intestine to absorb glucose in small intestine.

Evidence and Characteristics of Traditional Chinese Medicine for Coronary Heart Disease Patients With Anxiety or Depression: A Meta-Analysis and Systematic Review.

Aims: The objective of this study was to assess the efficacy and potential mechanisms of Chinese herbal medicine (CHM) for treating coronary heart disease (CHD) patients with anxiety or depression. Methods: A systematic literature search was performed. Screening studies, extracting data, and assessing article quality were carried out independently by two researchers. The active ingredients of CHM for the treatment of CHD with anxiety or depression were analyzed by the network pharmacology, and the main potential mechanisms were summarized by the database of Web of Science. Results: A total of 32 studies were included. The results showed that compared with the blank control groups, CHM was more beneficial in treating anxiety or depression in patients with CHD [anxiety: OR = 3.22, 95% CI (1.94, 5.35), p < 0.00001, I2 = 0%; depression: OR = 3.27, 95% CI (1.67, 6.40), p = 0.0005, I2 = 0%], and the efficacy of CHM was not inferior to that of Western medicine (WM) [anxiety: OR = 1.58, 95%CI (0.39, 6.35), p = 0.52, I2 = 67%; depression: OR = 1.97, 95%CI (0.73, 5.28), p = 0.18, I2 = 33%,]. Additionally, CHM also showed a significant advantage in improving angina stability (AS) in CHD patients with anxiety or depression compared with blank groups [anxiety: SMD = 0.55, 95%CI (0.32, 0.79), p < 0.00001, I2 = 0%; depression: p = 0.004] and WM groups [anxiety: SMD = 1.14, 95%CI (0.80, 1.47), p < 0.00001, I2 = 0%; depression: SMD = 12.15, 95%CI (6.07, 18.23), p < 0.0001, I2 = 0%]. Angina frequency (AF) and electrocardiogram (ECG) analysis after using CHM demonstrated similar trends. Based on the network pharmacology, quercetin, kaempferol, luteolin, beta-sitosterol, puerarin, stigmasterol, isorhamnetin, baicalein, tanshinone IIa, and nobiletin were most closely and simultaneously related to the pathological targets of CHD, anxiety, and depression. The main underlying mechanisms might involve anti-damage/apoptosis, anti-inflammation, antioxidative stress, and maintaining neurotransmitter homeostasis. Conclusion: CHM exhibited an obvious efficacy in treating CHD patients with anxiety or depression, especially for improving the symptom of angina pectoris. The most active compounds of CHM could simultaneously act on the pathological targets of CHD, anxiety, and depression. Multiple effective components and multiple targets were the advantages of CHM compared with WM.

Clinical features of adverse events associated with Xiyanping-Ribavirin combination: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Xiyanping (XYP) has been widely used in combination with Ribavirin (RB) for the treatment of infectious diseases. It has been found that this combination may change the severity of XYP-associated adverse events (AEs). AIM: To provide a comprehensive review about the clinal features of AEs of XYP-RB combination from randomized controlled trials, cohort studies, case-control studies, case reports, case series, and data from the National Adverse Drug Reaction Monitoring Information System (NADRMIS). MATERIALS AND METHODS: Seven electronic databases were searched in March 2021. Articles on AEs associated with XYP published from January 2004 to December 2020 in the NADRMIS were included. Data on the incidence of AEs, distribution of AEs, occurrence time of AEs, type and possible signal of AEs, primary diseases, allergic history, family history of allergies, dosage, and combination interval were extracted. RESULTS: We included 228 cases of AEs with XYP-RB combination (63 cases from randomized controlled trials, 1 from a cohort study, and 164 from the NADRMIS). The most common primary disease was hand-foot-and-mouth disease. The main age distribution was 0-6 years (118 cases, 72%) and 8 cases (6.8%) experienced serious AEs. The combination group showed a significant reduction than the RB group in the incidence of AEs in those with hand-foot-and-mouth disease (risk ratio = 0.54, 95% confidence interval = 0.38-0.78, P = 0.0008) and children with viral pneumonia (risk ratio = 0.36, 95% confidence interval = 0.14-0.95, P = 0.04). Allergic history and infusion interval were not described in the randomized controlled trials. AEs were reported in 57.9% of cases in the first combination (XYP-RB were combined for the first time) (NADRMIS), 56.4% of which were skin and appendage reactions, and the risk signal of skin and appendage reactions was a maximum (Information Component = 6.21). CONCLUSION: The major AE associated with XYP-RB combination was skin and appendage reactions. Most of the combination AEs were pseudo-allergic reactions. These findings suggest that we should increase awareness about the safety of XYP-RB combination treatment and standardize medication protocol, especially for children. Unless absolutely necessary, children should avoid combination therapy. More rigorous high-quality studies are needed to obtain more evidence.

Developing a core outcome set for assessing clinical safety outcomes of cardiovascular diseases in clinical trials of integrated traditional Chinese medicine and Western medicine: study protocol.

BACKGROUND: Integrative medicine is commonly used in China. Researchers prefer to report efficacy outcomes rather than safety outcomes in clinical trials; thus, evidence regarding safety in integrative medicine is unclear. Developing a core outcome set (COS) for safety outcomes is necessary. In this study, a representative example of the methodology for developing COS to assess safety outcomes of cardiovascular diseases in clinical trials investigating integrated medicine will be developed. METHODS AND ANALYSIS: Safety information will be extracted from package inserts and through systematic reviews of treatments for cardiovascular diseases (including angina pectoris, myocardial infarction, heart failure, arrhythmia, and hypertension) to develop an extensive list of safety outcomes, which will then be categorized according to whether subjective or objective outcomes. Questionnaires for clinician-reported safety outcomes and patient-reported safety outcomes will be developed. Two rounds of the Delphi survey will then be conducted for different stakeholders (traditional Chinese medicine clinicians and researchers in cardiovascular diseases, Western medicine clinicians and researchers in cardiovascular diseases, integrated medicine clinicians and researchers of cardiovascular diseases, pharmacologists, methodologists of evidence-based medicine, and patients). After round 2 of the Delphi analysis, a face-to-face consensus meeting will be held to determine the final COS for assessing safety outcomes in cardiovascular diseases. DISCUSSION: A COS for safety outcomes in cardiovascular diseases may improve the consistency of reporting results and will help identify potential bias of selective reporting in the future. TRIAL REGISTRATION: This study was registered in the Core Outcome Measures in Effectiveness Trials database as study 1564 .

The Improvement of Cardiac and Endothelial Functions of Xue-Fu-Zhu-Yu Decoction for Patients with Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Xue-Fu-Zhu-Yu decoction (XFZYD) is a traditional Chinese prescription that has been used to treat patients with blood stasis in China for many years. The present study aimed to evaluate the improvement of cardiac and endothelial functions of XFZYD for patients with acute coronary syndrome (ACS) through a systematic review and meta-analysis. METHODS: Six databases were searched to collect RCTs related to the treatment of XFZYD for ACS. The primary outcomes were cardiac and endothelial functions, including the levels of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) in echocardiography, as well as the changes in the levels of nitric oxide (NO), endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in the serum. The secondary outcomes were the blood levels of oxidative damage markers (including superoxide dismutase (SOD) and malondialdehyde (MDA)), C-reactive protein (CRP), brain natriuretic peptide (BNP), creatine kinase-MB (CK-MB), and cardiac troponin I (cTnI) as well as the incidence of adverse drug reactions (ADRs). Weighted mean difference (WMD) was estimated for all the outcomes with the random effects model. This type of analysis was conducted in the subgroups of the ACS subtypes, and the methodological quality was assessed using the handbook of Cochrane Collaboration. RESULTS: A total of 1,658 records were identified, and 16 randomized controlled trials (1,171 patients) were included. The primary outcomes suggested that XFZYD combined with routine treatment improved LVEF, reduced LVEDD and LVESD, and also improved the serum levels of NO, and reduced the levels of ET-1 and ICAM-1. XFZYD combination therapy significantly ameliorated the blood levels of SOD, MDA, BNP, CK-MB, and cTnI. However, the results indicated no significant difference between XFZYD plus routine treatment and routine treatment for the levels of VCAM-1 and CRP. Moreover, all the ADRs reported in the included studies were slight and the patients recovered soon. CONCLUSIONS: The present study suggested that XFZYD may improve the cardiac and endothelial functions of ACS patients without serious ADRs. However, based on the mediocre methodological quality, the aforementioned conclusion should be confirmed in a multicenter, large-scale, and accurately designed clinical trial.

Atheroprotective Effects and Mechanisms of Postmarketing Chinese Patent Formulas in Atherosclerosis Models: A Systematic Review.

BACKGROUND: Some postmarketing Chinese patent formulas have been widely used to treat atherosclerosis (AS) and play critical roles in Chinese healthcare. However, the usage of these herbs is yet controversial due to unclear effects and lack of understanding of the mechanism of action. With the modernization of traditional Chinese formulas, we are to elucidate the atheroprotective properties of these remedies from successful postmarketing experiments in vivo. METHODS: In this systematic review, we critically searched the databases, applied stringent criteria, assessed the methodological quality, and examined the current evidence in vivo. RESULTS: Consequently, 60 studies were included in the present qualitative synthesis. Data on models, high-fat diet, intervention time, outcome measures, efficacy, and mechanisms were collected. Finally, 23 formulas that could alleviate AS were correlated to the amelioration of plaques, improvement of plaque stability, modification of lipid level and lipid metabolism, and the effects of anti-inflammation and antioxidant stress with multiple components and targets. However, the methodological quality was low and incomplete among the included literature. CONCLUSIONS: Thus, taken together, the studies on postmarketing Chinese patent formulas would provide a novel approach to improve the treatment of AS, and rigorously designed studies would provide high-quality evidence.

Chitosan-poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor benefit for antibacterial and wound healing.

Chitosan/poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor (ZnG/rhEGF@Chit/Polo) were developed as a convenient, safe and effective dressing for skin wound treatment. Their fabrication procedure and characterization were reported, and their morphology was examined by a scanning electron microscope. Antibacterial and biofilms activities were evaluated by in vitro tests to reveal the inhibitory effects and scavenging activity on the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. ZnG/rhEGF@Chit/Polo was also investigated as a potential therapeutic agent for wound healing therapy. In vivo wound healing studies on rats for 21 days proves that ZnG/rhEGF@Chit/Polo supplements the requisite Zn2+ and rhEGF for wound healing to promote the vascular remodeling and collagen deposition, facilitate fibrogenesis, and reduce the level of interleukin 6 for wound basement repair, and thus is a good wound therapy.

Problems with the outcome measures in randomized controlled trials of traditional Chinese medicine in treating chronic heart failure caused by coronary heart disease: a systematic review.

BACKGROUND: Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions. METHODS: We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures. RESULTS: A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min' walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting. CONCLUSIONS: The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.

New insight into the joint significance of dietary jujube polysaccharides and 6-gingerol in antioxidant and antitumor activities.

The combinatorial use of dietary jujube (Ziziphus jujuba) and ginger play a critical role in traditional Chinese medicines, folk medicine and dietary therapy. Joint effects were investigated from the viewpoint of the antioxidant (scavenging DPPH˙) and antitumor activities (against SW620 cells) of jujube polysaccharides and ginger 6-gingerol (G6G) alone and in combination. Jujube polysaccharides were extracted, purified, and characterized, and then their inhibiting and apoptotic effects alone and in combination with G6G were evaluated by the cytological tests, including Cell Counting Kit-8, colony-forming, Annexin V-FITC and propidium iodide, TdT-mediated dUTP nick end labeling (TUNEL) staining, and cell cycle assays. Results showed that the purified polysaccharide fraction (ZJPs-II) with average molecular weight of 115 kDa consisted of arabinose, rhamnose, glucose, xylose, and galactose. ZJPs-II and G6G alone dose-dependently scavenged DPPH˙ and inhibited the proliferation of SW620 cells, while their combination showed synergistic interactions (all combination index < 1). The studies further demonstrated that ZJPs-II and G6G alone reduced the cell colony-formation, induced apoptosis and arrested the cell-cycle at G2/M phase, while their combination achieved better effects and significantly arrested the growth at the G0/G1 phase. Collectively, our findings suggest enhancing the intake of jujube polysaccharides and G6G in a combinatorial approach for maintaining health and preventing cancer.

Status Quo and Analysis of the Cardiovascular Clinical Practice Guidelines/Expert Consensuses of Chinese and Integrative Medicine: A Systematic Review.

OBJECTIVE: To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment. METHODS: Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses. RESULTS: A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%). CONCLUSIONS: Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.

Tai Ji Quan as antihypertensive lifestyle therapy: A systematic review and meta-analysis.

BACKGROUND: Professional health organizations are not currently recommending Tai Ji Quan alongside aerobic exercise to treat hypertension. We aimed to examine the efficacy of Tai Ji Quan as antihypertensive lifestyle therapy. METHODS: Tai Ji Quan interventions published in English and Chinese were included when they involved healthy adults, reported pre- and post-intervention blood pressure (BP), and had a non-exercise/non-diet control group. We systematically searched 11 electronic databases for studies published through July 31, 2018, yielding 31 qualifying controlled trials. We (1) evaluated the risk of bias and methodological study quality, (2) performed meta-regression analyses following random-effects assumptions, and (3) generated additive models representing the largest possible clinically relevant BP reductions. RESULTS: Participants (n = 3223) were middle-aged (56.6 ± 15.1 years of age, mean ± SD) adults with prehypertension (systolic BP (SBP) = 136.9 ± 15.2 mmHg, diastolic BP (DBP) = 83.4 ± 8.7 mmHg). Tai Ji Quan was practiced 4.0 ± 1.4 sessions/week for 54.0 ± 10.6 min/session for 22.3 ± 20.2 weeks. Overall, Tai Ji Quan elicited significant reductions in SBP (-11.3 mmHg, 95%CI: -14.6 to -8.0; d+ = -0.75) and DBP (-4.8 mmHg, 95%CI: -6.4 to -3.1; d+ = -0.53) vs. control (p < 0.001). Controlling for publication bias among samples with hypertension, Tai Ji Quan trials published in English elicited SBP reductions of 10.4 mmHg and DBP reductions of 4.0 mmHg, which was half the magnitude of trials published in Chinese (SBP reductions of 18.6 mmHg and DBP reductions of 8.8 mmHg). CONCLUSION: Our results indicate that Tai Ji Quan is a viable antihypertensive lifestyle therapy that produces clinically meaningful BP reductions (i.e., 10.4 mmHg and 4.0 mmHg of SBP and DBP reductions, respectively) among individuals with hypertension. Such magnitude of BP reductions can lower the incidence of cardiovascular disease by up to 40%.

The current evidence for the treatment of sepsis with Xuebijing injection: Bioactive constituents, findings of clinical studies and potential mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing (XBJ) injection is a Chinese medicine containing extracts from Carthamus tinctorius L. (Carthami Flos, hong hua, Asteraceae), Paeonia lactiflora Pall. (Paeoniae radix rubra, chi shao, Ranunculaceae), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong, Umbelliferae), Salvia miltiorrhiza Bge. (Salviae miltiorrhizae Radix Et Rhizoma, dan shen, Labiatae) and Angelica sinensis (Oliv.) Diels (Angelicae sinensis Radix, dang gui, Umbelliferae). It has been approved for the treatment of sepsis in China since 2004 and has been widely used as an add-on treatment for sepsis or septic shock with few side effects. AIM OF THE STUDY: The aim of the present review was to analyse up-to-date information related to the treatment of sepsis with XBJ, including the bioactive constituents, clinical studies and potential mechanisms, and to discuss possible scientific gaps, to provide a reliable reference for future studies. MATERIALS AND METHODS: Scientific resources concentrating on treating sepsis with XBJ were searched through PubMed, the Chinese National Knowledge Infrastructure (CNKI) and WanFang databases from inception to November 2018. Dissertations were also searched, and eligible dissertations were selected. Studies related to the identification of constituents, bioactive components and their targets of action or pathways, clinical trials, and animal or cellular experiments that explored pharmacological mechanisms were manually selected. The quality of reporting and methodology of the included pharmacological experiments were assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tool. RESULTS: A total of 108 relative studies were eventually included, containing 12 bioactivity research studies, 10 systematic reviews on clinical trials and 86 animal or cellular experiments. We noted that as identification methods progressed, further constituents could be detected in XBJ. XBJ was also found to have "multi-ingredient, multi-target and multi-pathway" effects. The systematic review revealed that XBJ could improve the 28-day mortality and other indexes, such as the APACHE II score, body temperature, and white blood cell (WBC) count, to some extent. A major organ protection effect was demonstrated in septic rats. Pharmacological investigations suggested that XBJ acts in both the early and late stages of sepsis by anti-inflammatory, anti-coagulation, immune regulation, vascular endothelial protection, anti-oxidative stress and other mechanisms. However, most of the included studies were poorly reported, and the risk of bias was unclear. CONCLUSIONS: With respect to the multiple therapeutic mechanisms contributing to both the early and late stages of sepsis, the multiple effective constituents detected and randomized controlled trials (RCTs) performed to prove its efficacy, XBJ is a promising therapy for the treatment of sepsis. However, although XBJ has shown some efficacy for the treatment of sepsis, there are currently some scientific gaps. More studies concerning the pharmacokinetics, interactions with antibiotics, real-world efficacy and safety, pharmacological mechanisms of the bioactive components and large-scale clinical trials should be conducted in the future.

Initiate Danhong Injection before or after percutaneous coronary intervention for microvascular obstruction in ST-elevation myocardial infarction (DIRECTION): study protocol for a randomized controlled trial.

BACKGROUND: No treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain. METHODS: The DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators. DISCUSSION: This trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019.

Effect of Chinese Medicine on No or Slow Reflow after Percutaneous Coronary Intervention in Myocardial Infarction Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematic review the effect of Chinese medicine (CM) on no or slow reflow after percutaneous coronary intervention (PCI) in myocardial infarction (MI) patients. METHODS: The PubMed, EMBASE databases, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Knowledge Service Platform (Wanfang Database) and Chinese Scientific Journal Database (VIP) were searched up to December 2017. Randomized controlled trials (RCTs) which evaluated the effect of CM therapies on no or slow reflow after PCI in MI patients were included. The primary outcome was the effect of reperfusion. Secondary outcomes were left ventricular ejection fraction, incidence of major adverse cardiovascular events and adverse effect. RESULTS: Ten RCTs covering 814 patients were included. Two studies revealed that the incidence of no or slow reflow was less in Shenmai Injection () group than in the control group measured by thrombolysis in myocardial infarction (TIMI) ⩽ 2 (risk ratio=0.55, 95% confidence interval 0.38 to 0.81, P=0.003, I2=37%). Two studies indicated that Salvianolate Injection showed no additional benefit on no or slow reflow measured by corrected TIMI frame count compared with the conventional treatment (mean difference -4.24, 95% confidence interval -13.03 to 4.54, P=0.34, I2=86%). In addition, Tongxinluo Capsules (), Danhong Injection () and Xuesaitong Injection () may have the potential to reduce no or slow reflow measured during or after PCI in individual studies. CONCLUSIONS: Current evidence from RCTs are not sufficient to evaluate the effect of CM adjuvant therapies on no or slow reflow after PCI for MI patients. The included studies are limited by small sample size and unclear baseline conditions. Further rigorously designed researches and verification studies with sufficient number of patients are warranted.

Risk factors associated with the severity of adverse drug reactions by Xiyanping injection: A propensity score-matched analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiyanping injection (XYP), extraction of Andrographis paniculate (Andrographis paniculata (Burm. f.) Nees, chuan xin lian), is a Chinese patent medicine approved to treat bronchitis in China. In 2017, safety incidents associated with treatment of XYP began to emerge throughout China. However, the risk factors of severity of adverse reactions by XYP remain uncertain. AIM OF THE STUDY: To determine risk factors for the severity of XYP-associated adverse drug reactions (ADRs). MATERIALS AND METHODS: We analyzed a total of 26,317 cases of ADRs linked to the use of XYP injection in the China National Adverse Drug Reaction Monitoring Information System from 2004 to 2017. Data were analyzed with respect to age, gender, ethnicity, previous ADRs, family history of ADRs, dosage specification, medication frequency specification, body weight, route of administration, herb-drug interactions (ribavirin, cefatriaxone, penicillin sodium, ambroxol hydrochloride, clindamycin, cefoxitin sodium, azithromycin, ceftazidime, amoxicillin sodium and clavulanate potassium, levofloxacin, cefazolin sodium pentahydrate, acyclovir) by univariate analysis and multivariate analysis. Propensity score matching was used to compare severity of (general or serious) ADRs. RESULTS: We included 24,911 cases of general ADRs and 1406 cases of serious ADRs. Univariate analysis identified age (p â€‹< â€‹0.001), body weight (p â€‹< â€‹0.001), route of administration (p â€‹= â€‹0.008), co-administration of XYP with ribavirin (p â€‹= â€‹0.031) as risk factors of severity of ADRs. Multivariate analysis identified XYP â€‹+ â€‹ribavirin combination (p â€‹= â€‹0.048) and age (p â€‹< â€‹0.001) as the independent risk factors. Upon propensity score matching, the variables were relatively balanced amongst the two groups of patients with general or severe ADRs, and the level of severity in patients who received treatment of XYP â€‹+ â€‹ribavirin increased (p â€‹= â€‹0.020). CONCLUSIONS: Age and co-administration of ribavirin may be potential risk factors for the severity of XYP-associated ADRs. This reminds us to pay more attention to the safety of elderly medication. Minimizing the herb-drug-interaction effects of XYP and ribavirin is a viable treatment target for healthcare professionals in managing serious ADRs amongst patients receiving XYP injection.

Yoga as Antihypertensive Lifestyle Therapy: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the efficacy of yoga as antihypertensive lifestyle therapy and identify moderators that account for variability in the blood pressure (BP) response to yoga. METHODS: We systematically searched 6 electronic databases from inception through June 4, 2018, for articles published in English language journals on trials of yoga interventions that involved adult participants, reported preintervention and postintervention BP, and had a nonexercise/nondiet control group. Our search yielded 49 qualifying controlled trials (56 interventions). We (1) evaluated the risk of bias and methodological study quality, (2) performed meta-regression analysis following random-effects assumptions, and (3) generated additive models that represented the largest possible clinically relevant BP reductions. RESULTS: On average, the 3517 trial participants were middle-aged (49.2±19.5 years), overweight (27.9±3.6 kg/m2) adults with high BP (systolic BP, 129.3±13.3 mm Hg; diastolic BP, 80.7±8.4 mm Hg). Yoga was practiced 4.8±3.4 sessions per week for 59.2±25.0 minutes per session for 13.2±7.5 weeks. On average, yoga elicited moderate reductions in systolic BP (weighted mean effect size, -0.47; 95% CI, -0.62-0.32, -5.0 mm Hg) and diastolic BP (weighted mean effect size, -0.47; 95% CI, -0.61 to -0.32; -3.9 mm Hg) compared with controls (P<.001 for both systolic BP and diastolic BP). Controlling for publication bias and methodological study quality, when yoga was practiced 3 sessions per week among samples with hypertension, yoga interventions that included breathing techniques and meditation/mental relaxation elicited BP reductions of 11/6 mm Hg compared with those that did not (ie, 6/3 mm Hg). CONCLUSION: Our results indicate that yoga is a viable antihypertensive lifestyle therapy that produces the greatest BP benefits when breathing techniques and meditation/mental relaxation are included.

Normative Application of Xiyanping Injection: A Systematic Review of Adverse Case Reports.

PURPOSE: To summarize the characteristics and the relevant factors and to give references for preventing adverse drug reactions (ADRs) associated with xiyanping (XYP), we provide a systematic review of adverse case reports about XYP. METHODS: Seven medical databases were searched from inception to January 2018. Case reports detailing ADRs associated with XYP were included. Data were extracted independently by two reviewers. After the assessment of causality and severity, we carried out a descriptive analysis for the relevant ADRs. RESULTS: Forty-three articles involving a total number of 55 cases were included. Eight cases were off-label drug use. In the remaining 47 cases, 26 (55.3%) had probable causality and 23 (48.9%) were serious cases. XYP used in children (≤14 years old) accounted for 66.0%. Respiratory diseases (83.0%) were major primary diseases. No allergic history mentioned (55.3%) and unspecific drug combination (59.6%) were common in these reports. As for ADR types, anaphylaxis and anaphylactic shock were up to 97.9%. ADRs happened mostly when applying XYP within 30 minutes (70.2%) and the majority (95.7%) were cured when treated in time. CONCLUSIONS: Clinicians and patients are supposed to obey the package insert of XYP in clinical application. Through the results of XYP, normalization of ADR reports is also worthy of attention. High-quality researches are required to improve the drug instruction and evaluate the safety of XYP in effective diseases and different age groups. Mechanism of ADRs aiming at the hypersensitivity and the drug combination should still be further identified.