Objective. To summarize the characteristics and analysis of relevant factors and to give references for prevention and further study of liver damage associated with Polygonum multiflorum Thunb. (HSW), we provide a systematic review of case reports and case series about liver damage associated with HSW. Methods. An extensive search of 6 medical databases was performed up to June 2014. Case reports and case series involving liver damage associated with HSW were included. Results. This review covers a total of 450 cases in 76 articles. HSW types included raw and processed HSW decoction pieces and many Chinese patent medicines that contain HSW. Symptoms of liver damage occur mostly a month or so after taking the medicine, mainly including jaundice, fatigue, anorexia, and yellow or tawny urine. Of the 450 patients, two cases who received liver transplantation and seven who died, the remaining 441 cases recovered or had liver function improvement after discontinuing HSW products and conservative care. Conclusion. HSW causes liver toxicity and may cause liver damage in different degrees and even lead to death; most of them are much related to long-term and overdose of drugs. Liver damage associated with HSW is reversible, and, after active treatment, the majority can be cured. People should be alert to liver damage when taking HSW preparations.

An increasing number of clinical trials of traditional Chinese medicine are being conducted in the treatment of non-valvular atrial fibrillation (NVAF) in China. However, the heterogeneity of outcomes and outcome measurement instruments has produced little evidence for traditional Chinese medicine in treating NVAF because many trials cannot be included in a meta-analysis. The majority of the trials did not report endpoint outcomes, side effects or other important outcomes for patients, which makes it difficult to evaluate the efficacy and safety of traditional Chinese medicine. Therefore, it is important to develop a core outcome set (COS). Although there are two related COSs for clinical trials of atrial fibrillation, the methodology is limited, and the perspectives of Chinese experts and patients are unclear. Therefore, we will develop a COS and recommend outcome measurement instruments after finishing the COS, which can be used for clinical trials of traditional Chinese medicine in NVAF.

Management for patients with diabetes experiencing myocardial infarction remains a challenge. Here the authors show that hyperglycemia- and hyperinsulinemia-induced microRNA-24 (miR-24) reduction and O-GlcNAcylation in the diabetic heart contribute to poor survival and increased infarct size in diabetic myocardial ischemia/reperfusion (I/R). In a mouse model of myocardial I/R, pharmacological or genetic overexpression of miR-24 in hearts significantly reduced myocardial infarct size. Experimental validation revealed that miR-24 targets multiple key proteins, including O-GlcNac transferase, ATG4A, and BIM, to coordinately protect the myocardium from I/R injury. These results establish miR-24 as a promising therapeutic candidate for diabetic I/R injury.

Invasive coronary revascularization has been shown to improve prognoses in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), but the optimal timing of intervention remains unclear. This meta-analysis is to evaluate the outcomes in immediate (<2 h), early (<24 h), and delayed invasive group and find out which is the optimal timing of intervention in NSTE-ACS patients. Studies were identified through electronic literature search of Medline, PubMed Central, Embase, the Cochrane Library, and CNKI. Data were extracted for populations, interventions, outcomes, and risk of bias. All-cause mortality was the pre-specified primary end point. The longest follow-up available in each study was chosen. The odds ratio (OR) with 95% CI was the effect measure. The fixed or random effect pooled measure was selected based on the heterogeneity test among studies. In the comparison between early and delayed intervention, we found that early intervention led to a statistical significant decrease in mortality rate (n = 6,624; OR 0.78, 95% CI: 0.61-0.99) and refractory ischemia (n = 6,127; OR 0.50, 95% CI: 0.40-0.62) and a non-significant decrease in myocardial infarction (MI), major bleeding and revascularization. In the analysis comparing immediate and delayed invasive approach, we found that immediate intervention significantly reduced major bleeding (n = 1,217; OR 0.46, 95% CI: 0.23-0.93) but led to a non-significant decrease in mortality rate, refractory ischemia and revascularization and a non-significant increase in MI. In conclusion, early invasive strategy may lead to a lower mortality rate and reduce the risk of refractory ischemia, while immediate invasive therapy shows a benefit in reducing the risk of major bleeding.

Shengmai injection (SMI) is made from purified ginseng, Radix Ophiopogonis, and Schisandra chinensis. It has cardiotonic effects and is clinically used for the adjuvant treatment of chronic heart failure (CHF). However, its efficacy and safety are uncertain. The purpose of this study was to systematically evaluate the existing efficacy and safety evidence in randomized controlled trials (RCTs) that studied SMI for the treatment of CHF.

To assess the reporting quality of randomised controlled trials (RCTs) of massage, particularly whether necessary elements related to massage interventions were adequately reported.

Protein disulfide isomerase (PDI), an oxidoreductase, possesses two vicinal cysteines in the -Cys-Gly-His-Cys-motif that either form a disulfide bridge (S-S) or exist in a sulfhydryl form (-SH), forming oxidized or reduced PDI, respectively. PDI has been proven to be critical for platelet aggregation, thrombosis, and hemostasis, and PDI inhibition is being evaluated as a novel antithrombotic strategy. The redox states of functional PDI during the regulation of platelet aggregation, however, remain to be elucidated. Endoplasmic reticulum (ER) oxidoreductin-1α (Ero1α) and PDI constitute the pivotal oxidative folding pathway in the ER and play an important role in ER redox homeostasis. Whether Ero1α and PDI constitute an extracellular electron transport pathway to mediate platelet aggregation is an open question. Here, we found that oxidized but not reduced PDI promotes platelet aggregation. On the platelet surface, Ero1α constitutively oxidizes PDI and further regulates platelet aggregation in a glutathione-dependent manner. The Ero1α/PDI system oxidizes reduced glutathione (GSH) and establishes a reduction potential optimal for platelet aggregation. Therefore, platelet aggregation is mediated by the Ero1α-PDI-GSH electron transport system on the platelet surface. We further showed that targeting the functional interplay between PDI and Ero1α by small molecule inhibitors may be a novel strategy for antithrombotic therapy.

Chronic pain is highly prevalent and poorly controlled, of which the accurate underlying mechanisms need be further elucidated. Herbal drugs have been widely used for controlling various pain disorders. The systematic integration of pain herbal data resources might be promising to help investigate the molecular mechanisms of pain phenotypes. Here, we integrated large-scale bibliographic literatures and well-established data sources to obtain high-quality pain relevant herbal data (i.e. 426 pain related herbs with their targets). We used machine learning method to identify three distinct herb categories with their specific indications of symptoms, targets and enriched pathways, which were characterized by the efficacy of treatment to the chronic cough related neuropathic pain, the reproduction and autoimmune related pain, and the cancer pain, respectively. We further detected the novel pathophysiological mechanisms of the pain subtypes by network medicine approach to evaluate the interactions between herb targets and the pain disease modules. This work increased the understanding of the underlying molecular mechanisms of pain subtypes that herbal drugs are participating and with the ultimate aim of developing novel personalized drugs for pain disorders.

Background: Dyspnea is the most common presenting symptom among patients hospitalized for acute heart failure (AHF). Dyspnea relief constitutes a clinically relevant therapeutic target and endpoint for clinical trials and regulatory approval. However, there have been no widely accepted dyspnea measurement standards in AHF. By systematic review and mapping the current evidence of the applied scales, timing, and results of measurement, we hope to provide some new insights and recommendations for dyspnea measurement. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception until August 27, 2020. Randomized controlled trials (RCTs) with dyspnea severity measured as the endpoint in patients with AHF were included. Results: Out of a total of 63 studies, 28 had dyspnea as the primary endpoint. The Likert scale (34, 54%) and visual analog scale (VAS) (22, 35%) were most widely used for dyspnea assessment. Among the 43 studies with detailed results, dyspnea was assessed most frequently on days 1, 2, 3, and 6 h after randomization or drug administration. Compared with control groups, better dyspnea relief was observed in the experimental groups in 21 studies. Only four studies that assessed tolvaptan compared with control on the proportion of dyspnea improvement met the criteria for meta-analyses, which did not indicate beneficial effect of dyspnea improvement on day 1 (RR: 1.16; 95% CI: 0.99-1.37; p = 0.07; I 2 = 61%). Conclusion: The applied scales, analytical approaches, and timing of measurement are in diversity, which has impeded the comprehensive evaluation of clinical efficacy of potential therapies managing dyspnea in patients with AHF. Developing a more general measurement tool established on the unified unidimensional scales, standardized operation protocol to record the continuation, and clinically significant difference of dyspnea variation may be a promising approach. In addition, to evaluate the effect of experimental therapies on dyspnea more precisely, the screening time and blinded assessment are factors that need to be considered.

Traditional Chinese medicine (TCM) has accumulated some experience in curing stable angina pectoris (SAP) and efficacy has been demonstrated. Chinese patent medicines, known as modern dosage forms of TCM, can attain the desired effect in clinical application only with the guidance of TCM syndrome theory. However, due to their use by a large number of persons with little knowledge of TCM theories and practices, their efficacy and reputation have been seriously affected.

Treatment of cardiac syndrome X with unknown pathological mechanism remains a big challenge for clinicians. Complementary and alternative medicine may bring a new choice for its management. The aim of this study is to evaluate the clinical effects of traditional Chinese medicine on cardiac syndrome X patients.

Chronic heart failure (CHF) is a global public health problem. Therefore, novel and effective drugs that show few side-effects are needed. Early literature studies indicated that Huangqi injection is one of the most commonly used traditional Chinese patent medicines for CHF in China. As a large number of clinical studies has been carried out and published, it is essential to evaluate the effectiveness and safety of Huangqi injection. Therefore, we carried out this systematic review under the support of the framework of the Joint Sino-Italian Laboratory (JoSIL).

The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD).

The present report systematically reviewed the basic research of Shen Zhi Ling oral liquid (Tiao Xin preparation) treatment on Alzheimer's disease (AD).

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.

Atrial fibrillation (AF) occurs in up to 11% of cancer patients treated with ibrutinib. The pathophysiology of ibrutinib promoted AF is complicated, as there are multiple interactions involved; the detailed molecular mechanisms underlying this are still unclear. Here, we aimed to determine the electrophysiological and molecular mechanisms of burst-pacing-induced AF in ibrutinib-treated mice. The results indicated differentially expressed proteins in ibrutinib-treated mice, identified through proteomic analysis, were found to play a role in oxidative stress-related pathways. Finally, treatment with an inhibitor of NADPH oxidase (NOX) prevented and reversed AF development in ibrutinib-treated mice. It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-β protein expression. It was interesting that ibrutinib group also significantly increased the expression of ox-CaMKII, p-CaMKII (Thr-286) and p-RyR2 (Ser2814), causing enhanced abnormal sarcoplasmic reticulum (SR) Ca2+ release and mitochondrial structures, as well as atrial fibrosis and atrial hypertrophy in ibrutinib-treated mice, and apocynin reduced the expression of these proteins. Ibrutinib-treated mice were also more likely to develop AF, and AF occurred over longer periods. In conclusion, our study has established a pathophysiological role for ROS signaling in atrial cardiomyocytes, and it may be that ox-CaMKII and p-CaMKII (Thr-286) are activated by ROS to increase AF susceptibility following ibrutinib treatment. We have also identified the inhibition of NOX as a potential novel AF therapy approach.

Myocardial infarction (MI) is the most dangerous complication in patients with coronary heart disease. In China, there is an increasing number of randomised controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating MI. However, the inconsistency of outcome reporting means that a large number of clinical trials cannot be included in systematic reviews to provide the best evidence for clinical practice. The aim of this study is to develop a core outcome set (COS) for future TCM clinical trials of MI, which may improve the consistency of outcome reporting and facilitate the synthesis of data across studies in systematic reviews.

Chemotherapy is widely used in the treatment of cancer patients, but the cardiotoxicity induced by chemotherapy is still a major concern to most clinicians. Currently, genetic methods have been used to detect patients with high risk of chemotherapy-induced cardiotoxicity (CIC), and our study evaluated the correlation between genomic variants and CIC. The systematic literature search was performed in the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), China Biology Medicine disc (CBMdisc), the Embase database, China National Knowledge Internet (CNKI) and Wanfang database from inception until June 2020. Forty-one studies were identified that examined the relationship between genetic variations and CIC. And these studies examined 88 different genes and 154 single nucleotide polymorphisms (SNPs). Our study indicated 6 variants obviously associated with the increased risk for CIC, including CYBA rs4673 (pooled odds ratio, 1.93; 95% CI, 1.13-3.30), RAC2 rs13058338 (2.05; 1.11-3.78), CYP3A5 rs776746 (2.15; 1.00-4.62) ABCC1 rs45511401 (1.46; 1.05-2.01), ABCC2 rs8187710 (2.19; 1.38-3.48), and HER2-Ile655Val rs1136201 (2.48; 1.53-4.02). Although further studies are required to validate the diagnostic and prognostic roles of these 6 variants in predicting CIC, our study emphasizes the promising benefits of pharmacogenomic screening before chemotherapy to minimize the CIC.

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).

Background. Clinically, electroacupuncture (EA) is the most common therapy for aging-related cognitive impairment (CI). However, the underlying pathomechanism remains unidentified. The aims of this study were to observe the effect of EA on cognitive function and explore the potential mechanism by which EA acts on the NLRP3/caspase-1 signaling pathway. Main Methods. Thirty male SAMP8 mice were randomly divided into the model, the 2 Hz EA and 10 Hz EA groups. Ten male SAMR1 mice were assigned to the control group. Cognitive function was assessed through the Morris water maze test. Hippocampal morphology and cell death were observed by HE and TUNEL staining, respectively. The serum IL-1β, IL-6, IL-18, and TNF-α levels were measured by ELISA. Hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1β, IL-18, Aβ, and tau proteins were detected by Western blotting. Key Findings. Cognitive function, hippocampal morphology, and TUNEL-positive cell counts were improved by both EA frequencies. The serum IL-1β, IL-6, IL-18, and TNF-α levels were decreased by EA treatment. However, 10 Hz EA reduced the number of TUNEL-positive cells in the CA1 region and serum IL-1β and IL-6 levels more effectively than 2 Hz EA. NLRP3/caspase-1 pathway-related proteins were significantly downregulated by EA, but 2 Hz EA did not effectively reduce ASC protein expression. Interestingly, both EA frequencies failed to reduce the expression of Aβ and tau proteins. Significance. The effects of 10 Hz EA at the GV20 and ST36 acupoints on the NLRP3/caspase-1 signaling pathway may be a mechanism by which this treatment relieves aging-related CI in mice.