Multicomponent reactions to access S-aryl dithiocarbamates via an electron donor-acceptor complex under open-to-air conditions.

A simple and efficient transition-metal/photocatalyst-free visible-light-driven one-pot three-component reaction between thianthrenium salts, carbon disulfide and amines under an air atmosphere for the preparation of biologically relevant S-aryl dithiocarbamates is developed. This methodology is robust and scalable, and exhibits a broad substrate scope and excellent functional group tolerance. Of note, a wide range of primary aliphatic amines bearing different groups are suitable for this strategy. The synthetic utility was further demonstrated by a two-step one-pot multi-component reaction and photo-flow decagram-scale synthesis. Preliminary mechanistic studies suggest that the association of the dithiocarbamate anion with thianthrenium salts formed an electron donor-acceptor complex, which upon excitation with visible light produced an aryl radical via single-electron transfer.

Identification of Serum-Based Metabolic Feature and Characteristic Metabolites in Paraquat Intoxicated Mouse Models.

Paraquat (PQ) is a widely used herbicide which can cause high mortality to humans. However, relatively few studies focus on metabolic feature of PQ intoxication for investigating the underlying mechanisms. Here we performed non-targeted metabolomics profiling of serum samples from acute and chronic PQ intoxicated mouse models by gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) to identify metabolic feature and characteristic metabolites of acute and chronic PQ intoxication. Results showed that 3-indolepropionic acid (IPA) and pathway of glycine, serine, and threonine metabolism were significantly altered after acute PQ intoxication; 2-hydroxybutyric acid and the ratio of L-serine/glycine were of significance between acute and chronic PQ intoxication. Then targeted metabolomics profiling was conducted by liquid chromatography-mass spectrometry (LC-MS) analysis to confirm the changes of IPA after acute PQ intoxication. Moreover, IPA-producing gut bacteria in feces were quantified by qRT-PCR to explain the varied IPA serum concentration. Clostridium botulinum and Peptostreptococcus anaerobius were significantly suppressed after acute PQ intoxication. The data suggested that PQ caused oxidative damage partially through suppression of anti-oxidative metabolite producing gut bacteria. In conclusion, we identified characteristic metabolites and pathway of acute and chronic PQ intoxication which could be potential biomarkers and therapeutic targets.

Kangai Injection Combined with Platinum-based Chemotherapy for the Treatment of Stage III/IV Non-Small Cell Lung Cancer: A Meta-analysis and Systematic Review of 35 Randomized Controlled Trials.

Objective: In an effort to inform evidence-based guidelines for clinical practice, we performed a meta-analysis to systematically evaluate the safety and efficacy of Kangai injection (KAI) plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer (NSCLC). Methods: Randomized controlled trials (RCTs) comparing KAI plus platinum-based chemotherapy (experimental group) to chemotherapy alone (control group) were electronically retrieved from the Cochrane Library, PubMed, EMbase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Biological Medicine (CBM) Database, Wanfang Database, and the VIP Database for Chinese Technical Periodicals. RCTs published from the date of inception to July 5, 2018, were included. All trials were assessed for methodological quality in accordance with the Cochrane Reviewer's Handbook for Systematic Reviews of Intervention. Meta-analysis was performed using RevMan5.3 Software and Comprehensive Meta-Analysis (CMA) 2.0. Results: The final analysis included 35 RCTs involving 2,618 patients. Our meta-analysis revealed that KAI combined with platinum-based chemotherapy was associated with significantly greater objective response rate (ORR) (RR=1.36, 95% CI: 1.25-1.49, P<0.00001) and disease control rate (DCR) (RR=1.14, 95% CI: 1.09-1.18, P<0.00001), improvements in quality of life (QOL) (RR=1.75, 95% CI: 1.59-1.93, P<0.00001), and decreases in the incidence of gastrointestinal reactions (RR=0.64, 95% CI: 0.54-0.77, P<0.00001), leukocytopenia (RR=0.54, 95% CI: 0.46-0.63, P<0.00001) and thrombocytopenia (RR=0.52, 95% CI: 0.36-0.76, P=0.0007) when compared with chemotherapy alone. In addition, combined treatment was associated with greater regulation of tumor immune function, as indicated by increases in the proportion of NK, CD3 + , and CD4 + cells (MD=2.27, 95% CI: 1.18-3.36, P<0.0001; MD=12.86, 95% CI: 11.64-14.08, P<0.00001; and MD=5.48, 95% CI: 2.68-8.28, P=0.0001) and decreases in the percentage of CD8 + cells (MD= -2.37, 95% CI from -4.51 to -0.23, P=0.03). Conclusions: From the available evidence, our results indicate that KAI plus platinum-based chemotherapy could be more effective in improving clinical efficacy, decreasing the incidence of adverse reactions and regulating the tumor immune function than chemotherapy alone in the treatment of stage III/IV NSCLC. Nevertheless, considering the limitations of the included studies, rigorous designed, high-quality, multicenter clinical trials are still need to further confirm the results.

Acupuncture for migraine: a protocol for a meta-analysis and meta-regression of randomised controlled trials.

INTRODUCTION: Although the effectiveness of acupuncture for episodic migraine has been confirmed by multiple clinical trials and Cochrane systematic reviews, the mechanisms underlying the specific effect of acupuncture for migraine remain controversial. We aim to evaluate the effectiveness and safety of acupuncture for both episodic migraine and chronic migraine by meta-analysis and explore the possible factors influencing the specific effect of acupuncture for migraine by meta-regression. METHODS AND ANALYSIS: We will search for randomised control trials of acupuncture for migraine in the following eight databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED (via OVID) and four Chinese databases (Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database and Wanfang Database) from inception to 31 December 2017. We will also search OpenSIGLE (opensigle.inist.fr) for conference abstracts. No language restriction will be applied. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies will be conducted independently by two reviewers. Standard meta-analysis and, if appropriate, meta-regression will be performed using the R packages Meta and Metafor. ETHICS AND DISSEMINATION: The results of this meta-analysis and meta-regression will be disseminated through publication in a peer-reviewed journal and presented at a relevant conference. The data used in this meta-analysis will not contain individual patient data; therefore, ethical approval is not required. PROSPERO REGISTRATION NUMBER: CRD42018087270.

[Compliance Control Strategy in the Practical Randomized Controlled Trial Study of Electroacupuncture Combined with Behavior Control for Overweight and Simple Obesity].

Electroacupuncture (EA) has been extensively used in clinical treatment of obesity. The effectiveness relies not only on the correct diagnosis and rational treatment, but also on the voluntary cooperation of patients, that is the satisfactory compliance. The patient compliance refers to his/her submissiveness and executive ability to medical advice, which is the indispensable factor for the clinical efficacy. The strength of it depends on the patient himself/herself, and moreover is improved through some therapeutic strategies. Based on the emphasis of individual treatment in the real world, the practical randomized controlled trial (RCT) study pays attention to patient's compliance at the beginning of trial design. In this paper, in terms of the influential factors and control strategies, the compliance of simple obesity patient in the practical RCT study was summarized systematically.

Comparative effectiveness of electro-acupuncture plus lifestyle modification treatment for patients with simple obesity and overweight: study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture is considered to be an effective and safe treatment for obese and overweight patients, although high-quality evidence regarding the effects of acupuncture on obesity are not conclusive. The aim of the current study is to investigate the effectiveness of electro-acupuncture plus lifestyle modification for treating obese and overweight patients, in comparison with lifestyle modification alone in China. METHODS/DESIGN: To compare the effectiveness of acupuncture plus lifestyle modification, a 2-armed, controlled trial with randomization using minimization will be conducted on 150 simple obesity and overweight patients, aged 18-50 years, for a 36-week study duration. All patients will be randomly assigned to one of two groups and will receive either acupuncture plus lifestyle modification or lifestyle modification alone. Outcomes will be evaluated at baseline and at 4 weeks, 8 weeks, and 12 weeks during treatment as well as at 6-week, 12-week, and 24-week follow-up. The primary endpoint is change of body mass index (BMI) during the 12th week. Secondary endpoints are body weight; waist-to-hip ratio; biochemical tests including serum cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) levels; and answers to the Short Form 36 (SF-36) and the Impact of Weight on Quality of Life Questionnaire-Lite Version (IWQOL-Lite). Statistical analyses will be based on the intention-to-treat (ITT) principle. The main endpoint will be analyzed by analysis of covariance (ANCOVA), and the objective outcome results will be analyzed by logistic regression analysis. To avoid potential confounding factors, additional sensitivity analyses will be conducted following these statistical analyses. DISCUSSION: This trial is the first to compare the effectiveness of acupuncture plus lifestyle modification for treating obesity relative to lifestyle modification treatment alone by using a pragmatic study design. We hope that the results of this study will contribute to advancing the current methodology of acupuncture trials for obesity and will facilitate the application of useful acupuncture strategies in real-world clinical settings. TRIAL REGISTRATION: ChiCTR-TRC- 12002762 . The date of registration is 31 October 2012.

Electroacupuncture at Acupoints Reverses Plasma Glutamate, Lipid, and LDL/VLDL in an Acute Migraine Rat Model: A (1) H NMR-Based Metabolomic Study.

Background. The objective of this study was to identify potential biomarkers of electroacupuncture (EA) on relieving acute migraine through metabolomic study. Methods. EA treatments were performed on both acupoints and nonacupoints on the nitroglycerin (NTG)-induced migraine rat model. NMR experiments and multivariate analysis were used for metabolomic analysis. Results. The number of head-scratching, the main ethology index of migraine rat model, was significantly increased (P < 0.01) after NTG injection. The plasma metabolic profile of model group was distinct from that of the control group. Glutamate was significantly increased (P < 0.01), whereas lipids were significantly decreased (P < 0.01) in model rats. After EA at acupoints, the metabolic profile of model rats was normalized, with decreased glutamate (P < 0.05) and increased lipids (P < 0.01). In contrast, EA at nonacupoints did not restore the metabolic profile, but with six metabolites significantly different from acupoints group. Interestingly, the number of head-scratching and glutamate level were significantly decreased (P < 0.05) after receiving EA at both acupoints and nonacupoints. Conclusions. EA at acupoints may relieve acute migraine by restoring the plasma metabolic profile and plasma glutamate, while EA at nonacupoints may modestly relieve acute migraine by decreasing plasma glutamate.