Clinical efficacy of Kuanxiong aerosol for patients with prehospital chest pain: A randomized controlled trial.

BACKGROUND: Kuanxiong Aerosol (KXA)(CardioVent®), consisting of Asarum sieboldii Miq. oil, Santalum album L. oil, Alpinia officinarum Hance oil, Piper longum L. oil and borneol, seems to relieve the symptoms of chest pain and serve as a supplementary treatment for prehospital chest pain in emergency department. STYLE OF THE STUDY: This randomized controlled trial aimed to determine the clinical effect and safety of KXA for patients with prehospital chest pain. METHODS: A total of 200 patients were recruited from Guangdong Provincial Hospital of Chinese Medicine and randomly divided into KXA group (n = 100) and Nitroglycerin Aerosol (NA) group (n = 100) by SAS 9.2 software. All patients were treated with standardized Western medicine according to the pre-hospital procedure. The experimental group and NA group was additionally treated with KXA and NA respectively. The primary outcome was the relieving time of prehospital chest pain (presented as relief rate) after first-time treatment. The secondary outcomes included the evaluation of chest pain (NRS scores, degree of chest pain, frequency of chest pain after first-time treatment), efficacy in follow-up time (the frequency of average aerosol use, emergency department visits, 120 calls, medical observations and hospitalization at 4 weeks, 8 weeks, 12 weeks), alleviation of chest pain (Seattle angina questionnaire, chest pain occurrence, and degree of chest pain at 12-weeks treatment) and the change of TCM symptoms before and after 12-weeks treatment. In addition, the safety of KXA was also assessed by the occurrence of adverse events. The database was created using Epidata software, and statistical analysis was conducted by SPSS 23.0 software. RESULTS: A total of 194 participants finally completed the trial, the results showed that after first-time treatment, KXA had a higher relief rate (72.2%) of chest pain within 30 min than that of NA group (59.4%, p = 0.038), KXA group had a lower degree of chest pain (p = 0.005), lower NRS score (p = 0.011) and higher reduction of NRS score (p = 0.005) than the NA. In the follow-up period, KXA group decreased the frequency of 120 call better than that of NA group at 4 weeks (p = 0.040), but KXA had a similar efficacy as NA in the improvement on the of frequency of chest pain, aerosol use, emergency department visits, 120 call, medical observation and hospitalization at 4 weeks, 8 weeks and 12 weeks (p>0.05). There also had no difference between the two groups on the occurrence of chest pain, degree of chest pain, physical limitation, angina stability, treatment satisfaction, and disease perception between the two groups at 12 weeks (p>0.05). In addition, KXA and NA both improved the patient's chest pain, but not the TCM symptoms. In terms of safety, KXA showed similar safety as NA in this study. CONCLUSIONS: KXA relieved prehospital chest pain faster than NA and had a better remission effect on the prehospital chest pain than that of the NA group in short-period. In long-period, KXA showed similar efficacy on the improvement of prehospital chest pain as NA. KXA may be a safe and reliable therapy for prehospital chest pain.

SBC (Sanhuang Xiexin Tang combined with Baihu Tang plus Cangzhu) alleviates NAFLD by enhancing mitochondrial biogenesis and ameliorating inflammation in obese patients and mice.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.

ScRNA-seq revealed targeting regulator of G protein signaling 1 to mediate regulatory T cells in Hepatocellular carcinoma.

BACKGROUND: Regulatory T cells (Tregs) are central to determine immune response, thus targeting Tregs for immunotherapy is a promising strategy against tumor development and metastasis. OBJECTIVES: The objective of this study was to identify genes for targeting Tregs to improve the outcome of HCC. METHODS: We integrated expression data from different samples to remove batch effects and further applied embedding function in Scanpy to conduct sub-clustering of CD4+ T cells in HCC for each of two independent scRNA-seq data. The activity of transcription factors (TFs) was inferred by DoRothEA. Gene expression network analysis was performed in WGCNA R package. We finally used R packages (survminer and survival) to conduct survival analysis. Multiplex immunofluorescence analysis was performed to validate the result from bioinformatic analyses. RESULTS: We found that regulator of G protein signaling 1 (RGS1) expression was significantly elevated in Tregs compared to other CD4+ T cells in two independent public scRNA-seq datasets, and increased RGS1 predicted inferior clinical outcome of HCC patients. Multiplex immunofluorescence analysis supported that the higher expression of RGS1 in HCC Tregs in tumor tissue compared to it in adjacent tissue. Moreover, RGS1 expression in Tregs was positively correlated with the expression of marker genes of Tregs, C-X-C chemokine receptor 4 (CXCR4), and three CXCR4-dependent genes in both scRNA-seq and bulk RNA-seq data. We further identified that these three genes were selectively expressed in Tregs as compared to other CD4+ T cells. The activities of two transcription factors, recombination signal binding protein for immunoglobulin kappa J region (RBPJ) and yin yang 1 (YY1), were significantly different in HCC Tregs with RGS1 high and RGS1 low. CONCLUSIONS: Our findings suggested that RGS1 may regulate Treg function possibly through CXCR4 signaling and RGS1 could be a potential target to improve responses for immunotherapy in HCC.

Screening of trypsin inhibitors in Cotinus coggygria Scop. extract using at-line nanofractionation coupled with semi-preparative reverse-phase liquid chromatography.

In this study, an at-line nanofractionation (ANF) platform was successfully fabricated in parallel with mass spectrometry and trypsin inhibitory bioactivity assessment for rapid screening of trypsin inhibitors (TIs) from natural products for the first time. After systematic optimization, the ANF platform was applied to screen and identify TIs in the extract of a traditional Chinese herb, i.e., Cotinus coggygria Scop. The semi-preparative reverse-phase liquid chromatography was used subsequently to further simplify and enrich the insufficiently separated components. After comprehensive evaluation and validation, the ANF platform successfully identified 12 compounds as potential TIs, including 8 flavonoids and 2 organic acids. Additionally, a comparison study was conducted using two other ligand fishing approaches, i.e., capillary monolithic and magnetic beads-based trypsin-immobilized enzyme microreactors, which successfully identified 8 identical flavonoids as TIs. Importantly, the molecular docking study showed the molecular interactions between enzymes and inhibitors, thus strongly supporting the experimental results. Overall, this work has fully demonstrated the feasibility of the established ANF platform for screening TIs from Cotinus coggygria Scop., and proved its great prospects for screening bioactive components from natural products.

Dynamic nitric oxide/drug codelivery system based on polyrotaxane architecture for effective treatment of Candida albicans infection.

The low permeability of antifungal agents to fungal biofilms, which allows the continued survival of the fungus inside, is a key issue that makes fungal infections difficult to cure. Inspired by the unique dynamic molecule motion properties of the polyrotaxane (PR) nanomedicine, herein, a dynamic delivery system Clo@mPRP/NONOate was fabricated by co-loading nitric oxide (NO) and the antifungal drug clotrimazole (Clo) onto the α-cyclodextrin (α-CD) PR modified mesoporous polydopamine (mPDA) nanoparticles, in which pentaethylenehexamine (PEHA) was grafted to α-CDs. The cationic α-CDs endowed this dynamic NO/Clo codelivery system with the ability to effectively attach to fungal biofilms through electrostatic interaction, while the introduction of PRs with flexible molecule motion (slide and rotation of CDs) enhanced the permeability of nanoparticles to biofilms. Meanwhile, NO could effectively inhibit the formation of fungal hyphae, showing an dissipating effect on mature biofilms, and could be further combined with Clo to completely eradicate fungi inside the biofilms. In addition, the dynamic system Clo@mPRP/NONOate could efficiently and synergistically eliminate planktonic Candida albicans (C. albicans) in a safe and no toxic side effect manner, and effectively cured C. albicans-induced vaginal infection in mice. Therefore, this dynamic NO/Clo codelivery system provided an effective solution to the clinical treatment of C. albicans-induced vaginal infection, and the application prospect could even be extended to other microbial infectious diseases. STATEMENT OF SIGNIFICANCE: A dynamic codelivery system based on cationized cyclodextrin polyrotaxane combining nitric oxide and antifungal drugs clotrimazole was prepared to deal with the issue of clinical fungal biofilm infection. This dynamic codelivery system could be attached to the Candida albicans biofilms and penetrate into biofilm via flexible molecular mobility to effectively eradicate the fungi. This dynamic codelivery system could synergistically and efficiently eliminate planktonic-state Candida albicans, but did not show significant cytotoxicity to normal somatic cells.

Effect of Vitamin D Supplementation on Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: Laboratory findings indicated that vitamin D might have a potent protective effect on breast cancer, but epidemiology studies reported conflicting results. The aim of the study was to conduct a systematic review and meta-analysis to clarify the efficacy of vitamin D supplementation on risk of breast cancer. Methods: MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and abstracts of three major conferences were searched (up to December 8, 2020). Parallel randomized controlled trials (RCTs) examining the efficacy of vitamin D supplementation on risk of breast cancer or change of mammography compared with placebo in females were included. Data were meta-analyzed using a random-effects model. Bayesian meta-analysis was conducted to synthesize the results using data from observational studies as priors. Results: Seven RCTs were identified for effect of vitamin D on risk of breast cancer, with 19,137 females included for meta-analysis. No statistically significant effect of vitamin D on risk of breast cancer was found in classical random-effects meta-analysis (risk ratio = 1.04, 95% confidence interval: 0.84-1.28, p = 0.71). When Bayesian meta-analyses were conducted, results remained non-significant. There was no statistically significant effect of vitamin D on mammography density observed: mean difference = 0.46, 95% confidence interval: -2.06 to 2.98, p = 0.72. Conclusion: There is insufficient evidence to support the efficacy of vitamin D supplementation in breast cancer risk and change of mammography density. The protective effect of vitamin D on risk of breast cancer from previous observational studies may be overestimated. Systematic Review Registration: PROSPERO, identifier CRD42019138718.

Quantitative and network pharmacology: A case study of rhein alleviating pathological progress of renal interstitial fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The current network pharmacology model focuses mainly on static and qualitative characterisation between drugs and targets or molecular pathway networks, but it does not reflect the multi-scale, dynamic and quantitative process of drug action. AIM OF THE STUDY: In this study, we developed a new model known as quantitative and network pharmacology (QNP) to characterise the dynamic and quantitative interventions of drugs within a multi-scale biological network. MATERIALS AND METHODS: Firstly, we used a systems biology method to construct a molecule-cell dynamic network model to simulate the pathological processes of diseases. Secondly, according to the principles of enzymatic kinetics, we generated a multi-scale drug intervention model to simulate the intervention of drugs in multi-scale networks at different concentrations and pathological stages. Finally, we took rhein treatment of renal interstitial fibrosis (RIF) as an example to illustrate the QNP model. RESULTS: We successfully constructed the a QNP model that includes both a multi-scale dynamic network disease model and drug intervention model. The QNP model accurately simulated the pathological process of RIF, and the simulation results were validated by a series of cell and animal experiments. Meanwhile, the QNP model demonstrated that rhein can delay the pathological process at the studied concentrations of 5 nM, 10 nM, and 20 nM, and can also exert a better therapeutic effect on fibrosis before the proliferation stage of RIF. Furthermore, through uncertainty and sensitivity analysis, we identified that FAK and Smad3 may be potential targets for RIF. CONCLUSION: Our QNP model provides a molecular-cellular understanding of the pathological mechanisms of RIF, serving as a new approach and strategy for the construction of dynamic multi-scale network model of diseases and drug intervention.

Rapid review for the anti-coronavirus effect of remdesivir.

The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.

Pilot and feasibility trials in traditional Chinese medicine: a literature review of current practice.

BACKGROUND: The guidelines for pilot and feasibility studies were published in 2016. Little is known about the guideline adherence of TCM (traditional Chinese medicine) pilot trials or whether the guidelines can significantly enhance the quality of implementation and reporting of TCM pilot trials. We aimed to investigate the guideline adherence, assess the impact of guidelines on TCM pilot trials, and discuss potential challenges specific to TCM pilot trials, by conducting a literature review. METHODS: We systematically searched MEDLINE, EMBASE, and CNKI to retrieve TCM pilot trials. We randomly chose 50 pilot trials from the eligible studies for analyses. The CONSORT extension to pilot and feasibility studies was used as a framework to assess the methodology and reporting quality of the studies. RESULTS: The included studies had a guideline adherence level ranging from 4 to 96%, where the lowest adherence was found in the item 6c (prespecified criteria used to judge progression to future definitive trial). The guidance published in 2016 seemed to exert minimal effect on guideline adherence in TCM pilot trials. The unidentified issues related to TCM pilot trials from the guidelines included blinding, lack of standard formula of interventions, difficulty in comparison for effect assessment of interventions, and difficulty in bias control. CONCLUSIONS: The current practice in TCM pilot trials required substantial improvement in the literature. Further endeavors are needed for training and dissemination of guideline adherence, and development of more detailed methodology in the field of TCM pilot trials.

Prediction model of artificial neural network for the risk of hyperuricemia incorporating dietary risk factors in a Chinese adult study.

BACKGROUND: Risk of hyperuricemia (HU) has been shown to be strongly associated with dietary factors. However, there is scarce evidence on prediction models incorporating dietary factors to estimate the risk of HU. OBJECTIVE: The aim of this study was to develop a prediction model to predict the risk of HU in Chinese adults based on dietary information. DESIGN: Our study was based on a cross-sectional survey, which recruited 1,488 community residents aged 18 to 60 years in Beijing from October 2010 to January 2011. The eligible participants were randomly divided into a training set (n 1 = 992) and a validation set (n 2 = 496) in the ratio of 2:1. We developed the prediction model in three stages. We first used a logistic regression model (LRM) based on the training set to select a set of dietary risk factors which were related to the risk of HU. Artificial neural network (ANN) was then used to construct the prediction model using the training set. Finally, we used receiver operating characteristic (ROC) curve analysis to assess the accuracy of the prediction model using training and validation sets. RESULTS: In the training set, the mean age of participants with and without HU was 39.3 (standard deviation [SD]: 9.65) and 38.2 (SD: 9.38) years, respectively. Patients with HU consisted of 101 males (77.7%) and 29 females (22.3%). The LRM found that food frequency (vegetables [odds ratio (OR) = 0.73], meat [0.72], eggs [0.80], plant oil [0.78], tea [0.51], eating habits (breakfast [OR = 1.28]), and the salty cooking style (OR = 1.33) were associated with risk of HU. In the ANN analysis, we selected a three-layer back propagation neural network (BPNN) model with 14, 3, and 1 neuron in the input, hidden, and output layers, respectively, as the best prediction model. The areas under the ROC of the training and validation sets were 0.827 and 0.814, respectively. HU would occur when the incidence probability is greater than 0.128. The indicators of accuracy, sensitivity, specificity, and Yuden Index suggested that the ANN model in our study is successful and valuable. CONCLUSIONS: This study suggests that the ANN model could be used to predict the risk of HU in Chinese adults. Further prospective studies are needed to improve the accuracy and to generalize the use of model.

Pharmacokinetics and Pharmacodynamics of the Combination of Rhein and Curcumin in the Treatment of Chronic Kidney Disease in Rats.

Objectives: The interaction between the components of traditional Chinese medicine (TCM) is an important basis for their synergy. Rhein and curcumin exert various pharmacological activities, including anti-tumour, anti-inflammatory, antioxidant, anti-fibrosis and renoprotective effects. However, no investigation has reported the synergistic anti-fibrosis effect yet. This study aims at determine the pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment for chronic kidney disease in rats. Design: Fifty two male Sprague-Dawley (SD) rats were randomly divided into rhein group, curcumin group and their combination group for pharmacodynamics studies. HE and Masson staining was conducted to observe the changes of renal morphology. Kits were used to detect the level of urea nitrogen (BUN) and creatinine (Scr). For pharmacokinetic study, 36 SD rats were randomly divided into rhein group, curcumin group and a combination group, the content of rhein and curcumin in plasma and renal tissue was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In additon, molecular docking method and cell experiments was used to disclose the interaction mechanism between curcumin and rhein. Results: The pharmacodynamic results showed that the degree of renal fibrosis was improved obviously by co-administration rhein and curcumin. Meanwhile, compared to single administration, the Cmax and AUC of rhein and curcumin in plasma and renal tissue were enhanced significantly after co-administration. Moreover, the result of molecular docking and cell experiments showed that both two compounds could interact with P-gp, CYP2C9 and CYP2C19. Conclusion: Together, these findings demonstrated that rhein and curcumin had a synergistic effect in ameliorateing chonic kidney disease, providing an important explanation on the synergistic mechanism of curcumin and rhein from a pharmacokinetic viewpoint.

Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly prescribed in clinical practice for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials are lacking, leaving an important clinical decision-making gap. We aimed to perform a systematic review and meta-analysis to summarize the evidence of observational studies for direct comparative effectiveness and safety amongst NOACs in patients with AF. Conference proceedings and electronic databases including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We included observational studies directly comparing individual NOACs in patients with nonvalvular AF who were aged ≥ 18 years for stroke prevention. Primary outcome included effectiveness outcome (stroke or systemic embolism) and safety outcome (major bleeding). Data were extracted in duplicated by two reviewers independently. A random-effects meta-analysis was conducted to synthesize the data from included observational studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to rate the overall quality of evidence for each outcome. Fifteen studies were included for qualitative synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and dabigatran were similar with regard to risk of stroke or systemic embolism (Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI 1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI 1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95; evidence quality: low). No differences in risk of stroke or systemic embolism was observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In this study, apixaban was found to have the most favorable safety profile amongst the three NOACs. No significant difference was observed in risk of stroke or systemic embolism between the NOACs. Such findings may provide some decision-making support for physicians regarding their choices amongst NOACs in patients with AF.Registration PROSPERO (identifier: CRD42016052908).

Relationship between hyperbaric oxygen therapy and quality of life in participants with chronic diabetic foot ulcers: data from a randomized controlled trial.

AIMS: To investigate the effect of hyperbaric oxygen therapy on health-related quality of life (HRQoL) in participants with diabetes and chronic foot ulcers. METHODS: Using data from a randomized controlled trial, we included 103 participants (49 in hyperbaric oxygen therapy group and 54 in sham group) for analyses. The primary outcome was HRQoL as measured by the EQ-5D-3L instrument, while secondary outcomes included quality of life evaluated by the Short Form 36 (SF-36) and Diabetic Foot Ulcers Scale-Short Form (DFS-SF). We used the analysis of covariance to assess whether the EQ-5D index values in hyperbaric oxygen therapy group differed from the sham group. Logistic regression was used to assess the relationship between hyperbaric oxygen therapy and the responses of 'problems' for the EQ-5D health states. RESULTS: No significant differences in EQ-5D index values were found between the hyperbaric oxygen therapy and sham groups: 0.01 (95% CI -0.25, 0.28; p = 0.93) at week 12; 0.07 (95% CI -0.21, 0.34; p = 0.64) at week 6. Hyperbaric oxygen therapy was found to be associated with fewer participants reporting 'problems' in mobility (OR 0.24, 95% CI 0.07, 0.85 at week 12) and pain or discomfort (OR 0.20, 95% CI 0.07, 0.61 at week 6; OR 0.32, 95% CI 0.11, 0.97 at week 12), compared with the sham group. No significant differences in SF-36 or DFS-SF were observed. CONCLUSIONS: No significant effect of hyperbaric oxygen therapy on HRQoL measured by EQ-5D index value was found in this study. Due to the potential insufficient power to assess statistical difference, more large-scale research is needed to further evaluate the effect of hyperbaric oxygen therapy on HRQoL in participants with chronic diabetic foot ulcers.

Curcumin improves bone microarchitecture in glucocorticoid-induced secondary osteoporosis mice through the activation of microRNA-365 via regulating MMP-9.

The present study aimed to investigate bone microarchitecture of the proximal tibia in glucocorticoid-induced osteoporosis (GIOP) mice, and the underlying molecular mechanisms of curcumin in DXM-induced osteoporosis were performed. DXM-treated facilitated to induce hypercalciuria in mice, and curcumin-treated showed a decrease in urine calcium. Curcumin reversed DXM-induced bone resorption, including an increase in serum OCN and a decrease in bone resorption markers CTX and TRAP-5b. H&E staining showed the increased disconnections and separation in trabecular bone network as well as the reduction of trabecular thickness throughout the proximal metaphysis of tibia in GIOP group. Importantly, curcumin reversed DXM-induced trabecular deleterious effects and stimulated bone remodeling. The further evidence showed that curcumin supplement significantly decreased the TRAP-positive stained area and inhibited the activity of OPG/RANKL/RANK signaling in the GIOP mice. Moreover, bioinformatics analysis suggested that miR-365 was a regulator of MMP9. The levels of miR-365 were markedly suppressed; however, curcumin treatment could reverse the downregulation of miR-365 in the tibia of GIOP mice. Simultaneously, the results demonstrated that the mRNA and protein expression of MMP-9 were significantly increased in GIOP mice compared with that of the control group. Curcumin treatment could suppress the expression of MMP-9 in the tibia of GIOP mice. The present study demonstrated the protective effects of curcumin against bone deteriorations in the experimentally DIOP mice, and the underlying mechanism was mediated, at least partially, through the activation of microRNA-365 via suppressing MMP9.

Effect of green tea supplementation on blood pressure among overweight and obese adults: a systematic review and meta-analysis.

BACKGROUND: Emerging randomized controlled trials (RCTs) investigating the effect of green tea or green tea extract (GTE) supplementation on blood pressure (BP) among overweight and obese adults reported inconsistent findings. OBJECTIVE: To conduct a systematic review and meta-analysis to clarify the efficacy of green tea or GTE on BP among overweight and obese adults. METHODS: Electronic databases, conference proceedings and gray literature were searched systematically to include parallel and cross-over RCTs examining the efficacy of green tea or GTE on BP compared with placebo. Data were meta-analyzed using a random-effects model, to compare the mean difference of the change in BP from baseline in the intervention and the placebo groups. RESULTS: Fourteen RCTs with 971 participants (47% women) were pooled for analysis. Green tea or GTE produced a significant effect on both SBP (mean difference -1.42 mmHg, 95% confidence interval -2.47 to -0.36, P = 0.008; I = 52%, P = 0.01 for heterogeneity) and DBP (mean difference -1.25 mmHg, 95% confidence interval -2.32 to -0.19, P = 0.02; I = 74%, P < 0.001 for heterogeneity), compared with placebo. The quality of evidence across studies was low. Similar results were found in subgroup and sensitivity analyses. CONCLUSION: Among overweight and obese adults, green tea or GTE supplementation is found to cause a small but significant reduction in BP. More high-quality RCTs with large sample sizes are needed to further confirm the efficacy on BP and make strong recommendations for green tea or GTE supplementation among the overweight and obese adults.

Fluid resuscitation in sepsis: a systematic review and network meta-analysis.

BACKGROUND: Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. PURPOSE: To examine the effect of different resuscitative fluids on mortality in patients with sepsis. DATA SOURCES: MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. STUDY SELECTION: Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. DATA EXTRACTION: Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. DATA SYNTHESIS: 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). LIMITATIONS: These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. CONCLUSION: Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. PRIMARY FUNDING SOURCE: The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.

Effect of green tea supplementation on blood pressure among overweight and obese adults: a protocol for a systematic review.

INTRODUCTION: Emerging randomised controlled trials (RCTs) exploring the effect of green tea (GT) supplementation or GT extract (GTE) on blood pressure (BP) among overweight and obese adults yielded inconclusive results. We aim to conduct a systematic review to summarise the evidence of RCTs until now, to clarify the efficacy of GT supplementation or GTE in BP in overweight and obese populations. METHODS AND ANALYSIS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ClinicalTrials.gov will be searched to retrieve potential RCTs. Unpublished studies will be identified by searching the abstract books or websites of the three major conference proceedings: the International Society of Hypertension, the Nutrition & Health Conference and the World Congress of Nutrition and Health. A random-effects meta-analysis will be performed to pool the mean difference for the change in BP from baseline (ie, postintervention BP minus baseline BP) between intervention groups and placebo groups of the included studies, presenting the pooled results with 95% CIs. Subgroups analyses will be conducted according to different doses of GT or GTE, trial duration, geographic regions, overweight versus obese participants, and participants with versus without change in body weight after intervention. Sensitivity analysis will be performed by excluding studies classified as having a high risk of bias, applying a fixed-effects model, using the postintervention BP for analyses and excluding trials with non-study cointerventions. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. It will be disseminated electronically and in print. Summarising the RCT evidence to clarify the efficacy in BP among overweight and obese adults will aid in making the dietary recommendation of GT and improving the clinical management of hypertension. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014007273.

Efficacy of vitamin D supplementation in depression in adults: a systematic review.

CONTEXT: Randomized controlled trials (RCTs) investigating the efficacy of vitamin D (Vit D) in depression provided inconsistent results. OBJECTIVE: We aim to summarize the evidence of RCTs to assess the efficacy of oral Vit D supplementation in depression compared to placebo. DATA SOURCES: We searched electronic databases, two conference proceedings, and gray literature by contacting authors of included studies. STUDY SELECTION: We selected parallel RCTs investigating the effect of oral Vit D supplementation compared with placebo on depression in adults at risk of depression, with depression symptoms or a primary diagnosis of depression. DATA EXTRACTION: Two reviewers independently extracted data from relevant literature. DATA SYNTHESIS: Classical and Bayesian random-effects meta-analyses were used to pool relative risk, odds ratio, and standardized mean difference. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: Six RCTs were identified with 1203 participants (72% females) including 71 depressed patients; five of the studies involved adults at risk of depression, and one trial used depressed patients. Results of the classical meta-analysis showed no significant effect of Vit D supplementation on postintervention depression scores (standardized mean difference = -0.14, 95% confidence interval = -0.41 to 0.13, P = .32; odds ratio = 0.93, 95% confidence interval = 0.54 to 1.59, P = .79). The quality of evidence was low. No significant differences were demonstrated in subgroup or sensitivity analyses. Similar results were found when Bayesian meta-analyses were applied. CONCLUSIONS: There is insufficient evidence to support the efficacy of Vit D supplementation in depression symptoms, and more RCTs using depressed patients are warranted.