Mn-Doped Nano-Hydroxyapatites as Theranostic Agents with Tumor pH-Amplified MRI-Signal Capabilities for Guiding Photothermal Therapy.

Background: The integration of diagnostic and therapeutic functions into a biosafe nanoplatform with intelligent response functions at the tumor microenvironment (TME) is a promising strategy for cancer therapy. Methods: Mn-doped nano-hydroxyapatite (nHAPMn) nanoparticles were successfully prepared via a simple coprecipitation method for magnetic resonance imaging (MRI)-guided photothermal therapy. This study is the first to report on the use of Mn to render biodegradable hydroxyapatite suitable for MRI and effective photothermal therapy (PTT) simultaneously by regulating the pH of nHAPMn during the preparation process. Results: Combined with near-infrared (NIR) laser irradiation, a photothermal conversion efficiency of 26% and effective photothermal lethality in vitro were achieved. Moreover, the degradation of nHAPMn led to the release of Mn ions and amplified the MRI signals in an acidic TME, which confirmed that nHAPMn had a good pH-responsive MRI capacity in solid tumors. In animal experiments, tumors in the nHAPMn5+NIR group completely abated after 14 days of treatment, with no significant recurrence during the experiment. Conclusion: Therefore, nHAPMn is promising as a nanotheranostic agent and can be effective in clinical diagnosis and therapy for treating cancer.

Upconversion Luminescence-Initiated and GSH-Responsive Self-Driven DNA Motor for Automatic Operation in Living Cells and In Vivo.

In light of the worthy design flexibility and the good signal amplification capacity, the recently developed DNA motor (especially the DNA walker)-based fluorescent biosensors can offer an admirable choice for realizing bioimaging. However, this attractive biosensing strategy not only has the disadvantage of uncontrollable initiation but also usually demands the supplement of exogenous driving forces. To handle the above obstacles, some rewarding solutions are proposed here. First, on the surface of an 808 nm near-infrared light-excited low-heat upconversion nanoparticle, a special ultraviolet upconversion luminescence-initiated three-dimensional (3D) walking behavior is performed by embedding a photocleavage linker into the sensing elements, and such light-controlled target recognition can perfectly overcome the pre-triggering of the biosensor during the biological delivery to significantly boost the sensing precision. After that, a peculiar self-driven walking pattern is constructed by employing MnO2 nanosheets as an additional nanovector to physically absorb the sensing frame, for which the reduction of the widespread glutathione in the biological medium can bring about sufficient self-supplied Mn2+ to guarantee the walking efficiency. By selecting an underlying next-generation broad-spectrum cancer biomarker (survivin messenger RNA) as the model target, we obtain that the newly formed autonomous 3D DNA motor shows a commendable sensitivity (where the limit of detection is down to 0.51 pM) and even an outstanding specificity for distinguishing single-base mismatching. Beyond this sound assay performance, our sensing approach is capable of working as a powerful imaging platform for accurately operating in various living specimens such as cells and bodies, showing a favorable diagnostic ability for cancer care.

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.

Regulatory effects of transition metals supplementation/deficiency on the gut microbiota.

Transition metal ions are essential micronutrients for all living organisms and exert a wide range of effects on human health. The uptake of transition metal ions occurs primarily in the gastrointestinal tract, which is colonized by trillions of bacterial cells. In recent years, increasing studies have indicated that transition metals have regulatory effects on the gut microbiota. In view of the significant effect of the gut microbiota on human health and involvement in the pathogenesis of a wide range of diseases, in this paper, we provide a comprehensive discussion on the regulatory effects of four kinds of transition metal ions on the gut microbiota. A total of 20 animal model and human studies concerning the regulatory effects of four types of transition metal ions (i.e., iron, copper, zinc, and manganese) on gut microbiota were summarized. Both the deficiency and supplementation of these transition metal ions on the gut microbiota were considered. Furthermore, the potential mechanisms governing the regulatory effects of transition metal ions on the gut microbiota were also discussed. KEY POINTS : • Regulatory effects of iron, copper, zinc, and manganese on gut microbiota were reviewed. • Both deficiency and supplementation of metal ions on gut microbiota were considered. • Mechanisms governing effects of metal ions on gut microbiota were discussed.

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.

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.

Marked Reduction in 28-day Mortality Among Elderly Patients with Severe Community-acquired Pneumonia: Post Hoc Analysis of a Large Randomized Controlled Trial.

BACKGROUND: There were few studies on the case mortality of severe community-acquired pneumonia (CAP) in elderly people. Improved outcomes with XueBiJing (XBJ) injection vs placebo have been shown in overall trial populations. We investigated the efficacy and safety of XBJ vs placebo in subjects with severe CAP stratified by age (<65 and ≥65 years). METHODS: This post hoc analysis of a large randomized trial compared data from elderly and nonelderly patients with XBJ, 100 mL, q 12 h, or a visually indistinguishable placebo for five-to-seven days. RESULTS: Among subjects ≥65 years (n=291), 23 (16.0%) XBJ recipients and 41 (27.9%) placebo recipients (P=0.014) died within 28 days. Among subjects <65 years (n=360), XBJ still had lower mortality (XBJ 15.6% vs placebo 22.8%; P=0.082), without significantly statistical difference. Total duration of ICU stay and the time of mechanical ventilation were similar in both groups (P>0.05). XBJ also had a favorable safety profile, with no clinically relevant differences between the two groups. The overall incidence of adverse events was similar in both groups. CONCLUSION: XBJ was safe and effective for reduction in 28-day mortality among elderly patients with severe CAP. Additional confirmatory trials involving elderly patients are needed to further confirm the present results. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx. ChiCTR-TRC-13003534.

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.

Real-Time Monitoring of Temperature Variations around a Gold Nanobipyramid Targeted Cancer Cell under Photothermal Heating by Actively Manipulating an Optically Trapped Luminescent Upconversion Microparticle.

We demonstrate an effective approach to realize active and real-time temperature monitoring around the gold nanobipyramids (AuNBPs)-labeled cancer cell under 808 nm laser irradiation by combining optical tweezers and temperature-sensitive upconversion microparticles (UCMPs). On the one hand, the aptamer-modified AuNBPs that absorb laser at 808 nm not only act as an excellent photothermal reagent but also accurately and specifically bind the target cancer cells. On the other hand, the single optically trapped NaYF4:Yb3+, Er3+ UCMPs with a 980 nm laser exhibit temperature-dependent luminescence properties, where the intensity ratio of emission 525 and 547 nm varies with the ambient temperature. Therefore, real-time temperature variation monitoring is performed by 3D manipulation of the trapped single UCMP to control its distance from the AuNBPs-labeled cancer cell while being photothermally killed. The results show distance-related thermal propagation because the temperature increase reaches as high as 10 °C at a distance of 5 µm from the cell, whereas the temperature difference drops rapidly to 5 °C when this distance increases to 15 µm. This approach shows that the photothermal conversion from AuNBPs is sufficient to kill the cancer cells, and the temperature increase can be controlled within the micrometer level at a certain period of time. Overall, we present a micrometer-size thermometer platform and provide an innovative strategy to measure temperature at the micrometer level during photothermal killing of cancer cells.

Investigation of the genes associated with a male sterility mutant (msm) in Chinese cabbage (Brassica campestris ssp. pekinensis) using RNA-Seq.

In Chinese cabbage, hybrid seed production is performed using male sterility lines, an important approach to heterosis utilization. In this study, a stably inherited male sterile mutant msm was obtained from the 'FT'-doubled haploid line of Chinese cabbage using isolated microspore culture combined with 60Co γ-ray mutagenesis. The genetic backgrounds of 'FT' and msm were highly consistent; however, compared with wild-type 'FT', msm exhibited completely degenerated stamens and no pollen phenotype. Other characters showed no significant differences. Cytological observations revealed that stamen abortion in msm begins during the tetrad period and that tapetum cells were abnormally expanded and highly vacuolated, leading to microspore abortion. Genetic analysis indicated that the msm mutant phenotype is controlled by a single recessive nuclear gene. Comparative transcriptome analysis of 'FT' and msm flower buds using RNA-Seq technology revealed 1653 differentially expressed genes, among which, a large number associated with male sterility were detected, including 64 pollen development- and pollen tube growth-related genes, 94 pollen wall development-related genes, 11 phytohormone-related genes, and 16 transcription factor-related genes. An overwhelming majority of these genes were down-regulated in msm compared with 'FT'. Furthermore, KEGG pathway analysis indicated that a variety of carbohydrate metabolic and lipid metabolic pathways were significantly enriched, which may be related to pollen abortion. The expression patterns of 24 male sterility-related genes were analyzed using qRT-PCR. In addition, 24,476 single-nucleotide polymorphisms and 413,073 insertion-deletion events were specifically detected in msm. These results will facilitate elucidation of the regulatory mechanisms underlying male sterility in Chinese cabbage.

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.

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.

Acupuncture for Acute Pancreatitis: A Systematic Review and Meta-analysis.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of acupuncture plus routine treatment (RT) for acute pancreatitis (AP). METHODS: Literature searches were performed in 8 databases up to October 31, 2018. Randomized controlled trials comparing acupuncture plus RT with RT alone for AP were included. RESULTS: Twelve eligible studies were included finally. The meta-analysis showed that acupuncture plus RT compared with RT alone could significantly improve the total effective rate and gastrointestinal function and reduce the Acute Physiology, Age, Chronic Health Evaluation II score, tumor necrosis factor α count, the time of resuming to diets, and the length of hospital stay. Only 3 of the studies reported adverse events or reactions. CONCLUSIONS: This study suggested that acupuncture combined with RT may be effective for AP. However, more rigorously designed randomized controlled trials are warranted to confirm the current findings.

Efficacy and safety of acupuncture as an adjuvant treatment for acute pancreatitis: a protocol of systematic review and meta-analysis.

INTRODUCTION: Acupuncture may be effective for acute pancreatitis (AP). This systematic review aims to assess the efficacy and safety of acupuncture as an adjuvant treatment for AP. METHODS AND ANALYSIS: We will search PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, China National Knowledge Infrastructure, Wan Fang Data and Chinese Science Journal Database from inception to 30 June 2019 to identify any eligible study. Only randomised controlled trials will be included. The selection of studies, data extraction and management will be completed by two reviewers independently. The primary outcomes include the overall response rate, mortality during the treatment, the proportion of patients with severe acute pancreatitis transferred to the intensive care unit or scheduled for surgery, gastrointestinal function and the acute physiology and chronic health evaluation II scores. The secondary outcomes include visual analogue scale, the use of analgesics, the recovery time of blood amylase becoming normal, tumour necrosis factor α counts, IL-6 counts, IL-10 counts, length of hospital stay and adverse events related to acupuncture (such as fainting, nausea, haematoma and local infection). Review Manager V.5.3 software will be used for statistical analyses. The risk of bias of included studies will be assessed by the Cochrane 'risk of bias' tool. ETHICS AND DISSEMINATION: This study will not involve personal information. The ethical approval will not be required. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42018115099.

Development of a core outcome set (COS) and selecting outcome measurement instruments (OMIs) for non-valvular atrial fibrillation in traditional Chinese medicine clinical trials: study protocol.

BACKGROUND: 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. METHODS/DESIGN: The method of the study will include eight stages led by a national multidisciplinary Steering Committee: (1) A systematic review will be developed to identify currently reported outcomes and traditional Chinese medicine syndromes in clinical trials of NVAF, (2) Semi-structured interviews of patients will be conducted to fill gaps in potential outcomes, (3) Traditional Chinese medicine syndrome names will be identified from medical records, (4) A dataset of traditional Chinese medicine syndrome names will be developed, (5) The investigation of traditional Chinese medicine syndromes will be conducted from cross-sectional study, (6) Two rounds of Delphi surveys will be carried out, (7) A consensus meeting will be conducted to develop a COS, and (8) Recommendations of outcome measurement instruments (OMIs), which should be used in the COS, will be developed. DISCUSSION: The COS will improve the consistency of outcome reporting and reduce the reporting bias in NVAF clinical trials of traditional Chinese medicine to improve the value of traditional Chinese medicine clinical trials. TRIAL REGISTRATION: This study is not a clinical trial, so it is registered in Core Outcome Measures in Effectiveness Trials Initiative (COMET). Registration number: 941 . Registered on 22 December 2016.

Efficacy and safety of Xuebijing injection (a Chinese patent) for sepsis: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection (XBJ), a Chinese patent medicine that was approved for treating sepsis in China in 2004, consists of Carthamus tinctorius L. (Carthami Flos, hong hua), Paeonia lactiflora Pall. (Paeoniae Radix Rubra, chi shao), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong), Salvia miltiorrhiza Bge. (Salviae Miltiorrhizae Radix Et Rhizoma, dan shen) and Angelica sinensis (Oliv.) Diels (Angelicae Sinensis Radix, dang gui). AIM OF THE STUDY: This study aimed to assess the efficacy and safety of XBJ combined with routine treatment (RT) for treating sepsis through systematic review and meta-analysis. MATERIALS AND METHODS: Databases including Embase, PubMed, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP) and the Wanfang database were searched from inception to June 6, 2017 to collect relevant RCTs comparing XBJ combined with RT and RT alone for sepsis. The primary clinical outcomes were 28-day mortality and mortality during treatment. The secondary outcomes of our study included APACHE Ⅱ scores, WBC counts, body temperature, and adverse events or reactions. We excluded low-quality studies (Jadad score < 3) and calculated risk ratios (RR) for primary outcomes with fixed effects models. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: We identified 1602 records, and 16 RCTs (1144 patients) were included. Moderate-quality evidence suggested that combined therapy reduced 28-day mortality (934/1144, RR 0.62, 95% CI 0.51-0.76 P < 0.000 01, I2 = 0%), APACHE Ⅱ scores (792/1144, MD -3.53, 95% CI -4.49 to -2.54; P < 0.000 01, I2 = 59%) and body temperature (362/1144, MD -0.43, 95% CI -0.55 to -0.31; P < 0.000 01, I2 = 0%). Very low-quality evidence showed that WBC count improved with combined medication at high dosages (one study included, 40/1144, MD -8.00, 95% CI -10.18 to -5.82), but there was no reduction at moderate dosages (230/1144, MD -2.38, 95% CI -5.01 to 0.25; P = 0.08, I2 = 70%). However, moderate-quality evidence indicated positive results with low dosages (142/1144, MD -2.88, 95% CI -3.79 to -1.96; P < 0.000 01, I2 = 0%). Nevertheless, due to the insufficient number of studies and the poor quality of the current evidence, more studies of dose-effect relationships and safety concerns of XBJ are needed. Low-quality evidence showed no risk difference for mortality during treatment (210/1144, RR 0.65, 95% CI 0.36-1.17; P = 0.15, I2 = 0%). CONCLUSIONS: This study suggested that supplementation with XBJ in addition to regular treatment may improve the 28-day mortality rate, APACHE Ⅱ scores, WBC count and body temperature of sepsis patients without serious adverse events, but it may not reduce mortality during treatment, revealing a specific, remote effect of traditional Chinese medicine. However, given the high risk of bias and the low quality of the included trials, we may be unable to draw any conclusions about its routine use. Rigorously designed, multicentre, large-scale, methodologically sound trials are warranted.

Pectin methylesterase inhibitor (PMEI) family can be related to male sterility in Chinese cabbage (Brassica rapa ssp. pekinensis).

Pectin-related genes play significant roles in pollen development and pollen tube growth, and their allelic variations are one of the major reasons for the abnormal development of male gametophyte. Currently, little is known about the role of the PMEI family in male sterility of plants. In this study, 97 putative PMEI genes were identified in Brassica rapa genome. By a phylogenetic analysis, the PMEI family was divided into 10 clades with highly conserved structural characteristics. The publically available RNA-seq data on different tissues of B. rapa accession Chiifu-401-42 revealed that 23 PMEI isoforms were flower-specific genes. We created a recessive genic male sterile mutant (ftms) in Chinese cabbage. This mutant was a doubled haploid line with stable inheritance, derived from Chinese cabbage 'FT' generated through a combination of radiation mutagenesis and isolated microspore culture. The transcriptome profiles of the floral buds of ftms and its wild-type line 'FT' were determined using RNA-seq. A total of 17 PMEI genes were found to be differentially expressed; all of them were down-regulated in ftms compared to their levels in 'FT'. Consistent with the transcriptome data, all these genes were observed to be highly expressed in the floral buds of 'FT' using qRT-PCR analysis. Of these, eight genes were specifically expressed in the floral buds of 'FT'; three of these (Bra019903, Bra014099, and Bra032239) were stamen-specific genes. The results contribute to further elucidation of the regulatory mechanisms underlying male sterility in Chinese cabbage.

Wenxin Keli for Ventricular premature complexes with Heart failure: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: To evaluate the efficacy and safety of Wenxin Keli (WXKL) alone or combined with Western medicine in treating ventricular premature complexes (VPCs) with heart failure (HF). METHODS: We searched five databases to identify relevant randomized controlled trials (RCTs) published before May 2016. Two review authors independently searched and screened the literature, extracted the data as well as assessed the methodological quality of the included studies by using criteria from the Cochrane Handbook, and analyzed via using Review Manager 5.3 software. RESULTS: Eight studies of WXKL were included. The results of the Meta-analysis showed that WXKL was more significant on the frequency of VPCs (MD=-427.08, 95% CI: -526.73∼-327.43, P<0.01), left ventricular ejection fraction (LVEF) (MD=-4.12, 95% CI: 2.97∼5.27, P<0.01), the total effect of VPCs (RR=0.48, 95% CI: 0.34∼0.69, P<0.01) and 6-min walking test (MD=28.05, 95% CI: 19.56∼36.54, P<0.01). The treatment group presented a significant reduction at left ventricular end-diastolic diameter (LVED) (MD=-3.94, 95% CI: -6.57∼-1.31, P<0.01) when treatment time was 12 weeks, however, there was no statistical difference at 8 weeks. In addition, the included trials generally showed low methodological quality. CONCLUSIONS: Wenxin Keli may be effective and safe for treating VPCs and HF. However, further RCTs of larger scale, multi-center/country, longer follow-up periods, and higher quality are still required to verify the efficacy of Wenxin Keli in ventricular premature beat with heart failure.