Evaluation of the quality of evidence will be conducted using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS The present study will assess the effects of smoking and alcohol drinking on non-pathologic bone fracture healing in adult patients. CONCLUSION We hope that this systematic review and dose-response meta-analysis will provide high quality evidence on dose-response between smoking, alcohol drinking, and bone fracture healing. PROSPERO REGISTRATION NUMBER CRD42019131454.BACKGROUND To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P  less then  .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P  less then  .001; heterogeneity P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.Miscarriage is the spontaneous loss of a clinically established intrauterine pregnancy before the fetus has reached viability. In order to compare the performance of traditional G banding karyotyping with next-generation sequencing (NGS) for detecting common trisomies in products of conception (POC). Chromosome abnormalities were detected by high-resolution G banding karyotyping and NGS. A total of 48 miscarriage samples, including 20 samples without karyotype result and 28 with karyotype results were selected and coded for analysis by NGS. The multiplex PCR analysis of maternal and miscarriage DNA for single nucleotide polymorphism (SNP) markers were used to simultaneously monitor maternal cell contamination (MCC), chromosomal status, and sex of the miscarriage tissue. NGS detection results of 21 chromosome abnormalities were consisted with that in karyotyping examination. These chromosome abnormalities samples included 9 chromosome 16 trisomies, 3 chromosome 22 trisomies, 2 chromosome 7 trisomies, 2 chromosome 18 trisomies, 1 chromosome 4 trisomies, one chromosome 10 trisomies, 1 chromosome 13 trisomies, 1 chromosome 15 trisomies and 1 sex chromosomal aneuploidies (45, X). Meanwhile, NGS analysis of seven chromosome normalities was adapted to the karyotyping examination. Therefore, NGS combined with multiplex PCR is an effective method to test trisomies in POC.  https://www.selleckchem.com/products/s64315-mik665.html  The results mentioned above will contribute to a detailed understanding of the first-trimester spontaneous miscarriages.BACKGROUND The bloodletting device has been used by many institutions for about 100 years. Many patients feel fear from the pain caused by applying the bloodletting device for treatment. We used bloodletting device using the principle of "prestimulation neurodisturbance," which can mask the subject undetectable for pain. In this study, we will investigate pain of bloodletting device during blood collection and will identify the safety of the device. METHODS This study will be a randomized, controlled, double-blind, and matched-paired-designed clinical trial. Four groups, RTLC, LTRC, RCLT, and LCRT (T = test device, C = control device, L = left, R = right), will be randomly allocated. Total duration of the clinical trial will be 3 months. The subjects will be performed from 1 to 3 times only on the day of the procedure. The primary outcomes will be measured using pain visual analog scale score and the secondary outcomes will include verbal rating scale and the time at which the pain disappears after blood collection (second), the total number of "nonbleeding" cases and subjects, the number of "blood collection failure" and subjects, the presence of "delayed hemostasis," and the number of subjects. Repeated-measure analysis will be used to measure primary efficacy based on full analysis set. DISCUSSION This study has limited inclusion and exclusion criteria and a well-controlled intervention, and it will be the first randomized controlled trial to investigate pain of bloodletting device using the principle of "prestimulation neurodisturbance." This study provides insights into the underlying mechanisms of the pain-reducing effect of the developed bloodletting device and will lay the groundwork for further studies.INTRODUCTION Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in the treatment of cancer. Immunosuppressive therapy can control the cancer well and is suitable for the moderate to severe diseases. However, according to clinical observation, immune-related cardiac adverse events against PD-1or/and PD-L1 are inevitable, but generally reversible. Understanding the cardiac adverse events of PD-1 or/and PD-L1 inhibitors is crucial to improve the anti-cancer efficacy and ensure the life safety of patients. The variability of cardiac adverse events between different immunosuppressants and different cancers is not clear. METHODS AND ANALYSIS This protocol established in this study has been reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search the following electronic bibliographic databases PubMed, Cochrane Library, EMBASE databases and ClinicalTrials.gov from their inception to December 2019. We will use a combination of Medical Subject Heading, and free-text terms with various synonyms to search based on the Eligibility criteria.