The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity:A Meta-Analysis

Objective Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists(GLP-1RAs)on asthma,which is often comorbid with type 2 diabetes mellitus(T2DM)and obesity.Therefore,we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1(GLP-1)receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity.Methods PubMed,Web of Science,Embase,the Cochrane Central Register of Controlled Trials,and Clinicaltrial.gov were systematically searched from inception to July 2023.Randomized controlled trials(RCTs)of GLP-1 receptor-based agonists(GLP-1RA,GLP-1 based dual and triple receptor agonist)with reports of asthma events were included.Outcomes were computed as risk ratios(RR)using a fixedeffects model.Results Overall,39 RCTs with a total of 85,755 participants were included.Compared to non-GLP-1 receptor-based agonist users,a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments,although the difference was not statistically significant[RR=0.91,95%confidence interval(CI):0.68 to 1.24].Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users(RR=0.65,95%CI:0.43 to 0.99,P=0.043).We also performed sensitivity analyses for participant characteristics,study design,drug structure,duration of action,and drug subtypes.However,no significant associations were observed.Conclusion Compared with non-users,a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments.Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Investigation of the First Spermatorrhea Age of Males in Jiangsu Province, China

Background: The growth of adolescents is affected by economic development and education levels. We investigated the first spermatorrhea age of adolescents in urban area and in rural area of Jiangsu province, China. Methods: The data were obtained through anonymous questionnaire by using cross-sectional methods. From May 2016 to March 2017 in Jiangsu province, China, a total of 2131 Han nationality students were enrolled in cluster. The survey was contained date of birth, age, grade, age of first spermatorrhea and how long ago of the first spermatorrhea, all data were analyzed by Prism 8.0. Results: The questionnaire accounted for response was 97.3%, and the effective rate was 96.3%. The mean age of first spermatorrhea was (13.7 ± 1.5) years old, which included 13.6 ± 1.4 years in urban and 13.9 ± 1.5 years in rural. The first spermatorrhea occurred in the fifth and sixth grade primary school, and 1, 2, 3 grades of junior high school were 3.5%, 13%, 27.4%, 28.5% and 15.1%, respectively. There was 62.3% of first spermatorrhea occurred in summer. The rate of spermatorrhea with natural occurrence accounted for 95.1%, and with active accounted for 4.9%. Conclusions: Compared with rural area, the age of the first spermatorrhea of males in urban area is significant earlier. The adolescent’s first spermatozoa were mostly occurred in summer. The relevant physical and reproductive education should be started from the third grade of primary school. The reproductive health education should be carried out when the youth are 7 years old.

The Influence of Cabergoline and Coasting in Prevention of the Ovarian Hyperstimulation Syndrome in Patients Undergoing IVF/ICSI-ET Treatment: A Systematic Review and Meta-Analysis

Objective: To compare the effectiveness of two methods in preventing ovarian hyperstimulation syndrome (OHSS) with cabergoline and coasting. Design: Systematic review and meta-analysis of randomized clinical trials (RCTs). Patients: Women were considered as have risk of OHSS undergoing fertility treatment. Interventions: Cabergoline, coasting. Result: There were included five RCT studies. The clinical pregnancy rate was no significantly difference between two groups (RR 1.22, 95% CI [0.86, 1.71]), implantation rate (RR 1.00, 95% CI [0.75, 1.32]), severe OHSS (RR 0.93, 95% CI [0.38, 2.31]), fertilization rate (SMD 0.70, 95% CI [-0.10, 1.50]), number of oocytes retrieved (SMD 0.80, 95% CI [0.30, 1.30]), number of embryo transfer (SMD-0.04, 95% CI [-0.24, 0.17]), E2 value on the day of HCG injection (SMD 0.21, 95% CI [-0.25, 0.68]), number of MII oocytes (SMD 0.71, 95% CI [0.32, 1.11]), abortion rate (RR 0.61, 95% CI [0.21, 1.83]), number of follicles > 17 mm on day of HCG (SMD -0.01, 95% CI [-0.26, 0.24]), number of follicles 15 - 17 mm on day of HCG (SMD -0.08, 95% CI [-0.33, 0.17]), number of follicles 10 - 14 mm on day of HCG (SMD -0.06, 95% CI [-0.31, 0.19]). Conclusion: Both cabergoline and coasting prevent the occurrence of OHSS, but no statistically significant difference between them. Compared with coasting group, a daily dose of 0.5 mg cabergoline significantly increased the number of oocytes retrieved, MII oocytes, and fertilization rate, but decreased the abortion rate.

Automatic Target Description File Generation

Agile hardware design is gaining increasing momentum and bringing new chips in larger quantities to the market faster.However,it also takes new challenges for compiler developers to retarget existing compilers to these new chips in shorter time than ever before.Currently,retargeting a compiler backend,e.g.,an LLVM backend to a new target,requires compiler developers to write manually a set of target description files(totalling 10300+lines of code(LOC)for RISC-V in LLVM),which is error-prone and time-consuming.In this paper,we introduce a new approach,Au-tomatic Target Description File Generation(ATG),which accelerates the generation of a compiler backend for a new tar-get by generating its target description files automatically.Given a new target,ATG proceeds in two stages.First,ATG synthesizes a small list of target-specific properties and a list of code-layout templates from the target description files of a set of existing targets with similar instruction set architectures(ISAs).Second,ATG requests compiler developers to fill in the information for each instruction in the new target in tabular form according to the list of target-specific properties syn-thesized and then generates its target description files automatically according to the list of code-layout templates synthe-sized.The first stage can often be reused by different new targets sharing similar ISAs.We evaluate ATG using nine RISC-V instruction sets drawn from a total of 1029 instructions in LLVM 12.0.ATG enables compiler developers to gen-erate compiler backends for these ISAs that emit the same assembly code as the existing compiler backends for RISC-V but with significantly less development effort(by specifying each instruction in terms of up to 61 target-specific properties only).

Genotype-phenotype relationship in a large cohort of osteogenesis imperfecta patients with COL1A1 mutations revealed by a new scoring system

Background:Osteogenesis imperfecta (OI), a heritable bone fragility disorder, is mainly caused by mutations in COL1A1 gene encoding α1 chain of type I collagen.This study aimed to investigate the COL1A1 mutation spectrum and quantitatively assess the genotype-phenotype relationship in a large cohort of Chinese patients with OI.Methods:A total of 161 patients who were diagnosed as OI in Department of Endocrinology of Peking Union Medical College Hospital from January 2010 to December 2017 were included in the study.The COL1A1 mutation spectrum was identified by next generation sequencing and confirmed by Sanger sequencing.A new clinical scoring system was developed to quantitatively assess the clinical severity of OI and the genotype-phenotype relationship was analyzed.The independent sample t-test, analysis of variance, Mann-Whitney U-test, Chi-squared test, Pearson correlation, and multiple linear regression were applied for statistical analyses.Results:Among 161 patients with OI, 32.9% missense mutations, 16.8% non-sense mutations, 24.2% splice-site mutations, 24.8% frameshift mutations, and 1.2% whole-gene deletions were identified, of which 38 variations were novel.These mutations led to 53 patients carrying qualitative defects and 67 patients carrying quantitative defects in type I collagen.Compared to patients with quantitative mutations, patients with qualitative mutations had lower alkaline phosphatase level (296 [132, 346] U/L vs.218 [136, 284] U/L, P=0.009) and higher clinical score (12.2 ± 5.3 vs.7.4 ± 2.4, P<0.001), denoting more severe phenotypes including shorter stature, lower bone mineral density, higher fracture frequency, more bone deformity, vertebral compressive fractures, limited movement, and dentinogenesis imperfecta (DI).Patients would not present with DI if the glycine substitutions happened before the 79th amino acid in triple helix of α1 chains .Conclusions:This presented distinctive COL1A1 mutation spectrum in a large cohort of Chinese patients with OI.This new quantitative analysis of genotype-phenotype correlation would be helpful to predict the prognosis of OI and genetic counseling.

Cardiovascular risk profile and clinical characteristics of diabetic patients:a cross-sectional study in China

Background:Cardiovascular(CV)disease is the leading cause of morbidity and mortality in adults with type 2 diabetes(T2D).The aim of this study was to determine the CV risk in Chinese patients with T2D based on the 2019 European Society of Cardiology(ESC)and the European Association for the Study of Diabetes(EASD)guidelines on diabetes,pre-diabetes,and CV diseases.Methods:A total of 25,411 patients with T2D,who participated in the study of China Cardiometabolic Registries 3B study,were included in our analysis.We assessed the proportions of patients in each CV risk category according to 2019 ESC/EASD guidelines.Results:Based on the 2019 ESC/EASD guidelines,16,663(65.6%),1895(7.5%),and 152(0.6%)of patients were included in"very high risk,""high risk,"and"moderate risk"categories,respectively.The proportions of patients in each category varied based on age,sex,body mass index,and duration.While 58.7%(9786/16,663)of elderly patients were classified to"very high risk"group,89.6%(3732/4165)of patients with obesity were divided into"very high risk"group.Almost all patients with a duration of diabetes>10 years had"very high risk"or"high risk."However,6701(26.4%)of Chinese T2D patients,who had shorter duration,and one or two risk factors,could not be included in any category(the"unclear risk"category).Conclusions:In China,most patients with T2D have"very high"or"high"CV risk based on 2019 ESC/EASD guidelines.However,the risk of patients in"unclear risk"group needs to be further classified.