Objective This study aims to analyze the relationship between reproductive tract microecological changes,metabolic differences,and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy,which will be a breakthrough point for improving outcomes.Methods A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study.Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation,day 7 after estrogen replacement therapy started,the day when progesterone was added,and the day of transplantation.The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods.Results 1)The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation(P<0.01),but did not differ significantly on day 7 after oral estrogen replacement therapy started,the day of progesterone administration,and the day of transplantation(P≥0.1).2)Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points.3)Microbial analysis at different time points showed that there were significant differences in vaginal flora,including Peptoniphilus,Enterocloster,Finegoldia,Klebsiella,Anaerobutyricum,Agathobaculum,Sporanaerobacter,Bilophila,Prevotella,and Anaerococcus in the pregnant group(P<0.05).4)Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid,linatine,(R)-amphetamine,hydroxychloroquine,and L-altarate in the vaginal secretions of the pregnant group(P<0.05),and that there were significant differences in isocitric acid,quassin,citrinin,and 12(R)-HETE in the cervical secretions(P<0.05).5)Metabolite analysis at different time points showed that,in the non-pregnant group,there were significant differences in linatine,decanoyl-L-carnitine,aspartame,sphingosine,and hydroxychloroquine in the vaginal secretions(P<0.05),and the isocitric acid,quassin,ctrinin,and 12(R)-HETE in the cervical secretions(P<0.05).6)Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities,especially Klebsiella.Conclusions Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy,which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. Methods: Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. Results: From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. Conclusions This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

The most important harms of atrial fibrilation are stroke and the embolic events of the systemic circulation. The latest data have show n that the etiology of up to 1/3 of stroke patients w as atrial fibrilation. The stroke morbidity and mortality caused by atrial fibrilation are higher than other types of stroke. So the prevention of stroke is very important for patients with atrial fibrilation. The anticoagulant therapy is the core strategy for stroke prevention in patients with atrial fibrilation. This article reviews the advances in research on the safety and compliance of anticoagulation therapy in patients w ith atrial fibrilation.

Objective To investigate the effects of four interior-warming drugs( galangal,cinnamon,evodia rutaecarpa,and dried ginger)on the tension of ileum smooth muscle and Ca2+-ATPase on the cell membrane in rabbits. Methods The effects of galangal,cinnamon,evodia rutaecarpa,and dried ginger were examined on normal ileum smooth muscle,in vitro intestinal muscle contraction caused by acetylcholine(ACh),barium chloride(BaCl2 )and histamine(His), and ACh-induced calcium release by using BL-420E+ biological signal collection and processing system.The average tension was measured within 1 min before delivery and within 3 minutes after the treatment,and the inhibition rate was calculated according to the average tension value.The effects of sera containing galangal,cinnamon,evodia rutaecarpa,and dried ginger on Ca2+-ATPase activity on the cell membrane of the intestinal smooth muscle were examined by phosphorus method. Results Galangal,cinnamon,evodia rutaecarpa,and dried ginger at high concentrations could restrain in vitro intestinal contraction in normal circumstances(P<0.05 or P<0.01).Significant inhibitory effects on intestinal contraction caused by ACh,His and BaCl2 were found in low,medium and high concentration groups(P<0.01).There was a dose-effectiveness relationship between the inhibition rate and final drug concentrations.The ACh-induced intracellular and extracellular calcium dependent contraction were significantly inhibited by the four interior-warming drugs( P < 0. 05 or P < 0. 01). The Ca2+-ATPase activities were( 0. 384 ± 0.070),(0.302±0.016),(0.307±0.016),(0.296±0.016),(0.313±0.003)U·mg-1 ,respectively,in intestinal smooth muscle in normal control group and high concentration groups of galangal,cinnamon,evodia rutaecarpa,and dried ginger(P<0.01). Conclusion Interior-warming drugs may relax intestinal smooth muscle by reducing the intracellular calcium release and the extracellular calcium inflow via receptor-controlled calcium channels,and inhibiting the Ca2+-ATPase activity in smooth muscle.

Objective To investigate TORCH infections in neonatal hyperbilirubinemia ,and explore the relationship between them.Methods 644casesofneonatalhyperbilirubinemiainourhospitalfromJanuarytoDecemberin2014werechosenasneonatal hyperbilirubinemia group ,160 cases of healthy newborns in the same period were selected as control group .Chemiluminescence im‐munoassay and Enzyme‐linked immune‐sorbent assay (ELISA )were used to detect the TORCH‐IgM antibody .TORCH infections wereobservedbetweenthetwogroups.Results 58casesofpositiveTORCH‐IgMantibodywerefoundin644casesofneonatalhy‐perbilirubinemia group ,detection rate of TORCH‐IgM antibody was 9 .0% ,0 case of positive TORCH‐IgM antibody was found in 160 cases of the control group ,detection rate of TORCH‐IgM antibody was 0 .0% ,the difference was statistically significant be‐tween the two groups(P<0 .05) .The infection rate of B19 was the highest ,the positive rates of B19 ,CMV were 7 .3% ,1 .7% .Con‐clusion There would be a possible relation between TORCH infections and neonatal hyperbilirubinemia ,TORCH infection is one of the causes of neonatal hyperbilirubinemia ,and the screening of TORCH in neonatal hyperbilirubinemia is necessary .