Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.

Urinary extracellular vesicles (uEV) have recently garnered significant attention as crucial components in urine. Advances in high-throughput omics and single-vesicle technologies have deepened our understanding of the origins and contents of uEV, which include proteins, lipids, RNA, and DNA. These vesicles reflect the pathophysiological status of their source organs. uEV are highly stable, traceable, and can be enriched with various contents, making them promising biomarkers, particularly for urogenital diseases.

Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.

OBJECTIVETo identify pathogenic mutation of the TSC1 and TSC2 genes in a patient with tuberous sclerosis.

METHODSPeripheral venous blood samples and clinical data of a pregnant woman with tuberous sclerosis and 4 family members (parents, uncle and husband) were collected. Genomic DNA was extracted. All coding exons of the TSC1 and TSC2 genes and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing.

RESULTSThe patient has presented facial angiofibroma and prefrons fibrous plaque for 20 years, and lumbar connective tissue nevus for 10 years. She also had mental retardation but no epilepsy. A novel frame-shift mutation c.4258-4261delTCAG was detected in exon 34 of the TSC2 gene, which had led to a premature stop codon TAG after the 55th amino acids. The same mutation was not found in the unaffected family members and 100 unrelated healthy controls.

CONCLUSIONThe novel frame-shifting mutation c.4258-4261delTCAG (p.Ser1420GlyfsX55) in the TSC2 gene may be responsible for the disease in the patient.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Pregnancy ; Tuberous Sclerosis ; genetics ; Tumor Suppressor Proteins ; genetics ; Young Adult

Objective To explore the effect of irbesartan on cardiac endothelial-mesenchymal transition (EndMT) in diabetic rats.Methods The model of diabetic rat was induced by intraperitoneal injection with streptozotocin (STZ,35 mg/kg) in spontaneous hypertensive rats (SHR).Diabetic rats were divided into diabetic group and the Irbesartan treated group.The pathological changes were investigated by fluorescence microscope and electron microscope.The EndMT was studied in human aortic endothelial cells (HAEC) exposure to high glucose.The concentration of angiotensin Ⅱ in the supernatant was detected by radioimmunoassay.Immunofluorescence staining was performed to detect the co-localization of CD31 and FSP1.Results The significant myocardial fibrosis was presented in the diabetic group.Endothelial protrusions were prominent feature in myocardial microvascular of diabetic rat compared with the control group rats.Double staining of HAEC showed co-localization of CD31 and FSP1,which was decreased by the treatment of Irbesartan (P ＜ 0.05).When HAEC was exposed to high glucose,it showed some cells acquired spindle-shaped morphology and lost CD31 staining,and FSP1 and α-SMA protein expression levels were markedly upregulated,which attenuated by the treatment of Irbesartan.Conclusion Irbesartan might prevent diabetes from myocardial fibrosis via inhibition of EndMT in diabetic rats.

Objective To evaluate the value of echo‐contrast RT‐3DE for assessment of left ventricular volume and function in patients with left ventricular non‐compaction(LVNC) .Methods Twenty‐one patients of LVNC were involved and underwent non‐enhanced and contrast‐enhanced RT‐3DE to evaluate left ventricular end‐diastolic volume (LVEDV) ,left ventricular end‐systolic volume (LVESV) ,left ventricular ejection fraction (LVEF) .The endocardial border definition of LV was graded for each of the 16 LV segments as follows :0 = border invisible ,1 = border visualized only partially ,and 2 = complete visualization of the border .Three image‐quality groups (good ,fair ,and uninterpretable) were identified . Results ①Duringcontrast‐enhancedRT‐3DE,ascomparedwithnon‐enhancedRT‐3DE,thenumberof segments with complete visualization of the endocardial border increased significantly (55% vs 82% ,P <0.01) ,and the number of patients with a good‐quality echocardiogram increased significantly (33% vs 81% , P <0.01) .②Contrast‐enhanced RT‐3DE provided significantly larger values of LVEDV ( P < 0 0.1) and LVESV ( P < 0 0.1) as compared with non‐enhanced RT‐3DE ,the values of LVEF were not statistically different between the two techniques ( P =0.07) .③Intra‐and inter‐observer agreement for assessment of LV volumes and systolic function improved during contrast‐enhanced RT‐3DE ,as compared with non‐enhanced RT‐3DE .Conclusions Contrast‐enhanced RT‐3DE can increase the prevalence of good‐quality echocardiograms and significantly improve the reproducibility of LV volumes and function measurements .

Objective To investigate the effects of low density lipoprotein receptor (LDLr) pathway on podocyte injury in diabetic nephropathy (DN) under inflammatory stress.Methods Male db/db mice and db/m mice were randomly divided into four groups (8 mice in each group):db/m group (control),casein injected db/m group (db/m + casein),db/db group (db/db),and casein injected db/db group (db/db + casein).An inflamed model of DN was established according to our previous study.24-hour urinary protein was measured every week.The plasma lipid profile was detected by clinical biochemistry assay.Podocyte changes were evaluated by electron microscope and immunofluorescent staining.Lipid accumulation in the kidney was evaluated by oil red O staining and intracellular cholesterol quantitative assay.The protein expression of Wilm's tumor-1 (WT-1),nephrin,α-smooth muscle actin (t-SMA),and molecules correlated with LDLr pathway were examined by immunohistochemical staining or Western blotting.The colocalized protein expression of LDLr with WT-1 was examined by immunofluorescent staining and laser confocal microscopy.Results There were no differences in plasma levels of LDL and HDL among four groups.Compared with db/db group,the db/db+ casein group showed markedly increased 24-hour urinary protein,more significant podocyte foot process effacement and podocyte damage,increased lipid droplet accumulation in kidneys,increased protein expressions of LDLr,SCAP and SREBP-2 in kidneys (all P ＜ 0.05).Interestingly,increased LDLr protein expression in kidneys of db/db mice was negatively correlated with decreased nephrin protein expression (r =-0.855,P ＜ 0.01) and positively correlated with increased α-SMA protein expression (r=0.768,P ＜ 0.01).Conclusions The disruption of LDLr pathway induced by inflammation contributes to podocyte injuries in diabetic nephropathy.