Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Objective:To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia (AML)cells and its molecular mechanism,and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.Methods:After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol.The proliferation activity of cells was detected by CCK-8 method,and the expression changes of apoptotic proteins and PI3 K/AKT signaling pathway proteins were detected by Western blot. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR ) was used to detect the expression of Caspase family mRNA.Results:Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells,promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein (P<0.05).When Curcumol interferes with HL-60 and KG-1 cells,it can also induce programmed cell death of AML by inhibiting PI3 K/AKT signaling pathway.In addition,after the intervention of Curcumol,the expression of Caspase 3,Caspase 6,Caspase 8 and Caspase 9 were up-regulated in HL-60 cells (P<0.05 ),the expression of Caspase 3,Caspase 8 and Caspase 9 were significantly up-regulated in KG-1 cells (P<0.01),while the expression of Caspase 6 was weakly affected (P<0.05 ),but low concentration of Curcumol (<60 μg/ml)had no effect on the expression of Caspase 6 in KG-1 cells (P>0.05).Conclusion:Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway,affecting the expression of Bcl-2 family proteins,and promoting the activation of core members of Caspase family,so as to play an anti-leukemia role.

Objective:To investigate the influencing factors of participation in free health check-up among community residents.Methods:From 2012 to 2022 Xinzhuang Community Health Service Center of Shanghai Minhang district provided 5 free health check-up for local residents, once every 2 years. Among 5 904 eligible community residents with a mean age of (66.01±5.87) years, 682 (11.55 %), 912 (15.45 %), 842 (14.26 %), 934 (15.82 %), 1 061 (17.97 %) and 1 473 (24.95 %) participated in 5, 4, 3, 2, 1 and 0 health check-ups during 10 years, respectively. The influencing factors of participant frequency were analyzed with multivariate logistic regression model.Results:Multivariate logistic regression analysis showed that age 65 years and above ( OR=0.685, 95% CI: 0.625-0.751, P<0.001), exercising once a week or more ( OR=1.142, 95% CI: 1.031-1.266, P=0.011), and underweight ( OR=0.665, 95% CI:0.496-0.891, P=0.006) were independent factors influencing the participant in free health check-up among community residents. Conclusion:Community residents with older age or underweight are less likely to participate free health check-up, while those with frequent exercise like to participate.

Objective:To explore the risk factors of all-cause death in hypertensive patients in the community.Methods:A cohort of 4 049 hypertensive patients who participated in annual health checkups at Xinzhuang Community Health Service Centre of Shanghai Minhang district from January to December 2012 were enrolled in the study. All-cause death was the endpoint event of this study, and patients were divided into a fatal group and a survival group. The collection date for the endpoint event was December 2022. A multivariate Cox regression model was used to analyse the independent risk factors of all-cause mortality among hypertensive patients in the community.Results:Among 4 049 patients aged (67.9±7.1) years, 1 856 (45.8%) were males. There were 610 cases in the fatal group and 3 439 cases in the survival group. Multivariate Cox proportional regression showed that male gender ( HR=1.446, 95% CI: 1.200-1.742, P<0.001), older age ( HR=1.130, 95% CI: 1.118-1.143, P<0.001), higher waist-to-height ratio ( HR=8.117, 95% CI: 2.235-29.481, P=0.001), positive urinary protein ( HR=2.974, 95% CI: 2.202-4.016, P<0.001), high fasting blood glucose ( HR=1.070, 95% CI: 1.012-1.131, P=0.017), and history of stroke ( HR=1.819, 95% CI: 1.414-2.340, P<0.001) were independent risk factors for all-cause mortality in hypertensive patients, while exercise≥1/week ( HR=0.816, 95% CI: 0.668-0.996, P=0.046) and taking lipid-lowering medications ( HR=0.459, 95% CI: 0.223-0.947, P=0.035) were protective factors for all-cause mortality. Conclusion:For hypertensive patients, male gender, older age, higher waist-to-height ratio, positive urinary protein, high fasting blood glucose, and history of stroke are risk factors for all-cause mortality, while exercise≥1/week and taking lipid-lowering medications are protective factors.

Objective:To analyze the association between sleep status and ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.Methods:It was a cross sentional study. Hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring from May 2021 to April 2023 in Shanghai Xinzhuang Town were enrolled. The demographic information and sleep status of patients were obtained from the questionnaire. A TM-2430 blood pressure monitor was used to measure 24-hour ambulatory blood pressure, and the relevant indicators, including blood pressure level and blood pressure coefficient of variation were documented. The association between sleep status and blood pressure indicators was analyzed with multivariate linear regression model.Results:A total 1 135 patients aged (65.07±12.61) years were enrolled, and 473 (41.67%) of whom were males. The sleep time was<7 hours in 76 cases, 7- 8 hours in 219 cases and >8 hours in 840 cases; the bedtime was earlier than 22∶00 in 415 cases, between 22∶00 and 23∶00 in 474 cases and later than 23∶00 in 246 cases; the wake-up time was before 6∶00 in 230 cases, between 6∶00 and 7∶00 in 521 cases and after 7∶00 in 384 cases. Multivariate linear regression analysis showed that after controlling for gender and age, the sleep time was negatively associated with diurnal, noctumal and 24-hour diastolic blood pressure levels (all P<0.05), and positively associated with diurnal and noctumal systolic blood pressure coefficient of variation, noctumal diastolic blood pressure coefficient of variation, and 24-hour systolic blood pressure coefficient of variation (all P<0.05).The bedtime was positively associated with diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), diastolic blood pressure (all P<0.05); and negatively associated with diurnal systolic blood pressure coefficient of variation, diurnal diastolic blood pressure coefficient of variation, noctumal systolic blood pressure coefficient of variation, 24-hour systolic blood pressure coefficient of variation, and 24-hour diastolic blood pressure coefficient of variation (all P<0.05). The wake-up time was positively associated with diurnal systolic blood pressure, diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), and positively associated with diurmal systolic blood pressure and diastolic blood pressure (both P<0.05). Conclusion:Sleep status is closely associated with ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.

INTRODUCTION: Despite the challenges related to His bundle pacing (HBP), recent data suggest an improved success rate with experience. As a non-university, non-electrophysiology specialised centre in Singapore, we report our experiences in HBP using pacing system analyser alone. METHODS: Data of 28 consecutive patients who underwent HBP from August 2018 to February 2019 was retrospectively obtained. The clinical and technical outcomes of these patients were compared between two timeframes of three months each. Patients were followed up for 12 months. RESULTS: Immediate technical success was achieved in 21 (75.0%) patients (mean age 73.3 ± 10.7 years, 47.6% female). The mean left ventricular ejection fraction was 53.9% ± 12.1%. The indications for HBP were atrioventricular block (n = 13, 61.9%), sinus node dysfunction (n = 7, 33.3%) and upgrade from implantable cardioverter-defibrillator to His-cardiac resynchronisation therapy (n = 1, 4.8%). No significant difference was observed in baseline characteristics between Timeframe 1 and Timeframe 2. Improvements pertaining to mean fluoroscopy time were achieved between the two timeframes. There was one HBP-related complication of lead displacement during Timeframe 1. All patients with successful HBP achieved non-selective His bundle (NSHB) capture, whereas only eight patients had selective His bundle (SHB) capture. NSHB and SHB capture thresholds remained stable at the 12-month follow-up. CONCLUSION Permanent HBP is feasible and safe, even without the use of an electrophysiology recording system. This was successfully achieved in 75% of patients, with no adverse clinical outcomes during the follow-up period.
Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Bundle of His ; Follow-Up Studies ; Stroke Volume ; Retrospective Studies ; Treatment Outcome ; Cardiac Pacing, Artificial/adverse effects* ; Electrocardiography ; Ventricular Function, Left/physiology*