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:Successful uterine spiral artery remodeling is necessary for normal pregnancy,in which vascular smooth muscle cells are important cells.Interferon-γ is associated with the loss of vascular smooth muscle cells during early pregnancy.However,the specific mechanism is not fully understood. OBJECTIVE:To investigate the effects of interferon-γ on migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway. METHODS:Human vascular smooth muscle cells were divided into control group and interferon-γ group.The control group was cultured normally,and the interferon-γ group was treated with 10 ng/mL interferon-γ for 24 hours.The migration ability of vascular smooth muscle cells was detected by Transwell assay.The apoptosis of vascular smooth muscle cells was detected by TUNEL assay and flow cytometry.The mRNA expression levels of NLRP3 and caspase-1 were detected by qPCR.Western blot assay was utilized to detect NLRP3,caspase-1,and cleaved N-terminal GSDMD protein expression levels. RESULTS AND CONCLUSION:Compared with the control group,the migration ability and apoptosis rate of vascular smooth muscle cells in interferon-γ group were significantly increased(P<0.05).Compared with the control group,the mRNA expression levels of NLRP3 and caspase-1 in vascular smooth muscle cells of interferon-γ group were significantly increased(P<0.05).Compared with control group,the expression levels of NLRP3,caspase-1,and cleaved N-terminal GSDMD protein in vascular smooth muscle cells in the interferon-γ group were significantly increased(P<0.05).The results suggest that interferon-γ may regulate the migration and apoptosis of vascular smooth muscle cells through NLRP3/caspase-1/GSDMD pyroptosis pathway.

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.

There are complex neural mechanisms involved in speech production,and being well understood by clinicians and speech therapists can help them identify the abnormal speech and predict the severity of disorders.Dysarthria is a typical speech production problem by nerve injury,which would reduce the speech charity and intel-libility,and seriously affects patients'social communication and reduces the quality of life.The author summarizes the characteristics of dysarthria,neural pathway of normal speech production and neuromechanism of dysarthria based on the theory of motion control.The aim of this paper is to provide theoretical basis to conduct effective clini-cal assessment,management and treatment of speech disorders for clinians and speech therapists.

There are complex neural mechanisms involved in speech production,and being well understood by clinicians and speech therapists can help them identify the abnormal speech and predict the severity of disorders.Dysarthria is a typical speech production problem by nerve injury,which would reduce the speech charity and intel-libility,and seriously affects patients'social communication and reduces the quality of life.The author summarizes the characteristics of dysarthria,neural pathway of normal speech production and neuromechanism of dysarthria based on the theory of motion control.The aim of this paper is to provide theoretical basis to conduct effective clini-cal assessment,management and treatment of speech disorders for clinians and speech therapists.

Dry eye is a multifactorial disease caused by abnormal tear film and ocular surface.The clinical manifesta-tions include photophobia,pruritus,burning sensation,visual fatigue,vision fluctuation,and other eye discomfort.If not treated in time,severe dry eye may cause eye inflammation,corneal ulcers,visual impairment,and other complications.Topical drug therapy is currently the simplest and most commonly used treatment for dry eye.With the further exploration of dye eye's pathogenesis,many new topical drugs have been used in clinical practice.This article reviews the advances in the topical drug therapy for dry eye.

Objective To assess the nutritional status of vitamin D and associated factors among adults of six ethnic minority groups native to Yunnan Province,and provide evidence for policy making.Methods Between May 2019 and August 2020,a total of 690 adults were selected from Jinuo,Bulang,Jingpo,Deang,Achang and Pumi ethnic groups according to the sex and age composition in the 6th national census.A questionnaire survey and an anthropometric examination were conducted by trained health workers,and serum 25(OH)D levels were determined with high-performance liquid chromatography-tandem mass spectrometry.Results The median of serum 25(OH)D was 28.7(P25～P75∶24.3～33.8)ng/mL,and the prevalence of vitamin D sufficiency,insufficiency and deficiency were 44.2%、47.5%and 8.3%,respectively.There were significant differences in serum 25(OH)D levels among the six ethnic groups(χ2=139.29,P<0.01).Multivariate logistic regression showed that ethnic groups living in higher latitude areas(Pumi,Jingpo,Deang,and Achang),women,and those whose BMI≥24.0 were more likely to be vitamin D insufficient or deficient.Conclusion More than half of the ethnic adults suffer from vitamin D malnutrition which also varies across ethnicities.Further surveillance and interventions among key areas and populations are needed.

Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.