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.

[Objective]To observe the effect of Xiaoyu Xiezhuo Drink on podocyte apoptosis and hypoxia inducible factor 1 alpha(HIF1α)expression in db/db diabetic kidney disease(DKD)model mice.[Methods]Six db/m mice were chosen as negative control group,eighteen db/db mice were chosen and divided into DKD model group,low dosage Xiaoyu Xiezhuo Drink group,high dosage Xiaoyu Xiezhuo Drink group,with six mice in each group.After gastric irrigation for twelve weeks,the urine was collected to test the levels of protein,β2-microglobulin(β2-MG),albumin/creatinine ratio(Acr),β2-microglobulin/creatinine ratio(β2-MG/Ucr);blood was collected to test the level of triglyceride(TG),total cholesterol(TC),albumin(Alb),blood urea nitrogen(BUN),serum creatinine(Scr);the kidney tissue was collected to observe the pathological change by light and electron microscope,and to test HIF1α,nephrin mRNA by Real-time polymerase chain reaction(RT-PCR).[Results]Compared with negative control group,the levels of urine protein,β2-MG,Acr,β2-MG/Ucr,serum TG,TC,BUN,Scr were increased(P＜0.01),serum Alb was decreased(P＜0.01);glomerular volume increased,capillary loops lobed,mesangial cells and matrix hyperplasia,interstitial inflammation and fibrosis increased,foot process fusion increased,basement membrane thickened;podocyte apoptosis was increased;expression of HIF1α mRNA was elevated(P＜0.01),and nephrin mRNA was descended in kidney tissue of DKD model group(P＜0.01).Compared with DKD model group,the level of urine protein,β2-MG,Acr,β2-MG/Ucr,serum TG,TC,BUN,Scr were decreased(P＜0.01),serum Alb was incresed(P＜0.01);the pathological changes of the kidney was improved;the apoptosis of podocyte was reduced;the expression of HIF1α mRNA was decreased(P＜0.01),and nephrin mRNA was incresed(P＜0.01)in the kidney tissue of varied dosage Xiaoyu Xiezhuo Drink groups.There was no statistical significance in the level of urine protein,β2-MG,Acr,β2-MG/Ucr,serum TG,TC,BUN,Scr,Alb,podocyte apoptosis,and HIF1α,nephrin mRNA in the kidney tissue between different dosage Xiaoyu Xiezhuo Drink groups(P＞0.05).[Conclusion]Xiaoyu Xiezhuo Drink could improve urinary protein,renal function,renal structure lesion and podocyte apoptosis in DKD mice,which perhaps by regulating the expression of HIF1α.

Hepatoblastoma is the most common malignant tumor of the liver in childhood.The main clinical symptom of children is abdominal mass，and half of them are unable to completely be resected at initial diagnosis.In recent years，surgical treatment combined with chemotherapy can significantly improve the long-term survival rate of hepatoblastoma，and it has become the important treatment plan for hepatoblastoma.Especially the preoperative clinical staging，pathological types，chemotherapy，and surgery are important for the treatment of hepatoblastoma.This article reviews the latest research progress on the diagnosis and treatment of childhood hepatoblastoma in order to provide the help for clinical treatment.

Objective To explore the clinical efficacy of prone position ventilation(PPV)in improving hypoxemia in patients with severe brain damage.Methods A retrospective research method was conducted,140 patients with severe brain damage who were admitted to the department of critical care medicine of the First Affiliated Hospital,Zhejiang University School of Medicine from August 2020 to August 2021 were selected as subject objected.According to the inclusion and exclusion criteria,20 patients with oxygenation index≤200 mmHg(1 mmHg≈0.133 kPa)who were treated with PPV were statistically analyzed.The patients'blood gas analysis related indicators[including arterial partial pressure of oxygen(PaO2),fractional of inspired oxygen(FiO2),oxygenation index,arterial oxygen saturation(SaO2),arterial partial pressure of carbon dioxide(PaCO2),pH value],ventilator-related parameters[including peak inspiratory pressure(PIP),positive end-expiratory pressure(PEEP),tidal volume(VT),lung dynamic compliance(Cdyn),etc.],and mean arterial pressure(MAP),heart rate(HR)were compared before PPV,12 hours after PPV,and 12 hours after reverting to supine position.At the same time,the related complications of patients during PPV were recorded.Results There were 15 males and 5 females,the mean age of the patients was(46.10±17.22)years old,the average PPV time was(22.20±5.94)hours.Compared with before PPV,patients showed significant increases in PaO2,oxygenation index,SaO2,VT,and Cdyn at 12 hours after PPV and 12 hours after recovery from supine position[PaO2(mmHg):98.35±21.85,98.45±17.90 vs.72.15±10.14,oxygenation index(mmHg):198.82±40.51,202.27±46.39 vs.133.20±33.95,SaO2:0.97±0.02,0.97±0.01 vs.0.94±0.03,VT(mL):558.42±111.23,580.29±119.44 vs.484.82±123.77,Cdyn(mL/cmH2O):26.11±5.42,27.90±5.80 vs.24.15±6.13,all P<0.05];Compared with 12 hours after PPV,the Cdyn of the patient still showed a significant increase after 12 hours of recovery from supine position(P<0.05).There were no statistical differences in the FiO2,PaCO2,pH value,PIP,PEEP,HR,and MAP of patients at various time points before and after PPV(all P>0.05).Five patients developed redness and swelling at the skin compression site mainly on the face after PPV,which gradually improved after returning to a supine position.During this period,there was no occurrence of catheter detachment,malignant arrhythmia,or significant hemodynamic instability.Conclusion PPV has a certain clinical effect on improving hypoxemia in patients with severe brain damage.

OBJECTIVE To investigate the influence of Huayu xiaozhong decoction （HXD） on inflammatory response in rats with deep vein thrombosis （DVT）. METHODS The male SD rats were divided into control group （CK group）， model group （Model group）， HXD low-dose group （HXD-L group， HXD 10.86 mg/kg）， HXD medium-dose group （HXD-M group， HXD 21.71 mg/kg）， HXD high-dose group （HXD-H group， HXD 32.57 mg/kg）， positive control group （LMWHS group， low molecular weight heparin sodium 600 IU/kg）， silent information regulator 2 （SIRT2） inhibitor group （AK-7 group， AK-7 20 mg/kg）， HXD-M+AK-7 group （HXD 21.71 mg/kg+AK-7 20 mg/kg）， with 12 rats in each group. Except for the CK group， the DVT rat was induced by the Reyers method in other groups； after modeling， administration groups were given relevant medicine intragastrically/intraperitoneally， once a day， for consecutive 2 weeks. Twenty-four hours after the last medication， the coagulation function indexes [activated partial thromboplastin time （APTT）， thrombin time （TT）， prothrombin time （PT）， fibrinogen （FIB）] and inflammatory indexes in serum and inferior vena cava tissue [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] of rats were detected. The formation of thrombus was observed， and the wet and dry masses of the thrombus were weighed. The protein expressions of tissue factor （TF） and SIRT2 as well as the phosphorylation and acetylation levels of nuclear factor kappa B （NF-κB） p65 in inferior vena cava tissue were detected. RESULTS Compared with CK group， APTT， TT and PT of rats in Model group were shortened significantly（P＜0.05）； the content of FIB， the levels of IL-1β， IL-6 and TNF-α， wet weight and dry weight of venous thrombus， TF protein staining score， the phosphorylation and acetylation levels of NF-κB p65 protein increased significantly （P＜0.05）； the inferior vena cava was full of thrombus， and the protein expression of SIRT2 decreased （P＜0.05）. Compared with Model group， above indexes of HXD-L group， HXD-M group， HXD-H group and LMWHS group were improved， while the improvement effects of HXD-M group， HXD-H group and LMWHS group were significantly better than those of HXD-L group （P＜0.05）. The trends of the corresponding indicators in AK-7 group were opposite to the above （P＜0.05）； AK-7 attenuated the inhibitory effect of medium-dose HXD on the inflammatory response in model rats （P＜0.05）.CONCLUSIONS HXD may inhibit the inflammatory response of DVT rats by activating SIRT2/NF-κB signaling pathway.

ObjectiveTo picture the trajectory of changes in glucose and lipid metabolism among schizophrenic patients in long-term hospitalization. MethodsA total of 109 inpatients of Shenzhen Kangning Hospital from 2014 to 2022， who were diagnosed with schizophrenia based on the International Classification of Diseases， tenth edition （ICD-10） criteria， were recruited as subjects. Real-world follow-up data on longitudinal glucose metabolism （fasting blood glucose， glycosylated hemoglobin， C-peptide） and lipid metabolism （triglycerides， low density lipoprotein， high density lipoprotein， total cholesterol） were observed. The frequency of visit was once a year， with a total of 9 visits over 8 years. ResultsIn terms of glucose metabolism parameters， fasting blood glucose level decreased to 4.87 mmol/L at the 7^th visit， lower than the baseline level （P<0.01）. Glycated hemoglobin level was 6.08% at the 9^th visit， higher than the baseline level （P<0.05）. C-peptide level was 3.14 ng/mL at the 7^th visit， higher than the baseline level （P<0.01）. As for the trajectory of lipid metabolism parameters， high-density lipoprotein level were significantly lower than baseline level at the second visit （P<0.01） and stayed basically stable thereafter. Total cholesterol levels at the last three visits were 4.06， 4.07 and 3.95 mmol/L， respectively， all lower than the baseline level （P<0.01）. ConclusionThe changes of glycolipid metabolism parameters in long-term inpatients with schizophrenia were generally smooth during the 8-year follow-up period.

Objective To explore the relationship between different obesity indicators and carotid intima-media thickness(CIMT)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 1762 T2DM patients who visited the Endocrinology Department of Changzhou Second People's Hospital Affiliated with Nanjing Medical University and the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine from January 2019 to February 2022 were enrolled in this study.They were divided into youth group(18～44 years old,n=402),middle aged group(45～59 years old,n=1032),and elderly group(≥60 years old,n=328)according to WHO age classification criteria.The influencing factors for CIMT thickening in T2DM patients were analyzed using binary logistic regression,and the evaluation of the predictive effect of different obesity indicators on CIMT thickening was evaluated by receiver operating characteristic(ROC)curves.Results The subcuta-neous fat area,visceral fat area(VFA),neck circumference(NC),BMI,WC,cardiac metabolic index(CMI),Chinese visceral fat index(CAVI),visceral fat index,triglyceride glucose index,body roundness index,lipid aggregation index,HbA1c,DBP,TC,TG,HDL-C,LDL-C were lower in the middle aged and elderly groups than in youth group(P＜0.05).Binary logistic regression showed that VFA,NC,CMI in young T2DM patients,CAVI in middle aged T2DM patients,and NC in elderly T2DM patients were influ-encing factors for CIMT thickening.ROC curve analysis showed that VFA in young T2DM patients,CAVI in middle aged T2DM patients,and NC in elderly T2DM patients had a better predictive effect on CIMT thickening,with areas under the ROC curve of 0.567,0.574,and 0.573 respectively.Conclusion VFA,CAVI,and NC have a certain predictive effect on CIMT thickening in young,middle aged,and elderly T2DM patients.