Objective To investigate the correlation between the gene polymorphisms of rs7100927,rs10885409,rs4918789,rs290487 of TCF7L2 gene and type 2 diabetes mellitus(T2DM)of Uygur nationality and Han nationality.Methods 577 T2DM patients(T2DM group,293 Han and 284 Uyghu)were enrolled in the Department of Endocrinology,Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from December 2013 to August 2015.In the same period,307 healthy subjects were selected as normal control(NC)group,of which 208 were Han Chinese and 99 were Uyghu.The polymorphism of TCF7L2 gene rs7100927,rs10885409,rs4918789 and rs290487 were identified by imLDRTM multiple SNP typing technique.Results In Uygur,the frequency of allele G at rs7100927 and rs4918789 of TCF7L2 gene and the frequency of allele C at rs10885409 and rs290487 in T2DM group were lower than those in NC group(P<0.05).Conclusion The G allele at rs7100927 and rs4918789 and C allele at rs10885409 and rs290487 of TCF7L2 gene may be protective factors for T2DM in Xinjiang Uygur population.

Objective To explore the potential circular RNA(circRNA)biomarker of Uygur type 2 diabetes mellitus(T2DM).Methods A total of 120 T2DM patients and 120 subjects with normal glucose tolerance were recruited from the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Shihezi University and Shihezi community from October 2020 to August 2021,and divided into four groups:60 Uygur T2DM patients(Uygur T2DM group),60 Uygur subjects with normal glucose tolerance(Uygur NC group),60 Han T2DM patients(Han T2DM group)and 60 Han subjects with normal glucose tolerance(Han NC group).Hsa_circRNA_0042817,hsa_circRNA_0006532 and hsa_circRNA_0004131 were selected as candidate circRNA,and the expression in peripheral blood were detected by RT-qPCR.Logistic regression was used to analyze the influencing factors for Uygur T2DM,and the receiver operating characteristic(ROC)curve was used to evaluate the biomarker value of circRNA in Uygur T2DM.Results The expressions of hsa_circRNA_0042817,hsa_circRNA_0006532 and hsa_circRNA_0004131 were higher in Uygur T2DM group than in Uygur NC group(P<0.05).The expression of hsa_circRNA_0042817 was higher in Uygur T2DM group than in Han T2DM group(P<0.05).Logistic regression analysis showed that hsa_circRNA_0042817 was an influencing factor for T2DM in Uygur population[OR(95%CI)3.420(1.567～7.465)].ROC curve analysis showed that the area under the curve was the largest(0.798)in hsa_circRNA_0042817.Conclusion There were up-regulated circRNA in peripheral blood in Uygur T2DM patients,and hsa_circRNA_0042817 may be a biomarker for T2DM in Uygur patients.

Objective To evaluate the value of rs61330082 and rs4730153 polymorphisms of Visfatin locus for the diagnosis of type 2 diabetes mellitus(T2DM)in a high-risk population.Methods SNPscanTM high-throughput single nucleotide polymorphism typing technique was used to genotype Visfatin gene loci rs61330082 and rs4730153 in 346 T2DM patients(T2DM group)and 1426 normal controls(NC group).Logistic regression analysis was used to analyze T2DM risk factors.ROC curves were used to analyze the optimal cut-off values of Visfatin gene rs61330082 and rs4730153 for the diagnosis of T2DM.Results The proportion of women,age,obesity,smoking,hypertension,FPG,HbA1c and TG were higher in T2DM group than those in NC group(P<0.01)and HDL-C was lower than in NC group(P<0.01).The frequency of G allele and GG genotype was higher in T2DM group compared with NC group(P<0.05).Logistic regression analysis showed that age,female,obesity,hypertension,TG,and GG genotype at rs4730153 locus were risk factors for T2DM,HDL-C was a protective factor for T2DM.The area under the ROC curve of GG genotype at Visfatin rs4730153 mutation for diagnosis of T2DM was 0.668 and the optimal cut-off point for predicting T2DM was 20.04%,with sensitivity 60.1%and specificity 66.1%,respectively.Conclusion The GG genotype of Visfatin gene rs4730153 locus is associated with the risk of T2DM and can beused as a candidate gene for predicting phenotype of T2DM.

Objective To examine the differential expression of plasma circRNA in individuals with type 2 diabetes mellitus(T2DM)and to elucidate the potential role of circRNA in the pathogenesis and progression of T2DM.Methods A total of 33 newly diagnosed T2DM patients who were hospitalized in the Department of Endocrinology of Heze Municipal Hospital and 33 healthy subjects with normal glucose tolerance(NC)were enrolled in this study from March 2022 to March 2023.Three subjects with T2DM and 3 with NC were randomly selected from study population and underwent high-throughput sequencing to identify differentially expressed circRNA.Six circRNA with significant differences were selected,and validated in the remaining study population using Real-Time Quantitative Polymerase Chain Reaction(RT-qPCR).Bioinformatics analyses were conducted on the differentially expressed circRNA-associated genes,and their interaction with microRNA(miRNA)was predicted.Results Microarray analysis revealed 166 significantly differentially expressed circRNA(FC≥2,P<0.05)in the T2DM group compared with NC group.Among them,137 were up-regulated and 29 were down-regulated.RT-qPCR validation of six circRNA showed that the expression level of hsa_circ_0000705 was significantly higher,while the expression levels of hsa_circ_0005362 and hsa_circ_0042839 were significantly lower in T2DM group,consistent with the microarray results.However,hsa_circ_0117392,hsa_circ_0008311,and hsa_circ_0087641 showed no significant changes.Conclusion Differentially expressed circRNA are present in T2DM patients.Hsa_circ_0005362 was significantly down-regulated and may be involved in the development of T2DM through the regulation of related signaling pathways by targeting miR-128-1-5p.

Objective To investigate the relationship between polymorphism of resistin(RETN)gene and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients in middle and high altitude areas.Methods A total of 400 patients with T2DM in Qinghai area were recruited and divided into simple T2DM group(T2DM,n=200)and T2DM combined with MAFLD group(T2DM+ MAFLD,n=200)according to liver ultrasonography.Healthy individuals confirmed by physical examination were selected as the normal control group(NC,n=180).Plasma resistin levels were measured by ELISA.The polymorphism of RETN-420C/G and +299G/A genes were detected by PCR sequencing.Results By comparing the polymorphism of RETN-420C/G gene in each group,it was found that the frequencies of G/G genotype and G allele frequency in T2DM+MAFLD group were higher than those in NC group and T2DM group(P<0.05),while the frequencies of C/C genotype and C allele frequency were lower than those in NC group and T2DM group(P<0.05).The risk of MAFLD increased by 1.571,2.126 and 1.537 times respectively in T2DM patients with C/G,G/G genotype and G allele.Logistic regression analysis showed that G/G genotype was a risk factor for MAFLD in T2DM patients.By comparing the polymorphism of RETN+299G/A gene in each group,it was found that A allele frequency in T2DM+MAFLD group was higher than that in NC group and T2DM group,while G allele frequency was lower than that in NC group and T2DM group(P<0.05).The allele A increased the risk of MAFLD in T2DM patients by 1.432 times compared to allele G.Conclusion RETN gene-420C/G locus G/G genotype increases the risk of T2DM combined with MAFLD in middle and high altitudeareas.

Objective To explore the changes in Th1 cell,B cell and related gene expression during the healing of diabetic foot ulcers(DFU).Methods Lesional skin tissues from DFU patients surgically treated in our hospital from January 2022 to January 2023 were selected.DFU associated gene expression data were collected from GSE80178 and GSE143735 datasets.The expressions of genes(DEGs)between ulcer and no-ulcer patients were identified.Bioinformatics methods were used to identify abnormal immune cells and key genes.Finally,the key results were detected by RT-qPCR and flow cytometry.Results A total of 548 common DEGs were identified in two datasets.In 14 co-expression modules,darkgrey and darkgreen were most related to ulcer,which were mainly associated with the regulation of enzyme activity,immune function and endocrine regulation.Flow cytometry showed that Th1 and B cells were highly infiltrated in ulcer tissue and decreased in healing tissue.MMP13,S100A9 and STAT4 were involved in immune signaling pathways.MMP13 and STAT4 were lowly expressed in healed ulcers,whereas S100A9 was highly expressed.Conclusion Reduced levels of Th1 and B cell infiltration may promote DFU healing.

Objective To investigate the therapeutic effect of continuous blood purification on diabetic lactic acidosis(DLA).Methods 60 DLA patients who were treated at our hospital Blood Purification Center from January 2020 to January 2023 were randomly divided into conventional treatment group(Con)and continuous blood purification group(CBP),with 30 cases in each group.The changes of anion gap(AG),pH,lactic acid(Lac),FPG,2 hPG,HbA1c,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),serum creatinine(Scr),urea nitrogen(BUN),cystatin C(CysC),blood potassium(K+),C-reactive protein(C-RP),acute and chronic health evaluation scoring system Ⅱ(APACHEⅡ)and mortality within 28 days were compared between the two groups.Results After 48 h of treatment,the clearance rate of Lac in CBP group was higher than that in Con group(P<0.05).The pH value of CBP group was higher than Con group.The levels of AG,Lac,FPG,2 hPG,HbA1c,ALT,AST,TBIL,Scr,BUN,CysC,K+,C-RP and APACHEⅡ score were lower in CBP group than those in Con group(P<0.05).The 28-day mortality rate of the CBP group was lower than that of the Con group(P<0.05).Conclusion Continuous blood purification combined with routine treatment in DLA patients can increase Lac clearance and improve the prognosis.

Objective To explore the relationship between low bilirubin(T-BIL)levels and hyper-thyroidism in patients with type 2 diabetes mellitus(T2DM).Methods A total of 186 patients with T2DM admitted to the Endocrinology Department of our hospital were enrolled in this study from January 2019 to August 2022.They were divided into simple T2DM group(n=107)and hyperthyroidism group(HT,n=79)according to whether they were complicated with hyperthyroidism.The influence factors for T2DM patients complicated with hyperthyroidism were evaluated by logistic regression analysis.Results Compared with T2DM group,DM duration,FPG,the proportion of patients with salty taste and nervous increased in HT group(P<0.05),while BMI,T-BIL decreased in HT group(P<0.05).Pearson correlation analysis showed that T-BIL was positively correlated with TSH levels(P<0.05),and negatively correlated with TT3,TT4,FT3 and FT4(P<0.05).Logistic regression analysis showed that DM duration,salty taste,FPG and T-BIL were the influencing factors of T2DM patients with hyperthyroidism.The receiver operating characteristic(ROC)Curve showed that the AUC of the model was 0.812(95%CI 0.748～0.839),with sensitivity and specificity 87.4%and 82.6%respectively.Conclusion T-BIL was significantly correlated with TSH and FT3.Low T-BIL level is an independent risk factor for T2DM patients with hyperthyroidism,which is of great significance for predicting whether T2DM patients complicated with hyperthyroidism.

Objective To evaluate the protective effect of human nucleus pulposus cell by Liraglutide(Lir)under high-glucose environment via inhibition of NOD-like receptor family,pyrin domain containing 3(NLRP3)inflammasome activation and its mechanism.Methods Human nucleus pulposus cell lines were cultured and the third-generation nucleus pulposus cells were randomly divided into control group(Con group),high glucose group(HG group),and Liraglutide interference group(Lir group),and cultured for 48 h.ELISA was used to detect interleukin IL-1β;flow cytometry was used to testreactive oxygen species(ROS),and Western blot was used to evaluate the protein expressions of NLRP3,Pro-caspase-1,and Caspase-1.Results Compared with Con group,IL-1β,ROS,NLRP3,Pro-caspase-1,Caspase-1 protein expression and cell apoptosis were increased in HG and Lir groups(P<0.05).Compared with HG group,IL-1β,ROS,NLRP3,Pro-caspase-1,Caspase-1 protein expression and cell apoptosis were significantly decreased in Lir group(P<0.05).Conclusion Liraglutide protects human NPCs by inhibiting the activation of NLRP3 inflammasome,reducing IL-1β secretion,and inhibiting cell apoptosis.

Objective To investigate the role of PPARγ/GluT4 axis in insulin resistance(IR),cell proliferation and apoptosis of granulosa cells.Methods A total of 45 married women with PCOS who received routine IVF-ET assisted pregnancy treatment in Center of Reproductive Medicine,Qinghai Provincial People's Hospital were enrolled in this study from August 2018 to August 2020.All the patients were divided into IR group(PCOS-IR group,HOMA-IR≥2.57,n=23)and non-IR group(PCOS-NIR group,HOMA-IR<2.57,n=22)according to HOMA-IR.Meanwhile,21 married patients with infertility due to male or fallopian tube factors were enrolled as control group(Con).miR-27a mimics,miR-27a inhibitors(miR-27a inhibitor)and corresponding controls(mimics NC and inhibitor NC)transfected PCOS-IR granulosa cells,which were then divided into miR-27a mimics group,miR-27a inhibitor group,mimics-NC group and inhibitor-NC group.Double luciferase report test confirmed that miR-27a binded to PPARγ.Cell proliferation and apoptosis were detected by CCK-8 method and Annexinv-FITC/PI method.The expression of miR-27a,GluT4,PPARγ,Bax related to B lymphomas-2,Cleaved caspase-3 and B lymphomas-2(Bcl-2)were detected by RT-qPCR and Western blot respectively.Results Compared with Con group,the expression of miR-27a increased(P<0.01),while the expression of PPARγ mRNA and protein decreased in PCOS-NIR and PCOS-IR groups(P<0.01).Compared with PCOS-NIR group,the expression of miR-27a increased(P<0.05),while the expression of PPARγ mRNA and protein decreased in PCOS-IR group(P<0.01).The double luciferase report showed that there was a targeted binding site between PPARγ and miR-27a.Compared with inhibitor-NC group,the cell activity increased at 24 h,48 h,72 h and 96 h in miR-27a inhibitor group(P<0.05 or P<0.01),while the apoptosis rate decreased inmiR-27a inhibitor and mimics-NC group(P<0.05 or P<0.01).Compared with miR-27a inhibitor group,the apoptosis rate increased,and the cell activity decreased at 24,48,72 and 96 h in mimics-NC and miR-27a mimics groups(P<0.05 or P<0.01).Compared with the inhibitor-NC group,the expression of miR-27a,Bax and Cleaved caspase-3 increased(P<0.05 or P<0.01),while the expression of GluT4,PPARγ and Bcl-2 decreased in miR-27a mimics group(P<0.01).In miR-27a inhibitor group,the protein expressions of GluT4,PPARγ and Bcl-2 increased(P<0.05 or P<0.01),while miR-27a,Bax and Cleaved caspase-3 decreased(P<0.01).Compared with miR-27a inhibitor group,the expressions of miR-27a,Bax and Cleaved caspase-3 increased(P<0.01),while the expressions of GluT4,PPARγ and Bcl-2 decreased in mimics-NC and miR-27a mimics groups(P<0.05 or P<0.01).Conclusion The expression level of miRNA-27a is related to IR,cell proliferation,and apoptosis of granulosa cells,which may be related to PPARγ signal path.