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 investigate the role of miR-185-5p expression changes in inducing myo-cardial metabolic abnormalities mediated by inflammatory responses in patients with chronic heart failure(CHF).Methods A total of 228 CHF patients treated in our department from June 2022 to June 2024 were prospectively enrolled and served as observation group,and another 108 healthy individuals taking physical examinations were subjected as the control group.Cardioechography was used to detect ejection time,fractional shortening,stroke volume,left ventricular mass index(LVMI),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and left ventricular end-systolic diameter(LVESD).Then LV circumferential end-systolic wall stress(CESS)and MEE were calculated.The levels of IL-6,CRP,and TNF-α were detected with ELISA.Results The expression of miR-185-5p was significantly lower,and the levels of IL-6,CRP,and TNF-α were obviously higher in the observation group than the control group(P＜0.01).MiR-185-5p was negatively correlated with IL-6,CRP and TNF-α levels(r=-0.765,-0.558,-0.693,P＜0.01);MEE was negatively correlated with miR-185-5p(r=-0.594,P＜0.01)and positively with IL-6,CRP and TNF-α levels(r=0.712,0.684,0.559,P＜0.01).Multivariate logistic regression analysis showed that ejection time,fractional shortening,stroke volume,LVEF,and miR-185-5p were independent protective factors for MEE,while LVMI,LVESD,LVEDD,CESS,IL-6,CRP,and TNF-α were independent risk factors for MEE(P＜0.05,P＜0.01).Conclusion Low expression of miR-185-5p is associated with myocardial metabolic abnormalities mediated by inflammatory responses in CHF patients.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

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 investigate the role of miR-185-5p expression changes in inducing myo-cardial metabolic abnormalities mediated by inflammatory responses in patients with chronic heart failure(CHF).Methods A total of 228 CHF patients treated in our department from June 2022 to June 2024 were prospectively enrolled and served as observation group,and another 108 healthy individuals taking physical examinations were subjected as the control group.Cardioechography was used to detect ejection time,fractional shortening,stroke volume,left ventricular mass index(LVMI),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and left ventricular end-systolic diameter(LVESD).Then LV circumferential end-systolic wall stress(CESS)and MEE were calculated.The levels of IL-6,CRP,and TNF-α were detected with ELISA.Results The expression of miR-185-5p was significantly lower,and the levels of IL-6,CRP,and TNF-α were obviously higher in the observation group than the control group(P＜0.01).MiR-185-5p was negatively correlated with IL-6,CRP and TNF-α levels(r=-0.765,-0.558,-0.693,P＜0.01);MEE was negatively correlated with miR-185-5p(r=-0.594,P＜0.01)and positively with IL-6,CRP and TNF-α levels(r=0.712,0.684,0.559,P＜0.01).Multivariate logistic regression analysis showed that ejection time,fractional shortening,stroke volume,LVEF,and miR-185-5p were independent protective factors for MEE,while LVMI,LVESD,LVEDD,CESS,IL-6,CRP,and TNF-α were independent risk factors for MEE(P＜0.05,P＜0.01).Conclusion Low expression of miR-185-5p is associated with myocardial metabolic abnormalities mediated by inflammatory responses in CHF patients.

OBJECTIVE To explore the effects of ursolic acid （UA） on the growth， invasion， apoptosis and metastasis of human colorectal cancer cells SW620 and find out the underlying molecular mechanisms. METHODS The effects of different concentrations （0， 5， 10， 15， 20， 25， 30 μmol/L） of UA on the proliferation of SW620 cells for different durations （24， 48， 72 h） were detected by CCK-8 assay； the clone formation was detected by clone formation assay after SW620 cells were treated with different concentrations of UA （0，10，15，20 μmol/L） for 10 days. After SW620 cells were treated with different concentrations of UA （0， 10， 15， 20 μmol/L） for 24 hours， flow cytometry， Transwell invasion assay and Western blot assay were adopted to detect apoptosis and invasion of SW620 cells， and the expressions of B cell lymphoma 2 （Bcl-2）， cleaved-poly （ADP-ribose） polymerase （cleaved-PARP）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， p38 MAPK， E-cadherin， N-cadherin and zinc finger transcription factor Snail. The effects of p38 MAPK inhibitor （SB203580） combined with UA on the protein expressions of p-p38 MAPK， Bcl-2 and N-cadherin were investigated. RESULTS Compared with 0 μmol/L UA， the stone5999@163.com survival rates of SW620 cells treated with 5-30 μmol/L UA for 24， 48 and 72 h were significantly decreased （P＜0.05）. The clone formation rate of cells treated with 15 μmol/L and 20 μmol/L UA was significantly decreased （P＜0.05）. After being treated with 15 μmol/L and 20 μmol/L UA， the cell apoptosis rate， the protein expressions of cleaved-PARP and E-cadherin， and the phosphorylation of p38 MAPK protein were increased； but the number of transmembrane cells， and the protein expressions of Bcl-2， Snail and N-cadherin were decreased； there was statistical significance in difference of most indexes （P＜0.05）. Some indexes changed in a concentration-dependent manner （P＜0.05）. SB203580 could significantly inhibit the upregulation of p38 MAPK by UA and reverse the inhibitory effect of UA on the protein expressions of Bcl-2 and N-cadherin （P＜0.05）. CONCLUSIONS UA can inhibit the growth， invasion and metastasis of SW620 cells， and induce cell apoptosis， the mechanism of which may be attributed to the activation of p38 MAPK signaling pathway.

Psoriasis is a refractory disease mainly co-acted by immune,genetic and environment.Tumor necrosis factor α (TNF-α)-related biologics have brought the landmark advances in the treatment of psoriasis;however,the anti-TNF-α therapy has the adverse response,its limitation may be related to the different bio-logical functions exerted by activation of TNF-α different receptors.Tumor necrosis factor receptor 2 (TNFR2) is one of the key receptors for TNF-α,and after binding to TNF-α,it can activate multiple signaling pathways such as NF-κB,PI3K/Akt,MAPK,STAT3,etc.,which are involved in the regulation of inflamma-tion,epidermal homeostasis,cellular apoptosis,cellular proliferation,cellular autophagy and other biological processes.It is suggested that TNFR2 is closely related to the occurrence and development of psoriasis.Previ-ous studies have often overlooked the role of TNFR2 in anti-TNF-α therapies;therefore,this article reviews the structure and signaling pathways of TNFR2,research advances in the disease,and its relationship with psoriasis to provide new references for exploring the pathogenesis and treatment of psoriasis.

Activity-based protein profiling(ABPP)and affinity-based protein profiling(AfBPP)are reliable chemical proteomics techniques that exhibit significant advantages in identifying the direct acting targets of small molecule drugs and toxicants,which can help researchers understand the pharmaco-logical and toxicological mechanisms of active small molecules.This paper introduces ABPP and AfBPP technologies and summarizes the applications of this technique in drug off-target effect and target iden-tification of toxicants in recent years,such as drug off-target effect of crenolanib,BIA 10-2474,orlistat and target identification of VX,fenitrothion,acrolein.It is hoped that this review will give readers a better idea of ABPP/AfBPP and offer a line of thinking for researchers in the fields of pharmacology,toxicology and chemical biology.