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.

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

Objective To explore the clinical efficacy and safety of calcium dobesilate capsules combined with conbercept in the treatment of diabetic retinopathy with macular edema.Methods Patients with diabetic retinopathy complicated with macular edema were divided into control group and treatment group by cohort method.The control group was given intravitreal injection of conbercept ophthalmic injection 50 μL every time once a month.On the basis of the treatment in the control group,the treatment group was orally treated with calcium dobesilate capsules 0.5 g three times a day.Both groups were treated for 3 months.The efficacy after treatment,and ocular recovery indexes[best corrected visual acuity(BCVA),central macular thickness(CMT)],aqueous humor pro-angiogenic factors[vascular endothelial growth factor(VEGF),stromal cell-derived factor 1(SDF-1)]and aqueous humor hypoxic response factors[erythropoietin(EPO),hypoxia-inducible factor-1 α(HIF-1α)]were compared between two groups,and the safety of the two groups was evaluated.Results The treatment group and the control group were included in 48 cases and 56 cases,respectively.After 3 months of treatment,the total effective rates of the treatment group and the control group were 92.86％(52 cases/56 cases)and 79.17％(38 cases/48 cases),and the difference was statistically significant(P＜0.05).After 3 months of treatment,the BCVA of the treatment group and the control group were(0.58±0.14)and(0.45±0.12)logMAR,respectively;the CMT were(281.22±37.68)and(329.52±46.74)μm,respectively;the expression of VEGF in aqueous humor were(141.56±22.49)and(164.22±32.51)ng·L-1,respectively;the expression of EPO in aqueous humor were(8.03±2.72)and(9.69±3.11)mU·mL-1,respectively;the expression levels of HIF-1α in aqueous humor were(168.18±69.52)and(221.47±72.46)mg·L-1,respectively;the expression levels of SDF-1 in aqueous humor were(465.32±76.28)and(526.82±94.43)mg·L-1,respectively.The above indexes in the treatment group were significantly different from those in the control group(all P＜0.05).The adverse drug reactions in the treatment group and the control group mainly included transient elevated intraocular pressure,vitreous hemorrhage,and gastrointestinal reactions.The incidence of adverse drug reactions in the treatment group and the control group were 14.29％(8 cases/56 cases)and 12.50％(6 cases/48 cases),respectively.There was no statistically significant difference(P＞0.05).Conclusion Calcium dobesilate capsules combined with conbercept ophthalmic injection has an exact efficacy in the treatment of diabetic retinopathy with macular edema.It has obvious advantages in improving visual acuity and fundus microcirculation,and has good safety.

Aim To explore anti-inflammatory mecha-nism of urolithin A(Uro A)based on the miRNA155-5p-regulated MAPK/NF-κB pathway in a lipopolysac-charide(LPS)-stimulated RAW264.7 inflammatory cell model.Methods The mRNA expression of miR-15-5p,p38 MAPK,JNK and ERK was detected by transfection of overexpression of miR-155-5p-mimics and miR-NC into LPS-induced RAW264.7 cells,and the miR-15-5p,p38 MAPK,JNK,and ERK mRNA expressions in the cells were detected by RT-qPCR.The effect of Uro A on cell viability was detected by MTT assay.The NO content in cell supernatant was detected by Griess assay.The cell supernatant PGE2,IL-6,IL-1 β and TNF-α expression levels were detec-ted by ELISA.The iNOS,COX-2,TLR4,and the MAPK/NF-κB pathway-related protein expression lev-els were detected by Western blot.Results The p38 MAPK,JNK and ERK mRNA expression levels were significantly higher in the miRNA155-5p overexpres-sion group than those in the miR-NC group(P＜0.01).Compared with the model group,Uro A signif-icantly inhibited miRNA155-5p,NO,PGE2,TNF-α,IL-1β,and IL-6 levels(P＜0.01)as well as de-creased the expression levels of iNOS and COX-2 pro-teins(P＜0.01)in a concentration-dependent man-ner.Moreover,Uro A could significantly inhibit the expression levels of TLR4 protein and the expression levels of phosphorylation levels of p38 MAPK,JNK,NF-κB p65,and IκBα proteins in LPS irritated RAW264.7 cells(P＜0.05).However,Uro A did not show a significant inhibitory effect on ERK1/2 pro-tein phosphorylation.Conclusion Uro A could signif-icantly inhibit LPS-induced inflammatory response,and its mechanism may be related to miRNA155-5p-mediated TLR4/MAPK/NF-κB signaling pathway.

Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.

Objective:To explore the efficacy and prognosis factors of acute myeloid leukemia with a combination therapy of venetoclax.Methods:A retrospective analysis was performed on the clinical data of AML patients treated with a combination therapy of venetoclax from March 2020 to April 2023 in the First Hospital of Lanzhou University.The efficacy,adverse reactions and survival were observed,and the influencing factors were analyzed.Results:A total of 74 AML patients were included in this study,including 43 initially treated AML and 31 relapsed or refractory AML(R/R AML).The median age of 43 initially treated AML patients was 65 years old,the composite complete remission(cCR)rate was 67.4％(29/43),the objective response rate(ORR)was 72.1％(31/43),and the median overall survival(OS)was 17.3 months.The median age of 31 R/R AML patients was 51 years old,with a cCR rate of 38.7％(12/31),an ORR of 58.1％(18/31),and a median OS of 7.1 months.Sex,the blood cell count before VEN,gene mutation and prognosis stratification were related to whether to obtain cCR.Failure to obtain cCR was an independent risk factor for adverse outcomes.Conclusion:A combination therapy of venetoclax is safe and efficacious for AML.Its efficacy and survival are affected by molecular biology,cytogenetics and other factors.