ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

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.

Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P＜0.05,P＜0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P＜0.01,P＜0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P＜0.05,P＜0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P＜0.05,P＜0.01 or P＜0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.

Objective:To analyse the distribution and antimicrobial resistance profile of clinical bacterial isolates in Anhui province.Methods:Surveillance data was collected from 83 members of the Anhui Antimicrobial Resistance Surveillance Network（HuiNet）during October 2022 to September 2023，to analyze the resistance of major bacteria to commonly used antibiotics and the detection of clinically common drug-resistant bacteria. The data was analyzed using WHONET 5.6 and SPSS 25.0 software.Results:A total of 201 647 clinical bacteria isolates were collected，with Gram-negative bacteria accounting for 74.8%（150 847/201 647）. The most prevalent Gram-positive bacterial strains were Staphylococus aureus（32.8%，16 648/50 800），followed by Staphylococcus epidermidis（14.0%，7 098/50 800）， Enterococcus faecalis（10.7%，5 458/50 800）， Enterococcus faecium（9.1%，4 613/50 800）and Staphylococcus hominis（7.4%，3 778/50 800）；the most prevalent Gram-negative bacterial strains were Escherichia coli（28.9%，43 577/150 847），followed by Klebsiella pneumoniae（22.5%，34 006/150 847）， Pseudomonas aeruginosa（14.7%，22 171/150 847）， Acinetobacter baumannii complex（9.4%，14 194/150 847）and Enterobacter cloacae（3.5%，5 235/150 847）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococcus aureus（MRCNS）were 39.5%（6 442/16 325）and 75.7%（12 343/16 312），respectively. No vancomycin- and teicolanin-resistant Staphylococcus were detected. The prevalence of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis were 0.5% and 0.6%，respectively. The prevalence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae（CR-KPN）were 1.9%（805/42 956）and 11.7%（3 950/33 761），respectively. The resistance rate of CR-KPN to tigecycline was 3.9%. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CR-PAE）and Acinetobacter baumannii（CR-ABA）complex were 18.4%（3 936/21 447）and 62.9%（8 649/13 744），respectively，with low resistance rate to polycolistin B（6.9% and 1.7%，respectively）. The detection rates of MRSA，CR-ABA complex，third-generation cephalosporin-resistant Escherichia coli（CTX/CRO-R-ECO）and quinolone-resistant Escherichia coli（QNR-ECO）in northern Anhui were the highest（50.3%，72.9%，59.2% and 55.6%，respectively），which were higher than those in central and southern Anhui（ χ2=112.734 and 575.069，132.747 and 233.885，93.986 and 471.209，60.062 and 230.669，all P<0.001），and the detection rate in central Anhui was higher than that in southern Anhui（ χ2=278.671，29.219，207.395 and 80.267，all P<0.001）. The detection rates of CR-KPN and thirdgeneration cephalosporinresistant Klebsiella pneumoniae（CTX/CRO-R-KPN）in central Anhui were the highest（15.5% and 33.3%，respectively），which were higher than those in northern and southern Anhui（ χ2=156.237 and 325.533，76.928 and 180.686，all P<0.001），and the detection rate in northern Anhui was higher than that in southern Anhui（ χ2=32.202 and 25.539， P<0.001）. The detection rates of CTX/CRO-R-ECO and QNR-ECO were the highest in the elderly（55.2% and 55.8%，respectively），which were higher than those in children，and young and middle aged adults（ χ2=23.906 and 120.575，376.404 and 196.612， P<0.001）. The detection rate of CTX/CRO-R-KPN in neonates was the highest（57.1%），which was significantly higher than that in children，adults and the elderly（ χ2=46.141，38.843 and 32.093， P<0.001），and the detection rate in the elderly was higher than that in children and adults（ χ2=13.604 and 13.471， P<0.001）. The detection rates of MRSA and MRCNS were the highest in children（42.8% and 77.8%，respectively），which were higher than those in adults（ χ2=21.766 and 10.704， P<0.001）. Except MRSA and vancomycin-resistant Enterococcus faecium and faecalis，the detection rates of major drug-resistant bacteria in tertiary hospitals were higher than those in secondary hospitals（ P<0.05 or <0.01）. Conclusion:In 2023，the situation of antimicrobial resistance in Anhui province was serious，especially in northern and central Anhui，and targeted drug resistance control measures should be taken according to the monitoring results. At the same time，it is necessary to pay attention to the bacterial resistance in the elderly，newborns and children，and strengthen the rational use of antibiotics by clinicians to curb the spread of drug-resistant bacteria.

Objective:To evaluate the effect of different clear fluid fasting duration on the fluid responsiveness after anesthesia induction in pediatric patients with congenital heart disease.Methods:One hundred pediatric patients with congenital heart disease who underwent elective atrial septal defect or ventricular septal defect correction surgery at Shanghai Children′s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine from December 2023 to February 2024 were selected. They were of either sex, aged 6 months to 3 yr, with a body mass index of 13-19 kg/m 2, and classified as American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ. Patients who adhered to the prescribed preoperative clear fluid fasting regimen, with a fasting duration of 6 h or longer before surgery, were included in the long fasting (LF) group, while those who were prescribed multi-dimensional nutritional solution until 2 h before surgery with a solid fasting duration≥6 h were considered for inclusion in the short fasting (SF) group. The diastolic blood pressure (DBP) was recorded immediately before and after liver compression test at pre-induction of anesthesia and immediately before and after liver compression test at post-induction of anesthesia, and the changes in DBP before and after the liver compression test (ΔDBP) were calculated. Positive fluid responsiveness was defined as an increase in ΔDBP ≥ 6.25%. The positive rate of fluid responsiveness before and after anesthesia induction was calculated. Results:Sixty-four patients were finally included, and both LF and SF groups included 32 cases. Before the induction of anesthesia, the positive rate of fluid responsiveness induced by liver compression was 28.1% in LF group and 18.8% in SF group, and the difference was not statistically significant ( P>0.05). However, after the induction of anesthesia, the positive rate of fluid responsiveness induced by liver compression was 56.3% in LF group and 28.0% in SF group, with a statistically significant difference observed ( P<0.05). Compared with the baseline before anesthesia induction, the positive rate of fluid responsiveness was significantly increased in LF group( P<0.05), and no significant change was found in the positive rate of fluid responsiveness in SF group ( P>0.05). Conclusions:The prolonged clear fluid fasting may lead to an increase in the positive rate of fluid responsiveness following anesthesia induction in pediatric patients with congenital heart disease, presenting as a state of hypovolemia.