Objective:To explore the relationship between serum ferritin(SF), triglyceride-glucose(TyG) index, and metabolic dysfunction-associated fatty liver disease(MAFLD), and to assess their interaction on MAFLD risk in the health checkup population.Methods:A cross-sectional analysis was conducted with 1 439 participants from the Health Management Centre of Nanjing Drum Tower Hospital in 2022. Data were collected through physical examination, laboratory tests, and abdominal imaging. Differences in metabolic indicators, SF, and TyG index were compared between MAFLD and non-MAFLD groups. Logistic regression analysis was used to assess the associations of SF and TyG index with MAFLD, and their on MAFLD interaction was evaluated. Results:Both SF and TyG index were significantly higher in the MAFLD group between than those in the non-MAFLD group( P<0.05). After adjusting for sex, age, history of hypertension, history of diabetes, body mass index, waist circumference, haemoglobin, alanine aminotransferase, aspartate aminotransferase, and uric acid, the SF and TyG index were positively associated with the risk of MAFLD[ OR(95% CI), SF: 1.00(1.00-1.00); TyG index: 2.98(2.19-4.06). The additive interaction analysis showed that the risk of MAFLD was significantly higher in the G4 group(SF≥135.4 ng/mL, TyG index≥8.52) compared to the G1 group(SF<135.4 ng/mL, TyG index<8.52) [ OR 4.43(95% CI 2.70-7.25)]. Conclusions:Elevated SF and TyG index were independently associated with increased risk of MAFLD, with a significant synergistic interaction between the two.

Objective To investigate the role of JAK2/STAT3 signaling pathway mediated Treg/Th17 imbalance in children with cow's milk protein allergy and the effect of dietary avoidance on the imbalance.Methods A total of 103 children with cow's milk protein allergy in the hospital were enrolled and divided in-to the IgE-mediated group(n=38)and the non-IgE-mediated group(n=65).All patients underwent a 3-month strict dietary avoidance intervention.A total of 100 healthy children who underwent health checkups at the hospital's physical examination center during the same period,with no history of food allergy or other im-mune-related diseases,were selected as the healthy control group.The percentages of Treg and Th17 cells were measured by flow cytometry.The mRNA expression levels of JAK2,STAT3,SOCS1,and SOCS3 were determined by qPCR.Differences between groups,changes before and after dietary avoidance,and correlations between these indicators and clinical symptoms were analyzed using Pearson's test.Results At baseline,both the IgE-mediated group and the non-IgE-mediated group had significantly lower Treg percentages and SOCS1/SOCS3 mRNA levels,and higher Th17 percentages and JAK2/STAT3 mRNA levels compared to the healthy control group(P＜0.05).After dietary avoidance,Treg percentages and SOCS1/SOCS3 mRNA levels in-creased,while Th17 percentages and JAK2/STAT3 mRNA levels decreased in the IgE-mediated group and the non-IgE-mediated group(P＜0.05).The increase of Treg percentage and the decrease of Th17 percentage in the non-IgE-mediated group were greater than in the IgE-mediated group,whereas the increases of SOCS1 and SOCS3 mRNA levels were smaller in the non-IgE-mediated group(P＜0.05).Logistic regression identified JAK2,STAT3,SOCS1,and SOCS3 mRNA levels as factors influencing Treg and Th17 percentages(P＜0.05).Pearson correlation analysis revealed that allergic symptom scores and serum milk-specific IgE levels were positively correlated with JAK2/STAT3 mRNA levels and Th17 percentage,and negatively correlated with SOCS1/SOCS3 mRNA levels,Treg percentage,and the Treg/Th17 ratio(P＜0.05).Conclusion Dieta-ry avoidance can modulate the activity of JAK2/STAT3 signaling pathway,with a more pronounced improve-ment in non-IgE-mediated cow's milk protein allergy.

Objective To explore the influencing factors of prognosis and nursing strategies in sepsis combined with gastrointestinal dysfunction.Methods The clinical data of 102 patients with sepsis and gastrointestinal dysfunction who were admitted to Traditional Chinese Medicine Hospital of Guangdong Province(The Second Affiliated Hospital of Guangzhou University of Chinese Medicine)between June 2022 and December 2023 were retrospectively analyzed.According to the prognosis within 30 d,the patients were assigned to death group(n=38)or survival group(n=64).Clinical indexes were compared between the two groups.The main influencing factors of prognosis were analyzed by Logistic regression,and targeted nursing strategies were summarized.Results The mortality in the patients with sepsis and gastrointestinal dysfunction was 37.25%(38/102).Univariate analysis showed that age,Sequential Organ Failure Assessment(SOFA)score,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,gastrointestinal failure(GIF)score,and stay time in ICU were all influencing factors of prognosis in patients with sepsis and gastrointestinal dysfunction(all P<0.05).Logistic regression analysis showed that age≥65 years,SOFA score>6,APACHEⅡscore>17,GIF score>3,and stay time in ICU>7 d were independent risk factors of poor prognosis in patients with sepsis and gastrointestinal dysfunction(all P<0.05).Conclusion The poor prognosis of patients with sepsis and gastrointestinal dysfunction is related to age,SOFA score,APACHEⅡscore,GIF score,and stay time in ICU.It is essential to take preventive and nursing measures for these risk factors to reduce the incidence of poor prognosis.

Objective:To explore the relationship between serum ferritin(SF), triglyceride-glucose(TyG) index, and metabolic dysfunction-associated fatty liver disease(MAFLD), and to assess their interaction on MAFLD risk in the health checkup population.Methods:A cross-sectional analysis was conducted with 1 439 participants from the Health Management Centre of Nanjing Drum Tower Hospital in 2022. Data were collected through physical examination, laboratory tests, and abdominal imaging. Differences in metabolic indicators, SF, and TyG index were compared between MAFLD and non-MAFLD groups. Logistic regression analysis was used to assess the associations of SF and TyG index with MAFLD, and their on MAFLD interaction was evaluated. Results:Both SF and TyG index were significantly higher in the MAFLD group between than those in the non-MAFLD group( P<0.05). After adjusting for sex, age, history of hypertension, history of diabetes, body mass index, waist circumference, haemoglobin, alanine aminotransferase, aspartate aminotransferase, and uric acid, the SF and TyG index were positively associated with the risk of MAFLD[ OR(95% CI), SF: 1.00(1.00-1.00); TyG index: 2.98(2.19-4.06). The additive interaction analysis showed that the risk of MAFLD was significantly higher in the G4 group(SF≥135.4 ng/mL, TyG index≥8.52) compared to the G1 group(SF<135.4 ng/mL, TyG index<8.52) [ OR 4.43(95% CI 2.70-7.25)]. Conclusions:Elevated SF and TyG index were independently associated with increased risk of MAFLD, with a significant synergistic interaction between the two.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective To evaluate the relationship between ceftazidime-avibactam(CAZ-AVI)blood concentrations and efficacy in critically ill patients and to investigate the factors influencing blood levels.Methods The CAZ-AVI trough concentrations(Cmin)were detected in 29 patients who received CAZ-AVI treatment for at least 48 hours.The clinical materials of the patients were collected together for retrospective analysis.Results The Cmin of ceftazidime(CAZ)and avibactam(AVI)were(50.95±5.17)and(7.52±0.96)mg·L-1 in the effective group and(31.16±7.03)and(5.37±1.32)mg·L-1 in the ineffective group,respectively.The Cmin of CAZ in the effective group was significantly higher than in the ineffective group(P<0.05),and there was no significant difference in AVI Cmin between the two groups(P>0.05).Spearman's correlation analysis showed that CAZ Cmin was positively correlated with clinical efficacy(P<0.05),and no correlation between AVI Cmin and clinical efficacy(P>0.05).The optimal CAZ Cmin threshold was 24.59 mg·L-1.Multiple linear regression analysis showed that age and creatinine clearance was significantly correlated with the Cmin of CAZ,and creatinine clearance was significantly correlated with AVI Cmin(P<0.05).Conclusions The Cmin of CAZ correlates with efficacy,and it may be more beneficial for clinical treatment to keep the concentration of CAZ-AVI always greater than the minimum inhibitory concentration during the dosing interval.The creatinine clearance should be fully considered when optimizing CAZ-AVI dosage in critically ill patients.

Objective:To elucidate the complete genomic characteristics of the Akabane virus (AKV) DHL10M117 strain and the Tibet orbivirus (TIBOV) DH10M1019 strain, isolated from mosquito specimens collected in 2010 from Dehong prefecture, Yunnan province.Methods:The complete RNA virus sequences were obtained using metatranscriptomics and high-throughput sequencing.Results:The complete genome sequences of the DHL10M117 strain, consisting of the S, M, and L gene segments with lengths of 856 bp, 4 309 bp, and 6 869 bp, respectively, were acquired. Phylogenetic analysis indicated that the DHL10M117 strain is an AKV strain, closely related to the AKV strain DHL10M110, isolated from Yunnan. The S and M segment phylogenetic trees revealed that the strain is closely related to AKV strains circulating in southern China and Japan, and distantly related to strains from Australia, suggesting that this strain belongs to the Asian lineage with distinct regional characteristics. Homology analysis confirmed that the gene sequences of the S, M, and L segments of the DHL10M117 strain showed 100% nucleotide and amino acid identity with the DHL10M110 strain. Additionally, the complete genome sequences of the DH10M1019 strain, comprising ten gene segments (Seg-1 to Seg-10) with lengths of 3 950 bp, 2 904 bp, 2 769 bp, 1 978 bp, 1 772 bp, 1 638 bp, 1 165 bp, 1 142 bp, 1 103 bp, and 832 bp respectively, were obtained. Phylogenetic analysis showed that DH10M1019 is a TIBOV strain, with eight gene segments (Seg-1 to Seg-4, Seg-6, Seg-8 to Seg-10) clustering with known strains in the same major branch, while Seg-5 and Seg-7 formed distinct branches, independent of known reference strains, suggesting that DH10M1019 may represent a new serotype of TIBOV.Conclusions:Through complete genome sequence analysis, it was confirmed that DHL10M117 and DH10M1019 are AKV and TIBOV, which provided a scientific basis for the epidemiological characterisation, pathogenicity analysis and investigation of the two viruses.

Objective:The complete genome sequence characteristics of Quang Binh virus (QBV) and Manglie virus (MaV) isolated from mosquitoes in Daluo Town, Menghai county.Methods:Mosquitoes collected in Daluo Town, Menghai county in July 2012 were used for virus isolation. The nucleic acid was extracted from the supernatant of Aedes albopictus cell line (C6/36) showing cytopathic effect (CPE) positivity, and was sent to a company for sequencing after library construction. Phylogenetic and nucleotide/amino acid sequence similarity analysis was performed using DNAStar, Maff, and other softwares.Results:RNA libraries of strains BNDL1205 and BNDL1227 yielded 67 336 692 and 61 259 266 qualified gene sequences (reads) respectively. After assembly and alignment, sequences of lengths 10 865 bp and 10 864 bp were obtained. Sequence analysis indicated that they belong to QBV, with strains BNDL1205 and BNDL1227 clustering with QBV (strain VN180) isolated from Vietnam on the same evolutionary branch, sharing nucleotide similarity of 84.2% and 84.1%, and amino acid similarity of 94.6% and 94.4% respectively. RNA library of strain BNDL1223 yielded 48 622 610 qualified reads. After assembly and alignment, three gene fragments (Contigs) matched MaV. Further merging using SeqMan produced a complete nucleotide sequence of 9 219 bp. Analysis revealed that strain BNDL1223 is closely related to MaV isolated in Yunnan in 2018, sharing nucleotide similarity of 97.8% and amino acid similarity of 99.2%.Conclusions:During the investigation of arboviruses in mosquitoes in Daluo Town, Menghai county, three strains of viruses were identified: 2 strains of QBV and 1 strain of MaV. Local mosquitoes play a significant role in the transmission of QBV and MaV, necessitating enhanced monitoring and detection of local vector mosquitoes.

Objective To investigate the association between the immune microenvironment and gene expression in endometrial cancer(EC)and discuss its predictive value for prognosis,and to identify critical immune-related genes through bioinformatics analysis and machine learning techniques and construct a prognostic model for providing new directions for personalized treatment of EC.Methods Based on data from the Cancer Genome Atlas(TCGA)program,tools such as DESeq2,edgeR,and limma were utilized to screen for differentially expressed genes.Immune-related genes were selected by integrating data from the Immunology Database and Analysis Portal(ImmPort).Machine learning algorithms including Lasso regression,univariate feature selection,Boruta and random forest were employed to refine the selection of feature genes.Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the genes,followed by construction of a risk score model.Additionally,tumor immune infiltration was analyzed using CIBERSORT algorithm,and key gene expressions were validated through immunohistochemistry.Results The intersection of 3 difference analysis results and immune-related genes identified 62 differentially expressed immune genes,and 25 potential biomarkers which were selected by a variety of machine learning models were considered as prognosis related genes.Univariate and multivariate Cox regression analyses confirmed that INHBE,SLURP1 and TNFSF11 genes were significantly associated with survival in EC patients.The constructed risk score model effectively distinguished the survival rate of different prognostic groups,and was related to the degree of immune cell infiltration.Immunohistochemical analysis further verified the differences in the expression of these genes between tumor and normal tissues.Conclusion INHBE,SLURP1 and TNFSF11 are key prognostic biomarkers in EC immune microenvironment,and their expression levels are closely associated with immune cell infiltration and patient survival rate,providing theoretical basis for EC precision medicine.

Objective To investigate the association between the immune microenvironment and gene expression in endometrial cancer(EC)and discuss its predictive value for prognosis,and to identify critical immune-related genes through bioinformatics analysis and machine learning techniques and construct a prognostic model for providing new directions for personalized treatment of EC.Methods Based on data from the Cancer Genome Atlas(TCGA)program,tools such as DESeq2,edgeR,and limma were utilized to screen for differentially expressed genes.Immune-related genes were selected by integrating data from the Immunology Database and Analysis Portal(ImmPort).Machine learning algorithms including Lasso regression,univariate feature selection,Boruta and random forest were employed to refine the selection of feature genes.Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the genes,followed by construction of a risk score model.Additionally,tumor immune infiltration was analyzed using CIBERSORT algorithm,and key gene expressions were validated through immunohistochemistry.Results The intersection of 3 difference analysis results and immune-related genes identified 62 differentially expressed immune genes,and 25 potential biomarkers which were selected by a variety of machine learning models were considered as prognosis related genes.Univariate and multivariate Cox regression analyses confirmed that INHBE,SLURP1 and TNFSF11 genes were significantly associated with survival in EC patients.The constructed risk score model effectively distinguished the survival rate of different prognostic groups,and was related to the degree of immune cell infiltration.Immunohistochemical analysis further verified the differences in the expression of these genes between tumor and normal tissues.Conclusion INHBE,SLURP1 and TNFSF11 are key prognostic biomarkers in EC immune microenvironment,and their expression levels are closely associated with immune cell infiltration and patient survival rate,providing theoretical basis for EC precision medicine.