OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors（SGLT-2i） in patients with heart failure with preserved ejection fraction（HFpEF） in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics， comorbidities， and differences in drug treatment were compared between the two groups. Based on univariate analysis， multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF， followed by further stratified analysis. RESULTS Among 358 HFpEF patients， the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR＝9.063，95%CI（4.924-16.679） ] ， atrial fibrillation [OR＝3.135，95%CI（1.590-6.178） ] ， coronary artery heart disease [OR＝1.888，95%CI（1.072-3.327） ] and the use of loop diuretics [OR＝3.822， 95%CI （1.588-9.200） ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF （ P ＜0.05）. The results of the stratified descriptive analysis were consistent with those of the multivariate analysis， showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM，atrial fibrillation， coronary artery heart disease， and those receiving loop diuretics （ P ＜0.05）； whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function （ P ＞0.05）. CONCLUSIONS In the real-world clinical practice， the utilization of SGLT-2i in patients with HFpEF remains suboptimal， and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes， atrial fibrillation， coronary artery heart disease， and the use of loop diuretics.

Breast cancer is one of the most common malignant tumors among women worldwide, with an increasing incidence rate year by year, making it a significant public health concern. With the continuous advancement of tumor biology research, N 6-methyladenosine (m 6A) modification, as an important form of RNA modification, has attracted growing attention. The m 6A modification, the most prevalent RNA modification in eukaryotes, occurs in almost all types of RNA and plays a critical role in the occurrence, progression, and metastasis of breast cancer. It influences cell proliferation, apoptosis, and alterations in the tumor microenvironment, though the specific mechanisms underlying these effects require further in-depth investigation. Moreover, the specific patterns of m 6A modification demonstrate its potential as a novel biomarker for breast cancer, which could provide new directions for early diagnosis and prognosis evaluation.

[Objective] To analyze the prognostic value of prostate cancer (PCa) pyroptosis-related genes (PRGs) using gene expression databases and to explore the regulatory mechanism of nucleotidebinding oligomerization domain-like receptor containing pyrin domain 1 (NLRP1) in the pyroptosis of PCa cells. [Methods] Fragments per kilobase of exon model per million reads mapped (FPKM) data and clinical information from PCa and adjacent tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were obtained. Differentially expressed PRGs between PCa and adjacent tissues, classified subtypes and plotted survival curves were analyzed. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis were conducted to screen prognosis-related PRGs, risk scores were calculated, and a prognostic risk model was constructed and validated. Patients were divided into high and low risk groups based on the median risk scores from the training and validation sets, and gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis were conducted on differentially expressed PRGs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of NLRP1 in PCa cell lines, and pyroptosis was induced in DU145 and LNCaP cells while morphological changes were observed. Western blot (WB) was performed to detect the expression of pyroptosis-related molecules. [Results] A total of 6 prognostic-related PRGs were obtained, including CHMP4C, CYCS, GPX4, GSDMB, NLRP1, and PLCG1. The risk score was positively correlated with the risk of recurrence but negatively correlated with the progression-free survival (P<0.001). The area under the receiver operating characteristic curves (AUCs) for the training set at 1, 3, and 5 years were 0.769 (95%CI: 0.652-0.878), 0.804 (95%CI: 0.736-0.882), and 0.772 (95%CI: 0.631-0.905), respectively, while those for the validation set were 0.731 (95%CI: 0.647-0.826), 0.753 (95%CI: 0.674-0.818), and 0.763 (95%CI: 0.626-0.849), respectively. Differences in expression levels of the 6 PRGs were observed between the high and low risk groups in both the training and validation sets (P<0.05). Cox regression analysis showed that T stage, prostate specific antigen (PSA), Gleason grade, and risk score were independent predictors of PCa prognosis (P<0.05). Differences in risk scores were observed among patients of different ages, T stages, and Gleason grades (P<0.05). NLRP1 was found to be lowly expressed in PCa cell lines and was involved in the regulation of pyroptosis in DU145 and LNCaP cells. [Conclusion] The prognostic risk model constructed based on PRGs has a certain predictability for the prognosis of PCa patients, and NLRP1 may be involved in the regulation of pyroptosis in PCa cells.

Objective To analyze the efficacy of the"sandwich"technique for treating varicocele(VC).Methods A total of 310 patients with VC(365 affected veins)were selected and divided into interventional treatment group and non-interventional treatment group.The baseline data,hospitalization data,and 6-month follow-up data of the two groups were analyzed.Results The age of patients in the interventional treatment group was significantly lower than that in the non-interventional treatment group(P＜0.05).The surgical time and hospital stay in the interventional treatment group were significantly lower than those in the non-interventional treatment group(P＜0.05).In the non-interventional treatment group,two patients experienced surgical site infections,and one patient opted for interventional treatment due to recurrence after non-interventional treatment.After surgery,the diameter of the spermatic vein significantly decreased in both the interventional and non-interventional treatment(P＜0.05).Conclusion The"sandwich"technique(embolization coil combined with foam sclerotherapy)is an effective treatment for VC.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective:To investigate the differential expression profiles of long non-coding RNAs(LncRNAs) and messenger RNAs(mRNAs) regulated by soluble dipeptidyl peptidase-4(sDPP4) during vascular smooth muscle cell calcification, and to explore the potential underlying calcification mechanisms.Methods:DPP4 levels in blood vessels and peripheral blood of diabetic patients were measured using Western blotting(WB) and real-time quantitative PCR(RT-qPCR). A cellular calcification model was established by treating human aortic vascular smooth muscle cells(HASMCs) with sDPP4. The effects of sDPP4 on HASMCs were assessed by WB, RT-qPCR, alizarin red staining, and calcium content determination. High-throughput sequencing was performed to analyze the differential expression profiles of LncRNA and mRNA following sDPP4 treatment. Among them, LncRNA ENST00000540293, which exhibited the most pronounced downregulation and was located adjacent to the matrix metalloproteinase-1(MMP-1) gene, was selected for further investigation. The osteogenic transdifferentiation of HASMCs after silencing LncRNA ENST00000540293 was evaluated using WB, RT-qPCR, alizarin red staining, and immunofluorescence-based cytoskeletal staining.Results:DPP4 expression was significantly elevated in both blood vessels and peripheral blood of diabetic patients. sDPP4 stimulation upregulated the protein levels of osteopontin(OPN) and runt-related transcription factor 2(RUNX2) in HASMCs, enhanced alizarin red staining, and increased intracellular calcium deposition. RNA sequencing revealed significant downregulation of LncRNA ENST00000540293 following sDPP4 exposure, while GO and pathway analysis indicated a marked increase in extracellular matrix binding activity(GO: 0050840). Silencing LncRNA ENST00000540293 suppressed α-smooth muscle actin(α-SMA) expression, promoted OPN and RUNX2 expression, increased calcification as shown by positive alizarin red staining, and cytoskeletal staining demonstrated osteogenic transdifferentiation of HASMCs, accompanied by a significant rise in MMP-1 protein level.Conclusion:sDPP4 promotes osteogenic transdifferentiation of HASMCs, potentially by downregulating LncRNA ENST00000540293. MMP-1 may be a potential target regulated by LncRNA ENST00000540293.

Objective:To establish and validate a prediction model based on least absolute shrinkage and selection operator（LASSO）regression and classification and regression tree（CART）algorithm for acute kidney injury（AKI）in PICU.Methods:The prospective derivation cohort consisted of 350 critically ill children admitted to the PICU of Children′s Hospital of Soochow University from September 2020 to January 2021.The external data set consisting of 866 critically ill children admitted to the PICU of Children′s Hospital of Soochow University from February 2021 to February 2022 was employed for the external validation.Clinical data was obtained from the electronic medical record system，including demographic characteristics，laboratory data and the pediatric risk of mortality Ⅲ（PRISM Ⅲ）score.The variables associated with AKI were identified using LASSO regression.Subsequently，a decision tree prediction model was built using the CART algorithm.The predictive value of decision tree prediction model was evaluated using the receiver operating characteristic（ROC）curve，calibration curve，and decision curve analysis.Results:Among the 350 children in the derivation cohort，107（30.6%）developed AKI during the PICU stay；and of 866 children in the external validation cohort，165（19.1%）developed AKI during the PICU stay.The LASSO regression screened 16 candidate variables for further analysis，and the decision tree model ultimately identified 4 variables more closely associated with AKI，including fold change in serum creatinine from baseline，urine volume，PRISM Ⅲ，and C-reactive protein.The decision tree model exhibited high accuracy with AUC of 0.92，0.88，and 0.86 in the training，internal validation，and external validation cohorts，respectively.The model demonstrated good calibration and clinical applicability based on the calibration curve and decision curve analysis.Conclusion:The decision tree model based on the 4 identified clinical indicators，including fold change in serum creatinine from baseline，urine volume，PRISM Ⅲ，and C-reactive protein，is effective for the early prediction of AKI.

Objective To investigate the causal relationship between frailty and epilepsy based on the traditional Chinese medicine(TCM)theory of"epilepsy caused by frailty"utilizing a two-sample Mendelian randomization approach,to enrich the modern connota-tion of the"epilepsy caused by frailty"theory and provide a theoretical basis for treating epilepsy from a frailty perspective in TCM.Methods Data on frailty and epilepsy were extracted from publicly available genome-wide association study summary datasets.Single nucleotide polymorphism(SNP)were selected as instrumental variable under the conditions of P＜5 x 10-8,a linkage disequilibrium co-efficient of 0.001,and a linkage disequilibrium region width of 10000kb.Mendelian randomization analysis was performed using five methods:MR-Egger regression,weighted median,inverse variance weighting,simple mode and weighted mode,with inverse variance weighting as the primary analysis method.The causal relationship between frailty and epilepsy was interpreted using OR and 95％CI.Pleiotropy was assessed using the MR-Egger intercept and MR-PRESSO analysis methods,while heterogeneity was analyzed using MR-Egger Cochran's Q test,and sensitivity analysis was conducted using the leave-one-out method.Results The results of inverse variance weighting and weighted median analysis indicated that there was a positive causal relationship between frailty and epilepsy.This result passed pleiotropy tests,confirming its robustness.Conclusion Frailty is associated with an increased risk of epilepsy,which is consistent with the TCM understanding of"epilepsy caused by frailty".It is suggested that in clinical treatment,besides conventional ap-proaches such as resolving phlegm,eliminating blood stasis,calming wind,and opening orifices,there should be a greater emphasis on tonifying frailty and nurturing the body's vital energy.

Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.

Objective:To investigate the differential expression profiles of long non-coding RNAs(LncRNAs) and messenger RNAs(mRNAs) regulated by soluble dipeptidyl peptidase-4(sDPP4) during vascular smooth muscle cell calcification, and to explore the potential underlying calcification mechanisms.Methods:DPP4 levels in blood vessels and peripheral blood of diabetic patients were measured using Western blotting(WB) and real-time quantitative PCR(RT-qPCR). A cellular calcification model was established by treating human aortic vascular smooth muscle cells(HASMCs) with sDPP4. The effects of sDPP4 on HASMCs were assessed by WB, RT-qPCR, alizarin red staining, and calcium content determination. High-throughput sequencing was performed to analyze the differential expression profiles of LncRNA and mRNA following sDPP4 treatment. Among them, LncRNA ENST00000540293, which exhibited the most pronounced downregulation and was located adjacent to the matrix metalloproteinase-1(MMP-1) gene, was selected for further investigation. The osteogenic transdifferentiation of HASMCs after silencing LncRNA ENST00000540293 was evaluated using WB, RT-qPCR, alizarin red staining, and immunofluorescence-based cytoskeletal staining.Results:DPP4 expression was significantly elevated in both blood vessels and peripheral blood of diabetic patients. sDPP4 stimulation upregulated the protein levels of osteopontin(OPN) and runt-related transcription factor 2(RUNX2) in HASMCs, enhanced alizarin red staining, and increased intracellular calcium deposition. RNA sequencing revealed significant downregulation of LncRNA ENST00000540293 following sDPP4 exposure, while GO and pathway analysis indicated a marked increase in extracellular matrix binding activity(GO: 0050840). Silencing LncRNA ENST00000540293 suppressed α-smooth muscle actin(α-SMA) expression, promoted OPN and RUNX2 expression, increased calcification as shown by positive alizarin red staining, and cytoskeletal staining demonstrated osteogenic transdifferentiation of HASMCs, accompanied by a significant rise in MMP-1 protein level.Conclusion:sDPP4 promotes osteogenic transdifferentiation of HASMCs, potentially by downregulating LncRNA ENST00000540293. MMP-1 may be a potential target regulated by LncRNA ENST00000540293.