ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

Objective To investigate the detection rate of non-alcoholic fatty liver disease (NAFLD) and influencing factors in the elderly population undergoing physical examination in Nanjing. Methods People who participated in the elderly physical examination in Nanjing from 2018 to 2023 were selected as the study subjects according to the inclusion and exclusion criteria. Basic information and physical examination results were collected. The t-test and Chi-square test were used to compare the detection status of NAFLD in different characteristic populations, and multivariate logistic regression model was used to analyze influencing factors of NAFLD. Results A total of 41 066 people were included in the study, with a detection rate of 39.55%. The detection rate in males (24.12%) was significantly lower than that in females (49.75%) (χ² = 2702.442, P<0.001). Trend χ² test results showed that the detection rate of NAFLD increased gradually with BMI (χ²_trend = 4084.414, P_trend < 0.001). Multivariate logistic regression analysis showed that female (OR = 3.055, 95% CI : 2.911-3.206), primary school or below (OR = 1.075, 95% CI : 1.009-1.146), unmarried (OR = 1.107, 95% CI : 1.039-1.179), BMI (18.5kg/m²-23.9 kg/m²: OR = 4.876, 95% CI :3.340-7.119; 24.0 kg/m²-27.9 kg/m²: OR = 15.324, 95% CI : 10.503-22.358; ≥28.0 kg/m²: OR = 37.433, 95% CI : 25.591-54.753), hypertension (OR = 1.095, 95% CI : 1.040-1.153), diabetes mellitus (OR = 1.317, 95% CI :1.250-1.387), and dyslipidemia (OR = 1.574, 95% CI : 1.501-1.652) were risk factors for NAFLD (all P<0.05). Conclusion The detection rate of NAFLD in the elderly population undergoing physical examinations in Nanjing is relatively high. Women, unmarried people, people with low education, overweight and obesity, and people with hypertension, diabetes, and dyslipidemia are the high-risk groups.

Objective To explore the clinical values of non-invasive myocardial work (MW) and tissue motion annular displacement (TMAD) in evaluation of anthracycline therapy-related cardiac dysfunction in patients with non-Hodgkin lymphoma. Methods A total of 62 patients with non-Hodgkin lymphoma who received standardized chemotherapy based on doxorubicin. Two and three dimensional transthoracic echocardiography, along with two dimensional speckle tracking echocardiography, were performed one day before chemotherapy and at 3, 6, and 9 months after chemotherapy to assess left ventricular ejection fraction, global longitudinal strain (GLS), MW parameters, and TMAD. Logistic regression analysis was used to evaluate the risk factors for cancer therapy-related cardiac dysfunction (CTRCD). The receiver operating characteristic curve was used to assess the diagnostic values of MW- and TMAD-related parameters for CTRCD. Results Compared to baseline, GLS, global work index (GWI), global constructive work (GCW), global work efficiency (GWE), TMAD at midpoint (TMADmid), and TMADmid percentage of left ventricular long-axis diameter (TMADmid%) decreased at 3 months after chemotherapy, while global wasted work (GWW) increased at 6 months after chemotherapy (P＜0.05). Logistic regression analysis showed that the relative reduction in GLS and TMADmid% at 3 months after chemotherapy were independent predictors for CTRCD （P＜0.05), while MW parameters were not independent predictors for CTRCD. GLS reduction≥10.3% and TMADmid% reduction≥15.8% at 3 months after chemotherapy predicted CTRCD with 0.866 and 0.824 of area under the curve (AUC), 92% and 75% of sensitivity, and 74% and 80% of specificity, respectively. AUC of combination of two indexes improved to 0.905, with 75% of sensitivity and 90% of specificity. Conclusions In non-Hodgkin lymphoma patients, the combination of GLS and TMADmid% is helpful of predicting CTRCD early, TMAD may be a novel diagnostic index for CTRCD, and GLS has superior predictive performance than MW for CTRCD.

Objective: To investigate factors influencing perioperative blood transfusion in patients with scarred uterus during pregnancy undergoing cesarean section, construct and validate a transfusion risk prediction model, and provide evidence for preoperative assessment and blood management. Methods: Clinical data of 405 patients undergoing cesarean section for scarred uterus during pregnancy at the First Affiliated Hospital of Xi'an Jiaotong University from January 2020 to December 2024 were retrospectively collected. The dataset was randomly divided into a training set (n=284) and a validation set (n=121) at a 7∶3 ratio. Within the training set, Firth-penalized logistic regression was employed for multivariate analysis to identify independent factors influencing perioperative blood transfusion and construct a predictive model. Model performance was evaluated in the validation set. Results: Multivariate Firth regression analysis showed that severe placenta previa (OR=75.566, 95%CI: 8.603-9979.174) and placenta accreta (OR=4.591, 95%CI: 1.120-19.416) were independent risk factors for perioperative blood transfusion, while preoperative red blood cell count (OR=0.189, 95%CI: 0.083-0.405) and fibrinogen levels (OR=0.588, 95%CI: 0.395-0.855) were protective factors. The predictive model constructed based on these four variables demonstrated good discriminatory performance, with areas under the receiver operating characteristic curves of 0.803 (95%CI: 0.740-0.867) and 0.753 (95%CI: 0.644-0.862) in the training and validation sets, respectively. Conclusion: For patients with scarred uterus during pregnancy undergoing cesarean section, severe placenta previa and placenta accreta significantly increase the risk of transfusion, while higher preoperative red blood cell count and fibrinogen levels exert a protective effect. The predictive model established in this study facilitates the identification of patients requiring transfusion, thereby enabling preoperative blood preparation and optimized blood management.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

Objective:To explore the association between macrosomia delivery history and adverse pregnancy outcomes in subsequent pregnancies under different stratification of gestational weight gain(GWG).Methods:A retrospective study was conducted on 500 multiparous women with a history of macrosomia delivery who gave birth at The Second Hospital of Jilin University from January 2020 to November 2023.Meanwhile,1500 multiparous women without a history of delivering macrosomic infants were selected as the control group through 1∶3 matc-hing based on age(±1 year).The differences in general characteristics,GWG,and pregnancy outcomes be-tween the two groups were compared.According to the appropriate GWG values recommended by Chinese health industry standards,pregnant women in both groups were classified into insufficient GWG,appropriate GWG,and excessive GWG.Multivariate Logistic regression analysis was used to compare the relationship be-tween a history of macrosomia delivery and adverse pregnancy outcomes under different GWG stratifications.Re-sults:The History of macrosomia group had significantly higher rates of excessive GWG(50.60%vs.48.13%),incidence of gestational diabetes mellitus(GDM)(23.40%vs.17.07%),rate of cesarean section(60.20%vs.45.33%),and rate of macrosomia(26.60%vs.7.87%)compared to the control group(P<0.05).Multivariate Logistic regression analysis showed that a history of macrosomia delivery was an independent risk factor for GDM,cesarean section,and macrosomia in subsequent pregnancies(aOR>1,P<0.05).Stratified analysis based on GWG revealed that,compared with the control group,regardless of the GWG status,the risk of cesare-an section and macrosomia was higher in women with a history of macrosomia delivery(aOR>1,P<0.05).Mo-reover,for those with a history of macrosomia delivery and excessive weight gain during pregnancy,the risk of preeclampsia(aOR 3.167,P<0.05)and GDM(aOR 1.661,P<0.05)was significantly increased.When the GWG was appropriate for pregnant women with a history of macrosomia delivery,there was no significant correla-tion between a history of macrosomia delivery and preeclampsia or GDM(P>0.05).Conclusions:A history of macrosomia delivery increased the risk of multiple adverse pregnancy outcomes,such as GDM,cesarean section,and macrosomia.For multiparous women at different GWG levels,the risk of cesarean section and macrosomia was significantly increased in those with a history of macrosomia delivery.When GWG was appropriate,a history of macrosomia delivery was not found to be an independent risk factor for preeclampsia and GDM.

Objective:To investigate the application value of dual-energy computer tomo-graphy (CT) multi-parameter imaging in predicting the pathological grade of pancreatic ductal adeno-carcinoma (PDAC).Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 147 patients with PDAC who were admitted to The Fifth Affiliated Hospital of Wenzhou Medical University from January 2017 to August 2023 were collected. There were 102 males and 45 females, aged (59±10)years. All patients underwent preoperative dual-energy CT examination and postoperative histopathological examination. The 147 patients were divided into a training set of 103 cases and a test set of 44 cases by stratified random sampling at a ratio of 7∶3. The training set was used to construct the prediction model, and the test set was used to verify the effectiveness of prediction model. Observation indicators: (1) analysis of factors affecting the pathological grade of PDAC patients in the training set; (2) construction and evaluation of the fusion prediction model for pathological grade of PDAC. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. The performance of the model was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. The Delong test was used to analyze the effec-tiveness of model. The calibration curve and decision curve of Hosmer-Lemeshow test were used to evaluate the consistency and clinical application value of the nomogram, respectively. Results:(1) Analysis of factors affecting the pathological grade of PDAC patients in the training set. Results of multivariate analysis showed that tumor cystic necrosis, vascular invasion, standardized iodine concentration (NIC) in venous phase, effective atomic number (Zeff) in venous phase, and energy spectrum curve slope (λ HU) in venous phase were all independent factors affecting the pathological grade of PDAC patients in the training set ( odds ratio=4.326, 3.887, 4.155, 5.389, 3.164, 95% confidence interval as 1.167-16.033, 1.111-13.592, 1.707-10.113, 1.284-22.613, 1.247-8.028, P<0.05). (2) Construction and evaluation of the fusion prediction model for pathological grade of PDAC. Accor-ding to the results of multivariate analysis, tumor cystic necrosis, vascular invasion, NIC in venous phase, Zeff in venous phase and λ HU in venous phase were all included to construct the clinical-imaging fusion prediction nomogram model. The AUC, accuracy, sensitivity and specificity of the fusion prediction model in the training set were 0.938 (95% confidence interval as 0.896-0.981), 87.38%, 89.74% and 85.94%, respectively. The above indicators of the fusion prediction model in the test set were 0.893 (95% confidence interval as 0.802-0.985), 84.09%, 82.35% and 85.19%, respectively. Results of Delong test showed that there was no significant difference in AUC between the training set and the test set ( Z=0.343, P>0.05). Results of Hosmer-Lemeshow test showed that the fusion prediction model had a good fit in the training set and the test set ( χ2=3.042, 7.545, P>0.05). Results of calibration curve showed that the predictive ability of the fusion prediction model was good. Conclusions:Multiple parameters in venous phase of the dual-energy CT can be used as imaging markers for preoperative evaluation of the pathological grade of patients with PDAC. Establishing a clinical-imaging fusion prediction model can effectively predict the pathological grade of PDAC.

Objective To explore the effect of curcumin(CUR)on oxidative damage of keratinocytes induced by ultraviolet B(UVB)irradiation through Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/nucleotide-binding oligomerization domain-containing protein 3(NLRP3)signaling pathway.Methods Human keratinocytes of HaCaT were cultured normally in vitro,and the keratinocyte oxidative damage model was established by the irradiation of 57 mJ/cm2 UVB.The cells with normal culture were as the control group,the cells treated after modeling were as the UVB group,the cells treated with 5 μmol/L CUR after modeling were as the CUR group,the cells treated with 100 μg/L TLR4 inhibitor of TAK-242 after modeling were as the TAK-242 group,and the cells treated with 5 μmol/L CUR and 100 nmol/L TLR4 activator of lipopolysaccharide(LPS)were as the CUR+LPS group.qRT-PCR was applied to detect the relative expression levels of TLR4,NF-κB,and NLRP3 mRNAs of cells in each group.CCK-8 was applied to detect the cell proliferation in each group.The relative content of reactive oxygen species(ROS),the viabilities of superoxide dismutase(SOD)and catalase(CAT),and the concentrations of glutathione(MDA)and glutathione(GSH)of cells in each group were detected by fluorescence assay according to the kit instruction.ELISA kit was used to detect the expression of inflammatory factors of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)of cells in each group.Flow cytometry was applied to detect the cell apoptosis in each group.Western blot was applied to detect the expression of proliferation related protein of proliferating cell nuclear antigen(PCNA),apoptosis related proteins[B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)],and TLR4/NF-κB/NLRP3 signaling pathway related proteins(TLR4,NF-κB and NLRP3)of cells in each group.Results Compared with the Control group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the UVB group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Compared with the UVB group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the TAK-242 group and CUR group increased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 decreased(P<0.05).Compared with the CUR group,the cell survival rate,the expression levels of PCNA and Bcl-2 proteins,the viabilities of SOD and CAT,and the GSH concentration in the CUR+LPS group decreased,while the apoptosis rate,the level of Bax protein,the relative content of ROS,the concentration of MDA,the levels of TNF-α and IL-1β,and the mRNA and protein levels of TLR4,NF-κB and NLRP3 increased(P<0.05).Conclusion CUR can increase the antioxidant stress level of keratinocytes,alleviate inflammatory response,promote cell proliferation,and improve cell damage caused by UVB irradiation,which may be related to the inhibition of TLR4/NF-κB/NLRP3 signaling pathway.