ObjectiveTo investigate the effects of Tianma Goutengyin on the tumor necrosis factor-α （TNF-α）/signal transducer and activator of transcription 3 （STAT3）/α1-antichymotrypsin C-terminal tail fragment （α1ACT） signaling pathway and A1-type astrocytes in a rat model of vascular dementia. MethodsSeventy-two male Sprague-Dawley rats were randomly divided into six groups （n=12 per group）： Sham-operated group， model group， Tianma Goutengyin high-， medium-， and low-dose groups （5.13， 10.26， and 20.52 g·kg^-1）， and a nimodipine group （8.1 mg·kg^-1）. The vascular dementia model was established by permanent bilateral common carotid artery occlusion， followed by 4 weeks of intervention. Learning and memory ability were evaluated using the novel object recognition test， and behavioral performance was assessed using the forced swimming test. Levels of interleukin-6 （IL-6） and C-C motif chemokine ligand 2 （CCL2） in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal neuronal morphology was observed by Nissl staining， and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Immunohistochemistry was used to detect positive expression of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， and myelin basic protein （MBP）. Western blot analysis was performed to measure the protein expression levels of TNF-α， TNF receptor 1 （TNFR1）， phosphorylated STAT3 （p-STAT3）， α1ACT， IL-6， complement component 3 （C3）， BDNF， S100 calcium-binding protein A10 （S100A10）， and GFAP in hippocampal tissue. ResultsCompared with the sham-operated group， the model group showed a significantly reduced relative recognition index in the novel object recognition test （P<0.01）， prolonged immobility time and increased immobility frequency in the forced swimming test （P<0.01）. Hippocampal IL-6 and CCL2 levels were significantly increased （P<0.01）. Nissl staining revealed a marked reduction in neuronal number and loss of Nissl bodies （P<0.01）. MBP-positive expression was significantly decreased （P<0.01）， apoptosis was significantly increased （P<0.01）， BDNF-positive expression was significantly reduced （P<0.05）， and GFAP-positive expression was significantly increased （P<0.01）. In addition， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly elevated （P<0.01）， while BDNF and S100A10 expression levels were significantly decreased （P<0.01）. Compared with the model group， all Tianma Gouteng yin dose groups exhibited a significant increase in the relative recognition index （P<0.05）， shortened immobility time and reduced immobility frequency （P<0.05， P<0.01）. IL-6 and CCL2 levels were significantly decreased （P<0.01）， neuronal number was significantly increased （P<0.05， P<0.01）， and MBP-positive expression was significantly enhanced （P<0.01）. Apoptosis was significantly reduced （P<0.01）， BDNF-positive expression was significantly increased （P<0.05）， and GFAP-positive expression was significantly decreased （P<0.01）. Moreover， the protein expression levels of TNF-α， TNFR1， p-STAT3， α1ACT， IL-6， and C3 were significantly decreased （P<0.01）， while BDNF and S100A10 protein expression levels were significantly increased （P<0.01）. ConclusionTianma Goutengyin may inhibit A1-type astrocyte activation in rats with vascular dementia through the TNF-α/STAT3/α1ACT signaling pathway， thereby reducing neuronal apoptosis and improving learning and memory function.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective: To examine the association of joint effect of overweight and obesity with dyslipidemia on left ventricular hypertrophy (LVH) in children, so as to provide scientific evidence for the prevention of early cardiovascular damage in children. Methods: Data were obtained from the second followup crosssectional survey of Huantai Childhood Cardiovascular Health Cohort study in 2021, comprising 1 047 children aged 10-15 years with complete information. Based on overweight and obesity status and dyslipidemia status, all participants were divided into four groups:normal weight with normal lipid levels, normal weight with dyslipidemia, overweight and obesity with normal lipid levels, and overweight and obesity with dyslipidemia. Left ventricular mass index (LVMI) levels and prevalence of LVH across four groups were compared. Multivariate Logistic regression model was used to examine the association of joint effect of overweight and obesity with dyslipidemia on LVH in children. Results: There were significant differences in LVMI levels [(28.66±7.10, 29.63±4.71,31.49±5.86,32.65±4.80)g/m2.7] and prevalence of LVH (4.28%, 12.50%, 22.74%, 31.30%) across four groups (F/χ2=50.76, 90.92, P<0.05). After adjustment for confounding variables such as gender,age,screen time,sleep duration,fruit and vegetable intake,carbonated beverage consumption,physical activity and elevated blood pressure, compared to children with both normal weight and normal lipid levels, the risk of LVH in children with dyslipidemia alone increased (OR=3.27, 95%CI=1.57-6.82，P<0.05). Children with overweight and obesity alone also had a significantly increased risk of LVH (OR=6.33, 95%CI=3.76-10.66), and the highest risk was observed in those with both overweight and obesity with dyslipidemia (OR=9.66, 95%CI=5.35-17.43) (P<0.05). Conclusions The joint effect of overweight and obesity with dyslipidemia is positively correlated with LVH in children. To prevent LVH in children, both overweight and obesity with dyslipidemia should be paid attention to.

Objective: To investigate the association of serum alanine aminotransferase (ALT) with left ventricular hypertrophy (LVH) in adolescents, and to provide scientific evidence for the early screening and intervention strategy of cardiac structure damage. Methods: Data were obtained from the third follow up survey (October 2023) of the "Huantai Childhood Cardiovascular Health Cohort Study", including 1 156 healthy adolescents aged 12-17 with complete information. The sample population was stratified into low ( Q 1 group), medium ( Q 2 group), and high ( Q 3 group) ALT levels based on tertiles within the same gender and age groups. Inter group comparisons were conducted using analysis of variance and trend test. A multivariate Logistic regression model was used to analyze the association between ALT levels and LVH, and stratified analyses were performed by gender and age groups. Results: With the increase of ALT quantile level, the detection rate of LVH showed an increasing trend ( Q 1: 3.7%; Q 2: 10.6%; Q 3: 16.7%, Z= 5.89 , P <0.01). After adjusting for potential covariates, compared with the ALT group ( Q 1), the group ( Q 3) increased the risk of developing LVH in adolescents ( OR=2.09, 95%CI =1.21-4.12). Stratified analyses by age and sex showed a significant association only in boys and younger individuals aged 12 to 14 years [ OR (95% CI ) were 2.64(1.04-7.67) and 3.24( 1.35 -9.06), both P <0.05)]. Conclusion Elevated serum ALT levels are associated with an increased risk of LVH in adolescents, and early detection and control of abnormal liver enzyme levels can help reduce early vascular structural damage and prevent adverse cardiovascular events.

ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds.Search Genecards,OMIM,Drugbank,TTD,and PharmGKB databases to obtain targets for gastric cancer.The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer.The String database was utilized construct a protein-protein interaction(PPI)network.Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the shared targets.This process revealed significant regulatory pathways crucial for jolkinolide B's efficacy in treating gastric cancer.Cytoscape 3.7.1 software was utilized create the core network of"Potential Targets of Triptolide B in Gastric Cancer Treatment",and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.Results Jolkinolide B may target multiple proteins,including MAPK1,glycogen synthase kinae-3β(GSK-3β),and JUN,impacting the proliferation,invasion,and metastasis of gastric cancer,ultimately inhibiting its growth.Conclusion We predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

Objective To explore the relationship between the M1/M2 macrophages and severity of diabetic retinopathy(DR).Methods This retrospective study included 42 patients with or without DR who had type 2 diabetes mellitus(T2DM)and 19 healthy individuals undergoing cataract intraocular surgery without systemic or ocular diseases from Handan Central Hospital between April 2022 and November 2023.Patients with T2DM were divided into three groups:diabetes mellitus with non-dominant diabetic retinopathy(T2DM non-DR group,n=20),mild and moderate non-proliferative diabetic retinopathy(NPDR)(n=10)and severe NPDR/proliferative diabetic retinopathy(PDR)(n=12).Peripheral blood and aqueous humor were obtained at surgery initiation.The levels of VEGF-A,IL-8,Elafin and TGF-β in the samples were analyzed using kits,and the ratio of M1 macrophages to M2 macrophages was analyzed by flow cytometry.Results Among patients with T2DM,there were significant differences in the duration of diabetes,insulin and metformin use among the three groups(P<0.05).Aqueous humor levels of VEGF-A,IL-8,Elafin,M1 ratio,M2 ratio and TGF-β of each group were significantly different(F=17.40,9.492,4.792,11.32,5.768 and 20.38,all P<0.01).The levels of VEGF-A,IL-8,Elafin,M1 ratio,VD86 and TGF-β in severe NPDR/PDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05),and the levels of VEGF-A,IL-8 and Elafin in severe NPDR/PDR group were significantly higher than those in mild and moderate NPDR group(P<0.05).The levels of M1 proportion and TGF-β in aqueous humor of the mild to moderate NPDR group were significantly higher than those in healthy control group and T2DM non-DR group(P<0.05).The level of M1 in aqueous humor was positively correlated with the levels of M2,Elafin,TGF-β and VEGF-A(r=0.260,0.411,0.726 and 0.304,all P<0.05),and the level of M2 was positively correlated with the levels of Elafin and TGF-β(r=0.865,0.552,all P<0.01).Conclusion The elevation of IL-8 and M1 macrophages in the aqueous humor may promote the occurrence of DR,while the increase of Elafin and M2 macrophages may be a compensatory regulation to chronic inflammation,which is involved in the regulation of local microvascular lesions and fibrosis.

Objective: To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment. Methods: Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted. Results: Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses. Conclusion The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.

Objective: To explore the risk of endometrial polyp (EP) based on lipid metabolism and vaginal micro- ecology combined with uterine volume line drawing model. Methods: 143 EP patients treated by hysteroscopic sur- gery were selected as the experimental group , and 113 healthy women were selected as the control group at the same time. The data were randomly divided into training set and validation set according to the ratio of 7 : 3. The clinical data of the two groups were collected and recorded , and t/χ2 test , LASSO regression and multifactorial lo- gistic regression analysis were used to screen the independent risk factors , construct the prediction model , and draw the column line graph. The performance of the model was evaluated by applying subject operating characteristic (ROC) curves , calibration curves , Hosmer-Lemeshow test and clinical decision-making (DCA) curves. Results: Multifactorial logistic regression analysis showed that total cholesterol ( TC) , low-density lipoprotein cholesterol (LDL-C) , vaginal microecological balance , and uterine volume were independent risk factors for the development of EP. ROC curve analysis showed that the AUC values of the training and validation sets of the column line graph model were 0. 935 and 0. 887 , respectively , and its sensitivity and specificity were 90. 21% , 83. 46% and 86. 29% , 80. 66% respectively , The Hosmer-Lemeshow test showed that the model fits well ( training set : χ2 = 2. 261 , P = 0. 840 ; validation set : χ2 = 4. 837 , P = 0. 441) and the calibration curves of the training and validation sets were close to the ideal curves , which indicated that the model had good prediction accuracy; the analysis of DCA curves of the training and validation sets both showed that the column-line graph model had a good clinical benefit rate in predicting EP. Conclusion TC , LDL-C , vaginal microecological balance and uterine volume are independent risk factors for EP , and the column-line diagram model constructed by the model has high clinical ben- efit , calibration and accuracy in predicting the risk of EP.