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.

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.

ObjectiveTo investigate the effects of Ditantang on metabolic dysfunction-associated fatty liver disease （MAFLD） in rats by focusing on the regulation of glycogen synthesis mediated by the uridine diphosphate glucose （UDPG）-site-1-protease （S1P）-sterol regulatory element-binding protein （SREBP） axis. MethodsMAFLD was modeled in SD rats by feeding a high-fat diet for 12 weeks. Rats were randomized into a control group， a model group， low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） Ditantang groups， and a positive control （Yishanfu， 0.18 g·kg^-1·d^-1） group. Starting from week 9 of modeling， each treatment group received corresponding drug interventions via gavage. After the experiment， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured. The levels of TG， non-esterified fatty acids （NEFA）， glycogen， glucose-6-phosphate （G6P）， glucose-1-phosphate （G1P）， and UDPG in the liver tissue samples were measured by biochemical assay kits. Liver pathological morphology and lipid/glycogen deposition were observed via hematoxylin-eosin （HE） staining， oil red O staining， and Periodic acid-Schiff （PAS） staining. Immunofluorescence assay was conducted to detect the expression and localization of phosphoglucomutase-1 （Pgm1） and UDP-glucose pyrophosphorylase 2 （Ugp2） in the rat liver. Real-time PCR and Western blot were employed to quantify mRNA and protein levels， respectively， of key glycogen synthesis enzymes （Pgm1 and Ugp2）， key lipogenesis-related transcription factor SREBP and its target genes ［acetyl-CoA carboxylase （ACC）， fatty acid synthetase （FASN）， and stearoyl-CoA desaturase （SCD1）］， as well as S1P. ResultsCompared with the control group， the model group exhibited elevated levels of TC， TG， LDL-C in the serum and TG and NEFA in the liver， decreased serum HDL-C level （P<0.01）， reduced hepatic levels of G1P， G6P， UDPG， and glycogen （P<0.01）， appearance of fat vacuoles of varying sizes and abundant red lipid droplets， with prominent lipid deposition and reduced areas of deep glycogen staining in the liver tissue， upregulated mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.01）， and downregulated mRNA and protein levels of Pgm1 and Ugp2 （P<0.01）. Compared with the model group， all doses of Ditantang reduced the levels of TC and TG in the serum and TG and NEFA in the liver， while elevating the serum HDL-C level. Additionally， medium- and high-dose Ditantang reducted the LDL-C level （P<0.05）. Ditantang at all doses increased the hepatic levels of G1P， G6P， UDPG， and glycogen， alleviated hepatic steatosis and lipid deposition， enhanced glycogen storage， downregulated the mRNA and protein levels of SREBP1， S1P， ACC， FASN， and SCD1 （P<0.05）， while upregulating the expression of Pgm1 and Ugp2 （P<0.01）. Immunofluorescence analysis revealed decreased fluorescence intensity of S1P and enhanced fluorescence intensity of Ugp2 （P<0.01）. ConclusionDitantang can regulate glycogen synthesis through the UDPG-S1P-SREBP axis to prevent and treat MAFLD.

Objective:To explore the surgical efficacy of high position dacryocystorhinostomy (DCR) under nasal endoscopy in patients with chronic dacryocystitis secondary to failure of nasolacrimal duct stent implantation.Methods:A total of 101 patients with chronic dacryocystitis who were treated at People′s Hospital of Peking University from 2013 to 2024 were retrospectively selected, including 14 males and 87 females, aged (56.82±13.00) years (Mean±SD). The patients were divided into control group (53 cases, 59 eyes) and stent group (48 cases, 60 eyes). The control group consisted of randomly selected patients with simple dacryocystitis, while, the stent group included patients with secondary dacryocystitis after failure of nasolacrimal duct stent implantation. All patients underwent endoscopic high DCR with exposed the Rosenmüller valve, combined with intraoperative lacrimal silicone tube implantation. After the operation, the surgical efficacy was evaluated by methods such as Munk score, endoscopic observation of intranasal ostia, lacrimal duct irrigation, and fluorescein test. SPSS 27.0 software was used for data statistics.Results:All 101 patients were followed up for at least one year after DCR surgery. In the control group, one patient (two eyes) was lost to follow-up; while, in the stent group, three patients (three eyes) were lost to follow-up, with one case diagnosed with lacrimal sac cancer. Excluding the lost-to-follow-up cases and the patient with lacrimal sac cancer, anatomical success was achieved in 54 eyes (96.4%, 54/56) in the stent group, and both anatomical and functional success in 53 eyes (94.6%, 53/56); in the control group, 55 eyes (96.5%, 55/57) achieved both anatomical and functional success. No statistically significant difference was found in postoperative effectiveness efficacy between the two groups ( χ2=0.000, P=0.984). Conclusion:For patients with secondary dacryocystitis after nasolacrimal duct stent implantation, high position DCR with exposure of Rosenmüller valve combined with lacrimal duct silicone intubation can achieve better long-term efficacy.

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVES: To investigate the correlation between bone mineral density (BMD) and bone metabolic markers in preschool children and the influencing factors for BMD, and to provide a clinical basis for promoting bone health in children. METHODS: A retrospective analysis was performed for the data of 127 preschool children who underwent physical examination in the Department of Child Health Care of the First Affiliated Hospital of Xinjiang Medical University, from June to December 2024. BMD and bone metabolic markers were measured, and physical examination was performed. A multiple linear regression analysis was used to investigate the effect of general information on BMD Z-score in preschool children. Spearman's rank correlation test was used to investigate the correlation of BMD Z-score with 25-hydroxyvitamin D (25-OHD), serum bone Gla protein (BGP), and parathyroid hormone (PTH). RESULTS: BMD Z-score significantly differed by ethnicity, weight category, and height category (all P<0.05). The multiple linear regression analysis indicated that weight and height significantly influenced BMD Z-score (P<0.05), whereas sex, age, ethnicity, and parental education level did not (P>0.05). In children, BMD Z-score was positively correlated with 25-OHD level (r_s=0.260, P<0.001) and BGP level (r_s=0.075, P=0.025) and was negatively correlated with PTH level (r_s=-0.043, P=0.032). CONCLUSIONS Weight, height, 25-OHD, BGP, and PTH are influencing factors for BMD in preschool children. In clinical practice, combined measurement of bone metabolic markers may provide a scientific basis for early identification of children with abnormal BMD and prevention of osteoporosis and osteomalacia.
Humans ; Bone Density ; Child, Preschool ; Female ; Male ; Retrospective Studies ; Vitamin D/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteocalcin/blood* ; Bone and Bones/metabolism* ; Calcium-Binding Proteins/blood* ; Linear Models ; Matrix Gla Protein ; Extracellular Matrix Proteins/blood* ; Body Weight ; Infant

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.