ObjectiveTo investigate the safety and feasibility of intra-biliary drainage tube placement after laparoscopic common bile duct exploration in elderly patients with choledocholithiasis， and to provide more options for surgical procedures in the clinical management of elderly patients with choledocholithiasis. MethodsA retrospective analysis was performed for the clinical data of 52 elderly patients with choledocholithiasis who were admitted to Department of Hepatobiliary Surgery， Affiliated Dalian Friendship Hospital of Dalian Medical University， from November 2021 to October 2024. According to the biliary drainage method after surgery， the patients were divided into internal drainage group with 24 patients and T-tube drainage group with 28 patients， and there were 19 patients in each group after propensity score matching. The two groups were compared in terms of perioperative parameters and postoperative complications. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the T-tube drainage group， the internal drainage group had a significantly shorter length of postoperative hospital stay and a significantly lower volume of postoperative bile loss （Z=-2.845 and -5.633， both P<0.05）， while there were no significant differences between the two groups in time of operation， intraoperative blood loss， and drainage tube indwelling time （all P>0.05）. There were no significant differences between the two groups in postoperative bile leak， stone recurrence， biliary stricture， and drainage tube-related complications， and the internal drainage group had a significantly lower total complication rate than the T-tube drainage group ［1 （5.3%） vs 7 （36.8%）， P<0.05］. ConclusionFor elderly patients with choledocholithiasis， intra-biliary drainage tube placement after laparoscopic common bile duct exploration can shorten the length of postoperative hospital stay， reduce bile loss， and lower the incidence rate of postoperative complications， thereby helping to accelerate postoperative recovery.

Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals ; Astrocytes/drug effects* ; Neuralgia/pathology* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Signal Transduction/physiology* ; Male ; Mice ; Microglia/drug effects* ; Fibroblast Growth Factor 8/pharmacology* ; Mice, Inbred C57BL ; Hyperalgesia/drug therapy* ; Spinal Cord/drug effects* ; Complement C3/metabolism* ; Spinal Cord Dorsal Horn/metabolism*

Objective:This study based on comprehensive bioinformatics technology aimed to investigate the pathogenesis of ferroptosis in IgA nephropathy(IgAN)from an immunological perspective,and to identify the key genes and functional pathways.Methods:Differentially expressed ferroptosis-related genes(DE-FRGs)were identified from GSE93798 and analyzed by Kyoto Ency-clopedia of Genes and Genomes(KEGG)and Gene Ontology(GO).STRING and Cytoscape were used to construct a protein-protein interaction(PPI)network.Degree and MCODE algorithm were run.Combining LASSO regression,SVM-RFE and PLS-DA machine learning to construct the optimal feature selection hub gene.Cibersort and ssGESA algorithms were used to assess the immune infiltra-tion,as well as to explore the relationship between hub genes and immune infiltration.Single cell RNA sequence(scRNA-seq)data was used to analyze the location of hub genes in IgAN cell populations.Gene Set Enrichment Analysis(GSEA)was performed on hub genes.The HPA database was used to obtain the position of the specific protein of the hub genes,and the DsigDB database was used to predict the target drug.The GSE37460,GSE116626 and GSE73953 were treated as validation sets and diagnostic effectiveness evalua-tion.Collecting IgAN and healthy kidney tissue for immunohistochemical testing of hub genes expression.Results:This study identi-fied 94 DE-FRGs and 3 hub genes(JJUN,EGR1 and DDR2).KEGG and GO analysis indicated that the DE-FRGs were mainly con-centrated in pathways of ferroptosis,reactive oxygen species,responsing to oxidative stress and metal particles,mitochondrion,and transcriptional regulatory complex.GESA analysis involved in amino acid and fatty acid metabolism.The analysis of immune cell infil-tration in IgAN revealed an increased ratio of naive B cells,mast cells,and CD4+T cells.Differential analysis of immune function re-vealed that mechanisms such as chemokine receptor signaling pathways,human leukocyte antigen signaling pathways,and inflamma-tion promotion were more active in IgAN.Furthermore,the correlation was observed between immune infiltration and hub genes.ScRNA-seq analysis demonstrated that hub genes were localized in monocytes,macrophages,poximal convoluted tubule cells,princi-pal cells,and smooth muscle cells.Validations set analysis suggested that JUN and SIRT1 had a diagnostic value.The HPA database analysis showed that JUN was mainly located in the nucleus,while EGR1 was located in the membrane and cytoplasm.The 2 278 po-tential drugs for the treatment of IgAN were predicted.Finally,the results of immunohistochemistry and bioinformatics analysis were consistent.Conclusion:Ferroptosis may be associated with immune cell infiltration and immune related function during the occur-rence and development of IgAN.

Objective:To analyze the clinical characteristics of warfarin-related nephropathy (WRN).Methods:Medical records of patients with WRN admitted to Linyi People′s Hospital Affiliated to Shandong Second Medical University from January 1, 2020 to December 31, 2024 were collected. The patients′ basic information (gender, age), warfarin medication details (indications, dosage, frequency, etc.), comorbidities, concomitant medication usage, international normalized ratio (INR) and serum creatinine (Scr) test results before and after the occurrence of WRN, as well as the clinical manifestations, interventions, and outcomes of WRN were extracted. The causal relationship between warfarin and renal dysfunction was evaluated according to the Adverse Drug Reaction Reporting and Monitoring Manual. The clinical data of patients were descriptively and statistically analyzed. Results:A total of 11 patients were entered in the analysis, including 7 males and 4 females; the age ranged from 49 to 85 years, with a median age of 70 years, and 9 cases were older than 60 years. The causality evaluation showed that 3 patients were definite and 8 patients were probable. All the 11 patients had at least one comorbidity, including 6 cases of heart failure, 6 cases of hypoproteinemia, 4 cases of chronic kidney disease, 3 cases of hypertension, 3 cases of pulmonary infection, and 1 case of diabetes. Seven patients were treated with warfarin combined with broad-spectrum antibiotics, 6 combined with diuretics, and 3 combined with renin angiotensin system blockers. The time from the highest INR to the highest Scr level was 0-6 days, with a median time of 2 days, and it was ≤2 days in 9 patients. Six patients had bleeding manifestations such as microscopic hematuria, melena, epistaxis, hematochezia, and skin ecchymosis. Among the 11 patients, 10 stopped warfarin immediately and 1 reduced dosage. All patients received different doses of vitamin K 1 according to the INR level. Among the 6 patients of bleeding, 4 received symptomatic treatments such as omeprazole, tranexamic acid, somatostatin, thrombin powder and octreotide, and 2 patients received hemodialysis due to high Scr level. One patient with severe anemia received blood transfusion. After 1-5 days of treatments (with a median time of 2 days), the INR in all patients decreased to <3.00, of which 5 patients continued to take warfarin, 1 changed warfarin to rivaroxaban, and 5 did not continue anticoagulation therapy. After 2 to 14 days of treatments, Scr in 8 patients recovered to the reference value range, and Scr in 3 patients was still at a high level, of which 1 patient died of unexplained cardiac arrest. Conclusions:WRN is a common adverse reaction of warfarin, with or without bleeding. After the occurrence of WRN, the drug should be stopped as soon as possible and symptomatic treatment should be given. The prognosis is generally good, but it may also lead to chronic kidney disease.

Objective To investigate the clinical efficacy of infrared thermal imaging technology-assisted CT-guided spinal dorsal root ganglion pulse radiofrequency(DRG-PRF)combined with ozone therapy in treating patients with acute herpes zoster.Methods A total of 128 patients with acute herpes zoster,who were admitted to Hengshui Municipal People's hospital between March 2021 and March 2024 to receive treatment,were enrolled in this study.Using SPSS,the patients were simply and randomly divided into the control group(n=64,receiving conventional DRG-PRF combined with ozone therapy)and the study group(n=64,receiving infrared thermal imaging technology-assisted CT-guided DRG-PRF combined with ozone therapy).The patients were followed up for 3 months.The pain numerical score(NRS),Pittsburgh Sleep Quality Index(PSQI),36-item health survey Summary Form(SF-36)score,skin temperature difference(ΔT),and adverse reactions were compared between the two groups.Results Compared with the control group,in the study group the postoperative one-day,3-day,5-day,7-day,and one-month NRS scores were lower(P＜0.05);the postoperative one-month,2-month and 3-month PSQI scores and the ΔT were lower,and the postoperative one-month,2-month and 3-month SF-36 scores were higher(P＜0.05).No statistically significant difference in the incidence of adverse reactions existed between the two groups(P＞0.05).Conclusion In treating patients with acute herpes zoster,infrared thermal imaging technology-assisted CT-guided DRG-PRF combined with ozone therapy can significantly relieve pain,improve quality of sleep and life of patients,reduce the skin temperature difference on the affected side,besides,this technique carries certain clinical safety.

Objective:To analyze the clinical characteristics of warfarin-related nephropathy (WRN).Methods:Medical records of patients with WRN admitted to Linyi People′s Hospital Affiliated to Shandong Second Medical University from January 1, 2020 to December 31, 2024 were collected. The patients′ basic information (gender, age), warfarin medication details (indications, dosage, frequency, etc.), comorbidities, concomitant medication usage, international normalized ratio (INR) and serum creatinine (Scr) test results before and after the occurrence of WRN, as well as the clinical manifestations, interventions, and outcomes of WRN were extracted. The causal relationship between warfarin and renal dysfunction was evaluated according to the Adverse Drug Reaction Reporting and Monitoring Manual. The clinical data of patients were descriptively and statistically analyzed. Results:A total of 11 patients were entered in the analysis, including 7 males and 4 females; the age ranged from 49 to 85 years, with a median age of 70 years, and 9 cases were older than 60 years. The causality evaluation showed that 3 patients were definite and 8 patients were probable. All the 11 patients had at least one comorbidity, including 6 cases of heart failure, 6 cases of hypoproteinemia, 4 cases of chronic kidney disease, 3 cases of hypertension, 3 cases of pulmonary infection, and 1 case of diabetes. Seven patients were treated with warfarin combined with broad-spectrum antibiotics, 6 combined with diuretics, and 3 combined with renin angiotensin system blockers. The time from the highest INR to the highest Scr level was 0-6 days, with a median time of 2 days, and it was ≤2 days in 9 patients. Six patients had bleeding manifestations such as microscopic hematuria, melena, epistaxis, hematochezia, and skin ecchymosis. Among the 11 patients, 10 stopped warfarin immediately and 1 reduced dosage. All patients received different doses of vitamin K 1 according to the INR level. Among the 6 patients of bleeding, 4 received symptomatic treatments such as omeprazole, tranexamic acid, somatostatin, thrombin powder and octreotide, and 2 patients received hemodialysis due to high Scr level. One patient with severe anemia received blood transfusion. After 1-5 days of treatments (with a median time of 2 days), the INR in all patients decreased to <3.00, of which 5 patients continued to take warfarin, 1 changed warfarin to rivaroxaban, and 5 did not continue anticoagulation therapy. After 2 to 14 days of treatments, Scr in 8 patients recovered to the reference value range, and Scr in 3 patients was still at a high level, of which 1 patient died of unexplained cardiac arrest. Conclusions:WRN is a common adverse reaction of warfarin, with or without bleeding. After the occurrence of WRN, the drug should be stopped as soon as possible and symptomatic treatment should be given. The prognosis is generally good, but it may also lead to chronic kidney disease.

Objective:This study based on comprehensive bioinformatics technology aimed to investigate the pathogenesis of ferroptosis in IgA nephropathy(IgAN)from an immunological perspective,and to identify the key genes and functional pathways.Methods:Differentially expressed ferroptosis-related genes(DE-FRGs)were identified from GSE93798 and analyzed by Kyoto Ency-clopedia of Genes and Genomes(KEGG)and Gene Ontology(GO).STRING and Cytoscape were used to construct a protein-protein interaction(PPI)network.Degree and MCODE algorithm were run.Combining LASSO regression,SVM-RFE and PLS-DA machine learning to construct the optimal feature selection hub gene.Cibersort and ssGESA algorithms were used to assess the immune infiltra-tion,as well as to explore the relationship between hub genes and immune infiltration.Single cell RNA sequence(scRNA-seq)data was used to analyze the location of hub genes in IgAN cell populations.Gene Set Enrichment Analysis(GSEA)was performed on hub genes.The HPA database was used to obtain the position of the specific protein of the hub genes,and the DsigDB database was used to predict the target drug.The GSE37460,GSE116626 and GSE73953 were treated as validation sets and diagnostic effectiveness evalua-tion.Collecting IgAN and healthy kidney tissue for immunohistochemical testing of hub genes expression.Results:This study identi-fied 94 DE-FRGs and 3 hub genes(JJUN,EGR1 and DDR2).KEGG and GO analysis indicated that the DE-FRGs were mainly con-centrated in pathways of ferroptosis,reactive oxygen species,responsing to oxidative stress and metal particles,mitochondrion,and transcriptional regulatory complex.GESA analysis involved in amino acid and fatty acid metabolism.The analysis of immune cell infil-tration in IgAN revealed an increased ratio of naive B cells,mast cells,and CD4+T cells.Differential analysis of immune function re-vealed that mechanisms such as chemokine receptor signaling pathways,human leukocyte antigen signaling pathways,and inflamma-tion promotion were more active in IgAN.Furthermore,the correlation was observed between immune infiltration and hub genes.ScRNA-seq analysis demonstrated that hub genes were localized in monocytes,macrophages,poximal convoluted tubule cells,princi-pal cells,and smooth muscle cells.Validations set analysis suggested that JUN and SIRT1 had a diagnostic value.The HPA database analysis showed that JUN was mainly located in the nucleus,while EGR1 was located in the membrane and cytoplasm.The 2 278 po-tential drugs for the treatment of IgAN were predicted.Finally,the results of immunohistochemistry and bioinformatics analysis were consistent.Conclusion:Ferroptosis may be associated with immune cell infiltration and immune related function during the occur-rence and development of IgAN.

Objective To investigate the effect of microRNA-223(miR-223)on prostate cancer cell damage by regulating the Kelch-like epichlorohydrin related protein 1(Keap1)/nuclear factor E2 related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods The prostate cancer cell line PC3 was cultured and randomly divided into control,down-regulated miR-223,and up-regulated miR-223 groups.Changes in miR-223 expression,cell proliferation rate,cell migration number,cell invasion number,apoptosis rate,and expression level of Keap1/Nrf2/ARE signaling pathway were explored.Results Compared with the control group,the cell invasion number,cell migration number,cell proliferation rate,Nrf2 and ARE expression increased at 24,48 and 72 h in down-regulated miR-223 group,while the expressions of miR-223,Keap1 and apoptosis rate decreased(P<0.05).Compared with the down-regulated miR-223 group,24,48 and 72 h cell proliferation rate,cell invasion number,cell migration number,ARE and Nrf2 expression decreased in the up-regulated miR-223 group,while miR-223,apoptosis rate and Keap1 expression increased(P<0.05).Conclusion Regulation of miR-223 effectively ameliorates prostate cell injury,and the mechanism may be related to the Keap1/Nrf2/ARE signaling pathway.

Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.