ObjectiveTo investigate the safety and efficacy of transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy （EHL）. MethodsA retrospective analysis was performed for the clinical data of 60 patients with large common bile duct stones who were admitted to Department of Gastroenterology， Jilin People’s Hospital， from May 1， 2023 to January 31， 2026， and according to the treatment method， the patients were divided into transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group and peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group， with 30 patients in each group. The two groups were compared in terms of the rate of successful single-session stone fragmentation and removal， procedural time， duration of electrohydraulic lithotripsy， clinical success rate， and complications. The independent-samples t test or the Mann-Whitney U 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 peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group， the transparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy group had a significantly higher technical success rate （83.33% vs 60.00%， χ²=4.022， P=0.045） and significantly shorter procedural time ［46.00 （42.25 — 49.00） min vs 54.50 （42.00 — 65.00） min， Z=2.012， P=0.044］ and duration of electrohydraulic lithotripsy ［8.00 （6.25 — 11.75） min vs 13.50 （9.25 — 17.75） min， Z=2.749， P=0.006］. Both groups achieved a clinical success rate of 100%， with no significant difference in the incidence rate of complications （P>0.05）. ConclusionTransparent cap-assisted peroral cholangiopancreatoscopy-guided electrohydraulic lithotripsy has a high rate of successful single-session stone fragmentation and removal and a short procedural time， with good safety and efficacy， and therefore， it holds promise for clinical application.

Breast cancer is the most prevalent malignancy among women worldwide.In recent years,immune checkpoint inhibitors(ICIs)have emerged as a promising therapeutic strategy across different molecular subtypes of breast cancer,demonstrating significant clinical potential.This review systematically summarized the progress and clinical applications of ICIs in hormone receptor-positive(HR-positive),human epidermal growth factor receptor 2-overexpressing(HER2-positive),and triple-negative breast cancer(TNBC).In HR-positive breast cancer,the KEYNOTE-756 and CheckMate 7FL trials demonstrated that ICIs combined with neoadjuvant chemotherapy significantly improved the pathological complete response(pCR)rate,with greater benefits observed in programmed cell death-ligand 1(PD-L1)-positive patients.Furthermore,the PROMENADE study indicated that estrogen receptor(ER)-low HER2-negative breast cancer patients achieved a pCR rate closer to that of TNBC rather than HR-positive breast cancer following ICIs treatment.In metastatic HR-positive breast cancer,the SACI-IO and DOLAF studies suggested that ICIs combined with antibody-drug conjugates(ADC)or poly(ADP-ribose)polymerase(PARP)inhibitors may provide clinical benefits for specific subgroups of patients.For HER2-positive breast cancer,the Keyriched-1 and Neo-PATH studies revealed that ICIs combined with anti-HER2 therapy might improve pCR rates in HR-negative/HER2-positive patients.However,the Impassion-050 and KATE2 trials failed to demonstrate widespread clinical benefits of ICIs in HER2-positive breast cancer.In TNBC,long-term follow-up data from the KEYNOTE-522 study showed that ICIs combined with neoadjuvant chemotherapy not only improved pCR rates but also conferred long-term survival benefits.Additionally,the Impassion-130,KEYNOTE-355,and TORCHLIGHT studies confirmed that ICIs combined with chemotherapy prolonged both progression-free survival(PFS)and overall survival(OS)in PD-L1-positive advanced TNBC patients.Meanwhile,treatment strategies combining ICIs with anti-angiogenic therapy,PARP inhibitors and ADCs have demonstrated promising efficacy in TNBC(SPARK and BEGONIA trial).Currently,ICIs combined with chemotherapy remains the primary treatment approach,while combination strategies involving ICIs with anti-HER2 therapy,endocrine therapy,ADCs,and anti-angiogenic therapy are actively being explored.However,challenges remain,including complex resistance mechanisms,heterogeneous treatment responses,and the management of immune-related adverse events.Future research should focus on refining patient stratification strategies and developing more precise combination therapies to improve long-term survival outcomes for breast cancer patients.

Objective:To conduct a scoping review on the current status, assessment tools and influencing factors of malnutrition in elderly stroke patients, so as to provide new ideas for the development of individualized nutritional intervention programs.Methods:Studies related to malnutrition in elderly stroke patients were searched in China National Knowledge Infrastructure, VIP, WanFang Data, China Biology Medicine disc, PubMed, Web of Science, Embase and Clinical Trial Registration Center. The search period was from the establishment of the database to January 2024. Two researchers independently screened the literature, extracted information based on inclusion and exclusion criteria, and finally categorized and reported the findings.Results:A total of 33 papers were included. In elderly stroke patients, the prevalence of malnutrition varied between studies. There was a wide range of tools to assess the nutritional status of patients, but there was an overall lack of multidimensional and specific tools. Commonly used was the Short-form Mini-nutritional Assessment. Factors influencing malnutrition in patients included general demographic, disease-related and lifestyle factors, physiologic and biochemical indicators, functional correlates, nutrient literacy-related factors, psychological and supportive factors.Conclusions:Malnutrition in elderly stroke patients is influenced by a variety of factors and seriously affects patient prognosis. Standardized assessment tools should be adopted to detect timely and accurately, take targeted measures for each factor, and carry out personalized intervention programs to promote benign changes in the nutritional status of elderly stroke patients.

Purpose To explore the influence of thrombolysis therapy before percutaneous coronary intervention(PCI)on long-term left ventricular global and regional function in ST segment elevation myocardial infarction(STEMI)patients by cardiac magnetic resonance(CMR).Materials and Methods A retrospective analysis was conducted on 67 STEMI patients who were enrolled in a prospective study from November 2021 to August 2022 in the First Affiliated Hospital with Nanjing Medical University,the First People's Hospital of Lianyungang,the Affiliated Hospital of Jiangnan University,Changzhou No.2 People's Hospital and Huai'an Second People's Hospital and underwent CMR examination one year later.STEMI patients were divided into thrombolysis group and non-thrombolysis group according to whether a single half-dose of 5 mg recombinant staphylokinase(r-SAK)was given within two hours before the first medical contact and PCI.Based on CMR cine images,the traditional left ventricular function,global and segmental functional parameters were measured,and the differences between the two groups were compared.According to the degree of late gadolinium enhancement involvement,myocardial segments were divided into the following four types:transmural infarcted segments,non-transmural infarcted segments,locally infarcted segments,and non-infarcted segments.The parameters of the two groups were compared across these different segments.Results At the patient level,the cardiac index,left ventricular wall thickening and left ventricular wall motion in r-SAK thrombolysis group were higher than those in non-thrombolysis group(t/Z=-2.426,-4.307,-2.735,all P<0.05).At the segment level,compared with non-thrombolysis group,patients received r-SAK before primary PCI showed greater segmental radial strain in non-transmural infarcted segments(Z=-2.117,P=0.034);larger segmental wall motion in locally infarcted segments(Z=-2.235,P=0.025),and better segmental circumference strain in the non-infarcted segments(Z=-3.869,P<0.001).Conclusion The thrombolytic therapy before PCI in STEMI patients retain better long-term left ventricular global and regional function evaluating by CMR.

Breast cancer is the most prevalent malignancy among women worldwide.In recent years,immune checkpoint inhibitors(ICIs)have emerged as a promising therapeutic strategy across different molecular subtypes of breast cancer,demonstrating significant clinical potential.This review systematically summarized the progress and clinical applications of ICIs in hormone receptor-positive(HR-positive),human epidermal growth factor receptor 2-overexpressing(HER2-positive),and triple-negative breast cancer(TNBC).In HR-positive breast cancer,the KEYNOTE-756 and CheckMate 7FL trials demonstrated that ICIs combined with neoadjuvant chemotherapy significantly improved the pathological complete response(pCR)rate,with greater benefits observed in programmed cell death-ligand 1(PD-L1)-positive patients.Furthermore,the PROMENADE study indicated that estrogen receptor(ER)-low HER2-negative breast cancer patients achieved a pCR rate closer to that of TNBC rather than HR-positive breast cancer following ICIs treatment.In metastatic HR-positive breast cancer,the SACI-IO and DOLAF studies suggested that ICIs combined with antibody-drug conjugates(ADC)or poly(ADP-ribose)polymerase(PARP)inhibitors may provide clinical benefits for specific subgroups of patients.For HER2-positive breast cancer,the Keyriched-1 and Neo-PATH studies revealed that ICIs combined with anti-HER2 therapy might improve pCR rates in HR-negative/HER2-positive patients.However,the Impassion-050 and KATE2 trials failed to demonstrate widespread clinical benefits of ICIs in HER2-positive breast cancer.In TNBC,long-term follow-up data from the KEYNOTE-522 study showed that ICIs combined with neoadjuvant chemotherapy not only improved pCR rates but also conferred long-term survival benefits.Additionally,the Impassion-130,KEYNOTE-355,and TORCHLIGHT studies confirmed that ICIs combined with chemotherapy prolonged both progression-free survival(PFS)and overall survival(OS)in PD-L1-positive advanced TNBC patients.Meanwhile,treatment strategies combining ICIs with anti-angiogenic therapy,PARP inhibitors and ADCs have demonstrated promising efficacy in TNBC(SPARK and BEGONIA trial).Currently,ICIs combined with chemotherapy remains the primary treatment approach,while combination strategies involving ICIs with anti-HER2 therapy,endocrine therapy,ADCs,and anti-angiogenic therapy are actively being explored.However,challenges remain,including complex resistance mechanisms,heterogeneous treatment responses,and the management of immune-related adverse events.Future research should focus on refining patient stratification strategies and developing more precise combination therapies to improve long-term survival outcomes for breast cancer patients.

Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.

Low-intensity pulsed ultrasound（LIPUS），with its remarkable advantages of higher safety and better penetrability，has gradually become a novel method of physical adjuvant therapy. Previous studies have verified that LIPUS can modulate the immune response of different immune cells such as macrophage，T lymphocyte，and neutrophil by reducing the level of pro-inflammatory cytokines. Therefore，it plays a crucial role on acceleration of fracture healing，expedition of wound repair，and repairation of myocardial injury. The review summarizes the regulatory effects and potential mechanisms of LIPUS on abnormal immune cell responses triggered by various diseases.

Psoriasis is a chronic inflammatory skin disease with worldwide prevalence,primarily characterized by epidermal hyperplasia,abnormal keratinization,and immune cell infiltration,with a significant negative impact on patients' quality of life and mental well-being.The onset of psoriasis is closely associated with genetic susceptibility,immune dysregulation,and environmental factors.Despite research progress into the pathogenesis of psoriasis,existing treatment method still face problems including limited efficacy and obvious side effects.There is thus an urgent need for an in-depth analysis of its pathological network and the development of novel interventional strategies.The imiquimod-induced psoriasis animal model has accordingly become a crucial tool for studying psoriasis owing to its high reproducibility and excellent pathological simulation.This review systematically summarizes the core mechanism of action of the imiquimod-induced psoriasis model,expounds on the molecular basis of its action via pathways such as the cascade reaction of the core immune-inflammatory axis,the multi-regulatory network of downstream synergistic mechanisms,and the interaction between host and environmental factors.Research based on this model has successfully verified the therapeutic effects of various targeted therapies and natural products on psoriasis,demonstrating its important application value in therapeutic interventional research.We also discuss the limitations of the imiquimod-induced psoriasis model,and indicate future research directions,with the aim of providing references for further in-depth research and the treatment of psoriasis.

Purpose To explore the influence of thrombolysis therapy before percutaneous coronary intervention(PCI)on long-term left ventricular global and regional function in ST segment elevation myocardial infarction(STEMI)patients by cardiac magnetic resonance(CMR).Materials and Methods A retrospective analysis was conducted on 67 STEMI patients who were enrolled in a prospective study from November 2021 to August 2022 in the First Affiliated Hospital with Nanjing Medical University,the First People's Hospital of Lianyungang,the Affiliated Hospital of Jiangnan University,Changzhou No.2 People's Hospital and Huai'an Second People's Hospital and underwent CMR examination one year later.STEMI patients were divided into thrombolysis group and non-thrombolysis group according to whether a single half-dose of 5 mg recombinant staphylokinase(r-SAK)was given within two hours before the first medical contact and PCI.Based on CMR cine images,the traditional left ventricular function,global and segmental functional parameters were measured,and the differences between the two groups were compared.According to the degree of late gadolinium enhancement involvement,myocardial segments were divided into the following four types:transmural infarcted segments,non-transmural infarcted segments,locally infarcted segments,and non-infarcted segments.The parameters of the two groups were compared across these different segments.Results At the patient level,the cardiac index,left ventricular wall thickening and left ventricular wall motion in r-SAK thrombolysis group were higher than those in non-thrombolysis group(t/Z=-2.426,-4.307,-2.735,all P<0.05).At the segment level,compared with non-thrombolysis group,patients received r-SAK before primary PCI showed greater segmental radial strain in non-transmural infarcted segments(Z=-2.117,P=0.034);larger segmental wall motion in locally infarcted segments(Z=-2.235,P=0.025),and better segmental circumference strain in the non-infarcted segments(Z=-3.869,P<0.001).Conclusion The thrombolytic therapy before PCI in STEMI patients retain better long-term left ventricular global and regional function evaluating by CMR.

Objective:To investigate the effect of polystyrene microplastics(PS-MPs)combined with high-fat treatment on vascular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in the DMEM medium containing 5%fe-tal bovine serum.HUVECs were treated with conventional culture,high-fat treatment,and PS-MPs combined with high-fat treatment.The experiment was conducted in the three groups of control group,high-fat treatment group and PS-MPs+high-fat treatment group.CCK-8 assay was used to measure cell viability,F-actin staining was used to observe cell morphological changes,and flow cytometry,scratch assay,and tube formation assay were used to measure the apoptosis,migration,and tube-forming ability of cells.Results:After HUVECs were exposed to the high-fat environment,there was a significant reduction in cell viability,shrinkage of cells,a signifi-cant increase in cell apoptosis,and significant reductions in cell migration and tube-forming ability.Compared with the high-fat treat-ment group,there were no significant changes in cell viability,cell morphology,cell apoptosis,and cell migration ability after PS-MPs combined with high-fat treatment,but the tube-forming ability of cells was further impaired.Conclusion:High-fat treatment will affect cell viability,change cell morphology,and damage vascular endothelial cell function,and PS-MPs combined with high-fat treat-ment can aggravate the damage of vascular endothelial cell function.