Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Objective:To investigate alterations in brain function among elderly patients with interstitial cystitis/bladder pain syndrome(IC/BPS)during the resting state.Methods:We prospectively recruited seven elderly patients with IC/BPS admitted to the Urology Department of Beijing Hospital from December 2023 to May 2024 as the experimental group, and concurrently selected twelve elderly healthy individuals as the control group.After enrollment, all participants underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans.General clinical data, including age and gender, as well as standardized assessment scores from the Interstitial Cystitis Symptom Index(ICSI), Interstitial Cystitis Problem Index(ICPI), Visual Analogue Scale(VAS), Self-Rating Anxiety Scale(SAS), and Self-Rating Depression Scale(SDS), were collected.The data were processed using Matlab.This study employed a paired sample t-test to analyze the differences in gray matter volume between the two groups.The functional activities of the subjects' brains were analyzed using regional homogeneity(ReHo)and low-frequency amplitude(ALFF)algorithms.Based on the identified abnormal brain regions, further functional connectivity(FC)analysis was conducted to explore the connectivity patterns among the functional brain regions.Results:No significant differences were observed in age( t=-0.68, P=0.536)or gender( χ2=0.019, P=0.891)between the experimental group and the control group.The scores of SAS and SDS in the experimental group were significantly higher than those in the control group( P<0.001).No significant difference was observed in cerebral gray matter volume between the two subject groups.In contrast to the control group, the ALFF value of the left superior parietal lobe(MNI: x, y, z=-21, -66, 60; t=12.530 5)was elevated in elderly patients with IC/BPS, and the ReHo value of the left precuneus(MNI: x, y, z=-9, -54, 63; t=9.410 3)was also increased.Through FC analysis, it was revealed that elderly IC/BPS patients exhibited significantly lower FC values between the left superior parietal lobule and the central sulcus(MNI: x, y, z=21, 15, 3; t=-27.835 6), as well as between the left anterior cingulate and the left posterior cingulate gyrus(MNI: x, y, z=-12, 0, 42; t=-8.738 9)in comparison with the control group. Conclusions:In contrast to normal individuals, elderly IC/BPS patients demonstrate functional aberrations in the left superior parietal lobule and the left precuneus.Moreover, a decrease in functional connectivity is observed between the left superior parietal lobule and the central sulcus, as well as between the left precuneus and the left posterior cingulate gyrus.These abnormal functional alterations in the brain may be implicated in the maintenance and development of symptoms in IC/BPS patients.This study conducted research from the perspective of central nervous system regulation, presenting possible directions for further exploration of the pathophysiological mechanisms of IC/BPS.

Objective To evaluate the efficacy of non-ablative vaginal erbium-doped yttrium aluminum garnet(Er:YAG)laser therapy in improving symptoms in women with mild-to-moderate stress urinary incontinence(SUI).Methods A prospective,multicenter,randomized controlled trial was conducted.A total of 126 female SUI patients were enrolled and randomized in a 2∶1 ratio to the treatment group(n=84,receiving Er:YAG laser therapy)and the sham control group(n=42,undergoing non-energized laser device with shielded beam).Efficacy outcomes were compared between the two groups,including the International Consultation on Incontinence Questionnaire-Short Form(ICI-Q-SF)scores at baseline and 1,3,6 months after treatment,response rate 3 month after treatment,urine leakage volume,daily incontinence episodes and visual analog scale(VAS).Results One month and 3 months after treatment,the ICI-Q-SF scores in the treatment group(8.07±3.33 and 7.04±3.04,respectively)were significantly lower than those in the control group(9.57±4.03 and 9.65±3.27,respectively;both P＜0.05).The 3-month response rate was significantly higher in the treatment group(71.43％)compared to the control group(35.71％,P＜0.05).Improvements in urine leakage volume 1 and 3 months after treatment were significantly greater in the treatment group versus the control group(both P＜0.05).A statistically significant reduction in daily incontinence episodes was observed in the treatment group 1 month after treatment compared to the control group[2(0,5)times vs.4(2,8)times,P＜0.05].VAS score in the treatment group markedly decreased 1 month after treatment,comparable to the level observed in the control group[0(0,2.45)vs.0(0,0),P＜0.05].Conclusion Non-ablative vaginal Er:YAG laser therapy significantly alleviates symptoms in women with mild-to-moderate SUI and represents a viable treatment option for this condition.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

Solitay iliac aneurysms are a rare clinical condition characterized by insidious onset.Once they rupture,treatment becomes difficult,and the mortality rate is extremely high.Therefore,it is extremely important to detect the disease,classify it appropriately and select appropriate treatment options.In recent years,endovascular treatment has gradually replaced traditional laparotomy as the first-line therapeutic approach.Some scholars have proposed clinical classification of isolated iliac aneurysms based on anatomical morphology and imaging studies to better select appropriate endovascular treatment strategies.This review aims to summarize the treatment advancements for solitary iliac aneurysms and the classifications based on the published literature.

Objective To explore the expression levels of NOD-like receptor thermal protein domain-asso-ciated protein 3(NLRP3)and interleukin-6(IL-6)in children with bronchial asthma combined with pulmona-ry infection and its relationship with prognosis.Methods A sample of 150 children with bronchial asthma combined with pulmonary infection hospitalized in Nanjing University Medical College Teaching Hospital,North Jiangsu People's Hospital from January 2021 to December 2022 were prospectively enrolled as observa-tion group,All children were followed up for one year.Another 164 healthy children underwent health check-ups were concurrently selected as control group.According to the prognosis,the children in the observation group were divided into good prognosis groups(n=92)and poor prognosis groups(n=58).Serum IL-6 and NLRP3 expression levels were detected in all participants,and receiver operating characteristic(ROC)curve was plotted to evaluate the value of IL-6 and NLRP3 in predicting the poor prognosis in children with bronchi-al asthma combined with pulmonary infection.Results Serum IL-6 and NLRP3 expression levels in the obser-vation group were significantly higher than those in the control group(P＜0.05).Serum IL-6 and NLRP3 ex-pression levels in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The results of ROC curve analysis showed that the area under the curve of IL-6 alone for predicting the poor prognosis of children with asthma combined with pulmonary infection was 0.772,with a sensitivity of 79.3％and a specificity of 73.9％.The area under the curve(AUC)of NLRP3 alone for predicting the poor prognosis of children with asthma combined with pulmonary infection was 0.735,with a sensitivity of 55.2％and a spe-cificity of 88.0％.The AUC of the combination of IL-6 and NLRP3 for predicting poor prognosis in children with asthma combined with pulmonary infection was 0.851,which was higher than those of IL-6 and NLRP 3 alone for predicting poor prognosis in children(Z=1.563,2.003,P=0.059,0.045),and the sensitivity was 82.8％and specificity was 75.0％,with high predictive value.Conclusion The expression levels of serum IL-6 and NLRP3 is abnormally up-regulated in children with bronchial asthma combined with pulmonary infec-tion,and the two could serve as predictive indicators for poor prognosis.