1.Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression
Kepu ZHENG ; Leiyang DAI ; Shengning ZHANG ; Yingpeng ZHAO ; Wang LI ; Yang GAO ; Yuanyi MANG ; Lingfeng JIAO ; Yu TANG ; Jianghua RAN
Gut and Liver 2025;19(3):410-426
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.
2.Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression
Kepu ZHENG ; Leiyang DAI ; Shengning ZHANG ; Yingpeng ZHAO ; Wang LI ; Yang GAO ; Yuanyi MANG ; Lingfeng JIAO ; Yu TANG ; Jianghua RAN
Gut and Liver 2025;19(3):410-426
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.
3.Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression
Kepu ZHENG ; Leiyang DAI ; Shengning ZHANG ; Yingpeng ZHAO ; Wang LI ; Yang GAO ; Yuanyi MANG ; Lingfeng JIAO ; Yu TANG ; Jianghua RAN
Gut and Liver 2025;19(3):410-426
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.
4.Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression
Kepu ZHENG ; Leiyang DAI ; Shengning ZHANG ; Yingpeng ZHAO ; Wang LI ; Yang GAO ; Yuanyi MANG ; Lingfeng JIAO ; Yu TANG ; Jianghua RAN
Gut and Liver 2025;19(3):410-426
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.
5.Association of NLRP3 genetic variant rs10754555 with early-onset coronary artery disease.
Lingfeng ZHA ; Chengqi XU ; Mengqi WANG ; Shaofang NIE ; Miao YU ; Jiangtao DONG ; Qianwen CHEN ; Tian XIE ; Meilin LIU ; Fen YANG ; Zhengfeng ZHU ; Xin TU ; Qing K WANG ; Zhilei SHAN ; Xiang CHENG
Chinese Medical Journal 2025;138(21):2844-2846
6.In vitro cultured calculus bovis alleviates cerebral ischemia/reperfusion injury through regulating microglial polarization and inhibiting NLRP3.
Tanlu CHU ; Wei ZHANG ; Jingwen CHEN ; Zeyue PAN ; Lingfeng WANG ; Xiaoming ZHONG ; Fengmei QIU ; Zhen HUANG
Journal of Zhejiang University. Medical sciences 2025;54(3):360-371
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
7.Expression levels of serum IL-6 and NLRP3 in children with bronchial asthma combined with pulmonary infection and its relationship with prognosis
Hui WANG ; Mengyue WEI ; Lingfeng MIN
International Journal of Laboratory Medicine 2025;46(19):2334-2338
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.
8.Classification and Treatment of Solitary Iliac Artery Aneurysms
Mengjia WANG ; Kaixiong QING ; Lingfeng ZHAO
Journal of Kunming Medical University 2025;46(1):154-159
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.
9.Research on Construction of Test Environment for Assessment of RF-Induced Heating Effects of Implants
Yonghua LI ; Lingfeng LU ; Jing WANG ; Chengling LI ; Pengfei YANG ; Zhichao WANG ; Dajing WU ; Xun LIU ; Sheng HU
Chinese Journal of Medical Instrumentation 2024;48(3):281-284,297
In magnetic resonance examination,the interaction between implants and the radio frequency(RF)fields induces heating in human tissue and may cause tissue damage.To assess the RF-induced heating of implants,three steps should be executed,including electromagnetic model construction,electromagnetic model validation,and virtual human body simulations.The crucial step of assessing RF-induced heating involves the construction of a test environment for electromagnetic model validation.In this study,a hardware environment,comprised of a RF generation system,electromagnetic field measurement system,and a robotic arm positioning system,was established.Furthermore,an automated control software environment was developed using a Python-based software development platform to enable the creation of a high-precision automated integrated test environment.The results indicate that the electric field generated in this test environment aligns well with the simulated electric field,making it suitable for assessing the RF-induced heating effects of implants.
10.Diagnostic value of thromboelastography combined with conventional coagulation test for trauma-induced coagulopathy in patients with electric burns in the early stage
Quan LI ; Te BA ; Shengjun CAO ; Fang LI ; Zengqiang YAN ; Zhihui HOU ; Lingfeng WANG
Chinese Journal of Burns 2024;40(8):740-745
Objective:To explore the diagnostic value of thromboelastography (TEG) combined with conventional coagulation test (CCT) for trauma-induced coagulopathy (TIC) in patients with electric burns in the early stage.Methods:This study was a retrospective case series research. From February 2018 to February 2024, the clinical data of 128 electric burn patients and 118 thermal burn patients who met the inclusion criteria and admitted to the Department of Burn Surgery of the Third Affiliated Hospital of Inner Mongolia Medical University were collected, including 224 males and 22 females, aged (38±14) years. The patients were divided into electric burn group (128 cases) and thermal burn group (118 cases) according to their injuries. The incidence of TIC, the indicators of CCT, including prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen level, D-dimer level, platelet count, and the detection indicators of TEG, including coagulation reaction time, K value, coagulation angle, maximum thrombus amplitude, comprehensive coagulation index, and lysis rate at 30 minutes after maximum amplitude within 8 hours of admission were compared between the two groups of patients. The Kappa test was used to analyze the consistency between CCT and TEG in diagnosing TIC in patients with electric burns in the early stage after burns. The receiver operating characteristic curves of CCT, TEG, and TEG combined with CCT in diagnosing TIC in 128 patients with electric burns were drawn, and the area under the curve (AUC), the maximum Jordan index, and sensitivity and specificity at this time were calculated.Results:The proportion of patients diagnosed with TIC in electric burn group was 19.5% (25/128) within 8 hours of admission, which was significantly higher than 10.2% (12/118) in thermal burn group ( χ2=4.21, P<0.05). Compared with those in thermal burn group, prothrombin time was significantly shortened ( t=-2.32, P<0.05), D-dimer level, fibrinogen level, and platelet count were significantly increased (with Z values of -2.11 and -4.16, respectively, t=4.69, P<0.05), the coagulation reaction time was significantly shortened ( t=-2.51, P<0.05), and the maximum thrombus amplitude and lysis rate at 30 minutes after the maximum amplitude were significantly increased (with t values of 2.50 and 2.10, respectively, P<0.05) in patients in electric burn group within 8 hours of admission. There were no statistically significant differences in the other CCT indicators and TEG detection indicators between the two groups of patients ( P>0.05). The CCT and TEG showed high consistency in the diagnosis of TIC in patients with electric burns in the early stage after burns (Kappa=0.63, P<0.05). The AUCs of TEG combined with CCT, TEG, and CCT in diagnosis of TIC in 128 patients with electric burns were 0.92, 0.84, and 0.77 (with 95% confidence intervals of 0.86-0.97, 0.71-0.97, and 0.71-0.97, respectively), with the maximum Jordan indexes of 0.86, 0.57, and 0.65. At this time, the specificity was 93.7%, 83.2%, and 88.2%, respectively, and the sensitivity was 92.3%, 87.5%, and 76.5%, respectively. Conclusions:Patients with electric burns are in a state of hypercoagulability of coagulation system and hyperfunction of fibrinolysis system in the early stage after burns, and TEG combined with CCT can increase the diagnostic rate of TIC in patients with electric burns.

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