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.To investigate the association between gout-related gene polymorphisms and clinical phenotypic heteroge-neity in gout patients from the Foshan region
Qihong GUO ; Baolin ZHENG ; Ting LI ; Yutong JIANG ; Junli CHEN ; Yuanyi LI ; Haimei YANG ; Junguang LU
The Journal of Practical Medicine 2025;41(19):3060-3064
Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.
6.Comparison on texture features of medial gastrocnemius and biceps brachii muscles between young and elderly individuals based on ultrasound tomography
Yudong KONG ; Yi LI ; Yuanyi ZHENG
Chinese Journal of Medical Imaging Technology 2025;41(5):773-777
Objective To compare the texture features of medial gastrocnemius and biceps brachii muscles between young and elderly individuals with ultrasound tomography(UT).Methods Twenty healthy adults under 30 years old(young group)and 22 healthy adults greater than or equal to 60 years old(elderly group)were prospectively recruited.A ring-array UT system was used to collect images of upper and lower limbs,the texture features of medial gastrocnemius and biceps brachii muscles were extracted and compared between 2 groups.Results Significant differences of gray level mean(GLM),gray level variance(GLV),contrast(CON),homogeneity(HOM),entropy(ENT),gray-level non-uniformity(GLN)and run-length non-uniformity(RLN)of medial gastrocnemius,as well as of GLM,GLV,CON,HOM and ENT of biceps brachii muscles were found between groups(all P<0.05).Conclusion Significant differences of GLM,GLV,CON,HOM and ENT of medial gastrocnemius and biceps brachii muscles were found between young and elderly individuals,indicating that structural remodeling and functional changes in muscles happened in elderly individuals.
7.Comparison on texture features of medial gastrocnemius and biceps brachii muscles between young and elderly individuals based on ultrasound tomography
Yudong KONG ; Yi LI ; Yuanyi ZHENG
Chinese Journal of Medical Imaging Technology 2025;41(5):773-777
Objective To compare the texture features of medial gastrocnemius and biceps brachii muscles between young and elderly individuals with ultrasound tomography(UT).Methods Twenty healthy adults under 30 years old(young group)and 22 healthy adults greater than or equal to 60 years old(elderly group)were prospectively recruited.A ring-array UT system was used to collect images of upper and lower limbs,the texture features of medial gastrocnemius and biceps brachii muscles were extracted and compared between 2 groups.Results Significant differences of gray level mean(GLM),gray level variance(GLV),contrast(CON),homogeneity(HOM),entropy(ENT),gray-level non-uniformity(GLN)and run-length non-uniformity(RLN)of medial gastrocnemius,as well as of GLM,GLV,CON,HOM and ENT of biceps brachii muscles were found between groups(all P<0.05).Conclusion Significant differences of GLM,GLV,CON,HOM and ENT of medial gastrocnemius and biceps brachii muscles were found between young and elderly individuals,indicating that structural remodeling and functional changes in muscles happened in elderly individuals.
8.To investigate the association between gout-related gene polymorphisms and clinical phenotypic heteroge-neity in gout patients from the Foshan region
Qihong GUO ; Baolin ZHENG ; Ting LI ; Yutong JIANG ; Junli CHEN ; Yuanyi LI ; Haimei YANG ; Junguang LU
The Journal of Practical Medicine 2025;41(19):3060-3064
Objective To investigate the association between gout-related gene polymorphisms and clinical phenotypic heterogeneity among gout patients in the Foshan region,thereby providing a scientific basis for stratified clinical management.Methods A total of 125 gout patients diagnosed at the Foshan Hospital of Traditional Chinese Medicine between June 2022 and May 2025 were enrolled in this study.The collected data included demo-graphic characteristics,frequency of gout attacks,presence of tophi,levels of uric acid,creatinine,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),gout-related genes(ABCG2,SLC2A9,SLC22A12,MTHFR),and joint ultrasound findings.Group comparisons and rank correlation analyses were conducted to explore potential associations between gene polymorphisms and clinical heterogeneity.Results The male-to-female ratio was 11∶1;the mean age was(35.28±2.67)years;the mean disease duration was(6.03±0.68)years;and the mean frequency of acute attacks in the past 12 months was 4(2.0,7.25).Genotype distributions were as follows:ABCG2:wild-type(C/C),23.8%;heterozygous(C/A),53.2%;homozygous(A/A),23%.SLC2A9:wild-type(A/A),24.6%;heterozygous(A/G),50%;homozygous(G/G),25.4%.SLC22A12:wild-type(A/A),4.8%;heterozygous(A/C),31.7%;homozygous(C/C),63.5%.MTHFR:wild-type(C/C),68.3%;heterozygous(C/T),28.6%;homozygous(T/T),3.2%.Rank correlation analysis revealed that SLC2A9 polymorphisms were significantly correlated with tophi formation(ρ=0.193,P=0.031)and crystal deposition on ultrasound(ρ=0.202,P=0.025).SLC22A12 polymorphisms were associated with hypertension(ρ=0.269,P=0.003)and diabetes(ρ=0.200,P=0.026).MTHFR polymorphisms showed a correlation with diabetes(ρ=0.224,P=0.012).Conclusions Polymorphisms in SLC2A9,SLC22A12,and MTHFR are significantly linked to clinical phenotypic heterogeneity among gout patients.Genetic testing could facilitate the early identification of individuals at high risk for complications and support the development of stratified and individualized treatment approaches.
9.Application of Rabbit Carotid Atherosclerotic Plaque Neovascularization using Ultrasound Localization Microscopy
Junyi REN ; Wen-kun BAI ; Yuanyi ZHENG
Journal of Medical Research 2024;53(11):35-39
Objective To investigate the correlation between intraplaque neovascularization(IPN)parameters using ultrasound lo-calization microscopy(ULM)and pathological results.Methods Atherosclerosis of the carotid artery in rabbit was induced using balloon catheter damage and a high-cholesterol diet.ULM technology was used to measure the IPN,and the parameters of neovascularization density,diameter,distortion and velocity were quantified,and compared with pathological results,to evaluate the reliability of ULM tech-nique in detecting and measuring the parameters of IPN.Results ULM technology can perform ultra-high resolution imaging of the IPN in rabbit carotid atherosclerotic plaques,and can accurately measured the density of IPN.The correlation with pathological diagnosis was good(r=0.915,P<0.05).Conclusion ULM technique has a certain reliability in detecting the IPN in rabbit carotid atherosclerotic plaque.
10.Application of Rabbit Carotid Atherosclerotic Plaque Neovascularization using Ultrasound Localization Microscopy
Junyi REN ; Wen-kun BAI ; Yuanyi ZHENG
Journal of Medical Research 2024;53(11):35-39
Objective To investigate the correlation between intraplaque neovascularization(IPN)parameters using ultrasound lo-calization microscopy(ULM)and pathological results.Methods Atherosclerosis of the carotid artery in rabbit was induced using balloon catheter damage and a high-cholesterol diet.ULM technology was used to measure the IPN,and the parameters of neovascularization density,diameter,distortion and velocity were quantified,and compared with pathological results,to evaluate the reliability of ULM tech-nique in detecting and measuring the parameters of IPN.Results ULM technology can perform ultra-high resolution imaging of the IPN in rabbit carotid atherosclerotic plaques,and can accurately measured the density of IPN.The correlation with pathological diagnosis was good(r=0.915,P<0.05).Conclusion ULM technique has a certain reliability in detecting the IPN in rabbit carotid atherosclerotic plaque.

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