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.Impairment of TRPC1-BK complex in diabetic rat coronary artery.
Manqing SUN ; Lingling QIAN ; Lingfeng MIAO ; Ying WU ; Xiaoyu LIU ; Shipeng DANG ; Xu TANG ; Zhenye ZHANG ; Chao WANG ; Qiang CHAI ; Fu YI ; Jianfeng HAO ; Ruxing WANG
Chinese Medical Journal 2022;135(15):1873-1875
6.Development of a scoliosis rehabilitation robot and a preliminary study of its effectiveness in treating coronal deformity
Li WANG ; Chun WANG ; Nan XIA ; Lingfeng XIE ; Zhiwei TANG ; Jie HUANG ; Xiaolin HUANG
Chinese Journal of Physical Medicine and Rehabilitation 2021;43(10):899-903
Objective:To explore the appropriate use of a self-developed scoliosis rehabilitation robot in treating adolescent idiopathic scoliosis (AIS), and also its safety and effectiveness.Methods:The scoliosis rehabilitation robot consists of a closed-loop pneumatic control system and multi-segment torso, pelvis and upper extremity fixation devices. It provides three-dimensional synchronous correction. Eighteen AIS subjects first received 30min of robot-assisted treatment using the maximum tolerable orthotic force. The angles of their spinal processes were evaluated using ultrasound before the treatment and after 30 seconds, 5 minutes and 30 minutes of treatment, then 5min later. In a second 30sec course of treatment the transverse orthotic force was 10%, 15%, 20%, 25%, and 30% of the patient′s body weight. Any adverse effects were observed and recorded.Results:The robot ran smoothly and could apply intelligent and precise correction. No severe adverse effects were reported. The mean correction of the spinal process angles showed a significant cumulative effect with treatment time, reaching 104% at 30min. The mean process angle correction increased with the applied force. Force at 25% of the patient′s weight produced an average correction of 104% in patients with mild AIS and 65% in those whose AIS was moderate.Conclusion:The scoliosis rehabilitation robot is safe and immediately effective. Setting the transverse force at 25% of a patient′s weight gives the best corrective effect with mild AIS. Moderate AIS requires more force.
7.Clinical study on structural chest zones of gynecomastia
Lingfeng CHEN ; Baojin WU ; Sida PAN ; Zhaoping ZHOU ; Xinjie TANG ; Ronghu KE
Chinese Journal of Plastic Surgery 2020;36(12):1355-1359
Objective:To discuss the clinical significance of structural chest zones for gynecomastia.Methods:A total of 687 gynecomastia patients, aged from 14 to 45 years old, with an average age of 27.0, were admitted to the Department of Plastic Surgery, Huashan Hospital Fudan University from January 2012 to December 2018. Simon classification was used to record. Conduct Simon classification according to the preoperative measurement of the chest. Surgical area design, photo analysis, breast ultrasound examination and Derriford appearance scale evaluation were conducted as well. Six zones can be divided as follows: zone 0 nipple-areola zone, zone 1 gynecomastia zone, zone 2 accessory-breast zone, zone 3 lateral-roll zone, zone 4 IMF(inframammary fold) zone, zone T relative-contraindication zone. Positive and lateral images of the chest were taken before and one week, one month, three months, six months, and 12 months after the operation, and the preoperative and postoperative changes of each structural zone were compared. At the follow-up of 12 months after the operation, patients’ satisfaction was counted.Results:687 patients, according to Simon classification, were divided toⅠ degreein 65 cases, Ⅱa degree in 257 cases, Ⅱb degreein 194 cases, Ⅲ degree in 171 cases. Before operation, except for Simon Ⅰ degree in 65 cases showed just raised to 0 zone, most of the rest of the patients contains 1 zone raised, 2-4 zones come in different patients. After liposuction and glandular stripping were performed in different zones, postoperative follow-up was conducted one week, one month, three months, six months, and 12 months after the operation. The dynamic observation was made of the change process of chest shape shaping during the follow-up, whether there were postoperative complications, poor local shape, or bad regional shape. Evaluation results of patient satisfaction 12 months after surgery: among the 687 patients, there were 634 patients with 10 points of satisfaction, and 53 patients with 8-9 points, including 48 patients of zone 0 and zone 1, three patients of zone 3, and 2 patients of zone 4.Conclusions:The structural chest zones of gynecomastia provides plastic surgeons and male patients with simple, intuitive, and highly recognized preoperative evaluation, which can provide appropriate, simplified, and accurate guidance for the selection of surgical methods.
8.Clinical study on structural chest zones of gynecomastia
Lingfeng CHEN ; Baojin WU ; Sida PAN ; Zhaoping ZHOU ; Xinjie TANG ; Ronghu KE
Chinese Journal of Plastic Surgery 2020;36(12):1355-1359
Objective:To discuss the clinical significance of structural chest zones for gynecomastia.Methods:A total of 687 gynecomastia patients, aged from 14 to 45 years old, with an average age of 27.0, were admitted to the Department of Plastic Surgery, Huashan Hospital Fudan University from January 2012 to December 2018. Simon classification was used to record. Conduct Simon classification according to the preoperative measurement of the chest. Surgical area design, photo analysis, breast ultrasound examination and Derriford appearance scale evaluation were conducted as well. Six zones can be divided as follows: zone 0 nipple-areola zone, zone 1 gynecomastia zone, zone 2 accessory-breast zone, zone 3 lateral-roll zone, zone 4 IMF(inframammary fold) zone, zone T relative-contraindication zone. Positive and lateral images of the chest were taken before and one week, one month, three months, six months, and 12 months after the operation, and the preoperative and postoperative changes of each structural zone were compared. At the follow-up of 12 months after the operation, patients’ satisfaction was counted.Results:687 patients, according to Simon classification, were divided toⅠ degreein 65 cases, Ⅱa degree in 257 cases, Ⅱb degreein 194 cases, Ⅲ degree in 171 cases. Before operation, except for Simon Ⅰ degree in 65 cases showed just raised to 0 zone, most of the rest of the patients contains 1 zone raised, 2-4 zones come in different patients. After liposuction and glandular stripping were performed in different zones, postoperative follow-up was conducted one week, one month, three months, six months, and 12 months after the operation. The dynamic observation was made of the change process of chest shape shaping during the follow-up, whether there were postoperative complications, poor local shape, or bad regional shape. Evaluation results of patient satisfaction 12 months after surgery: among the 687 patients, there were 634 patients with 10 points of satisfaction, and 53 patients with 8-9 points, including 48 patients of zone 0 and zone 1, three patients of zone 3, and 2 patients of zone 4.Conclusions:The structural chest zones of gynecomastia provides plastic surgeons and male patients with simple, intuitive, and highly recognized preoperative evaluation, which can provide appropriate, simplified, and accurate guidance for the selection of surgical methods.
9. Effects of n-3 polyunsaturated fatty acid on store-operated calcium channels in coronary artery smooth muscle cells derived from diabetic rat
Xu TANG ; Lingling QIAN ; Shipeng DANG ; Ying WU ; Xiaoyu LIU ; Zhenye ZHANG ; Lingfeng MIU ; Ruxing WANG
Chinese Journal of Cardiology 2019;47(8):640-646
Objective:
To investigate the impact of n-3 polyunsaturated fatty acid (n-3 PUFA) on function and expression of store-operated calcium channels (SOCC) in coronary artery smooth muscle cells (SMC) derived from diabetic rat.
Methods:
A total of 180 healthy male Sprague-Dawley (SD) rats were randomly divided into normal group (N,
10.Effects of n?3 polyunsaturated fatty acid on store?operated calcium channels in coronary artery smooth muscle cells derived from diabetic rat
Xu TANG ; Lingling QIAN ; Shipeng DANG ; Ying WU ; Xiaoyu LIU ; Zhenye ZHANG ; Lingfeng MIU ; Ruxing WANG
Chinese Journal of Cardiology 2019;47(8):640-646
Objective To investigate the impact of n?3 polyunsaturated fatty acid (n?3 PUFA) on function and expression of store?operated calcium channels (SOCC) in coronary artery smooth muscle cells (SMC) derived from diabetic rat. Methods A total of 180 healthy male Sprague?Dawley (SD) rats were randomly divided into normal group (N, n=45), placebo?treated diabetic group (D, n=45), lose dose n?3 PUFA treated diabetic group (DL, n=45) and high dose n?3 PUFAs treated diabetic group (DH, n=45). Streptozotocin?induced diabetic rat animal model was established by two consecutive intraperitoneal injections. After modeling, rats in group DL and DH were treated with 10 mg·kg-1·d-1 and 50 mg·kg-1·d-1 n?3 PUFAs respectively per gavage for eight weeks. After eight weeks, rat coronary artery SMC was isolated by enzyme digestion. Changes of cytosolic calcium concentration in coronary artery SMC were examined by calcium fluorescence imaging technique, coronary artery tension was detected by myograph system, and protein expressions of SOCC on coronary artery SMC were measured by Western blot. Results SOCC induced ΔF340/F380 of group N, D, DL and DH were 0.425±0.023, 0.838±0.037, 0.342±0.052 and 0.364± 0.045 respectively, which was significantly lower in group N, DL, DH than in group D (P<0.05). SOCC induced changes of tensions were 0.94±0.09, 1.95±0.18, 1.35±0.24 and 1.01±0.18 in the group N, D, DL and DH, respectively, which was significantly lower in group N and DH than in group D (P<0.05). Protein expressions of STIM1, Orai1 and TRPC1 were significantly higher in diabetic rat coronary SMC than in group N (P<0.05). STIM1 protein expressions were significantly lower in group DL and DH than in group D, and Orai1 and TRPC1 protein expressions were similar among group. Conclusions Coronary artery tension, cytosolic calcium concentration and protein expressions of SOCC are higher in diabetic rat coronary artery SMC when compared with normal rats. n?3 PUFA intervention could downregulate the protein expression of SOCC, reduce cytosolic calcium concentration and coronary artery tension, and is protective to the diabetic injury in coronary artery.

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