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.Risk factors for Crohn's disease-like pouch in ulcerative colitis patients with ileal pouch-anal anastomosis
Yinan YAN ; Juan WEI ; Zhao YANG ; Ya YANG ; Hui TAO ; Liuying LI ; Hongqin WANG ; Yuanyi ZHAO ; Feng ZHU ; Ji XUAN ; Jianfeng GONG ; Fangyu WANG
Chinese Journal of Inflammatory Bowel Diseases 2025;09(3):211-217
Objective:To explore the incidence of Crohn's disease-like pouch (CDP) after ileal pouch-anal anastomosis (IPAA) and analyze the clinical characteristics and risk factors in ulcerative colitis (UC) patients.Methods:A retrospective cohort study was conducted. One hundred and eighty-two UC patients undergoing IPAA at Jinling Hospital affiliated to Nanjing University from November 2003 to November 2024 were enrolled. Patients were categorized into CDP and non-CDP groups. Clinical features and prognosis were compared, and multivariate Cox regression was performed to identify risk factors for CDP.Results:A total of 182 UC patients were included, with a median follow-up time of 45.00 (30.00, 75.25) months. The patients were divided into two groups based on the diagnosis of CDP, with 23 patients (12.64%) in the CDP group and 159 patients (87.30%) in the non-CDP group. Compared to the non-CDP group, patients in the CDP group had a lower body mass index (BMI) ( Z=-2.87, P=0.004), and were more likely to develop early postoperative pouchitis (χ 2=4.50, P=0.034). The median time from ileostomy closure to the development of CDP was 12 .00 (6.00, 28.00) months. Cox regression analysis showed that a preoperative BMI<18.5 kg/m 2 ( HR=2.84, 95% CI: 1.24~6.49, P=0.013) and early postoperative pouchitis ( HR=3.11, 95% CI: 1.22~7.93, P=0.018) were associated with an increased risk of CDP. Conclusions:Preoperative low BMI and pouchitis occurring within 3 months postoperatively are significant risk factors for CDP. Close monitoring and early intervention are recommended for high-risk patients.
6.Advances in immune checkpoint inhibitor therapy for breast cancer:research progress and future directions
Cheng ZENG ; Yuanyi WANG ; Jiani WANG ; Fei MA
China Oncology 2025;35(2):195-204
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.
7.Application of interventional teaching in undergraduate nursing internship in operating rooms
Xuemei YI ; Yuanyi WANG ; Huifeng TANG ; Li WANG ; Qian YANG ; Gang WANG
Chinese Journal of Medical Education Research 2025;24(9):1278-1283
Objective:To explore the application effect of interventional teaching in undergraduate nursing internship in operating rooms.Methods:A total of 98 undergraduate nursing students who worked as interns in the operating room during the two school years from June 2022 to February 2024 were selected as research subjects. Students who entered the program from June 2022 to February 2023 were enrolled into control group (50 students), and those who entered from June 2023 to February 2024 were enrolled into experimental group (48 students). The students conducted their internships in batches (with 4 to 5 students per subgroup) following a departmental rotation mechanism. The control group received routine teaching, while the experimental group received interventional teaching. At the end of the internship, the two groups were compared for their performance, including basic and specialized knowledge, skills, theory, and operation; patient reception, tripartite verification, and intraoperative cooperation for planned video-assisted thoracoscopic bullectomy; and their degrees of satisfaction with the teaching. The t-test was performed using SPSS 26.0. Results:The experimental group achieved significantly higher theoretical scores than the control group [(91.69±4.51) vs. (74.52±6.06)]. Meanwhile, the experimental group was significantly superior to the control group in operational performance, including surgical hand disinfection [(96.08±1.93) vs. (92.14±3.07)] and wearing and removing sterile surgical gowns and sterile gloves [(97.00±1.75) vs. (94.10±3.48)). In terms of specialized knowledge and skills, specifically, patient reception and third-party verification in simulated surgical nursing, the experimental group achieved higher scores than the control group [(98.77±0.69) vs. (94.04±2.56); (98.54±0.65) vs. (94.64±2.65)]. In terms of intraoperative cooperation, the experimental group showed a slight advantage over the control group. The experimental group had higher degrees of satisfaction with teaching than the control group, including course design, implementation methods, course arrangement, teaching attitude, teaching methods, degree of participation, gains, and assistance.Conclusions:After adopting interventional teaching, the teaching effect for nursing internship in operating rooms is better. It improves the various assessment scores of nursing students, enhances their comprehensive abilities and degrees of satisfaction with teaching, and reinforces the teaching abilities in operating rooms.
8.Advances in immune checkpoint inhibitor therapy for breast cancer:research progress and future directions
Cheng ZENG ; Yuanyi WANG ; Jiani WANG ; Fei MA
China Oncology 2025;35(2):195-204
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.
9.Risk factors for Crohn's disease-like pouch in ulcerative colitis patients with ileal pouch-anal anastomosis
Yinan YAN ; Juan WEI ; Zhao YANG ; Ya YANG ; Hui TAO ; Liuying LI ; Hongqin WANG ; Yuanyi ZHAO ; Feng ZHU ; Ji XUAN ; Jianfeng GONG ; Fangyu WANG
Chinese Journal of Inflammatory Bowel Diseases 2025;09(3):211-217
Objective:To explore the incidence of Crohn's disease-like pouch (CDP) after ileal pouch-anal anastomosis (IPAA) and analyze the clinical characteristics and risk factors in ulcerative colitis (UC) patients.Methods:A retrospective cohort study was conducted. One hundred and eighty-two UC patients undergoing IPAA at Jinling Hospital affiliated to Nanjing University from November 2003 to November 2024 were enrolled. Patients were categorized into CDP and non-CDP groups. Clinical features and prognosis were compared, and multivariate Cox regression was performed to identify risk factors for CDP.Results:A total of 182 UC patients were included, with a median follow-up time of 45.00 (30.00, 75.25) months. The patients were divided into two groups based on the diagnosis of CDP, with 23 patients (12.64%) in the CDP group and 159 patients (87.30%) in the non-CDP group. Compared to the non-CDP group, patients in the CDP group had a lower body mass index (BMI) ( Z=-2.87, P=0.004), and were more likely to develop early postoperative pouchitis (χ 2=4.50, P=0.034). The median time from ileostomy closure to the development of CDP was 12 .00 (6.00, 28.00) months. Cox regression analysis showed that a preoperative BMI<18.5 kg/m 2 ( HR=2.84, 95% CI: 1.24~6.49, P=0.013) and early postoperative pouchitis ( HR=3.11, 95% CI: 1.22~7.93, P=0.018) were associated with an increased risk of CDP. Conclusions:Preoperative low BMI and pouchitis occurring within 3 months postoperatively are significant risk factors for CDP. Close monitoring and early intervention are recommended for high-risk patients.
10.Application of interventional teaching in undergraduate nursing internship in operating rooms
Xuemei YI ; Yuanyi WANG ; Huifeng TANG ; Li WANG ; Qian YANG ; Gang WANG
Chinese Journal of Medical Education Research 2025;24(9):1278-1283
Objective:To explore the application effect of interventional teaching in undergraduate nursing internship in operating rooms.Methods:A total of 98 undergraduate nursing students who worked as interns in the operating room during the two school years from June 2022 to February 2024 were selected as research subjects. Students who entered the program from June 2022 to February 2023 were enrolled into control group (50 students), and those who entered from June 2023 to February 2024 were enrolled into experimental group (48 students). The students conducted their internships in batches (with 4 to 5 students per subgroup) following a departmental rotation mechanism. The control group received routine teaching, while the experimental group received interventional teaching. At the end of the internship, the two groups were compared for their performance, including basic and specialized knowledge, skills, theory, and operation; patient reception, tripartite verification, and intraoperative cooperation for planned video-assisted thoracoscopic bullectomy; and their degrees of satisfaction with the teaching. The t-test was performed using SPSS 26.0. Results:The experimental group achieved significantly higher theoretical scores than the control group [(91.69±4.51) vs. (74.52±6.06)]. Meanwhile, the experimental group was significantly superior to the control group in operational performance, including surgical hand disinfection [(96.08±1.93) vs. (92.14±3.07)] and wearing and removing sterile surgical gowns and sterile gloves [(97.00±1.75) vs. (94.10±3.48)). In terms of specialized knowledge and skills, specifically, patient reception and third-party verification in simulated surgical nursing, the experimental group achieved higher scores than the control group [(98.77±0.69) vs. (94.04±2.56); (98.54±0.65) vs. (94.64±2.65)]. In terms of intraoperative cooperation, the experimental group showed a slight advantage over the control group. The experimental group had higher degrees of satisfaction with teaching than the control group, including course design, implementation methods, course arrangement, teaching attitude, teaching methods, degree of participation, gains, and assistance.Conclusions:After adopting interventional teaching, the teaching effect for nursing internship in operating rooms is better. It improves the various assessment scores of nursing students, enhances their comprehensive abilities and degrees of satisfaction with teaching, and reinforces the teaching abilities in operating rooms.

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