1.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.
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.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.
6.The reliability and validity of cervical movement sense measurement in patients with chronic non-specific neck pain
Lingfeng XIE ; Yimin ZHAO ; Qian ZHENG
Chinese Journal of Rehabilitation Medicine 2024;39(12):1829-1833
Objective:To observe the validity of the transversal 8(T8)graphs and zigzag(ZZ)graphs tests in the measure-ment of cervical movement sense(CMS),and to study their effectiveness in evaluating patients with chronic non-specific neck pain.Method:A total of 71 subjects were recruited,including 35 with chronic non-specific neck pain and 36 healthy subjects.Two groups of researchers separately conducted tests(T8 and ZZ)to the subjects twice,re-corded the test process and scored the test by slow playback.The intra-and inter-rater reliability was quanti-fied in terms of inter-class correlation coefficients(ICCs)and the difference in index between the two groups was also determined for validity.Result:The intra-and inter-rater ICC for ZZ graph and T8 graph tests were 0.813/0.832 and 0.892/0.908,the corresponding standard error of measurement(SEM)values were 1.15/1.10,1.24/1.37,while the minimal detect-able change(MDC)values were 3.18/2.73,3.44/3.05.There was a significant difference in the results of the ZZ graphs and the T8 graphs tests between patients with chronic non-specific neck pain and healthy individu-als(P<0.05).The ideal cut-off values using to distinguish normal individuals from patients with chronic non-specific neck pain are 10.5 for ZZ graphs test and 16.3 for T8 graphs test.Conclusion:The T8 graphs and ZZ graphs tests showed good intra-and inter-raters reliability in assessing cervi-cal movement sense,which can help distinguish patients with chronic non-specific neck pain and the healthy in-dividuals.They can be considered as a cervical movement sense assessment method in the patients with chron-ic non-specific neck pain.
7.Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation
Lingfeng XIAO ; Chunhui MA ; Shunli ZHAO ; Qing LI ; Chunying LIU ; Yamei NIU ; Weimin TONG
Chinese Journal of Pathology 2024;53(5):452-457
Objective:To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment.Methods:Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella.Results:Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P<0.05). Conclusions:Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.
8.The reliability and validity of cervical movement sense measurement in patients with chronic non-specific neck pain
Lingfeng XIE ; Yimin ZHAO ; Qian ZHENG
Chinese Journal of Rehabilitation Medicine 2024;39(12):1829-1833
Objective:To observe the validity of the transversal 8(T8)graphs and zigzag(ZZ)graphs tests in the measure-ment of cervical movement sense(CMS),and to study their effectiveness in evaluating patients with chronic non-specific neck pain.Method:A total of 71 subjects were recruited,including 35 with chronic non-specific neck pain and 36 healthy subjects.Two groups of researchers separately conducted tests(T8 and ZZ)to the subjects twice,re-corded the test process and scored the test by slow playback.The intra-and inter-rater reliability was quanti-fied in terms of inter-class correlation coefficients(ICCs)and the difference in index between the two groups was also determined for validity.Result:The intra-and inter-rater ICC for ZZ graph and T8 graph tests were 0.813/0.832 and 0.892/0.908,the corresponding standard error of measurement(SEM)values were 1.15/1.10,1.24/1.37,while the minimal detect-able change(MDC)values were 3.18/2.73,3.44/3.05.There was a significant difference in the results of the ZZ graphs and the T8 graphs tests between patients with chronic non-specific neck pain and healthy individu-als(P<0.05).The ideal cut-off values using to distinguish normal individuals from patients with chronic non-specific neck pain are 10.5 for ZZ graphs test and 16.3 for T8 graphs test.Conclusion:The T8 graphs and ZZ graphs tests showed good intra-and inter-raters reliability in assessing cervi-cal movement sense,which can help distinguish patients with chronic non-specific neck pain and the healthy in-dividuals.They can be considered as a cervical movement sense assessment method in the patients with chron-ic non-specific neck pain.
9.Investigation on the mechanism of Compound zaoren granules in improving insomnia based on serum meta-bonomics
Zekun WANG ; Shenlin LIU ; Xiaocong YU ; Danting LI ; Lingfeng ZHANG ; Yimeng ZHAO ; Chen CHEN ; Yajun CHEN ; Yachun SHU
China Pharmacy 2023;34(9):1093-1098
OBJECTIVE To study the mechanism of Compound zaoren granule in improving insomnia. METHODS Forty-nine mice were divided into blank group, model group, positive control group 1 (Estazolam tablets 0.5 mg/kg),control group 2 (Shumian capsule 0.6 g/kg), Compound zaoren granule low-dose, medium-dose and high-dose groups (2.5, 5, 10 g/kg), with 7 mice in each group. The insomnia model was established by chronic unpredictable mild stress combined with 4-chloro-DL- phenylacetic acid. The behavioral changes of mice were investigated through open field test and pentobarbital sodium synergistic hypnosis experiment, as well as the pathomorphology of mice hypothalamus tissue was observed by HE staining. The metabonomics analysis and multivariate statistical analysis of serum in mice were performed by UHPLC-Q-TOF-MS/MS, and the differential metabolites were screened out; the metabolic pathway analysis was conducted based on MetaboAnalyst 5.0 database. RESULTS Compared with blank group, the total travelling distance, the number of entering the central region and the moving distance in the central region of the model group were significantly reduced (P<0.05), the proportion of total rest time was significantly increased (P<0.05), the sleep duration of mice was significantly shortened (P<0.05), and hypothalamic nerve cells damaged and severely vacuolated. Compared with model group, the total travelling distance of Compound zaoren granule low-dose and medium-dose groups were increased significantly and the proportions of total rest time of those groups were decreased significantly (P<0.05), and the sleep duration of mice in Compound zaoren granule high-dose group was prolonged significantly (P<0.05); the hypothalamic nerve cells of mice in each administration group recovered to varying degrees, and the hypothalamus histiocytes of mice in the Compound zaoren granules high-dose group were closer to those in the blank group. A total of 18 differential metabolites (such as phenylalanine, taurine, norvaline, methionine) and 4 important amino acid metabolic pathways (L-phenylalanine, tyrosine and tryptophan biosynthesis; taurine and hypotaurine metabolism; L-phenylalanine metabolism; cysteine and methionine metabolism) were identified through metabolomics analysis. CONCLUSIONS Compound zaoren granules can normalize the disordered metabolism in vivo by regulating differential metabolites such as phenylalanine, taurine, and four amino acid metabolic pathways, so as to improve insomnia.
10.Mechanism of large-conductance calcium-activated potassium channel involved in inflammatory response in sepsis.
Kun WU ; Lingfeng ZHAO ; Yuping WANG ; Pan LIU ; Shenju CHENG ; Xiao YANG ; Ying WANG ; Yancui ZHU
Chinese Critical Care Medicine 2023;35(5):469-475
OBJECTIVE:
To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis.
METHODS:
The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis.
RESULTS:
The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05).
CONCLUSIONS
BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans
;
Histones
;
Caspase 1
;
Large-Conductance Calcium-Activated Potassium Channels
;
Lipopolysaccharides
;
NF-kappa B
;
NLR Family, Pyrin Domain-Containing 3 Protein
;
L-Lactate Dehydrogenase
;
Sepsis
;
RNA, Small Interfering
;
Caspases

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