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.

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.

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.

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.

Background::Fibrosis in the peripheral airways contributes to airflow limitation in patients with chronic obstructive pulmonary disease (COPD). However, the key proteins involved in its development are still poorly understood. Thus, we aimed to identify the differentially expressed proteins (DEPs) between smoker patients with and without COPD and elucidate the molecular mechanisms involved by investigating the effects of the identified biomarker candidate on lung fibroblasts.Methods::The potential DEPs were identified by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. The messenger RNA and protein levels of clusterin (CLU) in COPD patients and 12% cigarette smoke extract (CSE)-treated human bronchial epithelial cells were determined at the indicated time points. Furthermore, an in vitro COPD model was established via the administration of 8% CSE to normal human lung fibroblasts (NHLFs) at indicated time points. The effects of CSE treatment and CLU silencing on proliferation and activation of lung fibroblasts were analyzed. Results::A total of 144 DEPs were identified between COPD patients and normal smokers. The iTRAQ-based proteomics and bioinformatics analyses identified CLU as a serum biomarker candidate. We also discovered that CLU levels were significantly increased ( P < 0.0001) in Global Initiative for Obstructive Lung Disease II, III, and IV patients and correlated ( P < 0.0001) with forced expiratory volume in 1 s ( R=-0.7705), residual volume (RV) ( R = 0.6281), RV/total lung capacity ( R = 0.5454), and computerized tomography emphysema ( R = 0.7878). Similarly, CLU levels were significantly increased in CSE-treated cells at indicated time points ( P < 0.0001). The CSE treatment significantly inhibited the proliferation, promoted the inflammatory response, differentiation of NHLFs, and collagen matrix deposition, and induced the apoptosis of NHLFs; however, these effects were partially reversed by CLU silencing. Conclusion::Our findings suggest that CLU may play significant roles during airway fibrosis in COPD by regulating lung fibroblast activation.

Objective To investigate the preventive and inhibitory effects of tumor cell lysate(TCL) combined with IL-2 on melanoma and the potential immune mechanism. Methods The B16F10 melanoma TCL cell were prepared using an ultrasonic disruptor. Twenty-four C57BL/6 mice were randomly divided into four groups which were immunized with PBS, IL-2, TCL and TCL+IL-2 for three weeks, and contra lateral tumors were implanted in the fourth week. We observed onset time of tumor and tumor size, collected peripheral blood continuously and monitored the expression of CD4⁺T and CD8⁺T cell subsets dynamically by flow cytometry. Spleen and tumor tissues of mice were also tested for CD4⁺T and CD8⁺T cell subsets by flow cytometry and immunohistochemistry, respectively. Results The preventive immunization of the TCL+IL-2 group significantly delayed the onset time of tumor (P=0.034); moreover, the tumor volume (P=0.023) and tumor weight (P=0.0015) were also significantly smaller than those in the control group. The expression of CD8⁺T cell subsets in the TCL+IL-2 group and the TCL-only group were significantly higher than that in the control group (P=0.0016, P=0.012). However, the CD4⁺T cell subsets of the TCL+IL-2 group decreased after tumor implantation, compared with the control group (P=0.0089). The expression of CD4⁺T and CD8⁺T cell subsets in spleen and tumor tissues were as same as those in peripheral blood. Conclusion The tumor vaccine of TCL combined with IL-2 could prevent the occurrence of melanoma in mouse and effectively inhibit tumor growth by activating CD8⁺T cells.

To evaluate the feasibility of magnetic navigation ultrasonography system in guiding the puncture of percutaneous posterior endoscopic cervical discectomy ( PPECD ) . Methods T he cervical CT data of 6 patients with cervical spondylosis were used to made 3D printing model ,then the localized puncture of the model was guided by the magnetic navigation ultrasonography system ,1‐mm‐slice transection CT scans were obtained to confirm the placement of the needle tips after puncture . T he total puncture time and the distance between the pinpoint in the lateral and longitudinal directions from the ＂V point＂were recorded . Results All the 36 puncture operations accurately located the target segment without penetrating the spinal canal . T he average lateral distance of the needle tip from the ＂V point＂was 2 .88 mm ( 0－7 .12 mm ) ,meanw hile the average longitudinal distance was 1 .64 mm ( 0 －4 .45 mm ) ,and the the w hole process took 3 .72 min( 2 .42－5 .20 min) . T hirty‐three of 36 points were in the circle with ＂V point＂as the center and 5mm as the radius ,puncture success rate was 91% . Conclusions T he puncture model established in this study can be used as a teaching tool ,magnetic navigation ultrasonography system has successfully guided the posterior cervical intervertebral disc puncture on the model ,and there is no radiation exposure during the operation process ,which has a promising clinical application prospect .

Objective To prepare a novel loaded NdFeB and Fe3O4 liquid-solid phase inversion poly (polylactic-co-glycolic acid,PLGA) in situ implant (PLGA 60％ NdFeB-20％ Fe3O4) for ultrasound-guided intratumoral injection,and to investigate its intensity of magnetism and therapeutic efficiency of nude mice bearing MDA-MB-231 breast cancer.Methods PLGA-60 ％ NdFeB-20 ％ Fe3O4 in situ implant was prepared.The microstructure of PLGA-60 ％ NdFeB-20 ％ Fe3O4 was tested with scanning electron microscope (SEM).Magnetometer was used to qualify the intensity of magnetism.For the in vitro assay,60 μl solid PLGA-60％ NdFeB-20％ Fe3O4 implant was put in the center of the electromagnetic induction heating coil.Infrared thermal video of the tubes was simultaneously recorded.The size of 2 cm × 2 cm× 2 cm fresh ex vivo bovine liver was prepared,and then 60 μl PLGA-60％ NdFeB-20％ Fe3O4 was injected into it.Similarly,ex vivo bovine liver was heated by the above intermittent time for 1,2,3,4 minutes,respectively,and the ablation volume was calculated.Finally,nude mice were equally divided into treatment group and control group.Mice in treatment group were discontinuously heated for 3 min after being injected with the above mentioned implant,while CEUS was performed before and after heating to observe the blood perfusion in the tumor.One nude mouse was executed on the next day in each group,then pathological sections and HE staining of tumor tissue were taken,whereas the growth of the remaining nude mice were observed daily.Results SEM showed the implant with rough and porous surface.The magnetism increased with the volume of material.The tube and bovine liver experiments showed that the PLGA-60 ％ NdFeB-20％ Fe3O4 generated heat efficiently.The bovine liver ablation experiment showed that the range of ablation of 60 μl PLGA-60 ％ NdFeB-20％ Fe3O4 implant reached (2.34±0.25)cm3 after 3 min heating.In vivo experiments showed that the tumor tissue began to form a scab on the 2nd day,and the scab began to desquamate on the 20th day.CEUS showed the original predominant enhancement disappeared significantly after the treatment.HE staining proved that cancer cells had coagulative necrosis,whereas tumors in control group became bigger.Conclusion PLGA-60％ NdFeB-20％ Fe3O4 in situ implant can produce obvious thermal effect under high frequency alternating magnetic field,therefore can be effectively ablated with nude mice MDA-MB-231 breast cancer during time interval heating.

Objective To investigate the reliability and validity of the medical outcomes by applying short form-36 (SF-36) in evaluating gout patients’ health related quality of life (HRQOL).Methods Gout patientswere enrolled between March 2016 and June 2016 in Foshan Hospital of Traditional Chinese Medicine.Patients completed the SF-36 questionnaire.Summary scores,physical component summary (PCS) and mental component summary (MCS) were calculated by summing factor-weighted scores across all 8 subscales,with factor weights derived from general population.The indicators of reliability and validity included internal consistency,test-retest reliability,structural and discriminant validity,ceiling and floor effect.Results Totally 306 patients were enrolled.The internal consistency test showed that the Cronbach α coefficients ranged from 0.782 to 0.822,and the test-retest reliability coefficients ranged from 0.720 to 0.986 (P＜0.01).Structural validity analysis showed that there were two items whose eigenvalues were greater than one with the cumulative contribution rate of 66.1％.The discriminant validity analysis found that patients with more numbers of tophi,higher frequency of flare,multi-arthrosis involved and more complications had less scores of PCS and MCS (P＜0.05).There was a high ceiling effect on physiological function and a higher ceiling and floor effect on role limitation and emotional function caused hy impaired physical health.Conclusion The SF-36 can be used for the assessment of HRQOL in Chinese gout patients but disease specific questionnaire are warranted.

With the continuous development of musculoskeletal ultrasound,ultrasound diagnosis of inflammatory arthri tis,especially early diagnosis had an increasing important role.Psoriatic arthritis (PsA) was a kind of inflammatory arthritis,which was closely related with psoriasis.It could involve the whole body's large and small joints,especially peripheral joints (often asymmetric),sacroiliac joint and spine.The course of PsA was protracted and easy to recur.Clinical and ima ging manifestations of PsA are similar to rheumatoid arthritis (RA),and need to identify diagnosis.The diagnosis and antidiastole in musculoskeletal ultrasound of PsA were reviewed in this article.