Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

To analyze the disease group structure and its trends in key departments of large public hospitals using diagnosis related group (DRG) data, explore the key points of intervention and optimization of disease groups in departments, and further promote the rational allocation of department resources.

Excessive N-acetyl-p-benzoquinone imine(NAPQI)formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen(APAP)overdose caused acute liver failure(ALF).S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity.Glutaredoxin-1(Glrx1),a glutathione-specific thioltransferase,is a primary enzyme to catalyze deglutathionylation.The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP.The Glrx1 knockout mice(Glrx1-/-)and liver-specific overexpression of Glrx1(AAV8-Glrx1)mice were produced and underwent APAP-induced ALF.Pirfenidone(PFD),a potential inducer of Glrx1,was administrated preceding APAP to assess its protective effects.Our results revealed that the hepatic total protein S-glutathionylation(PSSG)increased and the Glrx1 level reduced in mice after APAP toxicity.Glrx1-/- mice were more sensitive to APAP overdose,with higher oxidative stress and more toxic metabolites of APAP.This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a 11(Cyp3a11),which likely increased the activity of Cyp3a11.Conversely,AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11,which reduced the toxic metabolites of APAP and oxidative stress.PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress.We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose.Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

Objective:To analyze the risk factors of Intensive Care Unit-Acquired Weakness, and to develop and verify the model.Methods:A total of 247 patients admitted to ICU patients from November 2018 to October 2019 were selected, and risk factors between ICU acquired weakness group ( n=106) and non-ICU acquired weakness group( n=141)were compared using logistic regression for model construction.The Hosmer-Lemeshow test was used to verify the goodness of fit of the model. The area under the ROC curve was used to test the model to predict the effects. From November 2019 to May 2020, 106 patients were recruited for application of the model. Results:The incidence of ICU acquired weakness in this study was 42.91%(106/247), and 44.34%(47/106),the study finally included age ( OR=1.043) ,mechanical ventilation time ( OR=1.140) , APACHE II score ( OR=1.081) , blood sugar ( OR=1.117) , lactic acid( OR=1.459) ,and neuromuscular blockers ( OR=3.499) to construct the risk prediction. The model formula was P=1/1+exp (- Z) =1/1+exp (8.808-0.042×age -1.252×neuromuscular blockers-0.078×APACHE II score -0.110×blood sugar -0.378×lactic acid -0.131×mechanical ventilation time. The area under the ROC curve of this model was 0.896 (95% CI: 0.824-0.914) , the maximum value of the Youden index was 0.577, and the corresponding sensitivity was 0.754,the specificity was 0.823,the cutoff value was 0.503. The model verification results the sensibility of 70.2%, the specificity of 88.1%, and the accuracy of 80.2%. Conclusion:The predictic model of ICU acquired weakness couducted in this study has satisfactory prediction effect, which can provide a reference for clinical screening of high-risk patients.

Objective:To explore the risk factors for myelosuppression in elderly lung cancer patients undergoing chemotherapy and construct a risk prediction model for myelosuppression in elderly lung cancer patients undergoing chemotherapy.Methods:Using the convenient sampling method, data of 228 elderly patients with lung cancer undergoing chemotherapy in Respiratory Department of a Class Ⅲ Grade A hospital in Zhenjiang from May 2018 to May 2019 were selected, and risk factors of adverse reactions of myelosuppression in patients were analyzed statistically. The binomial Logistic regression was applied to construct the prediction model and the area under the ROC curve was used to test the prediction effect of the model. The patient data from January to May 2020 were collected to validate the model.Results:Among the 228 patients, 75 patients developed myelosuppression, with an incidence of 32.89%. Multivariate analysis results showed that platinum-containing chemotherapy regimens, combined with other adverse reactions, decreased albumin before chemotherapy and decreased hemoglobin before chemotherapy were independent risk factors for myelosuppression in elderly lung cancer patients during chemotherapy ( P<0.05) , which were included in the model. The area under the ROC curve of the final model was 0.823, the maximum Youden index was 0.5, sensitivity was 81.3%, and specificity was 70.5%. The results of the verification data showed that the area under the ROC curve was 0.846, sensitivity was 90.4% and specificity was 68.2%. Conclusions:The prediction effect of this model is good, which can provide reference basis for clinical treatment and formulating nursing measures to prevent myelosuppression.

Objective: In order to evaluate the therapeutic effects and safety of denosumab and bisphosphonates in glucocorticoid induced osteoporosis patients. Methods: Standard studies were obtained by searching CNKI, CBM, VIP, Wanfang, Pubmed, Embase and Cochrane databases. Results: Three RCTs with 869 patients were included in this study. It showed that the mean changes of lumbar spine, total hip and femoral neck bone mineral density (BMD) for patients in denosumab group were increased by 2.47%, 1.43% and 1.07% respectively compared to those of bisphosphonates group.There was no statistically significant difference between patients receiving denosumab and those receiving bisphosphonate in terms of adverse events and serious adverse events. Conclusions Denosumab has an effective increase for lumbar spine, total hip and femoral neck bone mineral density, and the safety of both is similar.

Objective: To study on the genomic stability of male workers engaged in e-waste dismantling area in Tianjin. Methods: In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. The exposed group included 146 workers who engaged in e-waste recycling work more than 1 year. The reference group included 121 farmers who never engaged in e-waste recycling work. Questionnaires were used to collect information of all subjects. The semen and peripheral blood were also collected. Trace elements and polychlorinated biphenyl concentration in blood were detected. DNA damage in peripheral blood and sperm was detected, and gene expression was analyzed. DNA damage was assessed using tail DNA% (TDNA%), tail moment (TM) and olive tail moment (OTM) of comet assay. Results: The ages of the exposed group and the reference group were (33.6±12.1) and (33.9±11.9) years old, respectively. The proportions of subjects with exposure time of ≤3, 4-6, ≥7 years were 43% (63 cases), 26% (53 cases) and 21% (30 cases), respectively. The Pb and polychlorinated biphenyl(PCB) concentrations in the exposed group [(90.4±15.3) μg/ml and (101±30) ng/ml, respectively] were higher than those in the reference group [Pb and PCB concentrations were (60.2±8.9) μg/ml, and (2.5±1.4) ng/ml, respectively (both P values <0.05)]. The TDNA%, TM and OTM of peripheral blood and sperm in the exposed group were 5.9%±0.3% and 2.6%±0.90%, 0.93±0.16 and 0.51±0.20, 0.82±0.09 and 0.56±0.07, respectively, which were all higher than those in the reference group [TDNA%, TM and OTM of peripheral blood and sperm were 1.8%±0.2% and 1.9%±0.2%, 0.21±0.04 and 0.32±0.10, 0.19±0.03 and 0.20±0.08, respectively (all P values <0.001)]. The results of gene expression showed that 20 differentially expressed genes, including 13 up-regulated genes and 7 down-regulated genes, were detected in the exposed group compared with the reference group. Conclusion There are obvious DNA damage and DNA repair gene disorder in male workers of an e-waste dismantling area in Tianjin. The current operation mode brings potential health risks to workers.

Objective: To study on the exposure of polychlorinated biphenyl (PCB) contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin. Methods: In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. A total of 60 subjects (30 in each of the exposed group and the reference group) were included. The peripheral blood (5 ml) of the study subject was collected, and the PCB concentration was detected. Eight independent subjects in the exposed group and the reference group were randomly selected by random number table method to detect the methylation level of the promoter region of all gene loci, and the mRNA transcript levels. Results: The PCB concentration in peripheral blood of the exposed group was higher than that of the reference group, and the difference was statistically significant (allP values <0.001). The methylation levels of the promoter region of the exposed group and the reference group showed obvious clustering, and 994 gene loci had different degrees of methylation. Compared with the reference group, there were 391 hypomethylation sites and 553 hypermethylation sites in the exposed group. The proportion of methylation sites in the high CpG-rich region was 59.2% and 48.1%, respectively. The mRNA level of the hypomethylated gene in the exposed group was higher (FAM131A, HBM), and the transcription level of the hypermethylated gene was lower (CAPN15, NFIC, SHISA5, FGF13, GRAMD1A, CLEC3B, LILRB2, DCAF7). The mRNA transcription levels of 10 genes above in the exposed group and the reference group were statistically significant (all P values <0.001). Conclusion The PCB concentration of peripheral blood in the exposed population of e-waste is high. PCB exposure changes the methylation level of specific genes and affects the mRNA transcription level of some genes.

Objective To investigate the effects of Olaparib on cell proliferation and radiosensitization of human non-small cell lung cancer cells.Methods Non-small cell lung H460 and H1299 cell lines were cultured in vitro and the cells in logarithmic growth phase were selected for experiments.MTT and colony formation assays were used to determine cell proliferation and radiosensitization,respectively.Single cell gel electrophoresis assay (comet assay) was used to detect irradiation-induced DNA damage.Results The results of MTT assay showed that Olaparib inhibited the proliferation of H460 and H1299 cells in a dose-dependent pattern (all P＜0.05).H1299 cell line was more sensitive to Olaparib than H460 cells.The results of colony formation assay showed that Olaparib enhanced the radiosensitizition of H460 and H1299 cells (all P＜0.05).The results of comet assay showed that Olaparib increased γ ray-induced DNA damage.Conclusions Olapani can enhance the radiosensitization of human non-small cell lung cancer cells,and the radiosensitization effect of Olaparib may be associated with the inhibition of cell proliferation and induction of irradiation-induced DNA damage.

Objective To investigate the clinical features and related risk factors of osteoporosis and osteoporotic fracture (OPF) in patients with rheumatic diseases (RD),and the fracture predictive values of fracture risk assessment tool fracture risk assessment (FRAX(R))for Han patients.Methods A total of 313 untreated RD patients were included.Each individual BMD was measured at lumbar spine and femoral neck with Dual-energy X-ray absorptionary.Ten-year probability of fracture (％) was calculated by fracture risk assessment tool FRAX(R) of Chinese model.Each individual previous fracture was confirmed by X-ray or CT examination.The associations between BMD,FRAX),previous fracture and age,bone mass index,nationality,erythrocyte sedimentation rate (ESR) and RD types were analyzed.T test or Wilcoxon test was used to compare the difference between groups for statistical analysis.Pearson/Spearman rank order and binary regression were used to analyze the correlations between variables of normal/non-normal and two classification distribution.Results ① The BMD of patients with untreated RD was significantly lower than that of control group (P=0.000).Individuals diagnosed with "osteopenia" in the RD group and control group were accounted for 39.3％ (123/313) and 15.8％ (47/296) respectively.Individuals diagnosed with "osteoporosis" in RD group and control group were accounted for 11.5％ (36/313) and 5.4％ (16/296) respectively.② The next 10-year probability of the hip (Z=-2.28,P=0.02) and major osteoporotic fracture (Z=-1.98,P=0.03) were higher than those of the control group,as well as the actual incidence of OPF (x2=25.11,P=0.00),the difference was statistically significant.③ 27.3％(18/66) and 55.0％(11/20) of the previous OPF patients in RD group and control group achieved the diagnostic criteria of "high risk" of hip fracture.And 12.1％ (8/66) and 35.0％ (7/20) achieved the "high risk" of major osteoporotic fracture.④ Patients with RA,SLE and pSS had significantly increased risk of fracture.Ten-year fracture risks were negatively related to advanced age,female gender and ESR.Conclusion Bone loss and increased fracture risk are prevalent in the early stage of untreated rheumatism patients.RA,SLE plays an important role in low bone mass.The FRAX China model may underestimate 10-year fracture probability of RD patients and controls.Further explore should be done to predict the FRAX China model on different areas and different RDs.