Objective:To analyze the characteristics of CD4 + T cell subsets and cytokines in patients with mixed connective tissue disease (MCTD) and the correlation of MCTD disease activity, laboratory data, and clinical symptoms with cytokines. Methods:A total of 48 MCTD patients (including 24 newly diagnosed patients and 24 treated patients) were enrolled from the Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University from 2018 to 2021. Meanwhile, 49 healthy subjects who underwent physical examination were recruited (healthy control group). The absolute counts of CD4 + T cell subsets in peripheral blood samples were analyzed by flow cytometry. The levels of serum cytokines were detected by flow bead array. Analysis of variance and Mann-Whitney U test were used to compare the differences between groups. Pearson or Spearman correlation analysis was used for correlation analysis. Logistic regression analysis was used to analyze related factors. The receiver operating characteristic curve was used to detect the best cut-off value and effectiveness. Results:The absolute counts of Th1 ( P<0.01), Th2 ( P<0.01) and Treg cells ( P<0.01) in the newly diagnosed MCTD patients and the treated MCTD patients were lower than those in the healthy subjects. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) in the two MCTD groups were higher than those in the healthy control group ( P<0.01). Further analysis revealed that the cardiac enzymes in MCTD patients included creatine kinase, creatine kinase-MB, aspartate aminotransferase, α-hydroxybutyrate dehydrogenase, and lactate dehydrogenase were positively correlated with cytokines ( P<0.05). In addition, it was found that IL-2 was positively correlated with erythrocyte sedimentation rate ( r=0.477, P<0.001), but it was negatively correlated with complement C3 ( r=-0.546, P=0.002) and complement C4 ( r=-0.422, P=0.02). IL-10 was correlated with the myositis symptoms in MCTD patients and the area under the receiver operator characteristic curve was 0.745 (95% CI: 0.576-0.915, P<0.05). Conclusions:This study provides insights into the unique immunological characteristics of CD4 + T lymphocyte subsets and cytokines in patients with MCTD, and also reveals a close correlation between cytokines and cardiac enzymes in MCTD patients. IL-2 has been shown to be associated with disease activity in MCTD patients. The level of IL-10 may be related to the occurrence of myositis symptoms in MCTD.

Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

Objective:To analyze the characteristics of CD4 + T cell subsets and cytokines in patients with mixed connective tissue disease (MCTD) and the correlation of MCTD disease activity, laboratory data, and clinical symptoms with cytokines. Methods:A total of 48 MCTD patients (including 24 newly diagnosed patients and 24 treated patients) were enrolled from the Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University from 2018 to 2021. Meanwhile, 49 healthy subjects who underwent physical examination were recruited (healthy control group). The absolute counts of CD4 + T cell subsets in peripheral blood samples were analyzed by flow cytometry. The levels of serum cytokines were detected by flow bead array. Analysis of variance and Mann-Whitney U test were used to compare the differences between groups. Pearson or Spearman correlation analysis was used for correlation analysis. Logistic regression analysis was used to analyze related factors. The receiver operating characteristic curve was used to detect the best cut-off value and effectiveness. Results:The absolute counts of Th1 ( P<0.01), Th2 ( P<0.01) and Treg cells ( P<0.01) in the newly diagnosed MCTD patients and the treated MCTD patients were lower than those in the healthy subjects. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) in the two MCTD groups were higher than those in the healthy control group ( P<0.01). Further analysis revealed that the cardiac enzymes in MCTD patients included creatine kinase, creatine kinase-MB, aspartate aminotransferase, α-hydroxybutyrate dehydrogenase, and lactate dehydrogenase were positively correlated with cytokines ( P<0.05). In addition, it was found that IL-2 was positively correlated with erythrocyte sedimentation rate ( r=0.477, P<0.001), but it was negatively correlated with complement C3 ( r=-0.546, P=0.002) and complement C4 ( r=-0.422, P=0.02). IL-10 was correlated with the myositis symptoms in MCTD patients and the area under the receiver operator characteristic curve was 0.745 (95% CI: 0.576-0.915, P<0.05). Conclusions:This study provides insights into the unique immunological characteristics of CD4 + T lymphocyte subsets and cytokines in patients with MCTD, and also reveals a close correlation between cytokines and cardiac enzymes in MCTD patients. IL-2 has been shown to be associated with disease activity in MCTD patients. The level of IL-10 may be related to the occurrence of myositis symptoms in MCTD.

Objective:To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values.Methods:A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed.Results:Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis.Conclusions:Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

Systemic lupus erythematosus (SLE) shows a significant gender difference. In addition to X chromosome inactivation (XCI) abnormalities, which may lead to the gender difference in SLE, studies have found that estrogen plays a key role in regulating Th17/Treg immune balance in SLE. Estrogen indirectly affects the quantity and function of Th17 and Treg cells by acting on B cells. In this process, the mutual influence and the interaction between B and T cells promote the development of SLE. Recent studies have reported gender differences in intestinal microbiota, which may lead to sex-dependent genetic susceptibility and epigenetic changes in autoimmune diseases represented by SLE. The interaction between estrogen and intestinal microbiota in SLE affects the immune balance of Th17/Treg cells. This paper mainly reviews the way estrogen works, and the mechanisms by which estrogen regulates Th17/Treg immune balance and the interaction between B and T cells in SLE, hoping to provide new targets for new therapeutic strategies such as selective estrogen receptor modulators.

Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway, as an important part of the innate immune system, is the main pathway for cytoplasmic DNA recognition and cGAS can be triggered by a variety of cytoplasmic dsDNA. This pathway has become an important bridge connecting autoimmunity, aseptic inflammatory response and cell aging. In recent years, cGAS-STING pathway has attracted increasing attention in autoimmune diseases. In rheumatoid arthritis (RA), neutrophil extracellular traps (NETs) induce typeⅠ interferon response and accelerate the production of anti-citrullinated peptide antibody (ACPA) through the cGAS-STING pathway. In addition, the cGAS-STING pathway also participates in synovitis, bone destruction and RA progression by promoting the proliferation and activation of fibroblast-like synovitis cells and the polarization of M1 macrophages. Inhibition of the cGAS-STING pathway or its downstream signaling pathway can reduce synovial inflammation in RA, suggesting that cGAS-STING pathway may be a potential therapeutic target for RA.

Objective To systematically review the efficacy of different artificial liver support systems in the treatment of acute-on-chronic liver failure (ACLF) using a network Meta-analysis. Methods PubMed, Embase, the Cochrane library, Clinical Trial, CNKI, SinoMed, and Wanfang Data were searched for randomized controlled trials (RCTs) on different artificial liver support systems in the treatment of ACLF. Literature screening, data extraction, and method ological quality assessment were performed according to inclusion and exclusion criteria, and Stata15.1 software and R4.1.0 software were used to perform a network Meta-analysis. Results A total of 14 RCTs were included, with 1141 patients in total. The network meta-analysis showed different intervention methods had no significant difference in reducing mortality rate based on cross comparison (all P > 0.05). The probability ranking diagram showed that plasma exchange (PE) showed the best effect in reducing 30-day mortality rate, followed by extracorporeal liver assist device (ELAD), fractionated plasma separation and adsorption with Prometheus system, molecular adsorbent recirculating system (MARS), Biologic-DT liver dialysis device, and PE+MARS. PE showed the best effect in reducing 90-day mortality rate, followed by Prometheus, ELAD, and MARS. Biologic-DT showed the best effect in improving hepatic encephalopathy, followed by MARS, PE+MARS, and ELAD. Patients undergoing ELAD had the lowest risk of bleeding, and compared with standard medical treatment, Biologic-DT might increase the risk of bleeding [risk ratio=1.9×10 8 , 95% confidence interval: (4.6-6.2)×10 27 ]. Conclusion PE might be the best option for reducing 30- and 90-day mortality rates in ACLF patients. Biologic-DT has a better effect in improving hepatic encephalopathy, but it may increase the risk of bleeding.

Psoriatic arthritis is a chronic systemic autoimmune disease, characterized by psoriasis skin lesions and inflammation of the spine and joint. It has complicated clinical manifestations and individual variations. Nearly half of the patients will have joints erosion in two years, which is crippling. The severity of the skin and joint disease frequently do not correlate with each other. Currently, the understanding of the disease is insufficient in China with the lack of standardized diagnosis and treatment. Therefore, researchers from the Chinese Rheumatology Association formulated this specification based on the diagnosis and management experience together with guidelines at home and abroad. The specification summarizes the present situation of domestic diagnosis and treatment, aiming to standardize the diagnosis process and treatment protocols of psoriatic arthritis. Furthermore, it can reduce misdiagnosis and missed diagnosis, as well as improve the prognosis.

Objective:To investigate the changes of intestinal mucosal barrier function related indexes [diamine oxidase and secretory immunoglobulin A (sIgA)] in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with peripheral immune function.Methods:A total of 40 patients with RA who admitted to the Rheumatology and Immunology department of the Second Hospital of the Shanxi Medical University were enrolled. We collected their clinical and laboratory data, and selected 20 age and gender matched people as the control group. Enzyme-linked immunosorbnent assay (ELISA) was used to detect the level of DAO and sIgA in the peripheral blood, the lymphocytes and CD4 + T subsets were detected by flow cytometry. Then t-test, rank sum test and correlation analysis were conducted for statistical analysis. Results:① The level of DAO in patients with RA was higher than that of healthy controls [205(164, 251) ng/ml vs 364 (276, 483) ng/ml, Z=-4.48, P<0.001], while the level of sIgA was decreased [3.64 (2.76, 4.83)×10 5 ng/ml vs 6.83 (4.80, 9.44)×10 5, Z=-3.84, P<0.001]. ② The absolute number of B and CD4 + T cells were increased in RA, the difference were statistically significant, but the absolute number of T, natural killer cells (NK) and CD8 + T cells were not significantly different between the two groups. For CD4 + T subsets, the absolute number of T helper cells (Th)1 and Treg cells in RA group were significantly decreased than healthy controls, but there were no statistical significant difference in the number of Th2 and Th17 cells. ③ The level of DAO was positively correlated with absolute number of Th17 cells in patients with RA ( r=0.36 P=0.038), and positively correlated with age and white blood cell count ( r=0.40, P=0.021; r=0.40, P=0.020), but no significant correlation among other indicators were found. ④ The serum sIgA level of RA patients in antimutated citrullinated vimentin antibody (MCV), antiperinuclear factor (APF) and antikeratin antibody (AKA) positive group were higher than those in the negative group [3.99(2.99, 5.58)×10 5 ng/ml vs 2.73(2.29, 3.05)×10 5 ng/ml, Z=-2.55, P=0.011; 5.49 (3.26, 5.70)×10 5 ng/ml vs 3.12 (2.29, 4.04)×10 5 ng/ml, Z=-2.28, P=0.023; 4.07 (3.19, 5.65)×10 5 ng/ml vs 2.88 (2.24, 3.86)×10 5 ng/ml, Z=-2.42, P=0.016], while there was no significant difference in DAO level between groups. ⑤ The DAO level of RA patients with pulmonary interstitial fibrosis was significantly higher than that in the group without pulmonary interstitial fibrosis [421 (216, 528) ng/ml vs 191 (150, 223) ng/ml, Z=-2.81, P=0.005], while there were no significant differences in DAO and sIgA levels among other groups. Conclusion:In RA patients with inte-stinal mucosal barrier impairment, the DAO level is increased, while the sIgA is decreased, and in addition, elevated peripheral blood Th17 may be involved in the process of intestinal mucosal barrier impairment.

Objective:To investigate the characteristics of lymphocyte subsets in peripheral blood of patients with immunoglobulin G4-related disease (IgG4-RD) and the correlation between T helper 17 cell (Th17)/regulatory T cells (Treg) cell imbalance and cytokines.Methods:A total of 31 patients with IgG4-RD who were admitted to the Rheumatology and Immunology Department of the Second Hospital of Shanxi Medical University from January 2016 to June 2020 were included. We collected their clinical and laboratory data, and selected 30 age and sex matched healthy people as the control group. Flow cytometry was used to detect the percentage and absolute number of lymphocyte subsets [T, B, natural killer cell (NK), CD4 +T, CD8 +T] and CD4 +T subsets [Th1, Th2, Th17, CD4 +CD25 +forkhead box protein 3 (Foxp3) +Treg] in peripheral blood of IgG4-RD patients and healthy controls. The serum interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ levels in the IgG4-RD patients were measured by cytometric bead array (CBA). Correlation between Th17/Treg ratio and disease-related indicators was also analyzed. We used χ2 test, Mann-Whitney U test and Spearman correlation analysis for statistical analysis. Results:① The percentage of CD4 +T cells in the peripheral blood of IgG4-RD patients was higher than that of healthy controls [45.00%(33.97%, 51.48%) vs 39.36%(33.78%, 43.30%), Z=-2.142, P<0.05]. ② The percentage and absolute number of Th17 cells was increased in IgG4-RD patients [1.13%(0.70%, 1.55%) vs 0.77%(0.43%, 1.07%), Z=-2.229, P<0.05; 7.90(5.20, 12.23) cells/μl vs 5.60(3.12, 8.47) cells/μl, Z=-2.568, P<0.05], while the percentage of Treg cells was decreased [3.37%(2.82%, 5.65%) vs 4.96%(4.18%, 6.34%), Z=-2.986, P<0.01]. But the number of Treg cells showed no difference between the two groups. ③ Th17/Treg ratio was significantly increased in IgG4-RD patients [0.29(0.16, 0.46) vs 0.15(0.08, 0.23), Z=-3.119, P<0.01], and it was positively correlated with IgG4-RD response index score ( r=0.491, P<0.01). ④ Serum IL-6 [13.72(9.29, 26.06) pg/ml vs 2.23(1.94, 3.10) pg/ml, Z=-4.815, P<0.01], IL-10 [5.46(4.28, 15.38) pg/ml vs 1.81(1.59, 2.02) pg/ml, Z=-5.298, P<0.01], TNF-α [4.25(1.47, 7.26) pg/ml vs 1.15(1.05, 1.45) pg/ml, Z=-3.146, P<0.01] and IFN-γ [3.89(1.76, 6.61) pg/ml vs 1.41(1.24, 1.65) pg/ml, Z=-3.172, P<0.01] in IgG4-RD group were significantly higher than those in healthy control group. Moreover, Th17/Treg ratio was negatively correlated with IL-2 level ( r=-0.554, P<0.05). Conclusion:Th17/Treg disorder exists in IgG4-RD patients, and it is related to disease activity, indicating that Th17/Treg imbalance may be an important mechanism in IgG4-RD. IL-2 plays an important role in regulating Th17/Treg balance and may be a potential immunotherapy target in future.