Objective:To investigate the clinical characteristics of adult patients with autoimmune disease-associated hemophagocytic syndrome (AID-HPS) and enhance clinical recognition of this condition.Methods:A retrospective analysis was performed on 85 adult AID-HPS patients admitted to the department of rheumatology and immunology at Peking Union Medical College Hospital from January 2012 to December 2020. Clinical data included demographics, predisposing factors, manifestations, laboratory/imaging findings, treatments, and outcomes. Patients were stratified into three groups based on underlying AIDs: adult-onset Still′s disease with HPS (AOSD-HPS) group, systemic lupus erythematosus with HPS (SLE-HPS) group, and other AID with HPS (other AID-HPS) group. Comparative analyses were conducted to identify intergroup differences. Continuous variables were analyzed using one-way ANOVA, Welch′s test, or Kruskal-Wallis′s test based on data distribution and homogeneity of variance. Categorical variables (rates and proportions) were compared with the chi-square test or Fisher-Freeman-Halton exact test according to expected cell frequencies.Results:Among 85 patients, 67 were female. Underlying AIDs included AOSD (32 cases, 37.6%), SLE (32 cases, 37.6%), and other AIDs (21 cases, 24.7%). Infections (≥1 type) were identified in 54 patients (63.5%), predominantly viral (48 cases, 56.5%), including cytomegalovirus (CMV) (40 cases), Epstein-Barr virus (EBV) (11 cases), and 6 cases were coinfected with both CMV and EBV. All patients presented with fever; hepatomegaly, splenomegaly, and lymphadenopathy were observed in 39 (45.9%), 59 (69.4%), and 70 (82.4%) cases, respectively. Additional manifestations included arthralgia (63 cases, 74.1%) and rash (65 cases, 76.5%). Pancytopenia in 31 cases (36.5%) and bicytopenia in 29 cases (34.1%). Liver dysfunction was noted in 79 cases (92.9%). Elevated lactate dehydrogenase (LDH) (83 cases, 97.6%), elevated triglyceride (TG) (76 cases, 89.4%), decreased fibrinogen (Fbg) (55 cases, 64.7%), and elevated serum ferritin (SF) (84 cases, 98.8%) were common. Elevated soluble CD25(sCD25) (53cases) and reduced NK cell activity (49 cases) were observed. Bone marrow examination revealed hemophagocytosis in 49 cases. There were statistically significant differences in age( F=3.763, P=0.031), lymphadenopathy( χ2=7.098, P=0.029), rash( χ2=12.816, P=0.002), reductions in WBC( H=22.284, P<0.001)、NEU( H=18.882, P<0.001)、PLT( H=15.127, P=0.001), and elevations in LDH( H=7.842; P=0.020)、TG( H=6.177, P=0.046)、CRP( H=6.915, P=0.032)、SF( H=9.661, P=0.008)、sCD25( χ2=5.154, P=0.035) among the three groups: (1) The SLE-HPS group was significantly younger [(28.1 ± 10.4) years) than the other AID-HPS group [(39.5 ± 17.3) years, P=0.028]. (2) The AOSD-HPS group had higher incidence rates of lymphadenopathy (93.8%) and rash (93.8%) than the SLE-HPS group (68.8% and 56.3%, respectively), (lymphadenopathy: χ2=7.098, P=0.029; rash: χ2=12.816, P=0.002). (3) ① WBC in the SLE-HPS group [1.62 (1.18, 2.92) ×10 9/L] were significantly lower than those in the AOSD-HPS group [5.66 (2.75, 11.57)×10 9/L] and the other AID-HPS group [6.05 (2.49, 14.55)×10 9/L] ( Z=-4.032, P<0.001; Z=3.993, P<0.001). ② NEU in the SLE-HPS group [1.10 (0.60, 1.93)×10 9/L] were markedly reduced compared to the AOSD-HPS group [3.73 (1.54, 9.04)×10 9/L] and the other AID-HPS group [2.23 (1.43, 11.57)×10 9/L] ( Z=-3.859, P<0.001; Z=3.506, P=0.001). ③ PLT in the SLE-HPS group [59.50 (28.50, 81.00)×10 9/L] were significantly lower than those in the AOSD-HPS group [109.00 (65.75, 232.00)×10 9/L] and the other AID-HPS group [150.00 (55.00, 221.00)×10 9/L] ( Z=-3.421, P=0.002; Z=3.179, P=0.004). (4) LDH levels in the AOSD-HPS group [1 178 (645, 1 875) U/L] were significantly higher than those in the other AID-HPS group [598 (410, 771) U/L] ( Z=2.795, P=0.016). (5) TG levels in the SLE-HPS group [3.61 (2.46, 6.09) mmol/L] were significantly higher than those in the other AID-HPS group [2.68 (1.71, 3.30)mmol/L] ( Z=2.402, P=0.049). (6) CRP and SF levels in the AOSD-HPS group [79.20 (28.02, 179.53)mg/L and 30 225 (13 494, 53 598)μg/L, respectively] were significantly higher than those in the SLE-HPS group [26.05 (9.41, 83.31)mg/L and 9 862 (4 467, 22 315) μg/L, respectively] ( Z=2.547, P=0.033; Z=3.069, P=0.006 ). (7) The incidence rates with elevated sCD25 in the AOSD-HPS group (100.0%) was significantly higher than that in the other AID-HPS group (76.9%), ( χ2=5.154, P=0.035). After treatment, 83 patients improved, while 2 deaths occurred in the other AID-HPS group. Conclusion:Adult AID-HPS predominantly affects young to middle-aged females, with SLE and AOSD being the most common underlying AIDs. The condition manifests with severe clinical features, frequently triggered by viral infections (particularly CMV and EBV). Distinct differences in clinical and laboratory profiles exist among AID-HPS subtypes. Early recognition and aggressive treatment are critical for improving prognosis.

Objective To study the correlation between serum adipsin and vulnerable plaques.Methods A total of 80 patients with coronary heart disease complicating diabetes mellitus due to chest pain hospitalized in the cardiovascular medicine department of Ulanqab Municipal Central Hospital from January 2023 to January 2024 were selected as the study subjects and conducted the coronary angiography and optical coherence tomo-graphy(OCT).The serum adipsin level was detected.The relationship between serum adipsin and thin fibrous cap atherosclerotic plaque(TCFA)was analyzed by binary logistic regression.The receiver operating charac-teristic(ROC)curve was used to analyze the diagnostic efficiency of adipsin in predicting TCFA.Results The levels of creatinine,low-density lipoprotein-cholesterol(LDL-C)and serum adipsin in the TCFA group were significantly higher than those in the non-TCFA group,and the difference was statistically significant(P＜0.05);the proportions of TCFA and acute myocardial infarction in the high adipsin group were higher than those in the low adipsin group,and the difference was statistically significant(P＜0.05).The binary logistic regression analysis results showed that creatinine,LDL-C and serum adipsin all were the independent predic-tive factors of TCFA(P＜0.05).The ROC curve showed that AUC of serum adipsin in predicting TCFA was 0.702(95％CI:0.589-0.815,P=0.002),the cut-off value was 2.845 ng/mL,the sensitivity was 0.897 and the specificity was 0.585.Conclusion As an independent predictive factor of TCFA,serum adipsin is closely related to the occurrence and development of vulnerable plaques in the patients with coronary heart disease complicating diabetes.

Tenecteplase is a third-generation thrombolytic drug.Compared with alteplase,it has the advantages of longer half-life and higher fibrin specificity.The effectiveness and safety of tenecteplase in the treatment of acute ischemic stroke have been extensively studied in clinical research.The article summarized the research progress of tenecteplase in the treatment of acute ischemic stroke based on completed randomized controlled studies and related Meta-analyses,and explored the pharmacological characteristics,effectiveness,and safety of tenecteplase,as well as current guideline recommendations,aiming to offer a reference for choosing more appropriate diagnostic and therapeutic methods for patients with acute ischemic stroke.

Objective:To investigate the clinical characteristics of adult patients with autoimmune disease-associated hemophagocytic syndrome (AID-HPS) and enhance clinical recognition of this condition.Methods:A retrospective analysis was performed on 85 adult AID-HPS patients admitted to the department of rheumatology and immunology at Peking Union Medical College Hospital from January 2012 to December 2020. Clinical data included demographics, predisposing factors, manifestations, laboratory/imaging findings, treatments, and outcomes. Patients were stratified into three groups based on underlying AIDs: adult-onset Still′s disease with HPS (AOSD-HPS) group, systemic lupus erythematosus with HPS (SLE-HPS) group, and other AID with HPS (other AID-HPS) group. Comparative analyses were conducted to identify intergroup differences. Continuous variables were analyzed using one-way ANOVA, Welch′s test, or Kruskal-Wallis′s test based on data distribution and homogeneity of variance. Categorical variables (rates and proportions) were compared with the chi-square test or Fisher-Freeman-Halton exact test according to expected cell frequencies.Results:Among 85 patients, 67 were female. Underlying AIDs included AOSD (32 cases, 37.6%), SLE (32 cases, 37.6%), and other AIDs (21 cases, 24.7%). Infections (≥1 type) were identified in 54 patients (63.5%), predominantly viral (48 cases, 56.5%), including cytomegalovirus (CMV) (40 cases), Epstein-Barr virus (EBV) (11 cases), and 6 cases were coinfected with both CMV and EBV. All patients presented with fever; hepatomegaly, splenomegaly, and lymphadenopathy were observed in 39 (45.9%), 59 (69.4%), and 70 (82.4%) cases, respectively. Additional manifestations included arthralgia (63 cases, 74.1%) and rash (65 cases, 76.5%). Pancytopenia in 31 cases (36.5%) and bicytopenia in 29 cases (34.1%). Liver dysfunction was noted in 79 cases (92.9%). Elevated lactate dehydrogenase (LDH) (83 cases, 97.6%), elevated triglyceride (TG) (76 cases, 89.4%), decreased fibrinogen (Fbg) (55 cases, 64.7%), and elevated serum ferritin (SF) (84 cases, 98.8%) were common. Elevated soluble CD25(sCD25) (53cases) and reduced NK cell activity (49 cases) were observed. Bone marrow examination revealed hemophagocytosis in 49 cases. There were statistically significant differences in age( F=3.763, P=0.031), lymphadenopathy( χ2=7.098, P=0.029), rash( χ2=12.816, P=0.002), reductions in WBC( H=22.284, P<0.001)、NEU( H=18.882, P<0.001)、PLT( H=15.127, P=0.001), and elevations in LDH( H=7.842; P=0.020)、TG( H=6.177, P=0.046)、CRP( H=6.915, P=0.032)、SF( H=9.661, P=0.008)、sCD25( χ2=5.154, P=0.035) among the three groups: (1) The SLE-HPS group was significantly younger [(28.1 ± 10.4) years) than the other AID-HPS group [(39.5 ± 17.3) years, P=0.028]. (2) The AOSD-HPS group had higher incidence rates of lymphadenopathy (93.8%) and rash (93.8%) than the SLE-HPS group (68.8% and 56.3%, respectively), (lymphadenopathy: χ2=7.098, P=0.029; rash: χ2=12.816, P=0.002). (3) ① WBC in the SLE-HPS group [1.62 (1.18, 2.92) ×10 9/L] were significantly lower than those in the AOSD-HPS group [5.66 (2.75, 11.57)×10 9/L] and the other AID-HPS group [6.05 (2.49, 14.55)×10 9/L] ( Z=-4.032, P<0.001; Z=3.993, P<0.001). ② NEU in the SLE-HPS group [1.10 (0.60, 1.93)×10 9/L] were markedly reduced compared to the AOSD-HPS group [3.73 (1.54, 9.04)×10 9/L] and the other AID-HPS group [2.23 (1.43, 11.57)×10 9/L] ( Z=-3.859, P<0.001; Z=3.506, P=0.001). ③ PLT in the SLE-HPS group [59.50 (28.50, 81.00)×10 9/L] were significantly lower than those in the AOSD-HPS group [109.00 (65.75, 232.00)×10 9/L] and the other AID-HPS group [150.00 (55.00, 221.00)×10 9/L] ( Z=-3.421, P=0.002; Z=3.179, P=0.004). (4) LDH levels in the AOSD-HPS group [1 178 (645, 1 875) U/L] were significantly higher than those in the other AID-HPS group [598 (410, 771) U/L] ( Z=2.795, P=0.016). (5) TG levels in the SLE-HPS group [3.61 (2.46, 6.09) mmol/L] were significantly higher than those in the other AID-HPS group [2.68 (1.71, 3.30)mmol/L] ( Z=2.402, P=0.049). (6) CRP and SF levels in the AOSD-HPS group [79.20 (28.02, 179.53)mg/L and 30 225 (13 494, 53 598)μg/L, respectively] were significantly higher than those in the SLE-HPS group [26.05 (9.41, 83.31)mg/L and 9 862 (4 467, 22 315) μg/L, respectively] ( Z=2.547, P=0.033; Z=3.069, P=0.006 ). (7) The incidence rates with elevated sCD25 in the AOSD-HPS group (100.0%) was significantly higher than that in the other AID-HPS group (76.9%), ( χ2=5.154, P=0.035). After treatment, 83 patients improved, while 2 deaths occurred in the other AID-HPS group. Conclusion:Adult AID-HPS predominantly affects young to middle-aged females, with SLE and AOSD being the most common underlying AIDs. The condition manifests with severe clinical features, frequently triggered by viral infections (particularly CMV and EBV). Distinct differences in clinical and laboratory profiles exist among AID-HPS subtypes. Early recognition and aggressive treatment are critical for improving prognosis.

Tenecteplase is a third-generation thrombolytic drug.Compared with alteplase,it has the advantages of longer half-life and higher fibrin specificity.The effectiveness and safety of tenecteplase in the treatment of acute ischemic stroke have been extensively studied in clinical research.The article summarized the research progress of tenecteplase in the treatment of acute ischemic stroke based on completed randomized controlled studies and related Meta-analyses,and explored the pharmacological characteristics,effectiveness,and safety of tenecteplase,as well as current guideline recommendations,aiming to offer a reference for choosing more appropriate diagnostic and therapeutic methods for patients with acute ischemic stroke.

Objective:To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI. Methods:The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay.Results:The patient was found to carry homozygous missense c. 677C>T (p.Ser226Leu) mutation of the WNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46, XX). Conclusion:A patient-specific WNT1 gene mutation ( WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.

Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.

OBJECTIVE: To investigate the mechanisms underlying allergic conjunctivitis caused by conjunctival epithelial cell damage, neutrophil migration and neutrophil extracellular traps (NETs) formation induced by crude extracts of Dermatophagoides farinae mite (CDM). METHODS: Human conjunctival epithelial cells were stimulated with 500, 1 000, 2 000, 4 000 ng/mL, and the expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-8 were detected using quantitative real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA). The culture supernatant of human conjunctival epithelial cells was collected and co-cultured with neutrophils. Neutrophil migration was measured using Transwell migration assay, and the expression of NETs markers myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) was quantified using immunofluorescence staining. Neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), and then NETs were collected for treatment of human conjunctival epithelial cells. Cell apoptosis was detected using flow cytometry, and the levels of IL-6, TNF-α, IFN-γ and IL-8 were measured in the cell culture supernatant using ELISA. RESULTS: Treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL up-regulated IL-6, TNF-α, IFN-γ and IL-8 expression in human conjunctival epithelial cells. Following treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL, the culture supernatant of human conjunctival epithelial cells promoted neutrophil migration and induced increases in the staining intensity of MPO and CitH3. In addition, increased NETs triggered the apoptosis of human conjunctival epithelial cells and IL-6, TNF-α, IFN-γ and IL-8 secretion in the culture supernatant of human conjunctival epithelial cells. CONCLUSIONS CDM induces human conjunctival epithelial cell damages, thereby promoting neutrophil migration and NETs formation, while the release of NETs further aggravates human conjunctival epithelial cell damages.
Animals ; Humans ; Extracellular Traps ; Neutrophils ; Interleukin-8/metabolism* ; Dermatophagoides farinae ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Epithelial Cells ; Interferon-gamma/metabolism* ; Tetradecanoylphorbol Acetate/pharmacology*

Objective : To investigate the mechanism of miRNAs in glycyrrhizic acid treatment of alcohol⁃induced liver injury in rats . Methods : 45 male SD rats were randomly divided into glycyrrhizin group , model group and control group . The rats in glycyrrhizin group were given 56% liquor and glycyrrhizin , the rats in model group were given 56% liquor , and the rats in control group were given distilled water for 8 weeks . The blood was collected and the serum was separated by centrifugation to detect the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) . RNA were extracted from liver tissues , miRNAs were detected by rat miRNA microarray , and their expression levels were analyzed . The miRNA target genes of differential miRNA were predicted . Gene Ontology (GO) and KEGG Pathway enrichment analysis were used to understand the function of differential miRNA , and the differential miRNA⁃mRNA⁃Pathway regulatory network was constructed using Cytoscape to further screen the regulatory key miRNA and key pathways . qRT⁃PCR was used to verify the expression of selected miRNA . Results : Compared with the model group , the glycyrrhizin group could significantly improve the liver tissue lesions , and reduce the liver serum AST and ALT levels (P < 0. 05) . Compared the microarray data of glycyrrhizin group and model group , a total of 13 differentially expressed miRNA were screened ( P < 0. 05 , fold change ≥ 1 . 5) , of which 10 were up⁃regulated and 3 were down⁃regulated . The GO classification annotation of differential miRNA target genes showed that differential miRNA were related to cell adhesion , antioxidant activity , metabolic process , biological process regulation , cell killing , immune system and other functions . The KEGG Pathway analyling pathway , Hippo signaling pathway , PI3K⁃Akt signaling pathway , wnt signaling pathway , apoptosis and other signaling pathways might play an important regulatory role in the improvement of alcoholic liver injury by glycyrrhic acid . Conclusion This study established the miRNA expression profile of glycyrrhizin in the treatment of alcoholic liver injury in rats , suggested that miR⁃615 , miR⁃107 ⁃3p and miR⁃292⁃5p might play an important role in the treatment of alcoholic liver injury by glycyrrhizin .

Objective To investigate the mechanisms underlying allergic conjunctivitis caused by conjunctival epithelial cell damage, neutrophil migration and neutrophil extracellular traps (NETs) formation induced by crude extracts of Dermatophagoides farinae mite (CDM). Methods Human conjunctival epithelial cells were stimulated with 500, 1 000, 2 000, 4 000 ng/mL, and the expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-8 were detected using quantitative real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA). The culture supernatant of human conjunctival epithelial cells was collected and co-cultured with neutrophils. Neutrophil migration was measured using Transwell migration assay, and the expression of NETs markers myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) was quantified using immunofluorescence staining. Neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA), and then NETs were collected for treatment of human conjunctival epithelial cells. Cell apoptosis was detected using flow cytometry, and the levels of IL-6, TNF-α, IFN-γ and IL-8 were measured in the cell culture supernatant using ELISA. Results Treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL up-regulated IL-6, TNF-α, IFN-γ and IL-8 expression in human conjunctival epithelial cells. Following treatment with CDM at concentrations of 2 000 ng/mL and 4 000 ng/mL, the culture supernatant of human conjunctival epithelial cells promoted neutrophil migration and induced increases in the staining intensity of MPO and CitH3. In addition, increased NETs triggered the apoptosis of human conjunctival epithelial cells and IL-6, TNF-α, IFN-γ and IL-8 secretion in the culture supernatant of human conjunctival epithelial cells. Conclusions CDM induces human conjunctival epithelial cell damages, thereby promoting neutrophil migration and NETs formation, while the release of NETs further aggravates human conjunctival epithelial cell damages.