The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Pregnancy ; Female ; Humans ; Pregnancy Outcome ; Cross-Sectional Studies ; Lupus Erythematosus, Systemic/epidemiology* ; Pregnancy Complications/epidemiology* ; Menstruation Disturbances

Objective:To investigate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) in patients with wake-up ischemic stroke (WUIS) of anterior circulation non-major arteries.Methods:Sixty-seven patients with WUIS of anterior circulation non-major arteries (time from falling asleep/last use of bathroom at night to intravenous thrombolysis≤9 h and >4.5 h) admitted to Department of Neurology, Beijing Shijingshan Hospital and Department of Neurosurgery, Beijing Muyangliu Hospital from January 1 st, 2017 to December 31 st, 2021 were chosen; these 35 patients accepted routine antiplatelet therapy after intravenous thrombolytic therapy were chosen as control group, and the other 32 patients accepted rt-PA arterial thrombolysis after intravenous thrombolytic therapy were chosen as study group. Vascular recanalization after arterial thrombolysis was observed in study group (cerebral infarction thrombolysis grading 2 and 3: good vascular recanalization). Neurological deficit improvement during treatment, clinical prognoses (modified Rankin scale scores of 0-2: good prognosis) and hemorrhagic transformation incidence 3 months after treatment were compared between the 2 groups. Results:The vascular thrombolytic recanalization rate of study group was 81.25% (26/32). Patients in study group had significantly decreased National Institute of Health stroke scale scores compared with those in control group 1, 7, and 14 d after thrombolytic therapy ( P<0.05). The good prognosis rate of study group (62.50%, 20/32) was significantly higher than that in control group (37.14%, 13/35, P<0.05). No significant difference in hemorrhagic transformation rate was noted between the 2 groups (15.6% [5/32] vs. 5.71% [2/35], P>0.05). Conclusion:Patients with WUIS of anterior circulation non-major arteries (time from falling asleep/last use of bathroom at night to intravenous thrombolysis≤9 h and >4.5 h) benefit from arterial thrombolysis with rt-PA, and risk of secondary intracerebral hemorrhage is not obviously increased.

Objective:In this article, we analyzed and discussed the clinical characteristics and S region gene sequencing of hepatitis B virus in HBsAg anti-HBs coexistent patients.Methods:Data of 5 serologic markers of hepatitis B and quantitative result, liver function and HBV DNA load of HBsAg positive patients were collected, and their basic clinical information were recorded. According to the positive and negative result of Anti-HBs, the clinical and virological characteristics of these two groups were analyzed. At the same time, among 17 320 patients with HBsAg positive HBV infection, 994 cases were tested by gene sequencing. The S region amino acid mutation, site mutation detection rate and genotype of 994 HBV infected patients with gene sequencing were statistically analyzed.Results:The positive rate of HBsAg and Anti-HBs was 4.36% (756/17 320). HBV-related cirrhosis in HBsAg+ /Anti-HBs+ group (19.71%) was significantly higher than that in HBsAg+ /Anti-HBs-group (15.94%), while chronic hepatitis B (62.04%) was significantly lower than that in HBsAg+ /Anti-HBs-group (67.06%). At the same time, the positive rates of HBsAg-quantification (QN) and ALT in HBsAg+ /Anti-HBs+ group were significantly lower than those in HBsAg+ /Anti-HBs-group, the positive rate of HBeAg was significantly higher than that in HBsAg+ /Anti-HBs-group, and the HBV DNA was higher than that in HBsAg+ /Anti-HBs-group, but the difference was no statistical significance. Gene sequencing was performed in 994 HBV patients. Genotype C (81.79%) had the highest proportion, genotype B (17.40%) was the second, and genotype D (0.80%) was the least in two groups. In genotype C HBV infected patients, the detection rate of sP120Q/T/A/S mutant in HBsAg+ /Anti-HBs+ group was significantly higher than that in HBsAg+ /Anti-HBs-group. Meanwhile, regardless of genotype B or C or overall comparison, the detection rate of sG145A/E/K/R mutant of HBV infected patients in HBsAg+ /Anti-HBs+ group was significantly higher than that in HBsAg+ /Anti-HBs-group, these differences were all statistically significant.Conclusions:The hepatitis B patients with coexistence of HBsAg and Anti-HBs were more likely to develop cirrhosis, and the hepatitis B patients with HBV gene sequencing results were mainly type C2. The drug resistance variation of S-region sP120Q/T/A/S and sG145A/E/K/R mutants of patients with HBV infection is an important reason for the coexistence of HBsAg and Anti-HBS.

Objective: To investigate the expression and role of LINC00052 during glycidyl methacrylate (GMA) -induced malignant transformation of 16HBE cells. Methods: Human bronchial epithelial (16HBE) cells were divided into GMA transformation group and corresponding DMSO control group, and the 10th, 20th and 30th generation cells of each group were collected LncRNA microarrays were used to analysis expression of LINC00052 in different stage of malignant transformation. Bioinformatics analysis was applied and the relative expression of LINC00052 and its potentially target genes was detected by real-time quantification PCR (qPCR) . Results: The results of microarray analysis showed that LINC00052 was up-regulated by 1.32-fold, down-regulated by 1.64-fold and down-regulated by 4.92-fold in the malignant transformation early (P10) , middle term (P20) and late (P30) , respectively, The results of qPCR showed that compared with the DMSO control group, the expression of LINC00052 was up-regulated by 1.55 times, down-regulated by 1.20 times and down-regulated by 2.35 times in P10, P20 and P30, respectively, and the difference was statistically significant (P<0.05) . There was a statistically significant difference in the relative expression of NTRK3 between the GMA transformation group of P10 and P30 generations with the corresponding DMSO control group (P<0.05) . Conclusion LINC00052 is highly expressed in early time of GMA-induced malignant transformation of 16HBE, and down-regulated in the middle and last stage of malignant transformation and may play a protective role in GMA-induced malignant transformation of 16HBE by influencing the expression of its target gene NTRK3.

Objective: To analyze the characteristics of pneumoconiosis patients and the basic status of medical treatment. Methods: Research objects were chosen by stratified sampling method and typical survey method from existing pneumoconiosis patients in China. The survey was carried out from March 2017 to January 2018 in nine provinces including provinces from east, medium and western region in China. Source of pneumoconiosis cases were inpatient cases, outpatient or physical-examined cases and household-investigation cases. The survey mainly included demographic and sociological characteristics, economic status, occupational history and dust exposure history, disease status, work-related injury insurance and social security status and related indicators of pneumoconiosis treatment. Results: Investigated 1037 pneumoconiosis cases which included 186 (19.9%) household-investigation cases, 212 (20.4%) outpatient or physical-examined cases and 639 (61.7%) inpatient cases. Demographic and sociological characteristics, individual monthly income, economic source, occupational history and work-related injury insurance were statistically significant among different source of pneumoconiosis patients (P<0.05) . Among all of the household-investigation cases, there were 74 cases (40.2%) had no income, 117 cases (62.9%) used to work in private enterprises, 36 cases (19.4%) had work-related injuries insurance, 95 cases (51.1%) were at three phase of pneumoconiosis, 108 cases (59.0%) haven't had any drugs for pneumoconiosis. 65 cases (39.4%) haven't went to the clinic, 53 cases (28.5%) hadn't seek medical advice although they needed medical treatment very much. Among all of the outpatient or physical-examined cases, there were 95 cases (46.1%) had no income, 36 cases (17.0%) had work-related injuries Insurance, 139 cases (65.6%) went to the clinic for treatment of pneumoconiosis, 81 cases (38.2%) went to the clinic for more than ten times. Among all the inpatient cases, 310 cases' (49.3%) personal monthly income was above 2000 yuan, 352 cases (55.1%) had work-related injuries Insurance, 588 cases (92.2%) were taking drugs for treatment of pneumoconiosis, 153 canses (24.2%) had hospitalization for than ten times. Conclusion Household-investigation cases have lower economic conditions, lower rates of Insurance coverage for work-related injuries, severer pneumoconiosis and higher clinical service utilization. Clinical or physical-examined cases have lower economic conditions, lower rates of Insurance coverage for work-related injuries and higher clinical service utilization. Hospitalized cases have better economic conditions, higher rates of insurance coverage for work-related injuries and higher hospitalization service utilization.