Objective: To investigate the impact of temperature changes between neighboring days (TCN) on the mortality risk of respiratory diseases, so as to provide the evidence for the study of deaths from respiratory diseases caused by climate change. Methods: The monitoring data of deaths from respiratory diseases in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance. The meteorological and air pollutant data of the same period were collected from China Meteorological Data Website and ChinaHighAirPollutants dataset. The effect of TCN on the risk of deaths from respiratory diseases was examined using a generalized additive model combined with a distributed lag non-linear model, and subgroup analyses for gender and age were conducted. The disease burden attributed to TCN at different intervals was assessed by calculating attributable fraction. Results: Totally 11 767 deaths from respiratory diseases were reported in Zibo City from 2015 to 2019, including 6 648 males (56.50%) and 5 119 females (43.50%). There were 1 307 deaths aged <65 years (11.11%), and 10 460 deaths aged 65 years and older (88.89%). A monotonically increasing exposure-response relationship was observed between TCN and deaths from respiratory diseases in the general population, females, and the population aged 65 years and older. The 95th percentile of TCN (P95, 3.84 ℃) reached the peak at a cumulative lagged of day 11 (RR=2.063, 95%CI: 1.261-3.376). The results of subgroup analyses showed greater impacts on females and the population aged 65 years and older, with cumulative lagged effects peaking at day 12 (RR=3.119, 95%CI: 1.476-6.589) and day 11 (RR=2.107, 95%CI: 1.260-3.523). The results of attributional risk analysis showed that next-day warming might increase the attributable risk of deaths from respiratory diseases, and next-day cooling might decrease the attributable risk. Conclusion Next-day warming may increase the mortality risk of respiratory diseases, and has greater impacts on females and the population aged 65 years and older.

Objective:To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models.Methods:The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups.Results:EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference ( P ?

Objective: To investigate the activation level of NLRP3 inflammasome in immune thrombocytopenia ( ITP) and the effect of inhibiting NLRP3 mediated inflammasome activation on polarization and immune function of M1 macrophages. Methods : The expression of NLRP3 mRNA in peripheral blood mononuclear cells (PBMC) and CD14 + monocytes of ITP patients (ITP group) and Control group (Control group) was detected by RT⁃qPCR. The levels of IL⁃1β and IL⁃18 in serum of the two groups were determined by ELISA. M0 macrophages (MDMs) from ITP group were divided into 4 groups : IgG control group ( IgG group) , MCC950 treatment group ( MCC950 group) , LPS , IFN⁃γ and IgG treatment group (LPS + IFN⁃γ + IgG group) and LPS , IFN⁃γ and MCC950 treatment group (LPS + IFN⁃γ + MCC950 group) ; mRNA and protein levels of M1 macrophage markers CD86 , iNOS and MCP⁃ 1 were detected by RT⁃qPCR and Western blot. Western blot was used to detect the expression of NLRP3 inflammasome associated protein , ASC , Cleaved caspase⁃1 and IL⁃ β . Flow cytometry was used to detect the phagocytosis of MDMs on platelets in each group , and CFSE was used to detect the proliferation of CD4 + T and CD8 + T. Results: Compared with the control group , the expression of NLRP3 mRNA in PBMC and CD14 + monocytes , and the concentration of IL⁃1β and IL⁃18 in serum of ITP group increased significantly ( P < 0. 05 ) . Platelet counts were negative correlated with NLRP3 mRNA expression in CD14 + monocyte and the concentration of IL⁃1β , IL⁃18 in serum in patients with ITP ( P < 0. 05) . Compared with IgG group , the mRNA and protein expressions of M1 macrophage markers CD86 , iNOS , MCP⁃1 , and the protein expression level of NLRP3 , ASC , cleaved caspase⁃1 and IL⁃ β , the platelet phagocytosis and the proliferation promoting ability of CD4 + T and CD8 + T cells significantly increased in LPS + IFN⁃γ + IgG group and LPS + IFN⁃γ + MCC950 group ( all P < 0. 05) . Compared with LPS + IFN⁃γ + IgG group , the above indexes significantly decreased in LPS + IFN⁃γ + MCC950 group (P < 0. 05) . Conclusion The activation level of NLRP3 inflammasome in ITP is abnormally elevated , which was related to the excessive M1 polarization of MDMs. Inhibiting NLRP3 mediated inflammasome activation could attenuate the M1 polarization and immune function of macrophages.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.