Objective: To estimate the influenza-associated excess mortality (IEM) in Zhejiang Province from 2016 to 2019, so as to provide insights into estimates of mortality burden due to influenza. Methods: The data pertaining to all-cause death and influenza surveillance in Zhejiang Province from 2016 to 2019 were retrieved from Zhejiang Provincial Cause of Death Registration System and Influenza Surveillance System to create distributed lag non-linear models (DLNMs). The year-, influenza subtype- and age-specific IEM rates were estimated. Results: The overall IEM was 18.67/105 (95%CI: 15.32/105-21.97/105) in Zhejiang Province from 2016 to 2019, with the lowest in 2016 (14.19/105, 95%CI: 12.00/105-16.37/105) and the highest in 2018 (22.92/105, 95%CI: 19.23/105-26.56/105). The IEM rates of influenza A (H1N1), influenza A (H3N2) and influenza B were 9.32/105 (95%CI: 7.65/105-10.98/105), 5.68/105 (95%CI: 4.24/105-7.11/105), and 3.66/105 (95%CI: 2.13/105-5.18/105). The greatest IEM was seen among residents at ages of 65 years and older (142.91/105, 95%CI: (115.99/105-169.55/105, followed by among individuals at ages of 15 to 64 years (2.74/105, 95%CI: 1.87/105-3.61/105), and the lowest was seen among individuals under 15 years of age (0.41/105, 95%CI: -0.33/105-1.14/105). Conclusions From 2016 to 2019, the highest IEM was seen in Zhejiang Province in 2018, and the elderly residents at ages of 65 years and above presented the greatest IEM, with influenza A (H1N1) as the predominant influenza subtype. Influenza surveillance and vaccination is recommended to be reinforced.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods: Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results: Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

Objective To understand the genotypic characteristics and the neutralizing antibody levels of Japanese encephalitis virus(JEV)and Japanese encephalitis(JE)in both vector mosquitoes and in healthy people of Zhejiang province. Methods Virus was isolated from mosquitos sampled from the Monitoring Stations located in Xianju county during 2012 to 2013. Phylogenetic and homological studies were carried out on the E gene. A total of 1 263 blood specimens from 642 healthy people were collected before and after the seasons of JE epidemics. JEV neutralizing antibody was detected by the micro-neutralization test. Results Twenty-five JEV strains were isolated from a total of 11 650 mosquitoes. The identity of nucleotide appeared as 87.8%-99.7% both from 2012 to 2013 and from 1982 to 2010 while as 87.7%-88.0%with vaccine strain SA14-14-2,in Zhejiang. The phylogeny tree of E gene indicated that the newly isolated virus belonged to genotypeⅠ but no mutation of amino acid sequence coding conformational epitope was identified in the envelop protein. Both positive rates and the geometric mean titer(GMT)of neutralizing antibody in healthy people were 31.5%-42.0%and 1∶2.56-1∶3.53 in Xianju county,during 2012 and 2013,respectively. Both of the two positive rates(χ2≤1.76,P>0.05)and the two GMTs(u≤0.64,P>0.5)for antibodies pre or post the epidemic season did not show significant differences. Conclusion JEV isolated in Xianju during 2012 and 2013 belonged to genotypeⅠ. The positive rates of JEV neutralizing antibody from healthy people in Xianju were less than 42.0%,which showed no significant differendes pre or post JE epidemic season.

OBJECTIVETo understand the genotypic characteristics and the neutralizing antibody levels of Japanese encephalitis virus (JEV) and Japanese encephalitis (JE) in both vector mosquitoes and in healthy people of Zhejiang province.

METHODSVirus was isolated from mosquitos sampled from the Monitoring Stations located in Xianju county during 2012 to 2013. Phylogenetic and homological studies were carried out on the E gene. A total of 1 263 blood specimens from 642 healthy people were collected before and after the seasons of JE epidemics. JEV neutralizing antibody was detected by the micro-neutralization test.

RESULTSTwenty-five JEV strains were isolated from a total of 11 650 mosquitoes. The identity of nucleotide appeared as 87.8%-99.7% both from 2012 to 2013 and from 1982 to 2010 while as 87.7%-88.0% with vaccine strain SA14-14-2, in Zhejiang. The phylogeny tree of E gene indicated that the newly isolated virus belonged to genotype I but no mutation of amino acid sequence coding conformational epitope was identified in the envelop protein. Both positive rates and the geometric mean titer (GMT) of neutralizing antibody in healthy people were 31.5%-42.0% and 1 : 2.56-1 : 3.53 in Xianju county, during 2012 and 2013, respectively. Both of the two positive rates (χ(2)≤1.76, P > 0.05) and the two GMTs (u≤0.64, P > 0.5) for antibodies pre or post the epidemic season did not show significant differences.

CONCLUSIONJEV isolated in Xianju during 2012 and 2013 belonged to genotype I. The positive rates of JEV neutralizing antibody from healthy people in Xianju were less than 42.0%, which showed no significant differendes pre or post JE epidemic season.

Amino Acid Sequence ; Animals ; Antibodies, Neutralizing ; blood ; Antibodies, Viral ; blood ; China ; Culicidae ; virology ; Disease Vectors ; Encephalitis Virus, Japanese ; genetics ; immunology ; isolation & purification ; Encephalitis, Japanese ; virology ; Epitopes ; Genotype ; Humans ; Neutralization Tests ; Phylogeny

OBJECTIVE: To evaluate the cost/benefit of different vaccination strategies related to chickenpox vaccine. METHODS: The direct economic cost and indirect economic cost caused by chickenpox were obtained through questionnaire survey. The epidemic characteristics of chickenpox in Zhejiang province were studied by literature review. Dynamic model was set up by Matlab software based on the parameters of chickenpox, to predict the incidence trends of chickenpox with different immunization strategies (no vaccination, 1-dose vaccination, 2-dose vaccination) in future 40 years (2017-2056). A cost-benefit analysis was conducted, and the sensitivities of the main parameters were analyzed. RESULTS: Through the questionnaire survey of 105 cases, the direct and indirect economic cost per case was 506.84 Yuan and 1045.39 Yuan respectively, with the total of 1552.23 Yuan. During the prediction period (40 years), there would be 7.0908 million cases in strategy 2, which was 59.71% less than strategy 1 (17.5989 million cases). Total vaccination costs in strategy 2 were 2.366 billion Yuan, with a total economic gain of 33.741 billion Yuan and benefit/cost ratio (BCR) of 14.26:1. If strategy 3 was adopted, 2.7249 million chickenpox cases would occur, with a decrease of 84.52% compared with strategy 1. Total vaccination costs in strategy 3 was 4.495 billion Yuan, with a total economic gain of 44.309 billion Yuan and BCR of 9.86:1. Analysis showed that the vaccine price was the most sensitive variable, followed by the incidence of chickenpox in the absence of vaccine. CONCLUSIONS In Zhejiang province, one-dose strategy and two-dose strategy were both cost effective. It is suggested that the chickenpox vaccination should be included in the immunization program in Zhejiang province.
Chickenpox ; prevention & control ; Chickenpox Vaccine ; Cost-Benefit Analysis ; Humans ; Immunization Programs ; economics ; methods ; Vaccination ; economics