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 investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals. Methods: Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. Results: A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively. Conclusions The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.

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.

Objective: To conduct an epidemiological investigation on the first reported case of coronavirus disease 2019 （COVID-19） in Zhejiang Province, so as to provide reference for prevention and control of the disease. Methods : According to the COVID-19 Diagnosis and Treatment Program （Trial） and the COVID-19 Prevention and Control Program （Trial） issued by National Health Commission of China, a field investigation was employed on a case of fever from Wuhan reported by Wenzhou in January 15, 2020; the real-time reverse transcription polymerase chain reaction （RT-PCR） assay was performed to detect the nucleic acid of severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） from the sputum specimens or throat swabs of the case; the close contacts of the case were tracked down; relevant prevention and control measures were implemented. Results : The case had lived in Wuhan for long. On January 4 of 2020, he felt cold and uncomfortable without obvious inducement, and drove back to Wenzhou with his wife. He had fever （up to 39 ℃）, cough and expectoration on the next day. On January 9, the chest computed tomographic （CT） scan showed bilateral high-density patchy shadowing with blurred edges. On January 16, his throat swab and sputum samples were collected and sent to Zhejiang Provincial Center for Disease Control and Prevention （CDC） for detection of SARS-CoV-2. The result turned out to be positive on January 17, then was rechecked and confirmed by Chinese CDC on January 20. Two weeks before the onset of the disease, the patient was engaged in the door-to-door persuasion of installing elevators in an old residential area of Wuhan, and he denied any connection with other COVID-19 cases,markets,（sick or dead） poultry or poultry products. Totally 26 close contacts were identified and kept in quarantine. During this period,three of them developed fever or respiratory symptoms, but were excluded from COVID-19. On the afternoon of January 16,the health system of Zhejiang Province and Wenzhou City launched an emergency plan and implemented a series of prevention and control measures such as isolation and treatment of cases,screening and isolation of close contacts,and public health education. Conclusion According to the epidemiological history,clinical features and laboratory test Results,the patient was identified as the first reported case of COVID-19 in Zhejiang Province.

Objective:To investigate the epidemiological characteristics for family clusters of COVID-19 in Zhejiang Province.Methods:The data including cases information of asymptomatic infected cases of family clusters of COVID-19 in Zhejiang Province were collected from Public Health Emergencies Reporting System of China Center for Disease Control and Prevention. Calculate the case number of subsequent cases, index cases, asymptomatic infected cases, exposure cases, and then, compute family secondary attack rate (SIR) and serial interval.Results:A total of 389 cases comprised 149 family index cases and 240 subsequent cases. The clinical symptoms between family index cases and subsequent cases (exclude asymptomatic infected cases ) were similar, fever was the most common symptoms in the two groups 115 (77.18%) and 110（48.67%）respectively, the cases with diarrhea symptoms accounted for the least proportion, which were 7 (4.70%) and 6 (2.65%) respectively. The serial interval between the family index cases and the subsequent cases [ M ( P25, P75)] was 4.00 (2.00, 6.00) days. Family secondary attack rate for subsequent cases was 34.43%, subsequent cases aged between 14 and 60 have the highest SIR (43.42%) compared with other two age groups, the difference was statistically ( P<0.001); the family SIR of the spouses of the family index cases is 68.57%, and are higher than that of parents (29.03%), children (25.00%) and other family members (24.21%), the difference was also statistically ( P<0.001). Conclusion:2019 novel coronavirus has shorter serial interval and higher family SIR, the SIR of spouses is higher than other family members.

Objective:To investigate the epidemiological characteristics for family clusters of COVID-19 in Zhejiang Province.Methods:The data including cases information of asymptomatic infected cases of family clusters of COVID-19 in Zhejiang Province were collected from Public Health Emergencies Reporting System of China Center for Disease Control and Prevention. Calculate the case number of subsequent cases, index cases, asymptomatic infected cases, exposure cases, and then, compute family secondary attack rate (SIR) and serial interval.Results:A total of 389 cases comprised 149 family index cases and 240 subsequent cases. The clinical symptoms between family index cases and subsequent cases (exclude asymptomatic infected cases ) were similar, fever was the most common symptoms in the two groups 115 (77.18%) and 110（48.67%）respectively, the cases with diarrhea symptoms accounted for the least proportion, which were 7 (4.70%) and 6 (2.65%) respectively. The serial interval between the family index cases and the subsequent cases [ M ( P25, P75)] was 4.00 (2.00, 6.00) days. Family secondary attack rate for subsequent cases was 34.43%, subsequent cases aged between 14 and 60 have the highest SIR (43.42%) compared with other two age groups, the difference was statistically ( P<0.001); the family SIR of the spouses of the family index cases is 68.57%, and are higher than that of parents (29.03%), children (25.00%) and other family members (24.21%), the difference was also statistically ( P<0.001). Conclusion:2019 novel coronavirus has shorter serial interval and higher family SIR, the SIR of spouses is higher than other family members.

Objective To understand the demographic characteristics and clinical features of hookworm infectors in high infection area in South Mountain area of Zhejiang Province,and to find the risk factors of infection,so as to provide the evidence for formulating prevention and control measures.Methods In 2018,according to the soil-borne nematode monitoring results of the previous year in Zhejiang Province,three villages with relatively more hookworm infections were selected from Qingtian County in South Mountain area of Zhejiang Province,and more than 10 cases of hookworm infection were selected from each survey site.A face to face questionnaire survey was conducted by all investigators using a questionnaire designed by the Center for Infectious Disease Control and Prevention,Zhejiang Provincial Center for Disease Control and Prevention,and information on the general condition,past diagnosis history,clinical symptoms and risk factors of infection of infected persons were collected.The stool samples were collected and tested for infection by modified Kato-Katz method to evaluate the drug deworming effect in the previous year.Results A total of 33 cases of hookworm infection were investigated,including 18 males and 15 females;the age ranged from 33-85 years old,mainly concentrated in 60-79 years old,a total of 23 cases (69.7％).Ten cases (30.3％) had been diagnosed with hookworm disease;19 cases (57.6％) had similar symptoms of hooky dermatitis;and 12 cases (36.4％) had gastrointestinal symptoms in the past three years.There were 31 cases (93.9％) worked in the field for more than one month each year,18 cases (54.5％) used fresh manure directly at home,6 cases (18.2％) were used to working barefoot in the field,and 30 cases (90.9％) used to wearing slippers in the field.A total of 32 eligible stool samples were examined,and 4 case (12.5％) were still positive for hookworm eggs.Conclusions Among the infectors,fertilizing with fresh stool,working barefoot or wearing slippers in the field may serve as the risk factors.There is a certain failure proportion to eliminate the infection status when adopting only one round anthelminthic treatment.For prevention and control hookworm infections,comprehensive intervention measures including infection source management,harmless treatment of stools,individual behavior intervention and environment improvement are suggested.

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

Antibody Formation ; Humans ; Meningitis, Meningococcal ; Meningococcal Vaccines

China ; Humans ; Meningococcal Infections ; Serogroup