medRxiv preprint generally longer incubation and serial interval of less severe cases suggests a high risk of longterm epidemic in the absence of appropriate control measures.

Metformin has garnered more interest as a chemo-preventive agent given the increased liver cancer risk in diabetic patients. This work was undertaken to better understand the effect of metformin use on liver cancer risk in diabetic patients.A comprehensive literature search was performed in PubMed, Embase, BIOSIS Previews, Web of Science, and Cochrane Library through July 30, 2016. Meta-analyses were performed using Stata version 12.0, with odds ratio (ORs) and 95% confidence intervals (CIs) as effect measures.Twenty-three studies were included. Meta-analysis of 19 studies involving 550,882 diabetic subjects suggested that metformin use reduced the ratio of liver cancer by 48% (OR = 0.52; 95% CI, 0.40–0.68) compared with nonusers. The protective effect was validated in all the exploratory subgroup analyses, except that pooled result of post hoc analyses of 2 randomized controlled trials found no significant difference between subjects with metformin and those without, with OR being 0.84 (95% CI, 0.10–6.83). After adjusting for hepatitis B/C virus infection, cirrhosis, obesity, behavioral factors, and time-related bias, the association was stable, pooled OR ranged from 0.42 to 0.75.A protective effect for liver cancer was found in diabetic metformin users. However, more randomized clinical evidence is still needed to verify the results.

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Background The estimates of several key epidemiological parameters of the COVID-19 pandemic are often based on small sample sizes or are inaccurate for various reasons. Objective The aim of this study is to obtain more robust estimates of the incubation period, serial interval, frequency of presymptomatic transmission, and basic reproduction number (R0) of COVID-19 based on a large case series. Methods We systematically retrieved and screened 20,658 reports of laboratory-confirmed COVID-19 cases released by the health authorities of China, Japan, and Singapore. In addition, 9942 publications were retrieved from PubMed and China National Knowledge Infrastructure (CNKI) through April 8, 2020. To be eligible, a report had to contain individual data that allowed for accurate estimation of at least one parameter. Widely used models such as gamma distributions were fitted to the data sets and the results with the best-fitting values were presented. Results In total, 1591 cases were included for the final analysis. The mean incubation period (n=687) and mean serial interval (n=1015 pairs) were estimated to be 7.04 (SD 4.27) days and 6.49 (SD 4.90) days, respectively. In 40 cases (5.82%), the incubation period was longer than 14 days. In 32 infector-infectee pairs (3.15%), infectees’ symptom onsets occurred before those of infectors. Presymptomatic transmission occurred in 129 of 296 infector-infectee pairs (43.58%). R0 was estimated to be 1.85 (95% CI 1.37-2.60). Conclusions This study provides robust estimates of several epidemiological parameters of COVID-19. The findings support the current practice of 14-day quarantine of persons with potential exposure, but also suggest the need for additional measures. Presymptomatic transmission together with the asymptomatic transmission reported by previous studies highlight the importance of adequate testing, strict quarantine, and social distancing.

The gasdermin (GSDM) family, a novel group of structure-related proteins, consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME/DNFA5, and PVJK/GSDMF. GSDMs possess a C-terminal repressor domain, cytotoxic N-terminal domain, and flexible linker domain (except for GSDMF). The GSDM-NT domain can be cleaved and released to form large oligomeric pores in the membrane that facilitate pyroptosis. The emerging roles of GSDMs include the regulation of various physiological and pathological processes, such as cell differentiation, coagulation, inflammation, and tumorigenesis. Here, we introduce the basic structure, activation, and expression patterns of GSDMs, summarize their biological and pathological functions, and explore their regulatory mechanisms in health and disease. This review provides a reference for the development of GSDM-targeted drugs to treat various inflammatory and tissue damage-related conditions.

Background:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. Methods:A total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. Results:A total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. : medRxiv preprint ConclusionsPatients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

These results indicate a strong relationship between H. pylori and chronic hepatitis B, particularly during HBV progression.

Purpose. Helicobacter pylori is a common gastric disease-inducing pathogen. Although an increasing number of recent studies have shown that H. pylori is a risk factor for liver disease, the potential association between H. pylori infection and chronic hepatitis C still remains controversial. The aim of our meta-analysis was to evaluate a potential association between H. pylori infection and chronic hepatitis C. Methods. We searched the PubMed, Embase, CNKI, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases between January 1, 1994, and May 1, 2015. Results. This study included a total of 1449 patients with chronic hepatitis C and 2377 control cases. The prevalence of H. pylori was significantly higher in patients with chronic hepatitis C than in those without chronic hepatitis C. The pooled odds ratio was 2.93. In a subgroup analysis, the odds ratios were 4.48 for hepatitis C virus- (HCV-) related cirrhosis and 5.45 for hepatocellular carcinoma. Conclusion. Our study found a strong association between H. pylori and chronic hepatitis C, particularly during the HCV progression stage; thus, we recommend active screening for H. pylori in patients with chronic hepatitis C.