Metformin Attenuates TGF-ß1-Induced Fibrosis in Salivary Gland: A Preliminary Study.

Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-ß1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin's anti-fibrotic properties. Elevated levels of TGF-ß1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-ß1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.

Investigation on the possibility of dynamic COVID-Zero strategy in China: a population-based transmission model analysis and economic evaluation.

OBJECTIVE: To explore the feasible and cost-effective intervention strategies to achieve the goal of dynamic COVID-Zero in China. DESIGN: A Susceptible-Exposed-Infectious-Recovered model combined economic evaluation was used to generate the number of infections, the time for dynamic COVID-Zero and calculate cost-effectiveness under different intervention strategies. The model simulated the 1 year spread of COVID-19 in mainland China after 100 initial infections were imported. INTERVENTIONS: According to close contact tracing degree from 80% to 100%, close contact tracing time from 2 days to 1 day, isolation time from 14 days to 7 days, scope of nucleic acid testing (NAT) from 10% to 100% and NAT frequency from weekly to every day, 720 scenarios were simulated. OUTCOME MEASURE: Cumulative number of infections (CI), social COVID-Zero duration (SCD), total cost (TC) and incremental cost-effectiveness ratio. RESULTS: 205 of 720 scenarios could achieve the total COVID-Zero since the first case was reported. The fastest and most cost-effective strategy was Scenario 680, in which all close contacts were traced within 1 day, the isolation time was 14 days and 10% of the national population was randomly checked for NAT every day. In Scenario 680, the CI was 280 (100 initial infections) and the SCD was 13 days. The TC was ¥4126 hundred million and the cost of reducing one infection was ¥47 470. However, when the close contact tracing time was 2 days and the degree of close contact tracing was 80%-90%, the SCD would double to 24-101 days and the TCs increased by ¥16 505 to 37 134 hundred million compared with Scenario 680. CONCLUSIONS: If all close contact was controlled within 1 day, the rapid social COVID-Zero can be achieved effectively and cost-effectively. Therefore, the future prevention and control of emerging respiratory infectious diseases can focus on enhancing the ability of close contact tracing.

Cost-effectiveness analysis on COVID-19 surveillance strategy of large-scale sports competition.

BACKGROUND: Nucleic acid test (NAT) could effectively control the spread of COVID-19 caused by large-scale sports competitions. However, quantitative analysis on the appropriate frequency of NAT is scarce, and the cost-effectiveness and necessity of high-frequency NAT remain to be fully explored and validated. This study aims to optimize the COVID-19 surveillance strategies through cost-effectiveness analysis for the Tokyo 2020 Olympic Games and the upcoming Beijing 2022 Olympic Winter Games. METHODS: A total of 18 scenarios were designed regarding the NAT frequency, symptom monitoring, and strengthening close-contact control. An agent-based stochastic dynamic model was used to compare the cost-effectiveness of different NAT scenarios and optimize the surveillance strategies. The dynamics of the proposed model included the arrival and departure of agents, transmission of the disease according to Poisson processes, and quarantine of agents based on regular NATs and symptom onset. Accumulative infections, cost, and incremental cost-effectiveness ratio (ICER) were simulated in the frame of the model. ICER was used to compare the cost-effectiveness of different scenarios. Univariate sensitivity analysis was performed to test the robustness of the results. RESULTS: In Scenario 16, where the competition-related personnel (CRP) received NAT daily and national sports delegation (NSD) with quarantined infections accepted an additional NAT daily, accumulative infection was 320.90 (90 initial infections), the total cost was (United States Dollar) USD 8 920 000, and the cost of detecting out each infection was USD 27 800. Scenario 16 would reduce the total cost by USD 22 570 000 (avoid 569.61 infections), USD 1 420 000 (avoid 47.2 infections) compared with Scenario 10 (weekly NAT, strengthened close contact control) and Scenario 7 (daily NAT, no strengthened close contact control), respectively. Sensitivity analysis showed that the result was most sensitive to the change in basic reproductive number. CONCLUSIONS: High-frequency NATs such as bidaily, daily, and twice a day were cost-effective. NAT daily for CRP with strengthening close-contact control could be prioritized in defense against COVID-19 at large-scale sports competitions. This study could assist policymakers by assessing the cost-effectiveness of NAT scenarios and provide the host country with an optimal COVID-19 surveillance strategy.

Impact of Regions with COVID-19 Cases on COVID-Zero Regions by Population Mobility - Worldwide, 2021.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Reducing population mobility and increasing the vaccination rate for severe acute respiratory syndrome coronavirus 2 can decrease the transmission of coronavirus disease 2019 (COVID-19). WHAT IS ADDED BY THIS REPORT?: In order to reduce the incidence of COVID-19 to the levels of influenza after restoring normal mobility, the efficacy against infection needs to be increased to 40% and the efficacy against symptomatic disease needs to be increased to 90%. The efficacy against infection has a more important impact compared to efficacy against symptomatic disease or death on the transmission of COVID-19 at the population level. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: The population should continue maintaining non-pharmaceutical interventions and minimize international movement to prevent transmission of COVID-19. Furthermore, developing new vaccines or promoting booster vaccinations should be considered to increase efficacy.

Association between human coronaviruses' epidemic and environmental factors on a global scale.

Environmental factors could influence the epidemic of virus in human; however, the association remains intricate, and the evidence is still not clear in human coronaviruses (HCoVs). We aimed to explore and compare the associations between HCoVs' epidemic and environmental factors globally. Four common HCoVs' data were collected by a systematic literature review, and data of MERS, SARS, and COVID-19 were collected from the World Health Organization's reports. Monthly positive rates of common HCoVs and incidence rates of MERS, SARS, and COVID-19 were calculated. Geographical coordinates were used to link virus data and environmental data. Generalized additive models (GAMs) were used to quantitatively estimate the association of environmental factors with HCoVs' epidemic. We found that there are wide associations between HCoVs and environmental factors on a global scale, and some of the associations were nonlinear. In addition, COVID-19 has the most similarities in associations' direction with common HCoVs, especially for HCoV-HKU1 in four environmental factors including the significantly negative associations with average temperature, precipitation, vegetation coverage (p<0.05), and the U-shaped association with temperature range. This study strengthened the relevant research evidences and provided significant insights into the epidemic rules of HCoVs in general. The similarities between COVID-19 and common HCoVs indicated that it is critically important to strengthen surveillance on common HCoVs and pay more attention to environmental factors' role in surveillance and early warning of HCoVs' epidemic.