Yong Wang

Objective To characterize the distribution and transmission of antibiotic resistance genes (ARGs) and antimicrobial-resistant bacteria (ARB) across pig farm environments in Shandong Province, China. Methods In June 2023, we collected 185 samples from two closed-system pig farms in Liaocheng and Dezhou, Shandong Province, China, including 28 metagenomes (manure, wastewater, soil) and 157 culture-based bacterial isolates. We applied metagenomic sequencing, whole-genome sequencing, antimicrobial susceptibility testing, and source tracking across pigpens, staff living areas, and surrounding soils. Results ARG and mobile genetic element (MGE) abundances peaked in wastewater, declined in manure and soil. Soil bacterial communities and ARG profiles exhibited a spatial gradient with increasing distance from farm boundaries. Transposases and integrases were the predominant MGEs driving ARG mobility. Multidrug-resistant Staphylococcus aureus (mecA-positive), Pseudomonas aeruginosa, and Bacillus cereus were detected across animal, environmental, and residential sites, indicating cross-compartment transmission. Conclusions Wastewater is the principal driver of environmental ARG dissemination in pig farming, facilitated by MGEs and ARB mobility.

Objective: Recently, 10 plasmid-mediated mobile colistin resistance genes, mcr-1 to mcr-10, and their variants have been identified, posing a new threat to the treatment of clinical infections caused by Gram-negative bacteria. Our objective was to develop a rapid, sensitive, and accurate molecular assay for detecting mcr genes in clinical isolates.Methods: The primers and corresponding TaqMan-MGB probes were designed based on the sequence characteristics of all reported MCR family genes, multiplex Taqman-MGB probe-based qPCR assays were developed and optimized, and the sensitivity, specificity and reproducibility of the method were evaluated. The assay contained 8 sets of primers and probes in 4 reaction tubes, each containing 2 sets of primers and probes.Results: The standard curves for both the single and multiplex systems showed good linearity (R² > 0.99) between the starting template amount and the Ct value, with a lower limit of detection of 10² copies/μL. The specificity test showed positive amplification results only for strains containing the mcr genes, whereas the other strains were negative. The results of intra-and inter-group repeatability experiments demonstrated the stability and reliability of the newly developed method. It was used to detect mcr genes in 467 clinically-obtained Gram-negative isolates, which were multidrug-resistant. Twelve strains containing the mcr genes were detected (seven isolates carrying mcr-1, four isolates carrying mcr-10, and one isolate carrying mcr-9). The products amplified by the full-length PCR primer were identified by sequencing, and the results were consistent with those of the multiplex qPCR method.Conclusion: The assay developed in this study has the advantages of high specificity, sensitivity, and reproducibility. It can be used to specifically detect drug-resistant clinical isolates carrying the mcr genes (mcr-1 to mcr-10), thus providing a better basis for clinical drug treatment and drug resistance research.

Background & Aims: Acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer caused by hepatitis C virus (HCV) are have imposed a sever burden at the global. The study aims to describe the burden and inequality analysis of HCV-related liver diseases at the global. Methods: Our study utilized data from the Global Burden of Diseases (GBD) 2019. Age-standardized rate of incidence (ASIR), prevalence (ASPR), death (ASDR), and disability-adjusted life years (DALYs) were employed to describe the burden of HCV-related liver diseases across different populations and regions worldwide. Additionally, we conducted an inequality analysis using the slope index of inequality and concentration index to explore the global disparities associated with HCV-related liver diseases burden. Results: HCV-related diseases caused 542, 316 global deaths in 2019. China (17% of total infections) and India (10% of total infections) had the largest numbers of HCV-related disease, but the ASPR was highest in Mongolia (9, 673.92 per 100, 000) and Cambodia (5, 445.82 per 100, 000). The burden of Acute hepatitis C (AHC) was more common in low socio-demographic index (SDI) regions, while HCV-related liver cancer caused more large burden among the regions with higher SDI. Conclusions: The burden of HCV-related liver diseases was still at a relatively high level worldwide, and SDI was a significant factor for differential distribution of the disease. Countries in the world should take active parts in alleviating the burden of HCV-related liver diseases, and take targeted measures according to their specific circumstances.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a significant zoonotic disease mainly transmitted by rodents. However, the determinants of its spatiotemporal patterns in Northeast China remain unclear. Objective: This study aimed to investigate the spatiotemporal dynamics and epidemiological characteristics of HFRS and detect the meteorological effect of the HFRS epidemic in Northeastern China. Methods: The HFRS cases of Northeastern China were collected from the Chinese Center for Disease Control and Prevention, and meteorological data were collected from the National Basic Geographic Information Center. Times series analyses, wavelet analysis, Geodetector model, and SARIMA model were performed to identify the epidemiological characteristics, periodical fluctuation, and meteorological effect of HFRS in Northeastern China. Results: A total of 52,655 HFRS cases were reported in Northeastern China from 2006 to 2020, and most patients with HFRS (n=36,558, 69.43%) were aged between 30-59 years. HFRS occurred most frequently in June and November and had a significant 4- to 6-month periodicity. The explanatory power of the meteorological factors to HFRS varies from 0.15 ≤ q ≤ 0.01. In Heilongjiang province, mean temperature with a 4-month lag, mean ground temperature with a 4-month lag, and mean pressure with a 5-month lag had the most explanatory power on HFRS. In Liaoning province, mean temperature with a 1-month lag, mean ground temperature with a 1-month lag, and mean wind speed with a 4-month lag were found to have an effect on HFRS, but in Jilin province, the most important meteorological factors for HFRS were precipitation with a 6-month lag and maximum evaporation with a 5-month lag. The interaction analysis of meteorological factors mostly showed nonlinear enhancement. The SARIMA model predicted that 8,343 cases of HFRS are expected to occur in Northeastern China. Conclusions: HFRS showed significant inequality in epidemic and meteorological effects in Northeastern China, and eastern prefecture-level cities presented a high risk of epidemic. This study quantifies the hysteresis effects of different meteorological factors and prompts us to focus on the influence of ground temperature and precipitation on HFRS transmission in future studies, which could assist local health authorities in developing HFRS-climate surveillance, prevention, and control strategies targeting high-risk populations in China.

Background Epidemiological studies have reported that among participants with impaired cognitive, overweight and mild obesity are associated with substantially improved survival, this finding has been termed the “obesity paradox” and has led to uncertainty about secondary prevention. Aims To explore whether the association of BMI with mortality differed in different MMSE score, and whether the obesity paradox in patient with cognitive impairment (CI) is real. Methods The study used data from CLHLS, a representative prospective population-based cohort study in China, which included 8348 participants aged ≥ 60 years between 2011 and 2018. The independent association between BMI and mortality in differed MMSE score by calculating hazard ratios (HRs) in multivariate Cox regression analysis. Results During a median (IQR) follow-up of 41.18 months, a total of 4216 participants died. In the total population, underweight increased the risk of all-cause mortality (HRs, 1.33; 95% CI 1.23–1.44), compared with normal weight, and overweight was associated with a decreased risk of all-cause mortality (HR 0.83; 95% CI 0.74–0.93). However, compared to normal weight, only underweight was associated with increased mortality risk among participants with MMSE scores of 0–23, 24–26, 27–29, and 30, and the fully-adjusted HRs (95% CIs) for mortality were 1.30 (1.18, 1.43), 1.31 (1.07, 1.59), 1.55 (1.34, 1.80) and 1.66 (1.26, 2.20), respectively. The obesity paradox was not found in individuals with CI. Sensitivity analyses carried out had hardly any impact on this result. Conclusion We found no evidence of an obesity paradox in patients with CI, compared with patients of normal weight. But underweight individuals may have increased mortality risk whether in the population with CI or not. And overweight/obese people with CI should continue to aim for normal weight.

Objective: Cognitive impairment (CI) has been demonstrated as a useful proxy measure of mortality in Western populations. However, the predictive value of CI in Chinese populations is unknown. We aimed to explore whether CI is independently associated with increased long-term all-cause and cardiovascular disease (CVD) mortality in Chinese older adults and the association of performance in specific MMSE sub-domains to subsequent mortality.Methods and results: A total of 4,499 older adults [mean (SD) age, 70.3(6.7) years] who received a sample investigation from 2011 to 2014 were followed up till 2021 for mortality. The Mini-Mental State Examination was used to assess cognitive function, and Cox's proportional hazard models were used to evaluate the effects of cognitive function on the risk of all-cause and CVD mortality. Demographic characteristics, lifestyle, and health status were included as covariates. During a 10-year follow-up, a total of 667 (14.8%) died. In the fully adjusted model, compared with cognitively normal participants with CI had a 1.33-fold [HR, 1.33; (95% CI, 1.10–1.61)] greater risk of all-cause mortality and a 1.45-fold [HR, 1.45; (95% CIs, 1.11–1.92)] greater risk of CVD mortality. After a similar multivariable adjustment, a per-SD increase in MMSE scores was associated with a reduced risk of all-cause mortality [HR, 0.85; (95% CI, 0.78–0.93)] and CVD mortality [HR, 0.74; (95% CI, 0.65–0.84)]. In the unadjusted model, MMSE sub-domains (apart from immediate recall) were associated with mortality. But only orientation and calculation and attention were still independently associated with all-cause and CVD mortality in a multivariable model.Conclusion: These findings confirmed that CI is a marker of all-cause and CVD mortality risk in Chinese older adults, independently of other commonly assessed risk factors, and some sub-domains of the MMSE may have stronger associations with mortality. Further research is needed to identify the mechanisms underlying the observed associations.

Background: Diabetes mellitus (DM) or cognitive impairment (CI) is known to be strongly associated with mortality. DM commonly coexists with CI and proportionally increases with age. However, little is known about the combined effect of cognitive function and diabetes on mortality. This study aimed to evaluate the combined effects of DM and CI on all-cause and cause-specific mortality in Chinese older adults.Methods: This prospective population-based cohort study was based on the Beijing Elderly Comprehensive Health Cohort Study. A total of 4,499 older adults were included. Cox’s proportional hazard models were utilized to calculate the effect of DM and CI on all-cause, cardiovascular disease (CVD) mortality and cancer mortality, and a multiplicative term was introduced to study a potential interaction between DM and CI on outcomes.Results: During a median follow-up of 6.8 years (ranging from 6.6 to 11.7 years), 667 (14.8%) participants died from all causes, 292 from CVD, and 215 from cancer. In the fully adjusted model, participants with coexisting DM and CI had the highest risk of all-cause mortality [hazard ratios (HRs), 3.08; 95% confidence intervals (CIs), 2.30,4.11] and CVD mortality (HRs, 3.85; 95% CIs, 2.60,5.71) compared with individuals with normal cognition and non-DM. We also found a multiplicative interaction between DM and CI in respect to all-cause (HRs, 2.46; 95% CI, 1.87,3.22) and CVD mortality (HRs, 3.15 95% CI, 2.19,4.55). In the diabetic population, CI was associated with an increased risk of all-cause mortality (HRs, 2.09; 95% CIs, 1.51,2.89) and CVD mortality (HRs, 3.16; 95% CIs, 2.02,5.05) compared with the normal cognition group. Restricted cubic spline revealed a linear inverse association between Mini-Mental State Examination (MMSE) score and all-cause, CVD mortality in the total sample and participants without diabetes. However, a nearly reverse J association was observed between MMSE and mortality from all causes and CVD in the diabetes group.Conclusion: The findings highlighted that cognitive impairment concomitant with diabetes further increases the risk of mortality. In addition to strengthening routine screening of cognitive functioning in older adults with early-stage diabetes, more extensive assessment of prognostic risks has high clinical value for developing comprehensive treatment plans.