Association between short-term exposure to ambient air pollution and upper respiratory tract infection in Kunshan.

The health effects of air pollution have become a major public health problem. Studies on the relationship between short-term exposure to air pollutants and upper respiratory tract infection (URTI) related clinic visits and expenditures were scarce. From January 1, 2019, to December 31, 2021, we included all the URTI cases that turned to 11 public hospitals in Kunshan, and summarized individual medical cost. Daily meteorological factors and 24-h mean concentrations of four common air pollutants, including particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and 10 µm (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2), were consecutively recorded. Generalized additive regression model was adopted to quantify the associations between each air pollutant and the daily clinic visits of URTI cases. We further calculated attributable number (AN) and attributable fraction, and performed sensitivity analysis by gender, age, and season. A total of 934,180 cases were retrieved during the study period. PM2.5, PM10, SO2, and NO2 showed significant associations with hospital visits and expenditures due to URTI. Relative risks for them were 1.065 (95% confidence interval [CI] 1.055, 1.076), 1.045 (95% CI 1.037, 1.052), 1.098 (95% CI 1.038, 1.163), and 1.098 (95% CI 1.085, 1.111) on lag 0-5 days, respectively. Thirty-one thousand four hundred fifty-five (95% CI 27,457, 35,436) cases could be ascribed to increased NO2 and accounted for 3.37% (95% CI 2.94%, 3.79%) of all clinic visits. Sensitivity analyses indicated that the effects of air pollution were generally consistent for male and female. PM2.5, PM10, and NO2 had stronger associations among people aged ≤ 18 years, followed by those aged 19-64 years and ≥ 65 years. The association strengths of air pollution varied seasonally. Short-term exposure to ambient air pollutants had significant associations with clinic visits and expenditures owing to URTI. Children and adolescents appeared to be more susceptible to adverse health effects of air pollution. NO2 may be a priority when formulating pollution control measures.

Metabolomics and incident dementia in older Chinese adults: The Shanghai Aging Study.

INTRODUCTION: Metabolomics provide a promising tool to understand the pathogenesis and to identify novel biomarkers of dementia. This study aimed to determine circulating metabolites associated with incident dementia in a Chinese cohort, and whether a selected metabolite panel could predict dementia. METHODS: Thirty-eight metabolites in baseline serum were profiled by nuclear magnetic resonance in 1440 dementia-free participants followed 5 years in the Shanghai Aging Study. RESULTS: Higher serum levels of glutamine and O-acetyl-glycoproteins were associated with increased risk of dementia, whereas glutamate, tyrosine, acetate, glycine, and phenylalanine were negatively related to incident dementia. A panel of five metabolites selected by least absolute shrinkage and selection operator within cross-validation regression analysis could predict incident dementia with an area under the receiver-operating characteristic curve of 0.72. DISCUSSION: We identified seven candidate serum metabolic biomarkers for dementia. These findings and the underlying biological mechanisms need to be further replicated and elucidated in future studies.

Spatial and Temporal Trends in Pancreatic Cancer Burden Attributable to High Body Mass Index at the Global and National Levels.

OBJECTIVES: To examine the spatiotemporal trends in pancreatic cancer (PC) disability-adjusted life years (DALYs) and mortality attributable to high body-mass index (BMI) by age, gender, and countries from 1990 to 2019. METHODS: Data were extracted from the Global Burden of Disease Study 2019 results. We presented the annual number of PC DALYs and mortality, and corresponding age-standardized rates (ASDR and ASMR), which were further stratified by age, gender, and countries. The estimated annual percentage change (EAPC) was computed to assess the longitudinal trends in ASRs. RESULTS: In 2019, 0.7 million DALYs and 31.9 thousand deaths worldwide were caused by PC attributable to high BMI, with the largest amount reported in high-income North America, Western Europe, and East Asia. The corresponding ASDR and ASMR were highest in females and in high SDI regions, while quite varied across countries. The global EAPC in ASDR and ASMR was 1.45 (95% uncertainty interval [UI]: 1.40, 1.50) and 1.44 (95% UI: 1.39, 1.49), respectively. Almost all involved countries demonstrated significant uptrends in ASRs from 1990 to 2019. CONCLUSIONS: More productive efforts to reduce the impact of modifiable risk factors, such as overweight, should be undertaken, and thus effectively curb the rise of PC burden.

Geographical resistome profiling in the honeybee microbiome reveals resistance gene transfer conferred by mobilizable plasmids.

BACKGROUND: The spread of antibiotic resistance genes (ARGs) has been of global concern as one of the greatest environmental threats. The gut microbiome of animals has been found to be a large reservoir of ARGs, which is also an indicator of the environmental antibiotic spectrum. The conserved microbiota makes the honeybee a tractable and confined ecosystem for studying the maintenance and transfer of ARGs across gut bacteria. Although it has been found that honeybee gut bacteria harbor diverse sets of ARGs, the influences of environmental variables and the mechanism driving their distribution remain unclear. RESULTS: We characterized the gut resistome of two closely related honeybee species, Apis cerana and Apis mellifera, domesticated in 14 geographic locations across China. The composition of the ARGs was more associated with host species rather than with geographical distribution, and A. mellifera had a higher content of ARGs in the gut. There was a moderate geographic pattern of resistome distribution, and several core ARG groups were found to be prevalent among A. cerana samples. These shared genes were mainly carried by the honeybee-specific gut members Gilliamella and Snodgrassella. Transferrable ARGs were frequently detected in honeybee guts, and the load was much higher in A. mellifera samples. Genomic loci of the bee gut symbionts containing a streptomycin resistance gene cluster were nearly identical to those of the broad-host-range IncQ plasmid, a proficient DNA delivery system in the environment. By in vitro conjugation experiments, we confirmed that the mobilizable plasmids could be transferred between honeybee gut symbionts by conjugation. Moreover, "satellite plasmids" with fragmented genes were identified in the integrated regions of different symbionts from multiple areas. CONCLUSIONS: Our study illustrates that the gut microbiota of different honeybee hosts varied in their antibiotic resistance structure, highlighting the role of the bee microbiome as a potential bioindicator and disseminator of antibiotic resistance. The difference in domestication history is highly influential in the structuring of the bee gut resistome. Notably, the evolution of plasmid-mediated antibiotic resistance is likely to promote the probability of its persistence and dissemination. Video Abstract.

Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma.

The standard therapy administered to patients with advanced esophageal cancer remains uniform, despite its two main histological subtypes, namely esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (AC), are being increasingly considered to be different. The identification of potential drug target genes between SCC and AC is crucial for more effective treatment of these diseases, given the high toxicity of chemotherapy and resistance to administered medications. Herein we attempted to identify and rank differentially expressed genes (DEGs) in SCC vs. AC using ensemble feature selection methods. RNA-seq data from The Cancer Genome Atlas and the Fudan-Taizhou Institute of Health Sciences (China). Six feature filters algorithms were used to identify DEGs. We built robust predictive models for histological subtypes with the random forest (RF) classification algorithm. Pathway analysis also be performed to investigate the functional role of genes. 294 informative DEGs (87 of them are newly discovered) have been identified. The areas under receiver operator curve (AUC) were higher than 99.5% for all feature selection (FS) methods. Nine genes (i.e., ERBB3, ATP7B, ABCC3, GALNT14, CLDN18, GUCY2C, FGFR4, KCNQ5, and CACNA1B) may play a key role in the development of more directed anticancer therapy for SCC and AC patients. The first four of them are drug targets for chemotherapy and immunotherapy of esophageal cancer and involved in pharmacokinetics and pharmacodynamics pathways. Research identified novel DEGs in SCC and AC, and detected four potential drug targeted genes (ERBB3, ATP7B, ABCC3, and GALNT14) and five drug-related genes.

Associations between serum metabolites and subclinical atherosclerosis in a Chinese population: the Taizhou Imaging Study.

Metabolomics provides a promising tool for understanding the pathophysiology and identifying biomarkers of atherosclerosis. We aimed to estimate the associations between circulating metabolites and subclinical atherosclerosis in a Chinese cohort. The baseline serum levels of 38 metabolites of 489 individuals were measured using nuclear magnetic resonance. Associations between metabolites and brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) were determined using a linear regression. A multivariate logistic regression was used to evaluate the associations of metabolites and subclinical atherosclerosis defined as high baPWV (>median) and increased IMT (>median). After adjusting for covariates and multiple testing corrections (false discovery rate; FDR), two branched-chain amino acids (BCAAs; leucine and isoleucine), one ketone (acetoacetate), and two lipids were positively associated with baPWV. Lactate was inversely associated with IMT. Elevated acetoacetate levels (odds ratio: 1.53, 95% confidence interval: 1.20-1.97; FDR <0.001) and four other lipid features were associated with an increased risk of high baPWV. Alterations in circulating lipids and BCAAs were associated with the risk of arterial stiffness in the middle-aged Chinese population. Our findings provide clues to understanding the potential mechanisms of subclinical atherosclerosis; however, further validation in a broader population context and the exploration of potential clinical applications are warranted.

ALDH2 rs671 polymorphisms and the risk of cerebral microbleeds in Chinese elderly: the Taizhou Imaging Study.

BACKGROUND: Cerebral microbleeds (CMBs) are more prevalent in Asian populations, and have been associated with increased risk of stroke, dementia and mortality. So far, risk factors for CMBs other than hypertension were merely known. Previous studies have shown that polymorphisms at aldehyde dehydrogenase 2 (ALDH2) gene were independently associated with the risk of stroke. Its role in CMBs, however, remains unclear. This study aimed to evaluate the associations of ALDH2 gene polymorphisms with CMBs in Chinese elderly. METHODS: Using bio-specimen and data collected at baseline survey of the population-based Taizhou Imaging Study (TIS) (phase I), we genotyped the single nucleotide polymorphisms (SNPs) at ALDH2 among 549 individuals aged 55-65 years, and rs671 was used as surrogate marker of ALDH2. CMBs were detected on brain magnetic resonance imaging (MRI), and further categorized as strictly lobar or as deep/mixed. Logistic regression models were used to evaluate the associations of the variants at ALDH2 and CMBs. RESULTS: CMBs were present in 103 individuals (18.8%). Forty-one point three percent participants were with ALDH2 *2 allele and 5.1% had ALDH2 *2/*2 genotype. Subjects with ALDH2 *1 allele were more likely to be drinker, have hypertension or CMBs than those with *2 allele (all P<0.05). Multivariate logistic regression model showed that the ALDH2 *1/*1 genotype was independently associated with CMBs (P=0.013), particularly for deep/mixed CMBs (P=0.008), and the association was more pronounced in men, non-drinkers or hypertension patients. CONCLUSIONS: The results suggest that Han Chinese with ALDH2 *1/*1 genotype may be more susceptible to CMBs than those with ALDH2 *2 allele.

Associations of Arterial Stiffness and Carotid Atherosclerosis with Cerebral Small Vessel Disease in a Rural Community-Based Population.

AIMS: We aimed to examine the associations of four extracranial artery indicators with cerebral small vessel disease (CSVD) and its total burden. METHODS: A total of 904 individuals aged 55-65 years old were included from the Taizhou Imaging Study. CSVD markers, including lacunes (LAC), white matter hyperintensities (WMH), cerebral microbleeds (CMB), and perivascular spaces (PVS), were rated based on brain magnetic resonance imaging. We also measured extracranial artery indices, including the brachial-ankle pulse wave velocity (baPWV), the ankle-brachial index, the carotid intima-media thickness (IMT), and carotid plaque. Linear and binary logistic regressions were adopted to test the associations among these four artery indicators and each CSVD marker when appropriate. Additionally, ordinal and multinomial logistic regressions were performed to assess the relationships between artery indicators and total CSVD score (range from 0-4 points). RESULTS: A total of 443 (49.0%) participants were found to have at least one of the CSVD markers, including 172 (19.0%) with WMH, 184 (20.4%) with LAC, 147 (16.3%) with CMB, and 226 (25.0%) with PVS. Increased baPWV was significantly associated with each CSVD marker, increasing carotid IMT was associated with LAC and PVS, and the presence of carotid plaque was associated with WMH volume and PVS. Moreover, per SD increment of baPWV (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.11-1.50) and the presence of carotid plaque (OR: 1.42, 95% CI: 1.05-1.92) were significantly associated with greater total CSVD scores. CONCLUSION: Increased baPWV and the presence of carotid plaque appear to be associated with total CSVD burden in rural regions in China.

Cerebral small vessel disease is associated with gait disturbance among community-dwelling elderly individuals: the Taizhou imaging study.

Gait disturbance is considered to be a significant clinical manifestation of cerebral small vessel disease (CSVD). We aimed to investigate the association between different imaging markers of CSVD or total CSVD burden and gait disturbance in a community-dwelling population. In the cross-sectional Taizhou Imaging Study (TIS), 314 participants free of neurological disorders underwent MRI scanning and gait assessment with quantitative wearable devices as well as clinical rating scales. In linear regression, after adjustment for demographics and vascular risks, total CSVD burden was associated with prolonged 3-m walking (ß=0.118, P=0.035), shorter stride length (ß=-0.106, P=0.042), and poorer Timed-Up-and-Go (TUG) performance (ß=0.146, P=0.009). Lacunes were positively associated with 3-m walking (ß=0.118, P=0.037) and duration of TUG test (ß=0.112, P=0.047). White matter hyperintensities and cerebral microbleeds were associated with prolonged stride time (ß=0.134, P=0.024) and increased stance phase time percentage (ß=0.115, P=0.038), respectively. Logistic regression revealed that participants with high CSVD burden or more lacunes were more likely to have an impaired gait velocity and an impaired TUG test. These results suggest that total CSVD burden and CSVD imaging markers are associated with gait disturbance among community-dwelling elderly people. Different CSVD imaging markers may cause gait disturbance through different pathways.

Total Cerebral Small Vessel Disease Burden Is Related to Worse Performance on the Mini-Mental State Examination and Incident Dementia: A Prospective 5-Year Follow-Up.

Individual cerebral small vessel disease (CSVD) may cause cognitive decline. However, the association between total burden of CSVD and cognitive deterioration in the general population remains unclear. We aimed to determine whether total CSVD score is associated with cognitive performance change and incident dementia in the general population. In the longitudinal population-based Taizhou Imaging Study, 556 participants free of neurological disorders underwent brain MRI and neuropsychological testing at baseline. A total of 456 participants were followed up for cognitive performance for a mean (standard deviation) of 4.6 (0.6) years. Total CSVD score (range 0-4) was calculated by assigning 1 point for the presence of each of the following markers: lacune, white matter hyperintensity, cerebral microbleed, and perivascular space. Beta regression was used to evaluate the association between total CSVD burden and MMSE score change. The association of prevalent CSVD with incident dementia was studied using Fisher's exact test. CSVDs were present in 262 individuals (47.1%). The total CSVD score was significantly associated with MMSE score decline (p = 0.001). Compared to those with no CSVD, participants with 4 CSVD markers had a steeper decline in MMSE score (ß: -0.53, 95% CI: -0.86 to -0.21; p = 0.001). A total of 15 participants developed dementia during follow-up. The presence of more than three CSVD markers at baseline was associated with a significantly higher risk of dementia (p = 0.020). Total CSVD burden appears to be associated with MMSE score decline and incident dementia in a general population in China.

Disparities in Cancer Incidence among Chinese Population versus Migrants to Developed Regions: A Population-Based Comparative Study.

BACKGROUND: The incidence of cancer was determined by genetic and environmental factors and varied across the world. The discrepancies in cancer profile among Chinese people living in different regions remained obscure. METHODS: Chinese people living in urban Shanghai, Hong Kong, Taiwan, Macau, Singapore, and Los Angeles were included in this study. The cancer case data and population data were collected from either the Cancer Incidence in Five Continents Plus database or the regional cancer registry. A rate model was applied to examine the regional differences in cancer risk with Shanghai set as the reference. RESULTS: From 1983 to 2013, the cancer profiles in most regions were changed. Significant differences in cancer incidence, by sex, period, and age, were detected across regions. The most pronounced disparities were found between Shanghai people and American Chinese in Los Angeles. For cancer site, the most significant differences were detected in prostate, gastrointestinal, gynecologic, oral cavity and pharynx, and brain and central nervous system (CNS) cancers. Specifically, Shanghai was significantly higher in stomach, liver, esophageal, pancreatic, and brain and CNS cancers, while lower in colon, prostate, breast, cervical, and oral cavity and pharynx cancers compared with the other five populations. CONCLUSIONS: Cancer profile was distinct across Chinese populations, which shared a similar genetic background but lived in different regions. The disparities indicate that cancer development was majorly determined by environmental factors, and suggests that region-tailored cancer prevention strategies were warranted. IMPACT: The cancer patterns in populations sharing the same genetic background were significantly influenced by different living conditions.

Metabolomics in the Development and Progression of Dementia: A Systematic Review.

Dementia has become a major global public health challenge with a heavy economic burden. It is urgently necessary to understand dementia pathogenesis and to identify biomarkers predicting risk of dementia in the preclinical stage for prevention, monitoring, and treatment. Metabolomics provides a novel approach for the identification of biomarkers of dementia. This systematic review aimed to examine and summarize recent retrospective cohort human studies assessing circulating metabolite markers, detected using high-throughput metabolomics, in the context of disease progression to dementia, including incident mild cognitive impairment, all-cause dementia, and cognitive decline. We systematically searched the PubMed, Embase, and Cochrane databases for retrospective cohort human studies assessing associations between blood (plasma or serum) metabolomics profile and cognitive decline and risk of dementia from inception through October 15, 2018. We identified 16 studies reporting circulating metabolites and risk of dementia, and six regarding cognitive performance change. Concentrations of several blood metabolites, including lipids (higher phosphatidylcholines, sphingomyelins, and lysophophatidylcholine, and lower docosahexaenoic acid and high-density lipoprotein subfractions), amino acids (lower branched-chain amino acids, creatinine, and taurine, and higher glutamate, glutamine, and anthranilic acid), and steroids were associated with cognitive decline and the incidence or progression of dementia. Circulating metabolites appear to be associated with the risk of dementia. Metabolomics could be a promising tool in dementia biomarker discovery. However, standardization and consensus guidelines for study design and analytical techniques require future development.

Deep/mixed cerebral microbleeds are associated with cognitive dysfunction through thalamocortical connectivity disruption: The Taizhou Imaging Study.

BACKGROUND: Cerebral microbleeds (CMBs) are considered to be risk factors for cognitive dysfunction. The specific pathology and clinical manifestations of CMBs are different based on their locations. We investigated the association between CMBs at different locations and cognitive dysfunction and explored the potential underlying pathways in a rural Han Chinese population. METHODS: We used baseline data from 562 community-dwelling adults (55-65 years old) in the Taizhou Imaging Study between 2013 and 2015. All individuals underwent multimodal brain magnetic resonance imaging (MRI) and 444 subjects completed neuropsychological tests: the Mini-Mental Status Examination and the Montreal Cognitive Assessment. Multinomial logistic regression was used to estimate the association between CMBs and cognitive dysfunction. The volume of brain regions and white matter microstructure were analyzed using Freesurfer and tract-based spatial statistics, respectively. RESULTS: CMBs were detected in 104 individuals (18.5%) in our study. Multinomial logistic regression found deep/mixed CMBs were associated with global cognitive dysfunction (OR 3.52; 95% CI 1.21 to 10.26), whereas lobar CMBs (OR 1.76; 95% CI 0.56 to 5.53) were not. Quantification of multimodal brain MRI showed that deep/mixed CMBs were accompanied by decreased thalamic volume and loss of fractional anisotropy of bilateral anterior thalamic radiations. CONCLUSION: Deep/mixed CMBs were associated with cognitive dysfunction in this Chinese cross-sectional study. Disruption of thalamocortical connectivity might be a potential pathway underlying this relationship.

[A study on the model of tuberculous pleurisy and intrapleural inflammatory and immunological responses in rats].

OBJECTIVE: To develop a rat model of tuberculous pleurisy and to explore the mechanism of intrapleural inflammatory and immunological responses. METHODS: Fifty Wistar rats were injected intrapleurally with 0.03 mg of standard human mycobacterium tuberculous bacilli H37Rv each. The rats were killed in group on days 1, 2, 3, 5, 7, 10, 15, 20, 30 and 60 after the day of intrapleural injection. The thorax was opened and the amount of pleural effusion was recorded, and histopathology of pleural tissues and lung tissues were observed. The white blood cell (WBC) count and differentials, levels of total protein (TP), glucose (GLU) and lactic dehydrogenase (LDH) of pleural effusions were determined. Pleural fluid was analyzed for the levels of soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta1 (TGF-beta1) and interferon gamma (IFN-gamma) by using appropriate bioassays. Ten rats were intrapleurally received 2 ml of normal saline and another 10 rats received 2 ml of undiluted PPD solution each as control. RESULTS: Bilateral pleural effusions appeared within 15 days in all rats intrapleurally received tuberculous bacilli. The peak amount of pleural fluid was on day 5 (6.7 +/- 0.5 ml). The neutrophils were the predominant cells for the first 24 hours, and then were followed by lymphocytes. In the pleural fluid, total protein concentration was between 51-55 g/L. The levels of glucose and LDH were 5.2 mmol/L and 18.1 micromol.s(-1).L(-1) on day 1 and changed to 2.8 mmol/L and 28.9 micromol.s(-1).L(-1) on day 15 respectively. The biochemistry parameters were in accordance with characteristics of tuberculous pleurisy. The sICAM-1 level increased early (21.9 ng/ml on day 1) and peaked on day 3 (38.0 ng/ml), then decreased over time (4.4 ng/ml on day 15). The level of IFN-gamma was 41.2 pg/ml on day 1 and increased and maintained at high levels over time. TGF-beta1 levels increased and peaked on day 7 (47.2 ng/ml), and then on day 15 decreased to a level lower than that of day 1. The ratio of IFN-gamma/TGF-beta1 increased from 1.32 on day 1 to 5.69 on day 15. Correlation analysis showed that sICAM-1 and IFN-gamma were closely related with WBC count and its differentials, as well as with LDH levels. Histopathological study revealed early pleural inflammation and late caseation. CONCLUSIONS: Wistar rats can be used as an experimental model for tuberculous pleurisy. Tuberculous inflammatory and immunological responses in acute tuberculous pleurisy is enhanced rather than suppressed.