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Abstract Background Climate change has raised scientific interest in examining the associations of weather conditions with adverse health effects, while most studies determined human thermal stress using ambient air temperature rather than the thermophysiological index. Objectives To evaluate the association between emergency ambulance dispatches (EADs) related to cardiovascular causes and heat/cold stress in Shenzhen, a city in southern China, with the aim of providing new insights for local policymakers. Methods A time series analysis using ambulance dispatch data of cardiovascular diseases in Shenzhen, China (2013–2019) was conducted. A quasi-Poisson nonlinear distributed lag model was applied to explore the relationship between emergency ambulance dispatches (EADs) due to cardiovascular causes and thermal stress (determined by Universal Thermal Climate Index, UTCI). Attributable fractions were estimated to identify which UTCI ranges have a greater health impact. Results The relationship between UTCI and EADs due to cardiovascular diseases exhibits a reverse J-shaped curve. The effects of cold stress were immediate and long-lasting, whereas the effects of heat stress were non-significant. Compared with the optimal equivalent temperature (71st percentile of UTCI, 29.22 °C), the relative risks for cumulative (0–21 days) exposures to cold stress (1st percentile, − 0.13 °C; 5th percentile, 7.68 °C) were 1.55 (95%CI:1.28,1.88) and 1.44 (95%CI:1.22,1.69), respectively. Thermal (cold and heat) stress was responsible for 10.81% (95%eCI: 5.67%,15.43%) of EADs for cardiovascular diseases, with 9.46% (95%eCI: 3.98%,14.40%) attributed to moderate cold stress (2.5th ~ 71st percentile). Greater susceptibility to cold stress was observed for males and the elderly. Heat stress showed harmful effects in the warm season. Conclusions Our results demonstrated that cold exposure elevates the risk of EADs for cardiovascular causes in Shenzhen, and moderate cold stress cause the highest burden of ambulance dispatches. Health authorities should consider effective adaptation strategies and interventions responding to cold stress to reduce the morbidity of cardiovascular diseases.

BackgroundThe emergence of optrA, which can confer resistance to phenicols and oxazolidinones in Enterococcus spp., poses a growing public health threat.Methods102 optrA-positive enterococci (OPEs) including various species were isolated from feces of 719 healthy volunteers in a Shenzhen community, China. Antimicrobial susceptibility of these isolates was tested. Whole-genome sequencing and bioinformatics analysis were performed to characterize molecular epidemiology of OPEs.ResultsCompared to optrA-negative enterococci (ONEs), antimicrobial resistance (linezolid, florfenicol, doxycycline, erythromycin and ciprofloxacin) and presence of antimicrobial resistance genes (ARGs) (fexA, cat, tet(M), erm(A), erm(B) and etc) were higher in OPEs. Phylogenetic analysis revealed that high similarly (19–338 SNPs) was observed between the optrA-positive E. faecalis from community and the strains from patients, animals, and environment. In 102 OPEs, the optrA gene was detected on the chromosome (n = 36), on plasmids (n = 62), or both (n = 4). A diverse range of optrA-carrying plasmid types was identified. The rep9-plasmid replicons were widely detected in E. faecalis (44/66), whereas repUS1-plasmid replicons were widely identified in other enterococcal species (7/66). Most of all ARGs harbored by isolates were co-existed on optrA-carrying plasmids, suggesting that the acquisition of optrA-carrying plasmids will pose a greater threat to public health. Notably, the pAD1 (rep9 family) + DOp1-type plasmids should receive more attention for the transfer of optrA given their high prevalence (36.36%), high number of co-located ARGs with optrA (83.87% of total ARGs) and presence in multiple sources. Tn6674, IS1216E, ISEnfa1 and ISEnfa5 are related to the transfer of chromosomal and plasmids-derived optrA, respectively. The bcrABDR gene cluster, fexA, and erm(A) were frequently identified surrounding optrA and may be transferred with optrA via IS1216E or ISEnfa1.ConclusionThe transfer of optrA gene is related to a variety of mobile elements (including plasmids, insertion sequences, transposons), which will promote the horizontal transfer of optrA. Moreover, many ARGs co-exist with optrA and could co-transfer with optrA. The acquisition of OPEs and optrA-carrying plasmids will pose a greater threat to public health and should be obtained more attention, especially optrA-positive E. faecalis and pAD1 + DOp1-type plasmids.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

IntroductionThe precise associations between temperature-related indices and mental and behavioral disorders (MBDs) have yet to be fully elucidated. Our study aims to ascertain the most effective temperature-related index and assess its immediate impact on emergency ambulance dispatches (EADs) due to MBDs in Shenzhen, China.MethodsEADs data and meteorological data from January 1, 2013, to December 31, 2020, in Shenzhen were collected. Distributed lag non-linear models (DLNMs) were utilized to examine the non-linear and lagged effects of temperature-related indices on EADs due to MBDs. The Quasi Akaike Information criterion (QAIC) was used to determine the optimal index after standardizing temperature-related indices. After adjusting for confounding factors in the model, we estimated the immediate and cumulative effects of temperature on EADs due to MBDs.ResultsThe analysis of short-term temperature effects on EADs due to MBDs revealed Humidex as the most suitable index. Referring to the optimal Humidex (3.2th percentile, 12.00°C), we observed a significant effect of Humidex over the threshold (34.6th percentile, 26.80°C) on EADs due to MBDs at lag 0–5. The cumulative relative risks for high temperature (90th percentile, 41.90°C) and extreme high temperature (99th percentile, 44.20°C) at lag 0–5 were 1.318 (95% CI: 1.159–1.499) and 1.338 (95% CI: 1.153–1.553), respectively. No significant cold effect was observed on EADs due to MBDs.ConclusionHigh Humidex was associated with more EADs due to MBDs in subtropical regions. Health authorities should implement effective measures to raise public awareness of risks related to high temperature and protect vulnerable populations.

Abstract Vascular calcification is a strong predictor of cardiovascular events. Essential metals play critical roles in maintaining human health. However, the association of essential metal levels with risk of aortic arch calcification (AoAC) remains unclear. We measured the plasma concentrations of nine essential metals in a cross‐sectional population and evaluated their individual and combined effects on AoAC risk using multiple statistical methods. We also explored the mediating role of fasting glucose. In the logistic regression model, higher quartiles of magnesium and copper were associated with the decreased AoAC risk, while higher quartile of manganese was associated with higher AoAC risk. The least absolute shrinkage and selection operator penalized regression analysis identified magnesium, manganese, calcium, cobalt, and copper as key metals associated with AoAC risk. The weighted quantile sum regression suggested a combined effect of metal mixture. A linear and positive dose–response relationship was found between manganese and AoAC in males. Moreover, blood glucose might mediate a proportion of 9.38% of the association between manganese exposure and AoAC risk. In summary, five essential metal levels were associated with AoAC and showed combined effect. Fasting glucose might play a significant role in mediating manganese exposure‐associated AoAC risk.

Per- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies have shown that a single exposure to PFAS may provoke abnormal liver function; however, few studies have investigated the overall effect of PFAS mixtures. We aimed to investigate associations between exposure to PFAS mixtures and liver function indices and explore the relevant mechanisms. This study included 278 adult males from Guangzhou, China. Serum metabolite profiles were analyzed using untargeted metabolomics. We applied weighted quantile sum (WQS) regression as well as Bayesian kernel machine regression (BKMR) to analyze the association of nine PFAS mixtures with 14 liver function indices. PFAS mixtures were positively associated with apolipoprotein B (APOB) and gamma-glutamyltransferase (GGT) and negatively associated with direct bilirubin (DBIL) and total bilirubin (TBIL) in both the WQS and BKMR analyses. In addition, Spearman’s correlation test showed individual PFAS correlated with APOB, GGT, TBIL, and DBIL, while there’s little correlation between individual PFAS and other liver function indices. In linear regression analysis, PFHxS, PFOS, PFHpS, PFNA, PFDA, and PFUdA were associated with APOB; PFOA, PFDA, PFOS, PFNA, and PFUdA were associated with GGT. Subsequently, a metabolome-wide association study and mediation analysis were combined to explore metabolites that mediate these associations. The mechanisms linking PFAS to APOB and GGT are mainly related with amino acid and glycerophospholipid metabolism. High-dimensional mediation analysis showed that glycerophospholipids are the main markers of the association between PFAS and APOB, and that (R)-dihydromaleimide, Ile Leu, (R)-(+)-2-pyrrolidone-5-carboxylic acid, and L-glutamate are the main markers of the association between PFAS and GGT. In summary, overall associations between PFAS and specific indices of liver function were found using two statistical methods; the metabolic pathways and markers identified here may serve to prompt more detailed study in animal-based systems, as well as a similar detailed analysis in other populations.

Abstract Epigenetics is closely related to cardiovascular diseases. Genome-wide linkage and association analyses and candidate gene approaches illustrate the multigenic complexity of cardiovascular disease. Several epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding RNA, which are of importance for cardiovascular disease development and regression. Targeting epigenetic key enzymes, especially the DNA methyltransferases, histone methyltransferases, histone acetylases, histone deacetylases and their regulated target genes, could represent an attractive new route for the diagnosis and treatment of cardiovascular diseases. Herein, we summarize the knowledge on epigenetic history and essential regulatory mechanisms in cardiovascular diseases. Furthermore, we discuss the preclinical studies and drugs that are targeted these epigenetic key enzymes for cardiovascular diseases therapy. Finally, we conclude the clinical trials that are going to target some of these processes.

Background: Potential adverse effects of non-optimum temperatures on human semen quality have drawn much concern worldwide; however, the exposure–response relationship remains less understood. Objectives: To quantitatively assess the association between exposure to ambient temperature and semen quality in South China, and to identify potential critical exposure windows. Methods: We conducted a longitudinal study to investigate 11,050 volunteers who lived in Guangdong province, China and intended to donate sperm in the Guangdong provincial human sperm bank during 2016–2021. Exposure to ambient temperature during 0–90 days before semen collection was assessed by extracting daily temperatures from a validated grid dataset at each subject’s residential address. Linear mixed models and linear regression models were used to perform exposure–response analyses. Results: During the study period, the 11,050 subjects underwent 44,564 semen analyses. Each 5 °C increase of lag 0–90 day exposure to ambient temperature was approximately linearly associated with a 3.11 (95 % confidence interval [CI]: 2.08, 4.14) × 106/ml, 9.31 (4.83, 13.80) × 106, 1.27 % (0.91 %, 1.62 %), 8.20 (5.33, 11.08) × 106, 1.37 % (1.01 %, 1.74 %), 8.29 (5.52, 11.06) × 106, 0.67 % (0.28 %, 1.05 %), and 4.50 (2.20, 6.80) × 106 reduction in sperm concentration, total sperm number, total motility, total motile sperm number, progressive motility, total progressive sperm number, normal forms, and total normal form sperm number, respectively (all p 0.05). We identified a critical exposure period of 10–14 days before semen collection for sperm motility, and 70–90 days before semen collection for sperm count and morphology. Conclusions: Our study provides consistent evidence that higher ambient temperature was significantly associated with a reduction in semen quality in South China. The findings highlight the needs to reduce high temperature exposures during 3 months before ejaculation to maintain better semen quality.

BackgroundMetal exposure affects human health. Current studies mainly focus on the individual health effect of metal exposure on hypertension (HTN), and the results remain controversial. Moreover, the studies assessing overall effect of metal mixtures on hypertension risk are limited.MethodsA cross-sectional study was conducted by recruiting 1,546 Chinese adults who attended routine medical check-ups at the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen. The plasma levels of 13 metals were measured using inductively coupled plasma mass spectrometry. Multivariate logistic regression model, restricted cubic spline (RCS) model and the Bayesian Kernel Machine Regression (BKMR) model were applied to explore the single and combined effect of metals on the risk of HTN.ResultsA total of 642 (41.5%) participants were diagnosed with HTN. In the logistic regression model, the adjusted odds ratios (ORs) were 0.71 (0.52, 0.97) for cobalt, 1.40 (1.04, 1.89) for calcium, 0.66 (0.48, 0.90), and 0.60 (0.43, 0.83) for aluminum in the second and third quartile, respectively. The RCS analysis showed a V-shaped or an inverse V-shaped dose-response relationship between metals (aluminum or calcium, respectively) and the risk of HTN (P for non-linearity was 0.017 or 0.009, respectively). However, no combined effect was found between metal mixture and the risk of hypertension.ConclusionsPlasma levels of cobalt, aluminum and calcium were found to be associated with the risk of HTN. Further studies are needed to confirm our findings and their potential mechanisms with prospective studies and experimental study designs.

Background: Metal exposure were assumed to be closely related with declined renal function, but the conclusions were controversial. We employed diverse statistical models and assessed the association between metal mixture exposure and mild renal impairment. Methods: A total of 13 plasma metals were measured in 896 general population from Southern China. Subjects with estimated glomerular filtration rate within 60–89 ml/min/1.73 m2 and urinary albumin-creatinine ratio

BackgroundMetabolic syndrome (MetS) has attracted great interest, with an increasing prevalence. Recent studies have shown that the serum uric acid-to-creatinine ratio (SUACr) might be an excellent biomarker for MetS risk prediction in diabetic patients and postmenopausal women. However, the relationship between SUACr and MetS in a middle-aged and older population remains unclear.MethodsA total of 1277 participants were included in this cross-sectional study. Logistic regression modelling was performed to assess the association between SUACr and MetS in the total population. The dose–response relationship of SUACr and MetS was further assessed by a restricted cubic spline model (RCS). Furthermore, to explore the relationships between the levels of SUACr and the number of metabolic components, analysis of covariance (ANCOVA) was applied.ResultsThe levels of SUACr were lower in the non-MetS participants (OR 1.60, 95% CI 1.36 to 1.89; P

Abstract Extensive evidence suggests that ambient air pollution contributes to a higher risk of hospital admissions for cerebrovascular diseases; however, its association with admissions for sequelae of stroke remains unclear. A time‐stratified case‐crossover study was conducted among 31,810 older adults who were admitted to hospital for sequelae of stroke in Guangzhou, China during 2016–2019. For each subject, daily residential exposure to fine particulate matter (PM2.5), inhalable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) was extracted from a validated grid data set. Conditional logistic regression models were used for exposure‐response analyses. In single‐pollutant models, each interquartile range (IQR) increase of lag 04‐day exposure to CO (IQR: 0.25 mg/m3) and lag 3‐day exposure to O3 (69.6 μg/m3) was significantly associated with a 4.53% (95% confidence interval: 1.67%, 7.47%) and 5.63% (1.92%, 9.48%) increase in odds of hospital admissions for sequelae of stroke, respectively. These associations did not significantly vary across age or sex. With further adjustment for each of the other pollutants in 2‐pollutant models, the association for CO did not change significantly, while the association for O3 disappeared. We estimated that 7.72% of the hospital admissions were attributable to CO exposures. No significant or consistent association was observed for exposure to PM2.5, PM10, SO2, or NO2. In conclusion, short‐term exposure to ambient CO, even at levels below the WHO air quality guideline, was significantly associated with an increased odds of hospital admissions for sequelae of stroke, which may lead to considerable excess hospital admissions.

Genetic polymorphisms may contribute to individual susceptibility to DNA damage induced by environmental exposure. In this study, we evaluate the effects of co-exposure to PAHs, smoking and XPC polymorphisms, alone or combined, on damage in exons. A total of 288 healthy male coke oven workers were enrolled into this study, and urinary 1-hydroxypyrene (1-OH-Pyr) was detected. Base modification in exons of KRAS and BRAF gene, and polymorphisms of XPC were determined in plasma by real-time PCR. We observed 1-OH-Pyr was positively related to damage in exon 2 of KRAS (KRAS-2) and in exon 15 of BRAF (BRAF-15), respectively, and KRAS-2 and BRAF-15 were significantly associated with increased 1-OH-Pyr. A stratified analysis found 1-OH-Pyr was significantly associated with KRAS-2 in both smokers and non-smokers, while 1-OH-Pyr was significantly associated with BRAF-15 only in smokers. Additionally, individuals carrying both rs2228001 G-allele (GG+GT) and rs3731055 GG homozygote (GG) genotype appeared to have more significant effect on KRAS-2. The high levels of 1-OH-Pyr were associated with KRAS-2 only in rs2228001 GG+GT genotype carriers and the high levels of 1-OH-Pyr were associated with KRAS-2 only in rs3731055 GG genotype carriers and the most severe KRAS-2 was observed among subjects carrying all four of the above risk factors. Our findings indicated the co-exposure effect of PAHs and smoking could increase the risk of KRAS-2 by a mechanism partly involving XPC polymorphisms.

Background and objectives: China has experienced a serious public health burden because of the increased incidence of ischemic stroke. Evidence describing the association between short-term exposure to nitrogen dioxide (NO2) and ischemic stroke morbidity is limited, and few studies have focused on the effects of season and temperature. This study aimed to evaluate the acute effects of NO2 on ischemic stroke incidence in Shenzhen, a southeastern city of China, considering the modified effects of season and temperature. Methods: A time-stratified case–crossover study was conducted between 2003 and 2014 among 98,482 ischemic stroke hospitalizations. Conditional quasi-Poisson regression was used to estimate the percentage changes in ischemic stroke admissions in relation to each 10 μg/m3 increment in NO2. Results: NO2 was positively associated with ischemic stroke onset over the full year, as well as in the cold season (November through April) and on cold days (ambient temperature≤median temperature), with significant single-day effects within 3 days after the exposure, and significant cumulative effects within the delayed five days. The maximum percentage changes were obtained at lag0–5, with 1.81% (95% confidence interval (CI) was 0.86–2.76%) over the full year, 2.75% (1.48–4.03%) in the cold season, and 3.04% (1.74–4.35%) on cold days. Additionally, the effects of exposure were found to be greater in males and people with higher education, and were lasting longer in subgroups of older individuals. Conclusions: Our findings provide evidence that reductions in NO2 levels might decrease ischemic stroke morbidity, and enhance the understanding of ischemic stroke occurrence associated with NO2 modified by season and temperature.

Background: Metal exposures have been reported to be related to the progress of metabolic syndrome (MetS), however, the currents results were still controversial, and the evidence about the effect of multi-metal exposure on MetS were limited. In this study, we intended to evaluate the relationships between metal mixture exposure and the prevalence of MetS in a mid-aged and older population of China. Methods: The plasma levels of 13 metals (aluminum, magnesium, calcium, iron, manganese, cobalt, copper, arsenic, zinc, selenium, cadmium, molybdenum and thallium) were detected by inductively coupled plasma mass spectrometry (ICP-MS) in 1277 adults recruited from the Eighth Affiliated Hospital of Sun Yat-Sen University (Shenzhen, China). Logistic regression, the adaptive least absolute shrinkage and selectionator operator (LASSO) penalized regression analysis and restricted cubic spline (RCS) analysis were used to explore the associations and dose-response relationships of plasma metals with MetS. To evaluate the cumulative effect of metals, the Bayesian Kernel Machine Regression (BKMR) model was applied. Results: The concentrations of magnesium and molybdenum were lower in the MetS group (p

A high premium has been put on researching the effects of cold spells because of their adverse influence on people's daily lives and health. The study aimed to find the most appropriate definition of the cold spell in Shenzhen and quantify the impact of cold spells on mortality. Based on the daily mortality data in Shenzhen from 2013 to 2017 and the meteorological and pollutant data from the same period, we quantified the effect of cold spells using eight different definitions in the framework of a distributed lag non-linear model with a quasi-Poisson distribution. In Shenzhen, low temperatures increase the risk of death more significantly than high temperatures (using the optimal temperature as the cut-off value). Comparing the quasi-Akaike information criterion value, attribution fraction (b-AF), and attribution number (b-AN) for all causes of deaths and non-accidental deaths, the optimal definition of the cold spell was defined as the threshold was 3rd percentile of the daily average temperature and duration for 3 or more consecutive days (all causes: b-AF = 2.31% [1.01–3.50%], b-AN = 650; non-accidental: b-AF = 1.92% [0.57–3.17%], b-AN = 471). For cardiovascular deaths, the best definition was the temperature threshold as the 3rd percentile of the daily average temperature with a duration of 4 consecutive days (cardiovascular: b-AF = 1.37% [0.05–2.51%], b-AN = 142). Based on the best definition in the model, mortality risk increased in cold spells, with a statistically significant lag effect occurring as early as the 4th day and the effect of a single day lasting for 6 days. The maximum cumulative effect occurred on the 14th day (all-cause: RR = 1.54 [95% CI, 1.20–1.98]; non-accidental: RR = 1.43 [95% CI, 1.11–1.84]; cardiovascular: RR = 1.58 [95% CI, 1.00–2.48]). The elderly and females were more susceptible to cold spells. Cold spells and their definitions were associated with an increased risk of death. The findings of this research provide information for establishing an early warning system, developing preventive measures, and protecting susceptible populations.

Many studies have documented that dental diseases were associated with an increased risk of cardiovascular diseases. Aortic arch calcification (AoAC) is a powerful predictor of cardiovascular diseases. However, whether the status of dental health is associated with AoAC is still unknown. 9463 participants over the age of 60 from Shenzhen community centers were included in the cross-sectional analysis. Physical examination data, blood biochemical tests, and AoAC scores calculated by chest radiography were collected and analyzed. Among them, 2630 participants were followed up for AoAC progression up to 36 months. Participants with AoAC suffered more tooth loss than those without AoAC (77.62% vs. 72.91%; p < 0.001). Association rule analysis suggested a strong association between dental diseases and AoAC. Tooth loss or decay increased the risk of AoAC progression (HR 1.459; 95%CI 1.284–1.658) after adjusting other risk factors including renal dysfunction. Dental diseases are potential predictors for AoAC in elderly people, which are independent of renal dysfunction.

BackgroundThe concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.MethodsWe detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy via double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies via enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics.ResultsA 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43–78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels.ConclusionThe age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.

Abstract Background Stroke, especially ischemic stroke (IS), has been a severe public health problem around the world. However, the association between air pollution and ischemic stroke remains ambiguous. Methods A total of 63, 997 IS cases aged 18 years or above in Shenzhen were collected from 2008 to 2014. We used the time-stratified case-crossover design combining with distributed lag nonlinear model (DLNM) to estimate the association between air pollution and IS onset. Furthermore, this study explored the variability across gender and age groups. Results The cumulative exposure-response curves were J-shaped for SO2, NO2 and PM10, and V-shaped for O3, and crossed over the relative risk (RR) of one. The 99th, 50th (median) and 1st percentiles of concentration (μg/m3) respectively were 37.86, 10.06, 3.71 for SO2, 116.26, 41.29, 18.51 for NO2, 145.94, 48.29, 16.14 for PM10, and 111.57, 49.82, 16.00 for O3. Extreme high-SO2, high-NO2, high-PM10, high-O3, and low-O3 concentration increased the risk of IS, with the maximum RR values and 95% CIs: 1.50(1.22, 1.84) (99th vs median) at 0–12 lag days, 1.37(1.13, 1.67) (99th vs median) at 0–10 lag days, 1.26(1.04, 1.53) (99th vs median) at 0–12 lag days, 1.25(1.04, 1.49) (99th vs median) at 0–14 lag days, and 1.29(1.03, 1.61) (1st vs median) at 0–14 lag days, respectively. The statistically significant minimal RR value and 95% CI was 0.79(0.66,0.94) at 0–10 lag days for extreme low-PM10. The elderly aged over 65 years were susceptible to extreme pollution conditions. Difference from the vulnerability of males to extreme high-SO2, high-NO2 and low-O3, females were vulnerable to extreme high-PM10 and high-O3. Comparing with the elderly, adults aged 18–64 year were immune to extreme low-NO2 and low-PM10. However, no association between CO and IS onset was found. Conclusions SO2, NO2, PM10 and O3 exerted non-linear and delayed influence on IS, and such influence varied with gender and age. These findings may have significant public health implications for the prevention of IS.

Background: Phytoestrogens (PEs) are naturally estrogen-like chemicals, and increasing evidences have indicated their endocrine disruption effects on male reproductivity, but the conclusions from previous epidemiological studies were controversial. Objective: To examine the associations between nine phytoestrogens in semen and semen quality in a Chinese population. Methods: In this cross-sectional study, a total of 1319 reproductive-aged men were recruited from Shenzhen, China. Semen phytoestrogens were measured by ultra-performance liquid chromatography and tandem mass spectrometry. Semen quality was assessed by sperm concentration, sperm count, progressive motility, total motility, volume, and the sperm motion parameters. Both multivariate linear regression and logistic regression models were conducted to evaluate the associations between semen phytoestrogens and semen quality with adjustment for confounders. Results: In logistic regression models, we found significant associations between semen secoisolariciresinol (SEC) and lower sperm concentrations (odd ratios (OR): 2.38; 95% confidence interval, 95% CI: 1.47, 3.93), sperm counts (OR: 2.27; 95% CI: 1.34, 3.94), and total motility (OR: 1.55; 95% CI: 1.08, 2.24). Negative associations were also observed for semen genistein (GEN) with sperm counts (OR: 2.28; 95% CI: 1.29, 4.14; p for trend = 0.04) and sperm concentrations (OR: 1.98; 95% CI: 1.21, 3.03; p for trend = 0.07). Semen naringenin (NAR) were found to be positively associated with progressive motility (OR: 0.57; 95% CI: 0.38, 0.83) and total motility (OR: 0.57; 95% CI: 0.40, 0.81). Results from multivariate linear regression models were similar to those from logistic regression models for semen SEC, GEN, and NAR. Conclusions: We suggested that semen levels of phytoestrogens may be associated with semen quality in men. Further investigations are warranted to confirm the findings in prospective studies and to explore the underlying mechanism. Keywords: Phytoestrogen, Isoflavones, Lignans, Semen quality, Exposure, Male reproduction

Background: Ischemic stroke (IS) is a major cause of morbidity and mortality globally. Environmental exposure to metals may be linked to the risk of IS, but the association remains uncertain in Chinese populations. Objectives: The present study aimed to examine the associations between the concentrations of 11 metals (aluminum, arsenic, cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, thallium, and zinc) in plasma and the risk of IS in a Chinese population. Methods: A total of 1277 pairs of newly diagnosed IS patients and controls matched on age (±3 years) and sex were recruited in our study. Plasma metal concentrations were measured using inductively coupled plasma mass spectrometry. Multivariable conditional logistic regression models were conducted to investigate the impacts of single and multiple metals, respectively. Results: In the single-metal model, exposure to seven metals (aluminum, arsenic, cadmium, cobalt, iron, manganese and selenium) was individually associated with the risk of IS based on the trend test. Further stepwise regression analyses with the multiple-metal model revealed increasing trends in the risk of IS associated with aluminum, arsenic, and cadmium quartiles and decreasing trends with iron and selenium quartiles (p-trend

Phorate is a systemic, broad-spectrum organophosphorus insecticide. Although it is commonly used worldwide, phorate, like other pesticides, not only causes environmental pollution but also poses serious threats to human and animal health. Herein, we measured the blood glucose concentrations of high-fat-diet-fed mice exposed to various concentrations of phorate (0, 0.005, 0.05, or 0.5 mg/kg); we also assessed the blood glucose concentrations of high-fat-diet-fed mice exposed to phorate; we also assessed the distribution characteristics of the resistance genes in the intestinal microbiota of these mice. We found that 0.005 and 0.5 mg/kg of phorate induced obvious hyperglycaemia in the high-fat-diet-fed mice. Exposure to phorate markedly reduced the abundance of Akkermansia muciniphila in the mouse intestine. The resistance genes vanRG, tetW/N/W, acrD, and evgS were significantly upregulated in the test group compared with the control group. Efflux pumping was the primary mechanism of drug resistance in the Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Synergistetes, Spirochaetes, and Actinobacteria found in the mouse intestine. Our findings indicate that changes in the abundance of the intestinal microbiota are closely related to the presence of antibiotic-resistant bacteria in the intestinal tract and the metabolic health of the host.

Background: All humans are now co-exposed to multiple toxic chemicals, among which metals and polycyclic aromatic hydrocarbons (PAHs) are of special concern as they are often present at high levels in various human environments. They can also induce similar early health damage, such as genetic damage, oxidative stress, and heart rate variability (HRV). Exposure to metals, PAHs, and their combined pollutants can alter microRNA (miRNA) expression patterns. Objectives: To explore the associations of metal-PAH co-exposure with miRNA expression, and of the associated miRNAs with early health damage. Methods: We enrolled 360 healthy male coke oven workers and quantified their exposure levels of metals and PAHs by urinary metals, urinary monohydroxy-PAHs (OH-PAHs), and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, respectively. We selected and measured ten miRNAs: let-7b-5p, miR-126-3p, miR-142-5p, miR-150-5p, miR-16-5p, miR-24-3p, miR-27a-3p, miR-28-5p, miR-320b, and miR-451a. For miRNAs influenced by the effect modification of metals or PAHs and/or metal-PAH interactions, we further evaluated their associations with biomarkers for genetic damage, oxidative stress, and HRV. Results: After adjusting for PAHs and other metals, miRNA expression was found to be negatively associated with aluminum, antimony, lead, and titanium, and positively associated with molybdenum and tin (p

Abstract Background Epidemiological studies have found that high whole grain intake may be associated with a reduced risk of breast cancer. However, the evidence has not been consistent. We conducted a meta-analysis to quantitatively assess the association between whole grain intake and breast cancer risk. Methods Relevant observational studies were identified by searching PubMed, Embase, Cochrane library databases, and Google Scholar through April 2017. Summary relative risk (RR) estimates were calculated using random-effects meta-analysis. Results A total of 11 studies, including 4 cohort and 7 case-control studies and involving 131,151 participants and 11,589 breast cancer cases, were included in the current meta-analysis. The pooled RR of breast cancer for those with high versus low whole grain intake was 0.84 (95% confidence interval [CI]: 0.74 to 0.96, p = 0.009; I 2 = 63.8%, p for heterogeneity = 0.002). Subgroup analysis by study design found a significant inverse association in the case-control studies (RR: 0.69; 95% CI: 0.56 to 0.87, p = 0.001; I 2 = 58.2%, p for heterogeneity = 0.026), but not in the cohort studies (RR, 0.96; 95% CI: 0.82 to 1.14, p = 0.69; I 2 = 66.7%, p for heterogeneity = 0.029). In addition, stratified analysis suggested that sample size could be a potential source of heterogeneity. Conclusions Results of the current meta-analysis suggest that high intake of whole grains might be inversely associated with a reduced risk of breast cancer, and the inverse association was only observed in case-control but not cohort studies. More large-scale cohort studies are needed to confirm the inverse association observed.

Abstract Background Reprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified. Methods Here, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4–1 (IGFBP4–1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4–1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4–1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR. Results Our results showed that lnc-IGFBP4–1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues (P

BACKGROUND: Extreme temperature events (ETEs), including heat wave and cold spell, have been linked to myocardial infarction (MI) morbidity; however, their effects on MI mortality are less clear. Although ambient fine particulate matter (PM2.5) is suggested to act synergistically with extreme temperatures on cardiovascular mortality, it remains unknown if and how ETEs and PM2.5 interact to trigger MI deaths. METHODS: A time-stratified case-crossover study of 202 678 MI deaths in Jiangsu province, China, from 2015 to 2020, was conducted to investigate the association of exposure to ETEs and PM2.5 with MI mortality and evaluate their interactive effects. On the basis of ambient apparent temperature, multiple temperature thresholds and durations were used to build 12 ETE definitions. Daily ETEs and PM2.5 exposures were assessed by extracting values from validated grid datasets at each subject's geocoded residential address. Conditional logistic regression models were applied to perform exposure-response analyses and estimate relative excess odds due to interaction, proportion attributable to interaction, and synergy index. RESULTS: Under different ETE definitions, the odds ratio of MI mortality associated with heat wave and cold spell ranged from 1.18 (95% CI, 1.14-1.21) to 1.74 (1.66-1.83), and 1.04 (1.02-1.06) to 1.12 (1.07-1.18), respectively. Lag 01-day exposure to PM2.5 was significantly associated with an increased odds of MI mortality, which attenuated at higher exposures. We observed a significant synergistic interaction of heat wave and PM2.5 on MI mortality (relative excess odds due to interaction >0, proportion attributable to interaction >0, and synergy index >1), which was higher, in general, for heat wave with greater intensities and longer durations. We estimated that up to 2.8% of the MI deaths were attributable to exposure to ETEs and PM2.5 at levels exceeding the interim target 3 value (37.5 µg/m³) of World Health Organization air quality guidelines. Women and older adults were more vulnerable to ETEs and PM2.5. The interactive effects of ETEs or PM2.5 on MI mortality did not vary across sex, age, or socioeconomic status. CONCLUSIONS: This study provides consistent evidence that exposure to both ETEs and PM2.5 is significantly associated with an increased odds of MI mortality, especially for women and older adults, and that heat wave interacts synergistically with PM2.5 to trigger MI deaths but cold spell does not. Our findings suggest that mitigating both ETE and PM2.5 exposures may bring health cobenefits in preventing premature deaths from MI. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p. The results suggest that the blood level of let-7e-5p was significantly higher in patients with ischemic stroke than in controls (p

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29-3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10-1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00-1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20-2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09-1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.

Dementia is most frequently caused by Alzheimer’s disease. The objective of this study was to investigate the potential targets of Alzheimer’s disease and its associated biological processes. We obtained gene expression profiles of the GSE5281, GSE48350 and GSE11882 datasets from the gene expression Omnibus database. Among the total datasets, 263 were of Alzheimer’s disease tissues and 204 were of healthy tissues. We selected differentially expressed genes from Alzheimer’s disease tissues and healthy tissues using the gene expression Omnibus 2R tool and Venn diagram software. Next, we used database for annotation, visualization and integrated discovery database, gene ontology database and Kyoto encyclopedia of genes and genomes pathways for analysis. Then, by using Cytoscape’s search tool for the retrieval of interacting genes, it is possible to see how these differentially expressed genes and protein-protein interactions interact with one another. In total, there were 270 consistently expressed genes, containing 193 down-regulated genes and 77 up-regulated genes. Additionally, 270 consistently expressed genes were found by chip analysis as the test set and 242 acquisitions of causative differentially expressed genes were sought via gene list automatically derived for you as the training set. ToppGene was then utilized to optimize these genes. Of the protein-protein interaction network, analysed by the molecular complex detection plugin, 14 regulated genes were selected. In conclusion, using integrated bioinformatics techniques, we have attempted to discover the substantially altered expression genes associated with a poorer prognosis in Alzheimer’s disease and the investigations may benefit their predictive and prognostic value in Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16), 1.38 × 10(-6) and 5.59 × 10(-9), respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

Air pollution has been associated with an increased risk of cardiopulmonary mortality and decreased heart rate variability (HRV). However, it is unclear whether coke oven emissions (COEs) and polycyclic aromatic hydrocarbons (PAHs) are associated with HRV.Our goal in the present study was to investigate the association of exposure to COEs and the urinary metabolite profiles of PAHs with HRV of coke oven workers.We measured benzene soluble matter, carbon monoxide, sulfur dioxide, particulate matters, and PAHs at different workplaces of a coke oven plant. We determined 10 urinary PAH metabolites and HRV indices of 1333 workers using gas chromatography-mass spectrometry and a 3-channel digital Holter monitor, respectively.Our results showed that there was a significant COEs-related dose-dependent decrease in HRV, and an inverse relationship between the quartiles of urinary 2-hydroxynaphthalene and five HRV indices (p(trend)

BackgroundRecent genome-wide association studies (GWAS) have mapped several novel loci influencing blood lipid levels in Caucasians. We sought to explore whether the genetic variants at newly identified lipid-associated loci were associated with CHD susceptibility in a Chinese Han population.Methodology/principal findingsWe conducted a two-stage case-control study in a Chinese Han population. The first-stage, consisting of 1,376 CHD cases and 1,376 sex and age- frequency matched controls, examined 5 novel lipid-associated single-nucleotide polymorphisms (SNPs) identified from GWAS among Caucasians in relation to CHD risk in Chinese. We then validated significant SNPs in the second-stage, consisting of 1,269 cases and 2,745 controls. We also tested associations between SNPs within the five novel loci and blood lipid levels in 4,121 controls. We identified two novel SNPs (rs599839 in CELSR2-PSRC1-SORT1 and rs16996148 in NCAN-CILP2) that were significantly associated with reduced CHD risk in Chinese (odds ratios (95% confidence intervals) in the dominant model 0.76 (0.61-0.90; P = 0.001), 0.67 (0.57-0.77; P = 3.4×10(-8)), respectively). Multiple linear regression analyses using dominant model showed that rs599839 was significantly associated with decreased LDL levels (P = 0.022) and rs16996148 was significantly associated with increased LDL and HDL levels (P = 2.9×10(-4) and 0.001, respectively).Conclusions/significanceWe identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.