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The scarlet fever incidence has increased drastically in recent years in China. However, the long-term relationship between climate variation and scarlet fever remains contradictory, and an early detection system is lacking. In this study, we aim to explore the potential long-term effects of variations in monthly climatic parameters on scarlet fever and to develop an early scarlet-fever detection tool. Data comprising monthly scarlet fever cases and monthly average climatic variables from 2004 to 2017 were retrieved from the Notifiable Infectious Disease Surveillance System and National Meteorological Science Center, respectively. We used a negative binomial multivariable regression to assess the long-term impacts of weather parameters on scarlet fever and then built a novel forecasting technique by integrating an autoregressive distributed lag (ARDL) method with a nonlinear autoregressive neural network (NARNN) based on the significant meteorological drivers. Scarlet fever was a seasonal disease that predominantly peaked in spring and winter. The regression results indicated that a 1 °C increment in the monthly average temperature and a 1-h increment in the monthly aggregate sunshine hours were associated with 17.578% (95% CI 7.674 to 28.393%) and 0.529% (95% CI 0.035 to 1.025%) increases in scarlet fever cases, respectively; a 1-hPa increase in the average atmospheric pressure at a 1-month lag was associated with 12.996% (95% CI 9.972 to 15.919%) decrements in scarlet fever cases. Based on the model evaluation criteria, the best-performing basic and combined approaches were ARDL(1,0,0,1) and ARDL(1,0,0,1)-NARNN(5, 22), respectively, and this hybrid approach comprised smaller performance measures in both the training and testing stages than those of the basic model. Climate variability has a significant long-term influence on scarlet fever. The ARDL-NARNN technique with the incorporation of meteorological drivers can be used to forecast the future epidemic trends of scarlet fever. These findings may be of great help for the prevention and control of scarlet fever.

Objective Tuberculosis (TB) is a major public health problem in China, and contriving a long-term forecast is a useful aid for better launching prevention initiatives. Regrettably, such a forecasting method with robust and accurate performance is still lacking. Here, we aim to investigate its potential of the error-trend-seasonal (ETS) framework through a series of comparative experiments to analyze and forecast its secular epidemic seasonality and trends of TB incidence in China. Methods We collected the TB incidence data from January 1997 to August 2019, and then partitioning the data into eight different training and testing subsamples. Thereafter, we constructed the ETS and seasonal autoregressive integrated moving average (SARIMA) models based on the training subsamples, and multiple performance indices including the mean absolute deviation, mean absolute percentage error, root-mean-squared error, and mean error rate were adopted to assess their simulation and projection effects. Results In the light of the above performance measures, the ETS models provided a pronounced improvement for the long-term seasonality and trend forecasting in TB incidence rate over the SARIMA models, be it in various training or testing subsets apart from the 48-step ahead forecasting. The descriptive results to the data revealed that TB incidence showed notable seasonal characteristics with predominant peaks of spring and early summer and began to be plunging at on average 3.722% per year since 2008. However, this rate reduced to 2.613% per year since 2015 and furthermore such a trend would be predicted to continue in years ahead. Conclusion The ETS framework has the ability to conduct long-term forecasting for TB incidence, which may be beneficial for the long-term planning of the TB prevention and control. Additionally, considering the predicted dropping rate of TB morbidity, more particular strategies should be formulated to dramatically accelerate progress towards the goals of the End TB Strategy.

Evidence on the long-term influence of climatic variables on pertussis is limited. This study aims to explore the long-term quantitative relationship between weather variability and pertussis. Data on the monthly number of pertussis cases and weather parameters in Chongqing in the period of 2004–2018 were collected. Then, we used a negative binomial multivariable regression model and cointegration testing to examine the association of variations in monthly meteorological parameters and pertussis. Descriptive statistics exhibited that the pertussis incidence rose from 0.251 per 100,000 people in 2004 to 3.661 per 100,000 persons in 2018, and pertussis was a seasonal illness, peaked in spring and summer. The results from the regression model that allowed for the long-term trends, seasonality, autoregression, and delayed effects after correcting for overdispersion showed that a 1 hPa increment in the delayed one-month air pressure contributed to a 3.559% (95% CI 0.746–6.293%) reduction in the monthly number of pertussis cases; a 10 mm increment in the monthly aggregate precipitation, a 1 °C increment in the monthly average temperature, and a 1 m/s increment in the monthly average wind velocity resulted in 3.641% (95% CI 0.960–6.330%), 19.496% (95% CI 2.368–39.490%), and 3.812 (95% CI 1.243–11.690)-fold increases in the monthly number of pertussis cases, respectively. The roles of the mentioned weather parameters in the transmission of pertussis were also evidenced by a sensitivity analysis. The cointegration testing suggested a significant value among variables. Climatic factors, particularly monthly temperature, precipitation, air pressure, and wind velocity, play a role in the transmission of pertussis. This finding will be of great help in understanding the epidemic trends of pertussis in the future, and weather variability should be taken into account in the prevention and control of pertussis.

Enterovirus (EV) 71 infection has been widely acknowledged as the leading cause of severe hand, foot and mouth disease (HFMD), which may rapidly lead to fatal pulmonary edema. In this study, we established a mouse model for EV71 infection exhibiting high incidence of severe symptoms with pulmonary edema. Mast cells (MCs) accumulation, activation and allergic inflammation were found in the brains, lungs and skeletal muscle of mice after EV71 infection, especially in the lungs of mice. Levels of histamine, platelet-activating factor (PAF), interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and noradrenaline (NA) were increased in EV71-infected lungs. In addition, EV71 infection reduced the number of pulmonary T cells, dendritic cells (DCs) and monocytes, and increased the number of lung eosinophils, Tregs and MCs. MCs number and tryptase expression in target organs or tissues posed a trend towards an increase from control to severe mice. There were positive correlations between MCs number in the brains (r = 0.701, P = 0.003), lungs (r = 0.802, P

// Dejian Dang 1 , Chao Zhang 1 , Rongguang Zhang 1, 2 , Weidong Wu 2, 3 , Shuaiyin Chen 1 , Jingchao Ren 2, 3 , Peng Zhang 1 , Guangyuan Zhou 3 , Demin Feng 4 , Tiantian Sun 1 , Ying Li 1 , Qiaoli Liu 1 , Mengchen Li 1 , Yuanlin Xi 1 , Yuefei Jin 1 and Guangcai Duan 1, 2 1 Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, People's Republic of China 2 Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang, People's Republic of China 3 School of Public Health, Xinxiang Medical University, Xinxiang, People's Republic of China 4 The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China Correspondence to: Guangcai Duan, email: gcduan@zzu.edu.cn Yuefei Jin, email: jinyuefeixuanchuan@163.com Keywords: hand foot mouth disease, enterovirus71, inducible nitric oxide synthase, mitochondrial damage, BALB/c mice Received: July 22, 2017 Accepted: August 28, 2017 Published: September 23, 2017 ABSTRACT Enterovirus71 (EV71) is recognized as the main causative agent of severe hand, foot and mouth disease (HFMD). However, the pathogenesis of EV71 infection has not been well characterized. Clinical evidence indicated that inducible nitric oxide synthase (iNOS) induction in the lung of HFMD patients contributes to the severe symptoms of pulmonary edema. In the present study, we recruited 142 subjects including HFMD patients and controls, and serum level of nitric oxide (NO) was determined. Next, cellular and animal model were used to further investigate the roles of iNOS and mitochondria damage during EV71 infection. Serum NO level in HFMD patients with mild or severe symptoms was higher than that in controls, and there was a trend towards an increase in the serum NO level of severe cases relative to mild cases. EV71 infection caused apoptosis and increased levels of NO, iNOS, superoxide dismutase (SOD) activity and malondialdehyde (MDA), and degraded mitochondrial membrane potential (ΔΨm) in vitro . Pathological alterations of mitochondrial morphology were observed in vitro and in vivo . Furthermore, the expression of iNOS levels in target organs including brain, spinal cord, skeletal muscle, lung and heart were increased with the progression of the pathogenesis of EV71 infection in mice. Taken together, iNOS and mitochondrial damage participate in the pathogenesis of EV71 infection.

Studies in animals suggest an adverse effect of high-level lead exposure on male reproductive outcomes. However, evidence of the effects of low-level lead exposure is inconsistent. The purpose of our study was to explore the relationship between low-level lead exposure from daily environmental contaminants and semen quality in a community population without occupational exposure. We recruited 751 students in the Male Reproductive Health in Chongqing College Students (MARHCS) study and 190 community males from Bishan, Chongqing. Eight urinary metals (Pb, Cd, As, Cu, Zn, Ni, Mn, and Cr), semen quality, and serum sex hormones were detected. Even if the blood lead concentration was below the US lead poisoning standard for children (100 μg/L), a significant dose-response relationship was found between lead exposure and a decrease in semen quality. Multilinear regression showed that urinary Pb was negatively associated with sperm concentration, total sperm count, progressive motility and total sperm motility (regression coefficient: -0.074, -0.103, -0.024, and -0.014, respectively; p:0.001,0.001, 0.007, and0.001, respectively), accompanied by decreased serum follicle-stimulating hormone, serum testosterone and the testosterone/luteinizing hormone ratio (β coefficient: -0.090, -0.082, and -0.020, respectively; p: 0.002,0.001, and 0.021, respectively). Logistic regression also indicated that the risk of having abnormal semen quality was higher in the high Pb group (OR: 2.501, 95% CI: 1.411, 4.435, p = 0.002) than in the low Pb group after adjusting for confounders, with a dose-response relationship in the trend test (p = 0.007). Our results revealed an inverse association between Pb exposure at low levels and semen quality.

Background Hand-foot-and-mouth disease (HFMD) is generally considered as a mild exanthematous disease to infants and young children worldwide. HFMD cases are usually mild and self-limiting but for few cases leads to complicated severe clinical outcomes, and even death. Previous studies have indicated that serum Ang II levels in patients with H7N9 infection were related to the severity of infection. However, the mechanisms underlying the pathogenesis of severe HFMD remain unclear. This study was undertaken to clarify the role of the renin-angiotensin system (RAS) in the progression of severe HFMD. Methods In the present study, 162 children including HFMD patients and healthy controls were recruited. The data was analyzed by time-series fashion. Concentrations of angiotensin II (Ang II) and noradrenaline (NA) in serum of patients were measured with ELISA. We established a mouse model for enterovirus 71 (EV71) infection and determined concentrations of Ang II, NA in tissue lysates at 3, 5 and 7 days post infection (dpi). Results The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. Additionally, the concentrations of Ang II and NA in serum of severe cases were significantly higher than those mild cases and the increased concentrations of Ang II and NA showed the same time trend during the progression of HFMD in the severe cases. Furthermore, the concentrations of Ang II and NA in target organs of EV71-infected mice including brains, skeletal muscle, and lungs were increased with the progression of EV71 infection in mice. Histopathological alterations were observed in the brains, skeletal muscle and lungs of EV71-infected mice. Conclusion Our study suggested that activation of the RAS is implicated in the pathogenesis of severe HFMD.

Background Enterovirus (EV) infection has been a serious health issue in Asia-Pacific region. It has been indicated that the occurrence of fatal hand foot and mouth disease (HFMD) cases following EV71 infection is mainly attributed to pulmonary edema. However, the development of pulmonary disorders after EV71 infection remains largely unknown. To establish an EV71-infected animal model and further explore the underlying association of central nervous system (CNS) invasion with pulmonary edema, we isolated a clinical source EV71 strain (ZZ1350) from a severe case in Henan Province. Methods We evaluated the cytotoxicity of ZZ1350 strain and the susceptibility in 3-day-old BALB/c mice with intraperitoneal, intracerebral and intramuscular inoculation. Various histopathological and immunohistochemical techniques were applied to determine the target organs or tissue damage after infection. Correlation analysis was used to identify the relationship between CNS injury and pulmonary disorders. Results Our experimental results suggested that ZZ1350 (C4 subtype) had high cytotoxicity against African green monkey kidney (Vero) cells and human rhabdomyosarcoma (RD) cells and neonatal BALB/c mice were highly susceptible to the infection with ZZ1350 through three different inoculation routes (2 × 106 pfu/mouse) exhibiting severe neurological and respiratory symptoms that were similar to clinical observation. Viral replication was found in brain, spinal cord, skeletal muscle, lung, spleen, liver, heart of infected mice and these sections also showed histopathological changes. We found that brain histology score was positive correlated with lung histology score in total experimental mice and mice under the three inoculation routes (P P Conclusions ZZ1350 strain is effective to establish animal model of EV71 infection with severe neurological and respiratory symptoms. The development of pulmonary disorders after EV71 infection is associated with severity of CNS damage.

Aim: To determine whether induced abortion (IA) increases breast cancer (BC) risk. Materials and Methods: A population-based case-control study was performed from Dec, 2000 to November, 2004 in Shanghai, China, where IA could be verified through the family planning network and client medical records. Structured questionnaires were completed by 1,517 cases with primary invasive epithelial breast cancer and 1,573 controls frequency- matched to cases for age group. The information was supplemented and verified by the family planning records. Statistical analysis was conducted with SAS 9.0. Results: After adjusting for potential confounders, induced abortions were not found to be associated with breast cancer with OR=0.94 (95%CI= 0.79-1.11). Compared to parous women without induced abortion, parous women with 3 or more times induced abortion (OR=0.66, 95%CI=0.46 to 0.95) and women with 3 or more times induced abortion after the first live birth (OR=0.66, 95%CI =0.45 to 0.97) showed a lower risk of breast cancer, after adjustment for age, level of education, annual income per capita, age at menarche, menopause, parity times, spontaneous abortion, age at first live birth, breast-feeding, oral contraceptives, hormones drug, breast disease, BMI, drinking alcohol, drinking tea, taking vitamin/calcium tablet, physical activity, vocation, history of breast cancer, eating the bean. Conclusions: The results suggest that a history of induced abortions may not increase the risk of breast cancer.

BACKGROUND In recent years, the prevalence of hand-foot-mouth disease (HFMD) in China and some other countries has caused worldwide concern. Mild cases tend to recover within a week, while severe cases may progress rapidly and tend to have bad outcome. Since there is no vaccine for HFMD and anti-inflammatory treatment is not ideal. In this study, we aimed to establish a valid forecasting model for severe HFMD using common laboratory parameters. METHODS Retrospectively, 77 severe HFMD cases from Zhengzhou Children's hospital in the peaking period between years 2013 to 2015 were collected, with 77 mild HFMD cases in the same area. The study recorded common laboratory parameters to assist in establishment of the severe HFMD model. After screening the important variables using Mann-Whitney U test, the study also matched the logistic regression (LR), discriminant analysis (DA), and decision tree (DT) to make a comparison. RESULTS Compared with that of the mild group, serum levels of WBC, PLT, PCT, MCV, MCH, LCR, SCR, LCC, GLO, CK-MB, K, S100, and B in the severe group were higher (p < 0.05), while MCR, EOR, BASOR, SCC, MCC, EO, BASO, NA, CL, T, Th, and Th/Ts were lower (p < 0.05). Five indicators including MCR, LCC, Th, CK-MB, and CL were screened out by LR and the same for DA, and five variables including EO, LCC, CL, GLO, and MCC screened out by DT. The area under the curve (AUC) of LR, DA, and DT was 0.805, 0.779 and 0.864, respectively. CONCLUSIONS The findings were that common laboratory indexes were effectively used to distinguish the mild HFMD cases and severe HFMD cases by LR, DA, and DT, and DT had the best classification effect with an AUC of 0.864.