Children's food allergy: Effects of environmental influences and antibiotic use across critical developmental windows.

BACKGROUND: Increasing studies linked outdoor air pollution (OAP), indoor environmental factors (IEFs), and antibiotics use (AU) with the first wave of allergies (i.e., asthma, allergic rhinitis, and eczema), yet the role of their exposures on children's second wave of allergy (i.e., food allergy) are unknown. OBJECTIVES: To investigate the association between exposure to OAP and IEFs and childhood doctor-diagnosed food allergy (DFA) during the pre-pregnancy, prenatal, early postnatal, and current periods, and to further explore the effect of OAP and IEFs on DFA in children co-exposed to antibiotics. METHODS: A retrospective cohort study involving 8689 preschoolers was carried out in Changsha, China. Data on the health outcomes, antibiotic use, and home environment of each child were collected through a questionnaire. Temperature and air pollutants data were obtained from 8 and 10 monitoring stations in Changsha, respectively. Exposure levels to temperature and air pollutants at individual home addresses were calculated by the inverse distance weighted (IDW) method. Multiple logistic regression models were employed to assess the associations of childhood DFA with exposure to OAP, IEF, and AU. RESULTS: Childhood ever doctor-diagnosed food allergy (DFA) was linked to postnatal PM10 exposure with OR (95% CI) of 1.18 (1.03-1.36), especially for CO and O3 exposure during the first year with ORs (95% CI) = 1.08 (1.00-1.16) and 1.07 (1.00-1.14), as well as SO2 exposure during the previous year with OR (95% CI) of 1.13 (1.02-1.25). The role of postnatal air pollution is more important for the risk of egg, milk and other food allergies. Renovation-related IAP (new furniture) and dampness-related indoor allergens exposures throughout all time windows significantly increased the risk of childhood DFA, with ORs ranging from 1.23 (1.03-1.46) to 1.54 (1.29-1.83). Furthermore, smoke-related IAP (environmental tobacco smoke [ETS], parental and grandparental smoking) exposure during pregnancy, first year, and previous year was related to DFA. Additionally, exposure to pet-related indoor allergens (cats) during first year and total plant-related allergens (particularly nonflowering plants) during previous year were associated with DFA. Moreover, exposure to plant-related allergy during first and previous year was specifically associated with milk allergy, while keeping cats during first year increased the risk of fruits/vegetables allergy. Life-time and early-life AU was associated with the increased risk of childhood DFA with ORs (95% CI) = 1.57 (1.32-1.87) and 1.46 (1.27-1.67), including different types food allergies except fruit/vegetable allergy. CONCLUSIONS: Postnatal OAP, life-time and early-life IEFs and AU exposure played a vital role in the development of DFA, supporting the "fetal origin of childhood FA" hypothesis.

Preconceptional, pregnant, and postnatal exposure to outdoor air pollution and indoor environmental factors: Effects on childhood parasitic infections.

BACKGROUND: Parasitic infections (PIs) are common and pose substantial health hazards in children globally, but the fundamental environmental variables exposure during crucial time window(s) are unclear. OBJECTIVES: To identify key indoor and outdoor environmental factors leading to childhood PIs throughout critical time window(s). METHODS: A combined cross-sectional and retrospective cohort study was performed on 8689 children residing in Changsha, China. Data was acquired pertaining to the health status and environmental exposure of the children in their homes. Personal exposure to outdoor air pollutants at the residential address during the preconceptional, perinatal, and postnatal periods was computed using data from ten air quality monitoring stations. An analysis of the relationships between childhood PIs and both indoor and outdoor factors was conducted using a multiple logistic regression model. RESULTS: Childhood PIs were associated with outdoor CO and ozone (O3) exposure during the 10th-12th months prior to pregnancy, with ORs (95 % CI) of 1.68 (1.24-2.27) and 1.60 (1.15-2.22), respectively; childhood PIs were also associated with CO exposure during one year prior to pregnancy and the first trimester in utero [ORs = 1.57 (1.14-2.15) and 1.52 (1.17-1.97)]. Childhood PIs were found to be associated with PM2.5 exposure during pregnancy and the first year, with odds ratios of 1.51 (1.14-2.00) and 1.95 (1.22-3.12) per IQR increase in pollutant exposure, respectively. Exposures to smoke, renovation-related indoor air pollution (IAP), dampness and plant-related indoor allergens in the early life and past year were all associated with childhood PI, with odds ratios (95 % CI) ranging from 1.40 (1.01-1.95) for environmental tobacco smoke (ETS) during pregnancy to 1.63 (1.12-2.37) for mold/damp stains in the past year. In terms of PI risk, the early life and present periods were critical time windows for outdoor and indoor exposures, respectively. Certain individuals were more vulnerable to the PI risk associated with both indoor and outdoor exposures. Antibiotic use during child's lifetime and early years increased and decreased the PI risk of exposure to outdoor and indoor environments, respectively. CONCLUSIONS: Exposure to outdoor air pollution in early life and indoor environments in the past year were found to be associated with childhood PI.

The IL-31/TRPV1 pathway mediates allergic asthma exacerbated by DINP dermal exposure in OVA-sensitized Balb/c mice.

BACKGROUND: The potential role of dermal exposure diisononyl phthalate (DINP) as an adjuvant in allergic inflammation and asthma has been suggested. However, the current findings do not provide enough evidence to support this claim. OBJECTIVES: The purpose of this investigation was to examine the impact and mechanisms of allergic asthma exacerbation through the dermal exposure to DINP. METHODS: The study was undertaken using OVA-sensitized mice. Lung histopathology and airway hyperreactivity (AHR) were assessed. Expression levels of immunoglobulins (t-IgE, OVA-IgE and OVA-IgG1), cytokines (IL-31, IL-4, IL-5, IL-6, IL-13 and INF-γ), and TRPV1 were measured. To investigate the mechanism by which allergic asthma worsens due to dermal exposure to DINP, the blockade analysis using the IL-31 antagonist SB-431542 and the TRPV1 antagonist capsazepine (CZP) were performed. RESULTS: The findings of the study revealed that the simultaneous exposure to DINP and OVA resulted in an increase in inspiratory resistance (Ri) and expiratory resistance (Re), a decrease in the minimum value of lung dynamic compliance (Cldyn), and worsened airway remodeling. Additionally, it was found that this exposure led to an increase in the levels of IL-31 and TRPV1, which are biomarkers of Th2 cytokines (IL-4, IL-5, IL-6, and IL-13), as well as immunoglobulins (Total IgE, OVA-lgE, and OVA-IgG1), while decreasing the biomarker of Th1 cytokines (IFN-γ). However, these impairments showed improvement after the administration of SB-431542 or CZP. CONCLUSION: The findings of this research indicate that the IL-31/TRPV1 pathway plays a moderating function in OVA-induced allergic asthma worsened by dermal exposure to DINP.

Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities: a cross-sectional study with interrupted time series analysis.

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.

Early life exposure to outdoor air pollution and indoor environmental factors on the development of childhood allergy from early symptoms to diseases.

BACKGROUND: The prevalence of childhood allergies has increased during past decades leading to serious hospitalization and heavy burden worldwide, yet the key factors responsible for the onset of early symptoms and development of diagnosed diseases are unclear. OBJECTIVE: To explore the role of early life exposure to ambient air pollution and indoor environmental factors on early allergic symptoms and doctor diagnosed allergic diseases. METHODS: A retrospective cohort study of 2598 preschool children was conducted at 36 kindergartens in Changsha, China from September of 2011 to February of 2012. A questionnaire was developed to survey each child's early onset of allergic symptoms (wheeze and rhinitis-like symptoms) and doctor diagnosis of allergic diseases (asthma and rhinitis) as well as home environments. Each mother's and child's exposures to ambient air pollutants (PM10, SO2, and NO2) and temperature were estimated for in utero and postnatal periods. The associations of early symptoms and diagnosed diseases with outdoor air pollution and indoor environmental variables were examined by logistic regression models. RESULTS: Childhood early allergic symptoms (33.9%) including wheeze (14.7%) and rhinitis-like symptoms (25.4%) before 2 years old were not associated with outdoor air pollution exposure but was significantly associated with maternal exposure of window condensation at home in pregnancy with ORs (95% CI) of 1.33 (1.11-1.59), 1.30 (1.01-1.67) and 1.27 (1.04-1.55) respectively, and was associated with new furniture during first year after birth with OR (95% CI) of 1.43 (1.02-2.02) for early wheeze. Childhood diagnosed allergic diseases (28.4%) containing asthma (6.7%) and allergic rhinitis (AR) (7.2%) were significantly associated with both outdoor air pollutants (mainly for SO2 and NO2) during first 3 years and indoor new furniture, redecoration, and window condensation. We found that sex, age, parental atopy, maternal productive age, environmental tobacco smoke (ETS), antibiotics use, economic stress, early and late introduction of complementary foods, and outdoor air pollution modified the effects of home environmental exposure in early life on early allergic symptoms and diagnosed allergic diseases. CONCLUSION: Our study indicates that early life exposure to indoor environmental factors plays a key role in early onset of allergic symptoms in children, and further exposure to ambient air pollution and indoor environmental factors contribute to the later development of asthma and allergic rhinitis.

Associations of Early-Life Exposure to Submicron Particulate Matter With Childhood Asthma and Wheeze in China.

Importance: Exposure to particulate matter (PM) has been associated with childhood asthma and wheeze. However, the specific associations between asthma and PM with an aerodynamic equivalent diameter of 1 µm or less (ie, PM1), which is a contributor to PM2.5 and potentially more toxic than PM2.5, remain unclear. Objective: To investigate the association of early-life (prenatal and first year) exposure to size-segregated PM, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood asthma and wheeze. Design, Setting, and Participants: This cross-sectional study was based on a questionnaire administered between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in 7 Chinese cities (Wuhan, Changsha, Taiyuan, Nanjing, Shanghai, Chongqing, and Urumqi) as the second phase of the China, Children, Homes, Health study. Exposures: Exposure to PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10 during the prenatal period and first year of life. Main Outcomes and Measures: The main outcomes were caregiver-reported childhood asthma and wheeze. A machine learning-based space-time model was applied to estimate early-life PM1, PM2.5, and PM10 exposure at 1 × 1-km resolution. Concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multilevel (city and child) logistic regression models were applied to assess associations. Results: Of 29 418 children whose caregivers completed the survey (15 320 boys [52.1%]; mean [SD] age, 4.9 [0.9] years), 2524 (8.6%) ever had wheeze and 1161 (3.9%) were diagnosed with asthma. Among all children, 18 514 (62.9%) were breastfed for more than 6 months and 787 (2.7%) had parental history of atopy. A total of 22 250 children (75.6%) had a mother with an educational level of university or above. Of the 25 422 children for whom information about cigarette smoking exposure was collected, 576 (2.3%) had a mother who was a current or former smoker during pregnancy and 7525 (29.7%) had passive household cigarette smoke exposure in early life. Early-life PM1, PM2.5, and PM10 exposure were significantly associated with increased risk of childhood asthma, with higher estimates per 10-µg/m3 increase in PM1 (OR, 1.55; 95% CI, 1.27-1.89) than in PM2.5 (OR, 1.14; 95% CI, 1.03-1.26) and PM10 (OR, 1.11; 95% CI, 1.02-1.20). No association was observed between asthma and PM1-2.5 exposure, suggesting that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood asthma. There were significant associations between childhood wheeze and early-life PM1 exposure (OR, 1.23; 95% CI, 1.07-1.41) and PM2.5 exposure (OR, 1.08; 95% CI, 1.01-1.16) per 10-µg/m3 increase in PM1 and PM2.5, respectively. Conclusions and Relevance: In this cross-sectional study, higher estimates were observed for the association between PM with smaller particles, such as PM1, vs PM with larger particles and childhood asthma. The results suggest that the association between PM2.5 and childhood asthma was mainly attributable to PM1.

Effect of preconceptional, prenatal and postnatal exposure to home environmental factors on childhood pneumonia: A key role in early life exposure.

BACKGROUND: Increasing evidence have associated pneumonia with early exposure to ambient air pollution. However, the role of indoor environmental factors exposure in early life on childhood pneumonia remains unclear. OBJECTIVE: To examine the association between indoor environmental factors exposure during different timing windows and childhood pneumonia, and to identify the key indoor factor(s) in different critical window(s). METHODS: A retrospective cohort study of 8689 pre-schoolers was performed in Changsha, China during 2019-2020. Our questionnaire survey was designed to collect information on pre-schooler's outcome and residential environmental exposure containing indoor pollution and allergens during 1 year before pregnancy, pregnancy, first year, and past year. The associations were further estimated stratified by personal exposure level of outdoor NO2, CO, temperature (T) and different covariates. Associations were assessed by multiple logistic regression model in terms of odds ratio (OR) of 95% confidence interval (CI). RESULTS: Pre-schooler's pneumonia was significantly related with exposure of new furniture, redecoration, mold/damp stains, and mold or damp clothing or bedding exposure during the four periods, with the strongest associations observed during 1 year before pregnancy based on multi-window model, with ORs (95% CI) of 1.27 (1.12-1.44), 1.26 (1.09-1.46), 1.34 (1.14-1.57), and 1.28 (1.05-1.56) respectively. Environmental tobacco smoke (ETS) including both parental and grandparental smoking were significantly related with increased risk of pre-schooler's pneumonia, and ETS played a more important role in early life, with ORs (95% CI) of 1.17 (1.01-1.36) and 1.19 (1.02-1.39) in pregnancy and first year. Indoor plants particularly nonflowering plants significantly elevated pneumonia risk but only in past year, with ORs (95% CI) of 1.17 (1.05-1.30) and 1.14 (1.03-1.26). Higher pneumonia risk was observed for renovation exposure in pre-birth compared to post-birth, while mold/dampness exerted an accumulative effect with the highest risk for exposure during both pre- and post-birth. Living near traffic road and exposure to high level of traffic-related air pollution and high temperature significantly increased pneumonia risk. Sensitivity analysis found that some sub-groups were more susceptible to pneumonia risk of home environment exposure. CONCLUSION: Early life exposure to indoor environmental factors plays an important role in pneumonia development, supporting the hypothesis of "Preconceptional and Fetal Origin of Childhood Pneumonia" and "Developmental Origins of Health and Pneumonia".

Extension of the CAVS model to the simulation of helical peptides in a membrane environment.

Considering the effect of peptide insertion on the dipole potential of the lipid membrane, we extend the CAVS coarse-grained (CG) model to the simulation of helical peptides in a membrane environment. In this approach, the CG scheme for a peptide backbone is similar to the treatment in the united-atom model, while we treated the side chain of an amino acid by grouping 1-3 heavy atoms into a CG unit. The CAVS CG force field for peptides is optimized by reproducing the experimental results for the backbone (φ, ψ) distribution and predicting the PMF profiles of transferring organic molecules in a lipid bilayer membrane obtained from all-atom simulations. The CAVS simulation of a helical peptide in a phosphatidylcholine (PC) lipid bilayer revealed that the insertion of a peptide increases the dipole potential of the PC lipid bilayer, in which the peptide and its neutralized ions make a significant contribution. Finally, we carried out the CAVS simulation for five different helical peptides in the PC lipid bilayer to explore the behavior of peptide tilt, showing excellent agreement with the all-atom simulations. Our work suggests that the peptide tilt should relieve the deformation stress from the lipid bilayer, and the peptide aggregation could reduce the peptide tilt by resisting the deformation stress from the surrounding lipids.

Impact of marital status on the prognosis of liver cancer patients without surgery and the critical window.

BACKGROUND: Liver cancer (LC) is the second leading cause of cancer-associated mortality. However, the critical time window during the marital status may influence the prognosis of LC is still unknown. METHODS: Information on a total of 4,933 patients diagnosed with primary LC who had not undergone surgery was collected from the Surveillance, Epidemiology, and End Results (SEER) database to analyze the impact of marital status on the risk of cancer-specific mortality (CSM). All confirmed patients were monitored from January 1, 2010 until December 31, 2015 for the occurrence of death. We performed 1:1 propensity score matching among the married and non-married groups to eliminate dissimilarities in age, sex, race and clinical characteristics. Cox proportional hazards regression model was adopted to investigate the associations between marital status and the risk of CSM. RESULTS: Married patients were significantly negatively associated with the risk of CSM among patients compared to non-married status, with a hazard ratio (HR) [95% confidence interval (CI)] of 1.15 (1.07-1.23). The strongest associations were observed for patients with Grade II, American Joint Committee on Cancer (AJCC) I and III. Furthermore, the protective effect of marriage on the prognosis of LC was independent of sex, age, race, grade, AJCC and SEER stage. Unmarried or separated patients may have a worse prognosis. CONCLUSIONS: Marriage was strongly associated with a positive prognosis among patients with LC, especially in the critical window of Grade II, AJCC I and III. This study highlights the important impact of marriage on cancer prognosis.

Combined effects of ambient air pollution and home environmental factors on low birth weight.

BACKGROUND: Low birth weight (LBW) remains a major public health problem worldwide, yet its crucial environmental risk factors are still unclear. OBJECTIVE: To examine the association between LBW (term and preterm LBW) and prenatal exposure to ambient air pollution and home environmental factors as well as their combination, in order to identify critical time window for exposure and key outdoor and indoor factors in LBW development. METHODS: A cohort study of 3509 preschool children was performed in Changsha, China during the period 2011-2012. A questionnaire was conducted to survey each child's birth outcome and each mother's exposure to home environmental factors including parental smoking, new furniture, redecoration, mold/damp stains, window pane condensation, and household pets during pregnancy. Maternal exposure to inhalable particulate matter (PM10), industrial air pollutant (SO2), and traffic air pollutant (NO2) was estimated during different time windows of gestation, including conception month, three trimesters, birth month, and whole gestation. Associations of term and preterm LBW with ambient air pollutants and home environmental factors were assessed by multiple logistic regression models in terms of odds ratio (OR) with 95% confidence interval (CI). RESULTS: Term LBW (TLBW) was significantly associated with exposure to ambient PM10 during pregnancy, with OR (95% CI) = 1.47 (1.00-2.14) for per IQR increase after adjustment for the covariates and home environmental factors. Specifically, we identified the significant association in early phase of pregnancy including conception month (1.90, 1.09-3.30) and the first trimester (1.72, 1.10-2.69). We further found that TLBW was significantly related with parental smoking at home, OR (95% CI) = 2.17 (1.09-4.33). However, no association was observed for preterm LBW (PLBW). The TLBW risk of ambient air pollution and home environmental factors was independent each other and hence the combined exposure to ambient PM10 and indoor parental smoking caused the highest risk. Sensitivity analysis suggested that foetus with younger mothers were significantly more susceptible to risk of indoor parental smoking, while those with smaller house and cockroaches were more sensitive to risk of outdoor PM10 exposure. CONCLUSION: Prenatal exposure to combined outdoor and indoor air pollution, particularly in critical window(s) during early pregnancy, significantly increases the risk of term LBW.

Forsythiaside A alleviates renal damage in adriamycin-induced nephropathy.

Nephrotic syndrome (NS) is a common urinary system disease that carries a poor progrnosis due to nonresponsivess to current treatments. The purpose of this study was to investigate the therapeutic effects of Forsythiaside (FA) in a rat model of adriamycin-induced nephropathy (AN). Compared with control group, FA treatment significantly reduced proteinuria, serum creatinine and urea nitrogen levels and reduced the number of apoptotic cells in the kidneys. FA alleviated Adr induced renal injury, and increased the sactivity of superoxide dismutase (SOD), while decreasing malondialdehyde (MDA) and lactate dehydrogenase (LDH) in the serum. In addition, FA, in a dose-dependent manner, decreased the levels of NF-kappaBp65/MIP-2 in the kidenys, reduced the serum level of pro-inflammatory cytokines (IL-6, IL-1 ß and TNF-alpha), and increased the survival rate of Adr treated rats. Taken together, the results show that FA alleviates renal dysfunction in adriamycin-induced nephropathy rats.

Outcomes of laparoscopic radical nephrectomy for elderly patients with localized renal cell carcinoma.

PURPOSE: This study was to compare the short- and long-term outcomes of elderly versus middle-aged patients with localized renal cell carcinoma who had undergone laparoscopic radical nephrectomy. METHODS: Between January 2012 and January 2018, a total of 54 patients aged 70 years and above with localized renal cell carcinoma (elderly group) underwent laparoscopic radical nephrectomy. The short- and long-term outcomes of these 54 patients were compared with those of 97 middle-aged patients (aged between 55 and 69 years; middle-aged group) who underwent laparoscopic radical nephrectomy due to localized renal cell carcinoma. RESULTS: The age, Charlson's comorbidity index, and American Society of Anesthesiologists (ASA) score were higher in the elderly group than in the middle-aged group. Other preoperative baseline data did not show any statistically significant differences. The differences in short-term outcomes, including operative time, intraoperative blood loss, transfer rate, postoperative 30-day complication rate and severity of complication, and pathological data were not statistically significant between the elderly and middle-aged groups. Long-term follow-up results showed that the tumor recurrence rates were similar in the two groups. Overall and disease-free survival rates were similar in the two groups. Multivariate analysis showed that age was not an independent predictor for overall and disease-free survival rates. CONCLUSIONS: Treatment with laparoscopic radical nephrectomy for elderly patients with localized renal cell carcinoma, could achieve short- and long-term outcomes, similar to those of middle-aged patients.

Blockage of ROS-ERK-DLP1 signaling and mitochondrial fission alleviates Cr(VI)-induced mitochondrial dysfunction in L02 hepatocytes.

Hexavalent chromium [Cr(VI)] is a common heavy metal pollutant widely used in various industrial fields. It is well known that mitochondria are the most vulnerable targets of heavy metals, but the key molecule/event that directly mediated mitochondrial dysfunction after Cr(VI) exposure is still unclear. The present study was aimed to explore whether Cr(VI) exposure could affect the mitochondrial fission/fusion process, and whether the related abnormal mitochondrial dynamics have been implicated in Cr(VI)-induced mitochondrial dysfunction. We found that the mitochondrial dysfunction caused by Cr(VI) exposure was characterized by decreased mitochondrial respiratory chain complex (MRCC) I/II activities and levels, collapsed mitochondrial membrane potential (MMP), depleted ATP, and increased reactive oxygen species (ROS) level. Cr(VI) induced abnormal mitochondrial fission/fusion events, the antioxidant Nacetyl-L-cysteine (NAC) restored the abnormal mitochondrial function as well as the fission/fusion dynamics. ROS was the up-stream regulator of extracellular regulated protein kinases (ERK) signaling, and the application of a specific ERK1/2 inhibitor PD98059 confirmed that activation of ERK1/2 signaling was associated with the abnormal mitochondrial fission/fusion and mitochondrial dysfunction. We also demonstrated that treatment with dynamic-like protein 1 (DLP1)-siRNA rescued mitochondrial dysfunction in Cr(VI)-exposed L02 hepatocytes. We reached the conclusion that blockage of ROS-ERK-DLP1 signaling and mitochondrial fission alleviates Cr(VI)-induced mitochondrial dysfunction in L02 hepatocytes, which may provide the new avenue for developing effective strategies to protect against Cr(VI)-induced hepatotoxicity.

Home environment and health: Domestic risk factors for rhinitis, throat symptoms and non-respiratory symptoms among adults across China.

Few studies exist from China on associations between home environment and adult health. We studied associations between home environment factors (other than dampness and mould) and rhinitis, throat and dermal symptoms and headache and fatigue among young parents in six cities across China (N = 36,541). They were recruited as parents from day care centers selected randomly and answered a questionnaire on medical symptoms and the home environment. Odds ratios (OR) were calculated by multilevel logistic regression adjusting for gender, atopy, smoking, home size and dampness/mould. Overall, 4.8% had skin symptoms 3.1% rhinitis, 2.8% eye, 4.1% throat symptoms, 3.0% headache and 13.9% had fatigue (all as weekly symptoms). Redecoration was associated with rhinitis, eye and skin symptoms, headache and fatigue. New furniture was associated with eye, throat and skin symptoms and fatigue. Gas cooking was associated with eye and throat symptoms, headache and fatigue. Biomass cooking was associated with eye and throat symptoms and headache. Burning incense was associated with eye, throat and skin symptoms, headache and fatigue. Presence of cockroaches and mosquitos or flies was associated with all six symptoms. Rats or mice were associated with eye and dermal symptoms. Cat keeping was associated with eye symptoms while dog keepers had less fatigue. Living near major roads was associated with rhinitis, eye, throat and skin symptoms and fatigue. Daily cleaning, a mechanical ventilation system in the kitchen or in the bathroom, living in older buildings and living in less urbanized areas were protective factors. In conclusion, urbanization, traffic exhaust, indoor emissions from redecoration and new furniture, gas cooking and air pollution from burning incense and biomass may cause dermal and mucosal symptoms, headache and fatigue among adults in China. Indoor animals (cats, mice/rats, cockroaches) were other risk factors. Daily cleaning, mechanical ventilation and living in older buildings can be protective.

Sources of indoor particulate matter (PM) and outdoor air pollution in China in relation to asthma, wheeze, rhinitis and eczema among pre-school children: Synergistic effects between antibiotics use and PM10 and second hand smoke.

We studied indoor sources of indoor particulate matter (PM), outdoor air pollution and antibiotic use in relation to asthma, rhinitis and eczema among pre-school children and investigated synergistic effects between PM and antibiotics use. Children (3-6y) from randomly selected day care centres in seven cities across China were included (n = 39,782). Data on ambient temperature and air pollution were collected from local monitoring stations. Data on indoor PM sources (ETS, burning of incense or mosquito coils and biomass for cooking), antibiotics use and health (doctor diagnosed asthma and rhinitis, lifetime eczema, current wheeze and current rhinitis) were assessed by a parental questionnaire. Associations were calculated by multilevel logistic regression. Asthma diagnosis was associated with outdoor temperature, NO2 and burning mosquito coils. Rhinitis diagnosis was associated with NO2, ETS, gas cooking and burning biomass for cooking. Lifetime eczema was associated with temperature, PM10, NO2, ETS, biomass cooking and burning mosquito coils. Burning incense was associated with current wheeze and current rhinitis. Children using antibiotics had more asthma, wheeze, rhinitis, and eczema. Excluding children with respiratory infections did not change associations with antibiotics use. Antibiotics use enhanced the effects of ETS and PM10 (a synergistic effect). In conclusion, a warmer climate, outdoor NO2 and PM10, ETS, gas cooking and burning biomass, incense and mosquito coils can increase the risk of asthma, wheeze, rhinitis and eczema among pre-school children in China. Antibiotics use is a risk factor for childhood asthma, wheeze, rhinitis and eczema and ETS and outdoor PM10 can enhance the effect.

Onset and remission of childhood wheeze and rhinitis across China - Associations with early life indoor and outdoor air pollution.

OBJECTIVE: Few longitudinal studies exist on childhood exposure to indoor and outdoor air pollution and respiratory illness in China. We studied associations between indoor and outdoor environment and prevalence, onset and remission of wheeze and rhinitis among children across China. METHODS: Children (3-6 y) were recruited from randomized day care centres in six cities. The main data analysis was restricted to children not moving since birth (N = 17,679). Data on wheeze, rhinitis and the home environment were assessed by a parental questionnaire. Prevalence in the first two years of life (baseline) and the last year (follow-up) was used to calculate onset and remission. Outdoor PM2.5, PM10, and NO2 at the day care centre were modelled from monitoring station data. Associations were calculated by multilevel logistic regression. RESULTS: Prenatal NO2 was associated with decreased remission of wheeze and increased prevalence and increased onset of rhinitis. Prenatal PM2.5 was associated with increased prevalence of wheeze. Postnatal NO2 and postnatal PM10 were associated with increased prevalence and lower remission of wheeze and rhinitis. Mould, window pane condensation, renovation and cockroaches at home were associated with increased prevalence and increased onset of wheeze and rhinitis. Gas cooking was associated with increased onset of rhinitis. Children of mothers with industrial work had more wheeze. CONCLUSIONS: Outdoor PM2.5, PM10 and NO2 can increase childhood wheeze and rhinitis. Dampness and mould can increase onset and decrease remission. Crowdedness, cockroaches at home and emissions from new building materials and gas cooking can be risk factors for wheeze and rhinitis.

Asthma and rhinitis among Chinese children - Indoor and outdoor air pollution and indicators of socioeconomic status (SES).

BACKGROUND: Few data exist on asthma and rhinitis across China in relation to indoor and outdoor air pollution, climate and socioeconomic factors. The main aim was to study associations between asthma, rhinitis and current respiratory symptoms among pre-school children across China and selected indoor and outdoor exposure and indicators of socio-economic status (SES) in mutually adjusted models. METHODS: Chinese children (3-6 yr.) (n = 39,782) were recruited from randomly selected day care centres in seven cities in China. Data on asthma, respiratory symptoms, rhinitis, indoor and outdoor exposure at home and SES were assessed by a parentally administered questionnaire. Lifetime mean ambient temperature, PM10, NO2, and GDP per capita on city level were calculated. RESULTS: Totally 7.4% had ever doctors' diagnosed (DD) asthma and 8.7% DD-rhinitis, 19.7% had current wheeze, 45.0% rhinitis and 16.9% cough. DD-asthma was associated with ambient temperature (OR = 1.15, 95% CI 1.11-1.20 per °C), NO2 (OR = 1.16, 95% CI 1.02-1.33 per 10 µg/m3), indoor mould/dampness (OR = 1.25, 95% CI 1.13-1.39) and living near major roads (OR = 1.13, 95% CI 1.02-1.25). DD-rhinitis was associated with ambient temperature (OR = 1.07, 95% CI 1.05-1.10 per °C), NO2 (OR = 1.20, 95% CI 1.09-1.32 per 10 µg/m3), GDP (OR = 1.03, 95% CI 1.01-1.06 per 10,000 RenMinBi/year), indoor mould/dampness (OR = 1.23, 95% CI 1.11-1.35), passive smoking (OR = 1.11, 95% CI 1.01-1.21), and living near major roads (OR = 1.14, 95% CI 1.03-1.25). Children in suburban or rural areas, in larger families (≥5 persons) and with prenatal farm exposure had less DD-asthma and DD-rhinitis. CONCLUSIONS: Economic development level of the city, higher SES, ambient temperature, NO2, PM10, traffic air pollution and mould/dampness can be risk factors for asthma and rhinitis and respiratory symptoms among pre-school children in China. Breastfeeding, large family size and early-life farm exposure could be protective factors.

Prenatal exposure to ambient temperature variation increases the risk of common cold in children.

BACKGROUND: Common cold is a frequent upper respiratory tract infection, but the role of ambient temperature in the infection is unclear. OBJECTIVE: We investigated the role of prenatal exposure to diurnal temperature variation (DTV), the difference between the daily maximal and minimal temperatures, in the risk of common cold in children. METHODS: We conducted a cohort study of 2598 preschool children in Changsha, China. Occurrence of common cold during the past year was surveyed using questionnaire. We then estimated each child's prenatal exposure to DTV during pregnancy. Multivariate logistic regression model was used to examine the association between occurrence of common cold and prenatal exposure to DTV in terms of odds ratios (OR) and 95% confidence interval (CI). RESULTS: About 45% children have common cold (≥3 times) during the past year. We found that common cold in children was associated with maternal DTV exposure during pregnancy, particularly during the first trimester with adjusted OR (95% CI) = 1.27 (1.10-1.46). Male and atopic children were more susceptible to the effect of DTV during pregnancy. The risk of common cold due to DTV is higher in children living in the suburban areas and the bigger houses and in those exposed to environmental tobacco smoke, mold/dampness, new furniture and redecoration. We observed that the risk of common cold in children has been increased in recent years due to increasing DTV. CONCLUSIONS: Common cold in children was associated with maternal exposure to temperature variation during pregnancy, suggesting that the risk of common cold may originate in pregnancy.

The effects of PM2.5 on asthmatic and allergic diseases or symptoms in preschool children of six Chinese cities, based on China, Children, Homes and Health (CCHH) project.

The urbanization and industrialization in China is accompanied by bad air quality, and the prevalence of asthma in Chinese children has been increasing in recent years. To investigate the associations between ambient PM2.5 levels and asthmatic and allergic diseases or symptoms in preschool children in China, we assigned PM2.5 exposure data from the Global Burden of Disease (GBD) project to 205 kindergartens at a spatial resolution of 0.1° × 0.1° in six cities in China (Shanghai, Nanjing, Chongqing, Changsha, Urumqi, and Taiyuan). A hierarchical multiple logistical regression model was applied to analyze the associations between kindergarten-level PM2.5 exposure and individual-level outcomes of asthmatic and allergic symptoms. The individual-level variables, including gender, age, family history of asthma and allergic diseases, breastfeeding, parental smoking, indoor dampness, interior decoration pollution, household annual income, and city-level variable-annual temperature were adjusted. A total of 30,759 children (average age 4.6 years, 51.7% boys) were enrolled in this study. Apart from family history, indoor dampness, and decoration as predominant risk factors, we found that an increase of 10 µg/m3 of the annual PM2.5 was positively associated with the prevalence of allergic rhinitis by an odds ratio (OR) of 1.20 (95% confidence interval [CI] 1.11, 1.29) and diagnosed asthma by OR of 1.10 (95% CI 1.03, 1.18). Those who lived in non-urban (vs. urban) areas were exposed to more severe indoor air pollution arising from biomass combustion and had significantly higher ORs between PM2.5 and allergic rhinitis and current rhinitis. Our study suggested that long-term exposure to PM2.5 might increase the risks of asthmatic and allergic diseases or symptoms in preschool children in China. Compared to those living in urban areas, children living in suburban or rural areas had a higher risk of PM2.5 exposure.

Small Nuclear Ribonucleoprotein Polypeptide A-Mediated Alternative Polyadenylation of STAT5B during Th1 Cell Differentiation.

T cells are activated and differentiated into Th cells depending on the rapid and accurate changes in the cell transcriptome. In addition to changes in mRNA expression, the sequences of many transcripts are altered by alternative splicing and alternative polyadenylation (APA). We profiled the APA sites of human CD4+ T cell subsets with high-throughput sequencing and found that Th1 cells harbored more genes with shorter tandem 3' untranslated regions (UTRs) than did naive T cells. We observed that STAT5B, a key regulator of Th1 differentiation, possessed three major APA sites and preferred shorter 3' UTRs in Th1 cells. In addition, small nuclear ribonucleoprotein polypeptide A (SNRPA) was found to bind directly to STAT5B 3' UTR and facilitate its APA switching. We also found that p65 activation triggered by TCR signaling could promote SNRPA transcription and 3' UTR shortening of STAT5B. Thus we propose that the APA switching of STAT5B induced by TCR activation is mediated by SNRPA.