How multiple air pollutants affect hand, foot, and mouth disease incidence in children: assessing effect modification by geographical context in multicity of Sichuan, southwest China.

BACKGROUND: Several studies have suggested a significant association of hand, foot, and mouth disease (HFMD) with ambient air pollutants. Existing studies have characterized the role of air pollutants on HFMD using only risk ratio measures while ignoring the attributable burden. And whether the geographical context (i.e., diverse topographic features) could modulate the relationships is unclear. METHODS: Daily reported childhood HFMD counts, ambient air pollution, and meteorological data during 2015-2017 were collected for each of 21 cities in Sichuan Province. A multistage analysis was carried out in different populations based on geographical context to assess effect modification by topographic conditions. We first constructed a distributed lag nonlinear model (DLNM) for each city to describe the relationships with risk ratio measures. Then, we applied a multivariate meta-regression to estimate the pooled effects of multiple air pollutants on HFMD from the exposure and lagged dimensions. Finally, attributable risks measures were calculated to quantify HFMD burden by air pollution. RESULTS: Based on 207554 HFMD cases in Sichuan Province, significant associations of HFMD with ambient air pollutants were observed mainly at relatively high exposure ranges. The effects of ambient air pollutants on HFMD are most pronounced on lag0 or around lag7, with relative risks gradually approaching the reference line thereafter. The attributable risks of O3 were much greater than those of other air pollutants, particularly in basin and mountain regions. CONCLUSIONS: This study revealed significant pooled relationships between multiple air pollutants and HFMD incidence from both exposure and lag dimensions. However, the specific effects, including RRs and ARs, differ depending on the air pollution variable and geographical context. These findings provide local authorities with more evidence to determine key air pollutants and regions for devising and implementing targeted interventions.

Lipid changes and molecular mechanism inducing cuproptosis in Cryptocaryon irritans after copper-zinc alloy exposure.

Cryptocaryons irritans is a ciliate parasite responsible for cryptocaryoniasis, leading to considerable economic losses in aquaculture. It is typically managed using a copper-zinc alloy (CZA), effectively diminishing C. irritans infection rates while ensuring the safety of aquatic organisms. Nevertheless, the precise mechanism underlying cuproptosis induced C. irritans mortality following exposure to CZA remains enigmatic. Therefore, this study delves into assessing the efficacy of CZA, investigate cuproptosis as a potential mechanism of CZA action against C. irritans, and determine the alterations in antioxidant enzymes, peroxidation, and lipid metabolism. The mRNA expression of dihydrolipoamide S-acetyltransferase was upregulated after 40 and 70 min, while aconitase 1 was implicated in cuproptosis following 70 min of CZA exposure. Furthermore, the relative mRNA levels of glutathione reductase experienced a significant increase after 40 and 70 min of CZA exposure. In contrast, the relative mRNA levels of glutathione S-transferase and phospholipid-hydroperoxide glutathione peroxidase were significantly decreased after 70 min, suggesting a disruption in antioxidant defense and an imbalance in copper ions. Lipidomics results also unveiled an elevation in glycerophospholipids metabolism and the involvement of the lipoic acid pathway, predominantly contributing to cuproptosis. In summary, exposure to CZA induces cuproptosis in C. irritans, impacts glutathione-related enzymes, and alters glycerophospholipids, consequently triggering lipid oxidation.

Influence of social and meteorological factors on hand, foot, and mouth disease in Sichuan Province.

BACKGROUND: Hand, foot and mouth disease (HFMD) caused by a variety of enteroviruses remains a major public health problem in China. Previous studies have found that social factors may contribute to the inconsistency of the relationship patterns between meteorological factors and HFMD, but the conclusions are inconsistent. The influence of social factors on the association between meteorology and HFMD is still less well understood. We aimed to analyze whether social factors affected the effect of meteorological factors on HFMD in Sichuan Province. METHOD: We collected daily data on HFMD, meteorological factors and social factors in Sichuan Province from 2011 to 2017. First, we used a Bayesian spatiotemporal model combined with a distributed lag nonlinear model to evaluate the exposure-lag-response association between meteorological factors and HFMD. Second, by constructing the interaction of meteorological factors and social factors in the above model, the changes in the relative risk (RR) under different levels of social factors were evaluated. RESULTS: The cumulative exposure curves for average temperature, relative humidity, and HFMD were shaped like an inverted "V" and a "U" shape. As the average temperature increased, the RR increased and peaked at 19 °C (RR 1.020 [95% confidence interval CI 1.004-1.050]). The urbanization rate, per capita gross domestic product (GDP), population density, birth rate, number of beds in health care centers and number of kindergartens interacted with relative humidity. With the increase in social factors, the correlation curve between relative humidity and HFMD changed from an "S" shape to a "U" shape. CONCLUSIONS: Relative humidity and average temperature increased the risk of HFMD within a certain range, and social factors enhanced the impact of high relative humidity. These results could provide insights into the combined role of environmental factors in HFMD and useful information for regional interventions.

Antiparasitic effect of copper alloy mesh on tomont stage of Cryptocaryon irritans in aquaculture.

Copper alloy sheets have been shown to prevent cryptocaryoniasis. Therefore, we studied the potential efficiency of copper alloy mesh (CAM) in aquaculture tanks to prevent cryptocaryoniasis outbreaks. The effectivenesses of CAM against the tomont stage of Cryptocaryon irritans and in protecting fish from cryptocaryoniasis were tested both in vitro and in vivo. The mortality rate of C. irritans tomonts increased as the contact time with CAM rose and peaked at 70 min (100% of mortality). Morphological changes were observed such as the shrinking of the protoplasm of the treated tomonts, resulting in a larger gap between the cytoplasm and the cyst wall. Mitochondrial dysfunction due to shrinkage in the inner portion, outer and inner mitochondrial membrane damage and cytoplasmic vacuolation was revealed by ultrastructural analysis. The use of CAM effectively preventing reinfection was also provided. In comparison with group B (infected fish without CAM), both groups A (uninfected fish as a control group) and C (infected fish treated with CAM) had a 100% survival rate until the end of the trial. CAM has the same anticryptocaryoniasis effect as copper alloy sheets but is more advantageous due to its lightweight, reduced labor cost and lower purchase cost. It is noticeable that CAM exposure also prevents the excessive accumulation of copper ions in aquaculture sea water.

Börjeson-Forssman-Lehmann syndrome: A case report. / Börjeson-Forssman-Lehmann综合征1例.

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.

Long-term air pollution levels modify the relationships between short-term exposure to meteorological factors, air pollution and the incidence of hand, foot and mouth disease in children: a DLNM-based multicity time series study in Sichuan Province, China.

BACKGROUND: Epidemiological studies have investigated the short-term effects of meteorological factors and air pollution on the incidence of hand, foot, and mouth disease (HFMD). Several meteorological indicators, such as relative humidity and the diurnal temperature range (DTR), significantly modify the relationship between short-term exposure to temperature and HFMD incidence. However, it remains unclear whether (and how) long-term air pollution levels modify the short-term relationships of HFMD incidence with meteorological factors and air pollution. METHODS: We obtained daily data on meteorological factors, air pollutants, and HFMD counts in children from 21 prefecture-level cities in Sichuan Province in Southwest China from 2015 to 2017. First, we constructed a distributed lag nonlinear model (DLNM) at each prefecture-level site to evaluate the short-term impacts of meteorological variables and air pollutants on HFMD incidence. Then, we assessed the pooled effects of the exposures and incorporated long-term city-specific air pollutant indicators as meta-predictors to examine their potential modification effects by performing multivariate meta-regression models. RESULTS: We found that long-term SO2 and CO concentrations significantly modified the short-term relationships between climatic variables and HFMD incidence. Specifically, high concentrations of CO (P = 0.027) and SO2 (P = 0.039) reduced the risk of HFMD at low temperatures. The relationship between relative humidity and HFMD incidence was weakened at high SO2 concentrations (P = 0.024), especially when the relative humidity was below the median level. When the minimum relative humidity (32%) was compared to the median relative humidity (77%), the risk ratio (RR) was 0.77 (95% CI: 0.51-1.17) in the 90th percentile of SO2 (19.6 µg/m3) and 0.41 (95% CI: 0.27-0.64) in the 10th percentile of SO2 (10.6 µg/m3). CONCLUSION: Our results indicated that long-term SO2 and CO levels modified the short-term associations between HFMD incidence in children and meteorological variables. These findings may inform health authorities to optimize targeted public health policies including reducing ambient air pollution and reinforcing self-protective actions to weaken the adverse health impacts of environmental factors on HFMD incidence.

How to improve infectious disease prediction by integrating environmental data: an application of a novel ensemble analysis strategy to predict HFMD.

This study proposed a novel ensemble analysis strategy to improve hand, foot and mouth disease (HFMD) prediction by integrating environmental data. The approach began by establishing a vector autoregressive model (VAR). Then, a dynamic Bayesian networks (DBN) model was used for variable selection of environmental factors. Finally, a VAR model with constraints (CVAR) was established for predicting the incidence of HFMD in Chengdu city from 2011 to 2017. DBN showed that temperature was related to HFMD at lags 1 and 2. Humidity, wind speed, sunshine, PM10, SO2 and NO2 were related to HFMD at lag 2. Compared with the autoregressive integrated moving average model with external variables (ARIMAX), the CVAR model had a higher coefficient of determination (R2, average difference: + 2.11%; t = 6.2051, P = 0.0003 < 0.05), a lower root mean-squared error (-24.88%; t = -5.2898, P = 0.0007 < 0.05) and a lower mean absolute percentage error (-16.69%; t = -4.3647, P = 0.0024 < 0.05). The accuracy of predicting the time-series shape was 88.16% for the CVAR model and 86.41% for ARIMAX. The CVAR model performed better in terms of variable selection, model interpretation and prediction. Therefore, it could be used by health authorities to identify potential HFMD outbreaks and develop disease control measures.

Antiparasitic Effect of Copper Alloy Surface on Cryptocaryon irritans in Aquaculture of Larimichthys crocea.

Copper and alloys containing >60% copper by weight are antimicrobial. In aquaculture, copper alloys are used as part of corrosion-resistant cages or as part of copper coating. To test whether a copper alloy surface prevents the outbreak of parasitosis in the aquaculture of Larimichthys crocea, we covered the bottom of the aquaculture tank with sheets of copper alloy containing 74% to 78% copper, and we cultured L. crocea juveniles that had been artificially infected with the protozoan parasite Cryptocaryon irritans Our results showed that these copper alloy sheets effectively blocked the infectious cycle of C. irritans within a 1-week period and significantly reduced the number of C. irritans trophonts and tomonts, thereby decreasing the mortality rate of L. crocea In in vitro assays, the cytoplasmic membranes of protomonts disintegrated and the cytoplasm overflowed after just 5 minutes of contact with copper alloy surfaces. Although the same cytoplasmic membrane disintegration was not observed in tomonts, the tomonts completely lost their capacity for proliferation and eventually died following direct contact with copper alloy sheets for 1 h; this is likely because C. irritans tomonts took in >100 times more copper ions following contact with the copper alloy sheets than within the control aquaculture environment. Exposure to copper alloy sheets did not lead to excessive heavy metal levels in the aquacultured fish or in the culture seawater.IMPORTANCECryptocaryon irritans, a parasitic ciliate that penetrates the epithelium of the gills, skin, and fins of marine fish, causes acute suffocation and death in cultured fish within days of infection. Much of the existing research centers around the prevention of C. irritans infection, but no cure has been found. Studies demonstrate that copper has strong antimicrobial properties, and fish grown in copper-containing cages have lower rates of C. irritans infection, compared to those grown in other currently used aquaculture cages. In this study, we found that an alloy containing 74% to 78% copper by weight effectively killed C. irritans cells and prevented cryptocaryoniasis outbreaks within a 1-week period. These findings offer a new perspective on the prevention and control of cryptocaryoniasis.

Clinical efficacy and safety of paclitaxel liposomes as first-line chemotherapy in advanced gastric cancer.

Aim: To compare the performance of first-line paclitaxel liposome + oxaliplatin and SOX (tegafur/gimeracil/oteracil + oxaliplatin) in advanced gastric cancer patients. Materials & methods: Stage IIb-IV gastric cancer patients underwent either first-line paclitaxel liposome + oxaliplatin (n = 52) or SOX (n = 69) between 2010-2013, and followed up until 2015 or death. Results: Both groups had similar objective response rate (p = 0.48) and disease control rate (p = 0.992) after two chemotherapy cycles, median progression-free survival (p = 0.495) and median overall survival (p = 0.208). Liposome group had significantly lower rate of grade I-II platelet decline and liver function damage (p = 0.04 and 0.019). Multivariate COX regression identified pre-treatment neutrophil-to-lymphocyte ratio as an independent prognostic factor. Conclusion: First-line paclitaxel liposome + oxaliplatin has comparable efficacy, but causes reduced adverse reactions in advanced gastric cancer as compared with SOX.

Thermal Extrusion 3D Printing for the Fabrication of Puerarin Immediate-Release Tablets.

Thermal extrusion (TE) 3D printing is a thermoplastic semisolid-based rapid prototyping process, which is capable of building complex structures. The aim of this study was to manufacture rapid-release puerarin tablets without solvent through TE 3D printing. Novel rapid-release tablets were fabricated with polyethylene glycol (PEG 4000) as the carrier at appropriate puerarin/PEG 4000 ratios, assessed through differential scanning calorimetry (DSC), solubility, and dissolution tests. The novel structures of 3D-printed tablets with five different values were formed by printing paths, which established a flexible way of adjusting in vitro drug release. An obvious acceleration (85% of cumulative release about 7.5 min at the soonest) was observed for the tablets with internal structural design. It was inferred that puerarin formed simple eutectic mixtures with PEG 4000 and that puerarin dispersed into the carrier based on DSC and X-Ray powder diffraction (XRD). This highlights the combined advantage of PEG as a soluble polymer with TE 3D printing and provides a suitable system for rapid puerarin release.

The association between diurnal temperature range and childhood hand, foot, and mouth disease: a distributed lag non-linear analysis.

In recent years, hand, foot, and mouth disease (HFMD) has been increasingly recognized as a critical challenge to disease control and prevention in China. Previous studies have found that meteorological factors such as mean temperature and relative humidity were associated with HFMD. However, little is known about whether the diurnal temperature range (DTR) has any impact on HFMD. This study aimed to quantify the impact of DTR on childhood HFMD in 18 cities in Sichuan Province. A distributed lag non-linear model was adopted to explore the temporal lagged association of daily temperature with age-, gender- and pathogen-specific HFMD. A total of 290 123 HFMD cases aged 0-14 years were reported in the 18 cities in Sichuan Province. The DTR-HFMD relationships were non-linear in all subgroups. Children aged 6-14 years and male children were more vulnerable to the temperature changes. Large DTR had the higher risk estimates of HFMD incidence in cases of EV71 infection, while small DTR had the higher risk estimates of HFMD incidence in cases of CV-A16 infection. Our study suggested that DTR played an important role in the transmission of HFMD with non-linear and delayed effects.

Comparisons between mild and severe cases of hand, foot and mouth disease in temporal trends: a comparative time series study from mainland China.

BACKGROUND: Over recent decades, hand, foot and mouth disease (HFMD) has emerged as a serious public health threat in the Asia-Pacific region because of its high rates of severe complications. Understanding the differences and similarities between mild and severe cases can be helpful in the control of HFMD. In this study, we compared the two types of HFMD cases in their temporal trends. METHODS: We retrieved the daily series of disease counts of mild and severe HFMD cases reported in mainland China in the period of 2009-2014. We applied a quasi-Poisson regression model to decompose each series into the long-term linear trend, periodic variations, and short-term fluctuations, and then we compared each component between two series separately. RESULTS: A total of 11,101,860 clinical HFMD cases together with 115,596 severe cases were included into this analysis. We found a biennial increase of 24.46 % (95 % CI: 22.80-26.14 %) for the baseline of disease incidence of mild cases, whereas a biennial decrease of 8.80 % (95 % CI: 7.26-10.31 %) was seen for that of severe cases. The periodic variations of both two series could be characterized by a mixture of biennial, annual, semi-annual and eight-monthly cycles. However, compared to the mild cases, we found the severe cases vary more widely for the biennial and annual cycle, and started its annual epidemic earlier. We also found the short-term fluctuations between two series were still significantly correlated at the current day with a correlation coefficient of 0.46 (95 % CI: 0.43-0.49). CONCLUSIONS: We found some noticeable differences and also similarities between the daily series of mild and severe HFMD cases at different time scales. Our findings can help us to deepen the understanding of the transmission of different types of HFMD cases, and also provide evidences for the planning of the associated disease control strategies.

Preparation and pharmacokinetics study on gastro-floating sustained-release tablets of troxipide.

The purpose of this research aimed at preparing gastro-floating sustained-release tablets of troxipide and a further study on in vitro release and in vivo bioavailability. Under the circumstances of direct powder compression, the floating tablets were successfully prepared with HPMC as main matrix material, Carbopol as assistant matrix material, octadecanol as floating agent and sodium bicarbonate as foaming agent to float by gas-forming. The floating time and accumulative release amount as evaluation indexes were utilized to perform pre-experiment screening and single-factor test, respectively, while central composite design response surface method was applied for formulation optimization, followed by in vivo pharmacokinetic study in beagles after oral administration for floating tablets and commercial tablets used as the control. The results indicated that the floating sustained-release tablets held a better capability for floating and drug release and more satisfactory pharmacokinetic parameters, such as a lower Cmax, a prolonged Tmax, but an equivalent bioavailability calculated by AUC0-24 compared to commercial tablets. So a conclusion was finally drawn that the floating sustained-release tablets possessing a good release property could be suitable for demands of design.

[A complicated case study: Hennekam syndrome].

Hennekam syndrome (HS) is a rare autosomal recessive syndrome characterized by defective lymphatic development. A 34-month-old boy with HS and who had unexplained developmental retardation and hypoalbuminemia as main clinical manifestations is reported here. He had a history of generalized edema and poor feeding. He was not thriving well. He manifested as facial anomalies (hypertelorism, flat nasal bridge and flat face), fracture of teeth, and superficial lymph nodes enlargement. He had low serum total protein, low serum albumin, and low serum immunoglobulin levels. Duodenal bulb biopsy revealed lymphangiectasia. Color Doppler ultrasound, magnetic resonance imaging and CT scan showed multi-site lymphangioma, and HS was thus confirmed. Mutations in CCBE1 and FAT4 have been found responsible for the syndrome in a part of patients. Diagnosis of the disease depends on the familial history, clinical signs, pathological findings and genetic tests.

Spatiotemporal patterns and risk mapping of provincial hand, foot, and mouth disease in mainland China, 2014-2017.

Background: Hand, foot, and mouth disease (HFMD) has remained a serious public health threat since its first outbreak in China. Analyzing the province-level spatiotemporal distribution of HFMD and mapping the relative risk in mainland China will help determine high-risk provinces and periods of infection outbreaks for use in formulating new priority areas for prevention and control of this disease. Furthermore, our study examined the effect of air pollution on HFMD nationwide, which few studies have done thus far. Methods: Data were collected on the number of provincial monthly HFMD infections, air pollution, meteorological variables, and socioeconomic variables from 2014 to 2017 in mainland China. We used spatial autocorrelation to determine the aggregate distribution of HFMD incidence. Spatiotemporal patterns of HFMD were analyzed, risk maps were developed using the Bayesian spatiotemporal model, and the impact of potential influencing factors on HFMD was assessed. Results: In our study, from 2014 to 2017, the HFMD annual incidence rate in all provinces of mainland China ranged from 138.80 to 203.15 per 100,000 people, with an average annual incidence rate of 165.86. The temporal risk of HFMD for 31 Chinese provinces exhibited cyclical and seasonal characteristics. The southern and eastern provinces had the highest spatial relative risk (RR > 3) from 2014 to 2017. The HFMD incidence risk in provinces (Hunan, Hubei, and Chongqing) located in central China increased over time. Among the meteorological variables, except for the mean two-minute wind speed (RR 0.6878; 95% CI 0.5841, 0.8042), all other variables were risk factors for HFMD. High GDP per capita (RR 0.9922; 95% CI 0.9841, 0.9999) was a protective factor against HFMD. The higher the birth rate was (RR 1.0657; 95% CI 1.0185, 1.1150), the higher the risk of HFMD. Health workers per 1,000 people (RR 1.2010; 95% CI 1.0443, 1.3771) was positively correlated with HFMD. Conclusions: From 2014 to 2017, the central provinces (Hunan, Hubei, and Chongqing) gradually became high-risk regions for HFMD. The spatiotemporal pattern of HFMD risk may be partially attributed to meteorological and socioeconomic factors. The prevalence of HFMD in the central provinces requires attention, as prevention control efforts should be strengthened there.

Advancing Spinal Cord Injury Bioimaging and Repair with Multifunctional Gold Nanodots Tracking.

High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.

Associations between ambient air pollutants and childhood hand, foot, and mouth disease in Sichuan, China: a spatiotemporal study.

Hand, foot, and mouth disease (HFMD) is a major public health concern in the Asia-Pacific region. Previous studies have implied that ambient air pollution may affect the incidence of HFMD, but the results among different regions are inconsistent. We aimed to deepen the understanding of the associations between air pollutants and HFMD by conducting a multicity study. Daily data on childhood HFMD counts and meteorological and ambient air pollution (PM2.5, PM10, NO2, CO, O3, and SO2) concentrations in 21 cities in Sichuan Province from 2015 to 2017 were collected. A spatiotemporal Bayesian hierarchical model framework was established, and then a distributed lag nonlinear models (DLNMs) was constructed to reveal exposure-lag-response relationships between air pollutants and HFMD while controlling for spatiotemporal effects. Furthermore, given the differences in the levels and seasonal trends of air pollutants between the basin region and plateau region, we explored whether these associations varied between different areas (basin and plateau). The associations between air pollutants and HFMD were nonlinear, with different lag responses. Low NO2 concentrations and both low and high PM2.5 and PM10 concentrations were associated with a decreased risk of HFMD. No significant associations between CO, O3, and SO2 and HFMD were found. The associations between air pollutant concentrations and HFMD were different between the basin and plateau regions. Our study revealed associations between PM2.5, PM10, and NO2 concentrations and HFMD, deepening the understanding of the relationships between air pollutants and HFMD. These findings provide evidence to support the formulation of relevant prevention measures and the establishment of an early warning system.

City-level meteorological conditions modify the relationships between exposure to multiple air pollutants and the risk of pediatric hand, foot, and mouth disease in the Sichuan Basin, China.

Background: Several studies have examined the effects of city-level meteorological conditions on the associations between meteorological factors and hand, foot, and mouth disease (HFMD) risk. However, evidence that city-level meteorological conditions modify air pollutant-HFMD associations is lacking. Methods: For each of the 17 cities in the Sichuan Basin, we obtained estimates of the relationship between exposures to multiple air pollutants and childhood HFMD risk by using a unified distributed lag nonlinear model (DLNM). Multivariate meta-regression models were used to identify the effects of city-level meteorological conditions as effect modifiers. Finally, we conducted subgroup analyses of age and sex to explore whether the modification effects varied in different subgroups. Results: The associations between PM2.5/CO/O3 and HFMD risk showed moderate or substantial heterogeneity among cities (I2 statistics: 48.5%, 53.1%, and 61.1%). Temperature conditions significantly modified the PM2.5-HFMD association, while relative humidity and rainfall modified the O3-HFMD association. Low temperatures enhanced the protective effect of PM2.5 exposure against HFMD risk [PM2.5 <32.7 µg/m3 or PM2.5 >100 µg/m3, at the 99th percentile: relative risk (RR) = 0.14, 95% CI: 0.03-0.60]. Low relative humidity increased the adverse effect of O3 exposure on HFMD risk (O3 >128.7 µg/m3, at the 99th percentile: RR = 2.58, 95% CI: 1.48-4.50). However, high rainfall decreased the risk of HFMD due to O3 exposure (O3: 14.1-41.4 µg/m3). In addition, the modification effects of temperature and relative humidity differed in the female and 3-5 years-old subgroups. Conclusion: Our findings revealed moderate or substantial heterogeneity in multiple air pollutant-HFMD relationships. Temperature, relative humidity, and rainfall modified the relationships between PM2.5 or O3 exposure and HFMD risk.

Evaluation of models for multi-step forecasting of hand, foot and mouth disease using multi-input multi-output: A case study of Chengdu, China.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a public health concern that threatens the health of children. Accurately forecasting of HFMD cases multiple days ahead and early detection of peaks in the number of cases followed by timely response are essential for HFMD prevention and control. However, many studies mainly predict future one-day incidence, which reduces the flexibility of prevention and control. METHODS: We collected the daily number of HFMD cases among children aged 0-14 years in Chengdu from 2011 to 2017, as well as meteorological and air pollutant data for the same period. The LSTM, Seq2Seq, Seq2Seq-Luong and Seq2Seq-Shih models were used to perform multi-step prediction of HFMD through multi-input multi-output. We evaluated the models in terms of overall prediction performance, the time delay and intensity of detection peaks. RESULTS: From 2011 to 2017, HFMD in Chengdu showed seasonal trends that were consistent with temperature, air pressure, rainfall, relative humidity, and PM10. The Seq2Seq-Shih model achieved the best performance, with RMSE, sMAPE and PCC values of 13.943~22.192, 17.880~27.937, and 0.887~0.705 for the 2-day to 15-day predictions, respectively. Meanwhile, the Seq2Seq-Shih model is able to detect peaks in the next 15 days with a smaller time delay. CONCLUSIONS: The deep learning Seq2Seq-Shih model achieves the best performance in overall and peak prediction, and is applicable to HFMD multi-step prediction based on environmental factors.

Modification effects of socioeconomic factors on associations between air pollutants and hand, foot, and mouth disease: A multicity time-series study based on heavily polluted areas in the basin area of Sichuan Province, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a serious threat among children in China. Some studies have found that air pollution is associated with HFMD incidence, but the results showed heterogeneity. In this study, we aimed to explore the heterogeneity of associations between air pollutants and the number of HFMD cases and to identify significant socioeconomic effect modifiers. METHODS: We collected daily surveillance data on HFMD cases in those aged less than 15 years, air pollution variables and meteorological variables from 2015 to 2017 in the basin area of Sichuan Province. We also collected socioeconomic indicator data. We conducted a two-stage multicity time-series analysis. In the first stage, we constructed a distributed lag nonlinear model (DLNM) to obtain cumulative exposure-response curves between each air pollutant and the numbers of HFMD cases for every city. In the second stage, we carried out a multivariable meta-regression to merge the estimations in the first stage and to identify significant socioeconomic effect modifiers. RESULTS: We found that PM10, NO2 and O3 concentrations were associated with the number of HFMD cases. An inverted V-shaped association between PM10 and the number of HFMD cases was observed. The overall NO2-HFMD association was a hockey-stick shape. For the relationships of PM10, SO2, NO2, O3 and CO with HFMD counts, approximately 58.5%, 48.4%, 51.0%, 55.6% and 52.5% of the heterogeneity could be explained, respectively. The proportion of primary school students, population density, urbanization rate, number of licensed physicians and number of hospital beds explained part of the heterogeneity and modified the relationships. CONCLUSION: Our study explored the heterogeneity of associations between air pollutants and HFMD counts. The proportion of primary school students, population density, urbanization rate, number of licensed physicians and number of hospital beds could modify the relationships. The results can serve as a reference for relevant public health decision making.