Modification effects of long-term air pollution levels on the relationship between short-term exposure to meteorological factors and hand, foot, and mouth disease: A distributed lag non-linear model-based study in Shandong Province, China.

The occurrence of hand, foot, and mouth disease (HFMD) is closely related to meteorological factors. However, location-specific characteristics, such as persistent air pollution, may increase the complexity of the impact of meteorological factors on HFMD, and studies across different areas and populations are largely lacking. In this study, a two-stage multisite time-series analysis was conducted using data from 16 cities in Shandong Province from 2015 to 2019. In the first stage, we obtained the cumulative exposure-response curves of meteorological factors and the number of HFMD cases for each city. In the second stage, we merged the estimations from the first stage and included city-specific air pollution variables to identify significant effect modifiers and how they modified the short-term relationship between HFMD and meteorological factors. High concentrations of air pollutants may reduce the risk effects of high average temperature on HFMD and lead to a distinct peak in the cumulative exposure-response curve, while lower concentrations may increase the risk effects of high relative humidity. Furthermore, the effects of average wind speed on HFMD were different at different levels of air pollution. The differences in modification effects between subgroups were mainly manifested in the diversity and quantity of significant modifiers. The modification effects of long-term air pollution levels on the relationship between sunshine hours and HFMD may vary significantly depending on geographical location. The people in age＜3 and male groups were more susceptible to long-term air pollution. These findings contribute to a deepening understanding of the relationship between meteorological factors and HFMD and provide evidence for relevant public health decision-making.

Spatio-temporal analysis of the relationship between climate and hand, foot, and mouth disease in Shandong province, China, 2008-2012.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is the most common communicable disease in China. Shandong Province is one of the most seriously affected areas. The distribution of HFMD had spatial heterogeneity and seasonal characteristic in this setting. The aim of this study was to explore the associations between climate and HFMD by a Bayesian approach from spatio-temporal interactions perspective. METHODS: The HFMD data of Shandong Province during 2008-2012 were derived from the China National Disease Surveillance Reporting and Management System. And six climatic indicators were obtained from the Meteorological Bureau of Shandong Province. The global spatial autocorrelation statistic (Moran's I) was used to detect the spatial autocorrelation of HFMD cases in each year. The optimal one among four Bayesian models was further adopted to estimate the relative risk of the occurrence of HFMD via Markov chain Monte Carlo. RESULTS: The annual average incidence rate of HFMD was 104.40 per 100,000 in Shandong Province. Positive spatial autocorrelation appeared at county level (Moran's I≥0.30, P<0.001). The best fitting Spatio-temporal interactive model showed that annual average temperature, annual average pressure, annual average relative humidity, annual average wind speed and annual sunshine hours were significantly positive related to the occurrence of HFMD. The estimated relative risk of 36, 87, 91, 79, 65 out of 140 counties for 2008-2012 respectively were significantly more than 1. CONCLUSIONS: There were obvious spatio-temporal heterogeneity of HFMD in Shandong Province, and the climatic indicators were associated with the epidemic of HFMD. Bayesian approach should be recommended to capture the spatial-temporal pattern of HFMD.

The Role of BTBD7 in Normal Development and Tumor Progression.

BTB/POZ domain-containing protein 7 (BTBD7) has a relative molecular weight of 126KD and contains two conserved BTB/POZ protein sequences. BTBD7 has been shown to play an essential role in normal human development, precancerous lesions, heat-stress response, and tumor progression. BTBD7 promotes branching morphogenesis during development and participates in the salivary gland, lung, and tooth formation. Furthermore, many studies have shown that aberrant expression of BTBD7 promotes heat stress response and the progression of precancerous lesions. BTBD7 has also been found to play an important role in cancer. High expression of BTBD7 affects tumor progression by regulating multiple pathways. Therefore, a complete understanding of BTBD7 is crucial for exploring human development and tumor progression. This paper reviews the research progress of BTBD7, which lays a foundation for the application of BTBD7 in regenerative medicine and as a biomarker for tumor prediction or potential therapeutic target.

Preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced oral mucositis: A protocol for systematic review and meta analysis.

BACKGROUND: Oral mucositis (OM), one of the most common side effects for cancer patients who have undergone chemotherapy, can cause severe impairment to patients' functional ability and impact their quality of life, resulting in delayed and/or incomplete treatment. Traditional Chinese medicine offers empirical herbal decoctions to gargle for the prevention of chemotherapy-induced OM; however, evidence for its clinical efficacy and safety is lacking. Therefore, we provide a protocol to evaluate the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. METHODS: We will comprehensively retrieve relevant articles published till August 15, 2020, in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. Only randomized controlled trials will be included. We will use the criteria provided by the Cochrane Handbook for quality assessment and risk assessment of the included studies and use the RevMan 5.3 software for meta-analysis of the preventive effect and safety. RESULTS: This study will assess the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. CONCLUSION: This systematic review will provide evidence-based medical corroboration for the clinical application of the Chinese herbal medicine mouthwash in chemotherapy-induced OM. PROSPERO REGISTRATION NUMBER: CRD42020206614.

Effects of Paclitaxel-conjugated N-Succinyl-Hydroxyethyl Chitosan Film for Proliferative Cholangitis in Rabbit Biliary Stricture Model.

BACKGROUND: Paclitaxel (PTX) could inhibit the growth of fibroblasts, which occurs in proliferative cholangitis and leads to biliary stricture. However, its use has been limited due to poor bioavailability and local administration for short time. This study designed and synthesized a new PTX-conjugated chitosan film (N-succinyl-hydroxyethyl chitosan containing PTX [PTX-SHEC]) and evaluated its safety and efficiency using in vivo and in vitro experiments. METHODS:: The SHEC conjugated with PTX was confirmed by nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FT-IR) measurements. Drug releases in vitro and in vivo were determined using high-performance liquid chromatography. Cell viability in vitro was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Rabbit biliary stricture model was constructed. All rabbits randomly divided into five groups (n = 8 in each group): the sham-operated rabbits were used as control (Group A), Groups B received laparotomies and suture, Group C received laparotomies and covered SHEC suture without the PTX coating, Group D received laparotomies and covered PTX-SHEC suture, and Group E received laparotomies and 1000 µmol/L PTX administration. Liver function tests and residual dosage of PTX from each group were measured by enzyme-linked immunosorbent assay. Histological data and α-smooth muscle actin (SMA) immunohistochemical staining of common bile duct were examined. RESULTS:: NMR and FT-IR indicated that PTX was successfully introduced, based on the appearance of signals at 7.41-7.99 ppm, 1.50 ppm, and 1.03 ppm, due to the presence of aromatic protons, methylene protons, and methyl protons of PTX, respectively. No bile leak was observed. The PTX-conjugated film could slowly release PTX for 4 weeks (8.89 ± 0.03 µg at day 30). The in vitro cell viability test revealed significantly different levels of toxicity between films with and without PTX (111.7 ± 4.0% vs. 68.1 ± 6.0%, P < 0.001), whereas no statistically significant difference was observed among the three sets of PTX-contained films (67.7 ± 5.4%, 67.2 ± 3.4%, and 59.1 ± 6.0%, P > 0.05). Histological examinations revealed that after 28 days of implantment, Groups D and E (but not Group C) had less granulation tissue and glandular hyperplasia in the site of biliary duct injury than Group B. The pattern was more obvious in Group D than Group E. Less α-SMA-positive cells were found in tissue from Groups D and E. Comparing with Group E, the liver function was improved significantly in Group D, including total bilirubin (2.69 ± 1.03 µmol/L vs. 0.81 ± 0.54 µmol/L, P = 0.014), alanine aminotransferase (87.13 ± 17.51 U/L vs. 42.12 ± 15.76 U/L, P = 0.012), and alkaline phosphatase (60.61 ± 12.31 U/L vs. 40.59 ± 8.78 U/L, P < 0.001). CONCLUSIONS: PTX-SHEC film effectively inhibites the myofibroblast proliferation and extracellular matrix over-deposition during the healing process of biliary reconstruction. This original film might offer a new way for reducing the occurrence of the benign biliary stricture.

[Preparation and application of polyclonal antibody against amelotin polypeptide].

OBJECTIVE: To prepare and identify the rabbit anti-mouse polyclonal antibody against amelotin polypeptide. METHODS: The polypeptide was synthesized based on the bioinformatics analysis of amelotin, and coupled with keyhole limpet hemocyanin (KLH) for immunization. The amelotin polypeptide-KLH was injected into New Zealand rabbits to prepare the polyclonal antibody. ELISA technology was used to detect the titer of the antibody. The specificity of the polyclonal antibody was identified by Western blotting. The expression of amelotin in the submandibular tissue of mice was observed by immunohistochemistry. RESULTS: ELISA showed that the titer of amelotin antibody was 1:1,000,000. Western blotting verified that the antibody had a high specificity. Immunohistochemistry indicated that amelotin was highly expressed in odontoprisis full-thick enamel of 3-day-old and 7-day-old mice, and also expressed in duct epithelial cytoplasm of submandibular glands of 7-day-old mice. CONCLUSION: The polyclonal antibody against amelotin polypeptide has been prepared successfully with high titer and high specificity.

The Impact of Ambient Temperature on Childhood HFMD Incidence in Inland and Coastal Area: A Two-City Study in Shandong Province, China.

Hand, foot and mouth disease (HFMD) has been a substantial burden throughout the Asia-Pacific countries over the past decades. For the purposes of disease prevention and climate change health impact assessment, it is important to understand the temperature-disease association for HFMD in different geographical locations. This study aims to assess the impact of temperature on HFMD incidence in an inland city and a coastal city and investigate the heterogeneity of temperature-disease associations. Daily morbidity data and meteorological variables of the study areas were collected for the period from 2007 to 2012. A total of 108,377 HFMD cases were included in this study. A distributed lag non-linear model (DLNM) with Poisson distribution was used to examine the nonlinear lagged effects of daily mean temperature on HFMD incidence. After controlling potential confounders, temperature showed significant association with HFMD incidence and the two cities demonstrated different impact modes ( I2= 96.1%; p < 0.01). The results highlight the effect of temperature on HFMD incidence and the impact pattern may be modified by geographical localities. Our findings can be a practical reference for the early warning and intervention strategies of HFMD.

Detecting the association between meteorological factors and hand, foot, and mouth disease using spatial panel data models.

OBJECTIVES: The aim of this study was to quantify the relationship between meteorological factors and the occurrence of hand, foot, and mouth disease (HFMD) among children in Shandong Province, China, at a county level, using spatial panel data models. METHODS: Descriptive analysis was applied to describe the epidemic characteristics of HFMD from January 2008 to December 2012, and then a global autocorrelation statistic (Moran's I) was used to detect the spatial autocorrelation of HFMD in each year. Finally, spatial panel data models were performed to explore the association between the incidence of HFMD and meteorological factors. RESULTS: Moran's I at the county level were high, from 0.30 to 0.45 (p < 0.001), indicating the existence of a high spatial autocorrelation on HFMD. Spatial panel data models are more appropriate to describe the data. Results showed that the incidences of HFMD in Shandong Province, China were significantly associated with average temperature, relative humidity, vapor pressure, and wind speed. CONCLUSIONS: Spatial panel data models are useful when longitudinal data with multiple units are available and spatial autocorrelation exists. The association found between HFMD and meteorological factors makes a contribution towards advancing knowledge with respect to the causality of HFMD and has policy implications for HFMD prevention and control.

Detecting spatial-temporal clusters of HFMD from 2007 to 2011 in Shandong Province, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) has caused major public health concerns worldwide, and has become one of the leading causes of children death. China is the most serious epidemic area with a total of 3,419,149 reported cases just from 2008 to 2010, and its different geographic areas might have different spatial epidemiology characteristics at different spatial-temporal scale levels. We conducted spatial and spatial-temporal epidemiology analysis to HFMD at county level in Shandong Province, China. METHODS: Based on the China National Disease Surveillance Reporting and Management System, the spatial-temporal database of HFMD from 2007 to 2011 was built. The global autocorrelation statistic (Moran's I) was first used to detect the spatial autocorrelation of HFMD cases in each year. Purely Spatial scan statistics combined with Space-time scan statistic were used to detect epidemic clusters. RESULTS: The annual average incidence rate was 93.70 per 100,000 in Shandong Province. Most HFMD cases (93.94%) were aged within 0-5 years old with an average male-to-female sex ratio 1.71, and the incidence seasonal peak was between April and July. The dominant pathogen was EV71 (47.35%), and CoxA16 (26.59%). HFMD had positive spatial autocorrelation at medium spatial scale level (county level) with higher Moran's I from 0.31 to 0.62 (P<0.001). Seven spatial-temporal clusters were detected from 2007 to 2011 in the landscape of the whole Shandong, with EV71 or CoxA16 as the dominant pathogen for most hotspots areas. CONCLUSIONS: The spatial-temporal clusters of HFMD wandered around the whole Shandong Province during 2007 to 2011, with EV71 or CoxA16 as the dominant pathogen. These findings suggested that a real-time spatial-temporal surveillance system should be established for identifying high incidence region and conducting prevention to HFMD timely.

Importance of two consecutive methionines at the N-terminus of a cellulose synthase (PtdCesA8A) for normal wood cellulose synthesis in aspen.

All known orthologs of a secondary wall-associated cellulose synthase (CesA) gene from Arabidopsis, AtCesA8, encode CesA proteins with two consecutive methionines at their N-termini (MM or 2M). Here, we report that these 2Ms in an aspen ortholog of AtCesA8, PtdCesA8A, are important for maintaining normal wood cellulose biosynthesis in aspen trees. Overexpression of an altered PtdCesA8A cDNA encoding a PtdCesA8A protein missing one methionine at the N-terminus (1M) in aspen resulted in substantial decrease in cellulose content and caused negative effects on wood strength, suggesting that both methionines are essential for proper CesA expression and function in developing xylem tissues. Transcripts from a pair of paralogous native PtdCesA8 genes, as well as introduced PtdCesA8A:1M transgenes were significantly reduced in developing xylem tissues of transgenic aspen plants, suggestive of a co-suppression event. Overexpression of a native PtdCesA8A cDNA encoding a CesA protein with 2Ms at the N-terminus did not cause any such phenotypic changes. These results suggest the importance of 2Ms present at the N-terminus of PtdCesA8A protein during cellulose synthesis in aspen.