Objective: To explore the prospective association between multidimensional sleep indicators and the risk of newlyonset dental caries, providing a reference for childrens oral healthrelated sleep intervention. Methods: In October 2021, 1 417 students in grades 1 to 4 (aged 6 to 11) from two elementary schools in Bengbu, Anhui Province, were selected by cluster sampling method. Surveys and followup visits were conducted at baseline (T1), November 2022 (T2), May 2023 (T3), and November 2023 (T4), respectively, including parental questionnaires, oral health and physical examination. Bedtime, sleep duration, sleep midpoint, social jet lag, weekend catchup sleep, and sleep habits were collected and calculated. A multifactorial Cox proportional risk regression model was used to analyze the association between multidimensional sleep indicators and newlyonset caries in schoolaged children after 2 years. Results: The prevalence of dental caries in children was 65.1% at baseline, and the prevalence was 59.0% at the end of the 2year followup. Cox proportional risk regression model showed that for every 1point increase in the childrens bedtime resistance, nocturnal awakenings, parasomnias, and daytime sleepiness scores, the risk of newlyonset caries increased by 12% (HR=1.12, 95%CI=1.08-1.15), 22% (HR=1.22, 95%CI=1.15-1.29), 12% (HR=1.12, 95%CI=1.08-1.17), and 15% (HR=1.15, 95%CI=1.12-1.19), respectively; the risk of newlyonset caries increased by 23% for each 1 h increase in the length of weekend catchup sleep (HR=1.23, 95%CI=1.14 -1.33); compared with children who went to bed before 21:00 on school days, those who went to bed later than 22:00 had a 57% higher risk of newlyonset caries (HR=1.57, 95%CI=1.22-2.03). Compared to children who slept adequately (≥9 h/d), those with insufficient sleep had a 67% higher risk of new caries (HR=1.67, 95%CI=1.43-1.95) (P<0.01). Conclusions These findings suggest a significant association between sleep patterns/sleep disorders and the development of childhood dental caries. Incorporating sleep behavior optimization and sleep quality improvement into comprehensive caries prevention and oral health management protocols may represent a promising intervention strategy to enhance childrens oral health outcomes.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Growth hormone deficiency (GHD) has become a serious healthcare burden, and presents a huge impact on the physical and mental health of patients. Here, we developed an actively separated microneedle patch (PAA/NaHCO₃-Silk MN) based on silk protein for sustained release of recombinant human growth hormone (rhGH). Silk protein, as a friendly carrier material for proteins, could be constructed in mild full-water conditions and ensure the activity of rhGH. After manually pressing PAA/NaHCO₃-Silk MN patch to skin for 1 min, active separation is achieved by absorbing the interstitial fluid (ISF) to trigger HCO₃ ^‒ in the active backing layer to produce carbon dioxide gas (CO₂). In rats, the MN patch could maintain the sustained release of rhGH for more than 7 days, and produce similar effects as daily subcutaneous (S.C.) injections of rhGH in promoting height and weight with well tolerated. Moreover, the PAA/NaHCO₃-Silk MN patch with the potential of painless self-administration, does not require cold chain transportation and storage possess great economic benefits. Overall, the PAA/NaHCO₃-Silk MN patch can significantly improve patient compliance and increase the availability of drugs, meet current unmet clinical needs, improve clinical treatment effects of GHD patients.

China is one of the countries with the highest population aging rate in the world, and the oral health of the elderly population has become increasing significant for the realization of healthy aging. Tooth loss is considered as the marker of oral disease burden. In recent years, a growing number of findings have suggested an association between tooth loss and cognitive decline. Also, given that cognitive function plays a crucial role in oral health, future researches should elucidate their bidirectional causal relationship, based on prospective cohort design that regularly monitors tooth loss and cognitive function. This article reviews the current research threads in terms of epidemiological evidences of the association, brain structure and function, and possible bidirectional associations and mechanisms, providing a theoretical basis for promoting healthy aging.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To develop and validate the accuracy of an independent dose calculation toolkit for the horizontal beamline of Shanghai Advanced Proton Therapy (SAPT) facility based on an open-source dose calculation engine.Methods:Machine data, such as absolute integral depth doses (IDDs) and lateral profiles in air were measured and lateral profiles in water were derived by Monte-Carlo simulations. The dose computation models for SAPT horizontal beamline pencil beams in water were achieved by combining machine data and dose calculation engine. The verification of the dose reconstruction toolkit included absolute dose verification and relative dose verification. The absolute dose verification is performed to mainly compare the reconstructed value and the measured value at different depths along the center axis of the beam direction of a cube plan. The relative dose verification is conducted to mainly compare the lateral profile or two-dimensional dose distribution between the measured value and the reconstructed value. Meanwhile, the precision of double-gaussian and single-gaussian lateral beam models was compared.Results:The deviations of the absolute dose between the calculated and measured values were basically within 2%. The deviations of 20%-80% penumbra between the measured and the calculated values were within 1 mm, and deviations of the full width at half height were within 2 mm. For 3 cube plans and 2 clinical cases, the two-dimensional gamma pass rates (3 mm/3%) between the measured and calculated dose distributions at the corresponding depths were greater than 95%. The double-gaussian lateral beam model was more accurate in the high dose gradient region and deeper depth.Conclusion:The precision of independent dose calculation toolkit is acceptable for clinical requirements, which can be employed to investigate other dose-related issues.

Objective:To analyze the influence of magnetic field on the proton beam delivery and dose distribution, and develop a correction method for the Bragg peak (BP) shift under the vertical magnetic field, providing reference for the dose calculation and beam delivery of MRI-guided proton therapy.Methods:Monte Carlo (MC) simulation was used to study the dose distribution of the proton beam in the water phantom under the magnetic field. The BP location was corrected by the method of" angle correction+ energy correction" , and the correction parameters were calculated by the analytical formula based on the simulation data.Results:The magnetic field caused the dose distortion and shift of BP location. The shift degree was increased with the increase of field strength and initial energy. Compared with MC simulation, the result of calculating proton deflection in the air by the analytical method yielded a deviation within 0.2%. Based on the simulation data and calculation formulas, the correction parameters under different conditions could be calculated within 1 s by using the MATLAB programming. The calculation results showed that the air layer with magnetic field, isocenter depth, irradiation direction exerted different influence on the correction parameters. After correction, the BP location was basically consistent with the expected (offset ≤0.2 mm).Conclusions:The BP shift under the vertical magnetic field can be effectively corrected by " the angle correction+ energy correction" method. The correction parameters under different conditions can be quickly and accurately calculated by the calculation formulas based on simulation data.

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.

Objective:To investigate the effect of short single reverse-α fixation of nasobiliary tube after endoscopic nasobiliary drainage.Methods:From January 2019 to October 2019, the patients who performed with endoscopic nasolbiliary drainage in Tongji University Affiliated Shanghai East Hospital were randomly divided into experimental group (short single reverse-α fixation, 155 cases) and control group (routine reverse-α fixation, 137 cases). The incidences of the fixation time, prolapse rate, nursing time, scores of nasal comfort and bile flow rate of nasobiliary duct were evaluated between the two groups.Results:The average time of nasobiliary duct fixation was (18.31±1.67) s, the prolapse rate was 5.2% (8/155) and the time of nursing was (35.03±2.68) s, which were lower than those of the control group (46.50±5.50) s, 13.9% (19/137) and (72.07±7.63) s. The difference was statistically significant ( t or χ 2 values were 60.795, 6.570, 56.629, P<0.01 or 0.05). The comfort score of the experimental group was (4.61±1.06) points, the bile flow rate was (241.52±53.95) ml/days, which were higher than (5.76±0.76) points and (174.09±47.55) ml/days of the control group, the difference was statistically significant ( t values were 10.448, 11.265, P<0.01). Conclusions:Shortening the length of nasobiliary duct combined with single reaction "α" method has the advantages of simper operation and nursing, low prolapse rate, high comfort and good drainage effect. It is worthy of clinical application.

Objective:To explore the status of HBV infection, immune response to hepatitis B vaccine and its influencing factors of one-year old children born to HBV infected mothers in real world.Methods:In this cross-sectional study, eligible mothers infected with chronic HBV and children who completed standard vaccination against hepatitis B vaccine and hepatitis B immunoglobulin injection were selected. Clinical biochemical, virological measurements, data of antiviral therapy and complications during pregnancy and childbirth were collected by HIS(Hospital Information System)system and LIS (Laboratoty Information Management System) system. At one year of age, the children were tested for HBsAg, HBsAb and HBV DNA in venous blood specimens.Results:A total of 1 302 eligible mothers and children were collected, including 600 in high viral load group (mothers’ HBV DNA≥2×10 5 IU/ml) and 702 in low viral load group (mothers’ HBV DNA<2×10 5 IU/ml). In high viral load group, 587 patients received antiviral drugs in the middle or late trimester (Treated group) and 13 patients did not receive antiviral drugs (Untreated group). No chronic HBV infection occurred in children of low viral load group, and in 5 cases (0.83%) the infection occurred in high viral load group. In the five HBV infected children, 3 cases (0.51%) were in the treated group, and 2 cases (15.38%) in untreated group. The failure rate of mother-to-child blocking in low viral load group was significantly lower than that in high viral load group ( χ2=5.87, P=0.015), and it was significantly lower in treated group than that in untreated group ( χ2=29.195, P=0.001). The percentages of HBsAb level <10 mIU/ml, 10- <100 mIU/ml and ≥100 mIU/ml in 1 297 children without HBV infection were 1.15%, 15.65% and 83.19%, respectively. Univariate and multivariate logistic regression analysis showed that maternal total bilirubin level and hypothyroidism during pregnancy were correlated with HBsAb level at 1 year of age ( χ2=29.003, P <0.05). Conclusions:Antiviral drugs taken during pregnancy by pregnant women with high HBV viral load can significantly reduce mother-to-child transmission of HBV. Follow-up on the response of children born to HBV-infected mothers to hepatitis B vaccine should be enhanced after birth.