Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

In past two decades, understanding of the role of the orexin system in regulating sleep and wakefulness has increased rapidly. Lemborexant, as a dual orexin receptor antagonist, has been approved in some countries for the treatment of insomnia disorders. Existing studies have shown that its safety and tolerability are significantly superior to traditional hypnotic drugs, and it will be new option for treating insomnia disorders. This article reviews the pharmacology, clinical efficacy and safety of lemborexant.

Objective:To explore the influences of times of venous thromboembolism (VTE) drug prophylaxis in formation of deep vein thrombosis (DVT) in patients with severe craniocerebral injury after surgical treatment.Methods:Ninety patients with severe craniocerebral injury, admitted to our hospital from February 2021 to December 2021, were chosen in our study; they were divided into early group ( n=47, less than 48 h from the time of admission) and late group ( n=43, more than 48 h from the time of admission) according to the times of initiation for VTE drug prophylaxis (low molecular weight heparin calcium injection [LMWH] 100 IU/Kg was injected subcutaneously once a d). One week after injection, the DVT formation in the lower limbs, intracranial rebleeding, gastrointestinal bleeding and death were compared in the two groups. Results:The times of initiation for drug prophylaxis in the early group and late group were (28.91±4.50) h and (71.56±8.89) h. The DVT formation in the early group was significantly lower than that in the late group (12.8% vs. 34.9%, P<0.05). There was no difference in the incidence of intracranial rebleeding, mortality or gastrointestinal bleeding between the two groups ( P>0.05). Conclusion:Early initiation of VTE drug prophylaxis can significantly reduce the incidence of DVT in patients with severe craniocerebral injury after surgical treatment, enjoying high safety.

Objective:To investigate the relationships between hyperuricemia and the incidence risk for cardiometabolic abnormity in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling at baseline survey. Follow-up investigation was conducted in 2019. Logistic regression model was used to analyze the relationships of uric acid quartiles and change in uric acid levels with incidence risks for cardiometabolic abnormity (hypertension, hyperglycemia and dyslipidemia).Results:A total of 8 807 children (4 376 boys, 4 431 girls) were included in the analysis, the average age of the children was (11.1±3.3) years at baseline survey. The adjusted odds ratios ( ORs) and 95% confidence intervals ( CIs) of incidence risk for hypertension in the third and fourth quartiles of the UA were 1.39 (1.11-1.75) and 1.56 (1.19-1.81), respectively. The ORs and 95% CIs of risk for high LDL-C in the second, third and fourth quartiles were 1.88 (1.16-3.05),1.98 (1.23-3.17) and 2.25 (1.42-3.57). The uric acid level increased by one standard deviation, the risk increased by 17% for hypertension and 27% for high LDL-C. The uric acid level increased by 10 μmol/L, the risk increased by 2.1% for hypertension and 2.9% for high LDL-C. The gender-stratified analysis showed that the similar results. The ORs and 95% CIs were 1.32 (1.09-1.60) and 1.50 (1.05-2.16) for hypertension, 1.90 (1.38-2.60) and 2.96 (1.58-5.52) for high TC, 1.78 (1.26-2.51) and 2.84 (1.60-5.03) for high LDL-C in the groups of newly diagnosed hyperuricemia and persistent hyperuricemia. Conclusions:Higher uric acid level was associated with increased incidence risks for hypertension, abnormal TC and LDL-C. Maintaining optimal uric acid level by children might contribute to the early prevention of cardiovascular diseases.

Objective:To analyze the influence of obesity status on the development of cardiometabolic disorders in school-age children.Methods:Information about children's body weight, body height and cardiovascular risk factors were collected in baseline survey in 2017 and follow-up survey in 2019. The school-age children were divided into four groups based on their baseline and follow-up obesity status, i.e. sustained non-obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Analysis of covariance was used to compare the difference of change in levels of cardiometabolic factors among the four groups. The multivariate logistic regression model was used to analyze the relationship between obesity status and the incidence risk of cardiometabolic disorders.Results:The present study included 11 379 school-age children (boys accounting for 49.6%). During the 2 years, the incidence of obesity was 3.2% (95% CI: 2.9%-3.5%) with the restoration ratio of obesity of 4.4% (95% CI: 4.0%-4.8%). Compared with the sustained non-obesity group, increases in SBP, DBP, TG, LDL-C and non-HDL-C were much higher in newly classified obesity group and persistent obesity group, but lower in restored obesity groups except for DBP (all P<0.05). In addition, the incidence risk of hypertension, high glucose, dyslipidemia and cardiometabolic disorders (≥2 risks) were much higher in newly classified and persistent obese children than in sustained non-obese children. No difference was found in incidence risks of most cardiovascular disorders between restored obese children and sustained non-obese children, except for hypertension and cardiometabolic risks. Conclusion:Both newly classified obesity and persistent obesity increased the incidence risks for multi cardiovascular disorders, while these risks could be reduced when non-obese status restore.

Objective:To investigate the incidence and risk factors of pediatric fracture in school-age children and adolescents in Beijing.Methods:A total of 12 056 students with complete fracture data of 2017 baseline survey and 2019 follow-up survey of School-based Cardiovascular and Bone Health (SCVBH) Promotion Program in Beijing were selected as study subjects. Logistic regression model was used to analyze associations of fracture incidence with age, BMI, fracture history and lifestyle.Results:The 2-year accumulative incidence rate of pediatric fracture was 3.1% (95% CI: 2.8%-3.4%) in school-age children and adolescents in Beijing, which was much higher in boys (4.1%) than in girls (2.1%) and increased with age in boys but decreased with age in girls. Fractures mainly occurred at upper-limb (69.0%), no gender and age specific significant in fracture sites were observed. Fracture history was the risk factor for fracture incidence in both boys and girls (boys: RR=1.81, 95% CI: 1.18-2.64; girls: RR=3.11, 95% CI: 1.74-5.13). In addition, higher duration and frequency of moderate to vigorous physical activities (≥120 min/day) and frequent consumption of sugar sweetened beverage (≥1 time/week) were also found to increase fracture risk in boys. Conclusion:The incidence of pediatric fracture was associated with gender, age, fracture history and lifestyle habits in school-age children and adolescents in Beijing. Targeted strategies are needed to prevent childhood fracture.

Objective:To investigate the association between vitamin D nutritional status and the body muscle mass in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling in baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey and the detection of serum 25-hydroxyvitamin D [25(OH)D] level were conducted. The bioelectrical impedance analysis (BIA) apparatus was used to measure body muscle mass, and muscle mass index (MMI) was calculated. Multivariable linear models were used to analyze the association of vitamin D nutritional status with the baseline and follow-up MMI measures.Results:A total of 10 890 children aged (11.5±3.3) years(boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, with an adequacy ratio of 11.1%. After multivariate linear regression adjustment for age, sex, body fat mass, smoking status, alcohol use status, dairy supplement, calcium supplement, physical activity, and pubertal development, no statistically significant association between vitamin D nutritional status and baseline MMI level was observed ( P>0.05). For the follow-up MMI, the Z-score increased by 0.008 ( P=0.058) for per 10 nmol/L increase in 25(OH)D, which were 0.002 ( P=0.815) and 0.037 ( P=0.031) higher in children with insufficient and adequate vitamin D than those with vitamin D deficiency, respectively ( P for trend =0.089). Subgroup analysis showed that in the normal BMI group, for per 10 nmol/L increase in 25 (OH) D, the MMI at baseline survey and MMI Z-score at follow-up of children with adequate vitamin D and increased by 0.019 and 0.014, respectively (both P<0.05). Conclusions:Vitamin D nutritional status was related to muscle mass in children, and children with adequate vitamin D tended to obtain higher MMI. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote body health.

Objective:To investigate the relationships between vitamin D nutritional status and the calcaneal bone mineral density (BMD) in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing selected through stratified cluster sampling were included in the baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey, detection of serum 25-hydroxyvitamin D [25(OH)D] level and ultrasound measurement of calcaneal BMD were conducted. Multivariable linear and logistic regression models were used to analyze the relationships between baseline vitamin D nutritional status and the follow-up calcaneal BMD.Results:A total of 10 914 children aged (11.5±3.3) years (boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, and the deficiency rate was 36.1%. After the adjustment for age, gender, body mass index, smoking status, alcohol use status, dairy products intake, vitamin D supplement, calcium supplement, physical activity, pubertal development, and baseline calcaneal BMD Z-score, for per 10 nmol/L increase in 25(OH)D, the follow-up calcaneal BMD Z-score increased by 0.01( P=0.041), and the OR(95% CI) of decreased calcaneal BMD Z-score after 2 years was 0.96 (0.93-1.00)( P=0.030). Compared with vitamin D adequacy, the follow-up calcaneal BMD Z-score of children with vitamin D insufficiency and deficiency decreased by 0.03( P=0.307) and 0.06 ( P=0.046), and the risk of decreased calcaneal BMD Z-score after 2 years increased by 15%( P=0.037) and 21%( P=0.006), respectively ( P for trend<0.05). Conclusions:Vitamin D nutritional status was closely related to calcaneal BMD, and children with adequate vitamin D nutritional status tended to obtain higher BMD. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote bone health.

Objective:To investigate the association of vitamin D with distribution of body fat in children and adolescents.Methods:Data were obtained from the baseline survey of School-based Cardiovascular and Bone Health Promotion Program in 2017. Multiple linear regression and multinomial logistic regression models were applied to analyze the relationships of body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), appendicular fat mass index (AFMI), and visceral fat area(VFA) with vitamin D level and status in children and adolescents.Results:A total of 11 960 children and adolescents were included in the analysis (boys accounting for 49.7%). The average age and serum vitamin D level of study population were (11.0±3.3) years and (35.0±11.9) nmol/L, respectively. The deficiency rate of vitamin D was 37.2%. Gender-specific associations of BMI, FMI, TFMI, and AFMI with vitamin D level were found ( P for interaction <0.05): they were inversely associated with vitamin D level in boys (BMI: β=-0.56; FMI: β =-0.59; TFMI: β=-0.60; AFMI: β=-0.59; all P<0.05), but not in girls ( P>0.05). VFA was positively associated with vitamin D deficiency and insufficiency in both boys and girls, and the risks of vitamin D deficiency and insufficiency all increased by 17%(95% CI: 9%-25%) for per increment of standard deviation in VFA. Conclusions:The higher level of visceral fat was associated with the lower vitamin D levels in children. Abdominal obese children and boys with excessive body fat are the key population in the prevention and control of vitamin D deficiency.