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.

Objective: To examine the association between noise exposure in daily life and depressive symptoms, so as to provide the evidence for reducing the impact of noise in daily life on depressive symptoms. Methods: Based on the 2015 to 2020 database of National Health and Nutrition Examination Survey, demographic information and noise exposure in daily life were collected from people aged 18 years and over. Depressive symptoms were evaluated using the Patient Health Questionnaire-9. The relationship between noise exposure in daily life and depressive symptoms were analyzed using a multivariable logistic regression model. Results: A total of 3 216 individuals were enrolled, including 1 707 males (53.08%) and 1 509 females (46.92%). The mean age was (49.30±18.07) years. There were 491 individuals with noise exposure in daily life, accounting for 15.27%. There were 265 cases with depressive symptoms, accounting for 8.24%. There were 66 individuals exposed to noise in daily life in the group with depression symptoms (24.91%), and 425 individuals exposed to noise in daily life in the normal group (14.40%), with statistically significant difference in noise exposure in daily life between the two groups (P<0.05). Multivariable logistic regression analysis showed that after adjusting for gender, age, educational level, marital status, household income poverty ratio, sleep duration, alcohol consumption and hearing, individuals who had noise exposure in daily life (OR=1.743, 95%CI: 1.258-2.413) were more likely to have high risk of depressive symptoms. Conclusion Noise exposure in daily life was associated with an increased risk of depressive symptoms.

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.

Objective: To observe the impact of Tiao Shen Tong Du (regulating the mind and unblocking the Governor Vessel) Tuina (Chinese therapeutic massage) on neuropsychological development of premature infants, discover effective early-stage intervention techniques, and improve the prognosis of premature infants.Methods: A total of 115 eligible premature infants were recruited and divided into a control group of 59 cases and an observation group of 56 cases based on different interventions. The control group received three-month physical therapy (PT) and conventional early-stage intervention, and the observation group received additional Tiao Shen Tong Du Tuina treatment. Before and after treatment and at the one-year follow-up, the Gesell developmental schedule was adopted to evaluate neuropsychological development. Results: After treatment, the gross motor development quotient (DQ) was higher in the observation group than in the control group, and the difference was statistically significant (P<0.05); there were no significant differences in the other four domains between the two groups (P>0.05). At the one-year follow-up, the observation group showed more notable improvements in all five domains' DQs than the control group, and the between-group differences were statistically significant (P<0.05 or P<0.01).Conclusion: Based on conventional intervention, Tiao Shen Tong Du Tuina can significantly improve the gross motor function of premature infants in the short term, alongside valid long-term efficacy for gross motor function, fine motor function, adaptive behaviors, language, and personal-social behaviors.

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 explore the expression of tiny RNA-25 (microRNA-25, miR-25) in the plasma、tissues of triple-negative breast cancer(TNBC) patients and cell lines, to investigate the potential molecular mechanisms of miR-25 on migration and invasion of TNBC. Methods Real-time fluorescent quantitative PCR was used to detect the expression of miR-25 in the plasma of TNBC patients. Linked omics web platform was used to analyse miR-25 level in samples of TNBC and non-TNBC. Real-time fluorescent quantitative PCR was also used to detect the miR-25 level in TNBC cell lines. The wound healing and transwell assay was applied to assess the effects on migration and invasion of TNBC cell lines which transfected with miR-25 inhibitor or the negative control. The luciferase reporter assay was used to validate the relationship between miR-25 and the sphingosine-1-phosphate phosphatase 1 (SGPP1) in HEK293T cell. The wound healing and transwell assay was used to detect the migration and invasion ability of TNBC cell lines when cotransfected with pCMV6-SGPP1 and miR-25. Furthermore, Western blot was performed to detect the SGPP1 level in TNBC cell lines. Results The expression of miR-25 was significantly elevated in the plasma of 86 TNBC patients compared with the healthy controls (P value was 0.031). LinkedOmics web platform analysis showed that miR-25 expression was significantly higher in TNBC samples than in non-TNBC samples with Luminal A or Luminal B (P value was<0.001 and 0.006). The level of miR-25 was also elevated in TNBC cell lines HS578T, HCC1806, MDA-MB-231 and BT549(P value was 0.006, 0.01, 0.029 and 0.046). The MDA-MB-231 and HS578T cells which transfected with miR-25 inhibitor exhibited a significant slower wound healing rate than control (P value was 0.035 and 0.001). At the same time, when transfected with miR-25 inhibitor, MDA-MB-231 and HS578T both exhibited a decreased invasion ability compared with the control group(P value was 0.002 and 0.001). LinkedOmics web platform analysis showed that sphingosine-1-phosphate phosphatase 1 (SGPP1) gene level was negatively correlated with miR-25 in the tissues of TNBC patients (P value was 0.037). The luciferase reporter assay validated that SGPP1 was a directed target of miR-25. The western blot assay indicated that the SGPP1 level was increased in MDA-MB-231 and HS578T after transfection with miR-25 inhibitor. Over-expression of SGPP1 could abrogate the positive effects of miR-25 on migration and invasion when pCMV6-SGPP1 was cotransfected with miR-25 (P value was all 0.002). Conclusions MiR-25 was elevated in both plasma and tissues of TNBC patients and also increased in TNBC cell lines. Transfection of MDA-MB-231 and HS578T cells with miR-25 inhibitor resulted in reduced migration and invasion. Moreover, SGPP1 was identified as a novel target of miR-25. The ability of miR-25 to promote TNBC cell migration and invasion is attributable to its effect on SGPP1 suppression.

Acute myeloid leukemia (AML) is the most common type of leukemia at present. Although clinical treatment has a certain effect on this disease, most patients still die of relapse or its treatment related diseases. Nowadays, chimeric antigen receptor (CAR) T cells therapy technology has developed rapidly, and has become a hot topic in tumor immunotherapy. The high expression of CD123 in AML cells, low expression or non expression in normal hematopoietic stem cells and tissues, make more and more researchers focus on the technology of CD123+cell immunotherapy. Some studies have confirmed that CD123 CAR-T cells have a certain effect on AML, which provides a new way for clinical treatment of relapsed or refractory AML. This review summarizes the structure, production and delivery methods of CD123 CAR-T cells, and the current research status and shortcomings of CD123 CAR-T cells.

The pathogenesis of narcolepsy type 1 is characterized by massive loss of hypocretin neurons in the lateral hypothalamus.Due to the extensive interaction between the hypocretin signalling pathway and the autonomic nerve centre of brain stem and spinal cord,narcolepsy type 1 patients often showed autonomic nervous dysfunctions,such as circadian rhythms/sleep abnormalities,energy metabolism and body temperature regulation disorder,pupil adjustment disorder,sexual dysfunction and autonomic fluctuations during cataplexy.We reviewed the autonomic dysfunction of the narcolepsy type 1 patients in general and during cataplexy,in order to strengthen the attention to autonomic nervous dysfunction in narcolepsy type 1.

Objective: To describe the status of cardiovascular health (CVH) of children and adolescents aged 6-16 years in Beijing during 2017-2018. Methods: The school-based Cardiovascular and Bone Health Promotion Program(SCVBH) was conducted from November 2017 to January 2018. 15 391 children and adolescents aged 6-16 years were selected from grade 1 to 4 in 8 primary schools, grade 1 in 21 middle schools and senior grade 1 in one twelve-year education school in Dongcheng, Fangshan, Miyun and Haidian Districts of Beijing by using a cluster sampling method. Seven cardiovascular health indicators, including smoking, body mass index, dietary intake, physical activity, blood pressure, blood glucose, and total cholesterol, were categorized as poor, intermediate, and ideal according to American Heart Association (AHA) criteria. The status of CVH was evaluated according to the criteria of the ideal CVH related behaviors and factors defined by AHA. Results: The proportion of children and adolescents with an ideal smoking, dietary intake and physical activity indicators reached 99.2%(4 982/15 108), 19.7%(2 921/14 805), 17.8% (2 499/14 056), respectively. The proportion of children and adolescents with 7 and 4-5 ideal cardiovascular health indicators was 1.7%(209/12 560) and 65.1%(8 176/12 560). The proportion of children and adolescents with 4-7 ideal cardiovascular health indicators, 2-4 ideal health behavior indicators and 2-3 ideal health factors was significantly higher in urban than that in rural all P values<0.001. The proportion of females with 4-7 ideal cardiovascular health indicators, 2-4 ideal health behavior indicators and 2-3 ideal health factors was significantly higher than that in males (all P values<0.001). Conclusion The prevalence of ideal cardiovascular health of children and adolescents aged 6-16 years in Beijing during 2017-2018 was very low, particularly for healthy dietary intake and physical activity. Effective public health interventions should be implemented to improve the status of cardiovascular health of them.

Objective To explore the relationship between the respiratory disturbance index (RDI) detected by cardiopulmonary coupling (CPC) and all parameters of polysomnography (PSG), and to analyze the correlation of the two different analytical techniques for the interpretation of sleep breathing events.Methods In this case-control study, the patients′ CPC and PSG were simultaneously recorded at the Sleep Clinic at Changzheng Hospital from Janunary 2016 to December 2016.Effective recordings were obtained from 292 patients (male/female: 173/119).According to PSG, these patients were divided into two groups: obstructive sleep apnea hyponea syndrome (OSAHS) group (n=173, aged (50.1±13.3) years) and non-OSAHS group (n=119, aged (50.5±11.7) years).All the PSG parameters and the RDI detected by CPC were compared between the two groups.Pearson correlation was used to analyze the relationship between the CPC-RDI and polysomnography parameters, and Bland-Altman chart was used to test the correlation of the two methods.The receiver operator characteristic curve was used to research the value of CPC-RDI in diagnosis of OSAHS.Results The OSAHS group showed higher levels of total sleep time (TST, (445.94±82.64) min), apnea times ((108.16±35.70)/h), hypopnea rate ((55.62±17.44)/h), apnea hyponea index (AHI, (22.78±20.73)/h), Epworth Sleeping Scale (ESS) scores ((11.21±5.30) scores), CPC-RDI ((32.98±22.19)/h) compared with the non-OSAHS group ((417.21±96.10) min,t=2.730;(7.89±5.41)/h,t=30.384;(11.05±2.23)/h, t=27.709;(5.51±3.11)/h,t=9.014;(7.61±2.29)scores,t=6.973;(11.16±8.63)/h,t=10.205, all P<0.01), and a significant decrease in N1 latency ((14.79±9.29) min vs (18.18±8.98)min, t=-3.106), N3% ((6.53±4.95)% vs(8.83±7.29)%,t=-3.212) and the lowest oxygen saturation (SaO2;(77.91±12.21)% vs(92.72±5.17)%, t=-12.479, all P<0.05 respectively).Pearson correlation analysis indicated that RDI was positively correlated with TST, N2 sleeping time, N3 sleeping time, AHI, microarousals index, leg movements index, and ESS scores (P<0.01 respectively).Remarkably, the correlation between CPC-RDI and PSG-AHI was excellent (r=0.801, P<0.01), and CPC-RDI was negatively correlated with lowest SaO2 (r=-0.765, P<0.01).Bland-Altman showed that the points in the limits of agreement accounted for more than 95% of all points.If CPC-RDI is higher than 18.95, the subjects were more likely with OSAHS.The sensitivity was 62.9% and the specificity was 88.7%.In addition, the enhanced low-frequency coupling parameters in the CPC analysis technique can clearly analyze the central respiratory rhythm disturbance.Conclusions CPC technology is an effective assessment technology to diagnose sleep-disordered breathing, and correlates well with AHI detected by traditional PSG.It shows the advantage of screening for central sleep apnea.