The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

Pulmonary hypertension(PH)is a severe cardiovascular disease characterized primarily by pulmonary vascular remodeling.Patients with PH typically exhibit significant metabolic abnormalities including disruptions in energy metabolism,alterations in lipid and amino acids metabolism.These metabolic disturbances are closely linked to pathophysiological processes such as pulmonary vascular remodeling,endothelial dysfunction and right ventricular hypertrophy.In recent years,there has been rapid progress in the field of metabolomics related to PH.From the early identification of differential metabolic products to the current exploration of potential therapeutic tar-gets,metabolomics has deepened the understanding of the pathogenesis of PH.These researches have accelerated the discovery and screening of potential therapeutic targets,with some findings already translated into clinical prac-tice to support diagnosis,treatment and prognostic evaluation of PH.

Objective: To explore the correlation between different nutritional status and depressive symptoms among adolescents, so as to provide a theoretical basis for targeted improvement of nutritional status and depressive symptoms in adolescents. Methods: A total of 8 102 adolescents aged 12-17 years in Shanghai, Urumqi, Changsha and Kunming were selected by random cluster sampling. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale(CES-D). Height and weight were measured. Kruskal Wallis H test, Chi square test and ordinal Logistic regression were used to analyze the relationship between nutritional status and depressive symptoms in adolescents. Results: The overall detection rate of depressive symptoms in adolescents was 25.6%, with girls (30.1%) higher than that of boys (21.1%) ( χ 2=87.60, P <0.01). There were statistically significant differences in the scores of depressive symptoms among girls with different nutritional status ( Z =8.34, P <0.05). The detectable rate of depressive symptoms increased with BMI among girls( χ 2 trend =6.04, P <0.05). After controlling for confounding factors, ordinal Logistic regression showed that the obese girls had higher risks in depressive symptoms detection compared with normal weight girls ( OR=1.45, 95%CI=1.10-1.91, P <0.05). Conclusion The nutritional status of girls is better than boys, but the prevalence of depressive symptoms is higher than boys. The risk of depressive symptoms in girls increases with BMI.

Abstract In recent years, mental health problems such as anxiety and depression among adolescents in China have attracted attention from all walks of life. Given that adolescence is a transitional and critical period for individual development, mental health affect the developmental opportunities. Therefore, in the review, the effects of environment, psychosocial factors and behavioral patterns on depressive symptoms are analyzed by combining with the characteristics of physical and mental development among adolescents. It is found that early adolescence and even childhood should be the key period for the prevention and intervention of depression. In order to formulate effective interventions and prevention strategies, it is proposed that future research should combine real situation in China with active exploration of protective factors and early predictors of depression.

Implanted brain-computer interface (iBCI) is a system that establishes a direct communication channel between human brain and computer or an external devices by implanted neural electrode. Because of the good functional extensibility, iBCI devices as a platform technology have the potential to bring benefit to people with nervous system disease and progress rapidly from fundamental neuroscience discoveries to translational applications and market access. In this report, the industrialization process of implanted neural regulation medical devices is reviewed, and the translational pathway of iBCI in clinical application is proposed. However, the Food and Drug Administration (FDA) regulations and guidances for iBCI were expounded as a breakthrough medical device. Furthermore, several iBCI products in the process of applying for medical device registration certificate were briefly introduced and compared recently. Due to the complexity of iBCI in clinical application, the translational applications and industrialization of iBCI as a medical device need the closely cooperation between regulatory departments, companies, universities, institutes and hospitals in the future.
Humans ; Brain-Computer Interfaces ; Brain/physiology* ; Electrodes, Implanted

Objective:To study the changes of early (i.e., within post injury day (PID) 14) coagulation function in patients with severe burns.Methods:A retrospective case series study was conducted. From December 2018 to December 2019, 50 severe burn patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University. According to the severity of burns, the patients were divided into severe burn group (17 cases, including 12 males and 5 females) and extremely severe burn group (33 cases, including 26 males and 7 females). The platelet count (PLT), and conventional coagulation indexe and thromboelastogram index levels of patients were collected at admission, post injury hour (PIH) 48 and 72, and on PID 7 and 14. The conventional coagulation indexes included prothrombin time (PT), thrombin time (TT), activated partial prothrombin time (APTT), and fibrinogen (FIB) and D-dimer levels. The thromboelastogram indexes included coagulation angle (i.e., α angle), coagulation composite index (CI), MA value, R value, and K value (reflecting maximum amplitude, coagulation reaction time, and blood agglutination time, respectively). Data were statistically analyzed with independent sample t-test, Wilcoxon rank sum test, and chi-square test. Verification of the mixed effect model was performed on each index data of patients in the two groups, while the repeated measures analysis of variance was performed on PLT. Pearson correlation analysis or Spearman correlation analysis were performed to analyze the correlation between the thromboelastogram index data (except CI) and the PLT and conventional coagulation index data, respectively. Results:At admission, PIH 48 and 72, and on PID 7 and 14, PLT of patients in severe burn group were (203±91), (148±70), (123±63), (203±62), (402±140)×10 9/L, respectively, PLT of patients in extremely severe burn group were (235±116), (145±71), (109±52), (235±106), (455±138)×10 9/L, respectively. In overall comparison, only the difference of the main effect of time factor was statistically significant ( F=92.55, P<0.05). In severe burn group, statistically significant differences were only identified in comparison of patients' PLT between PID 7 and the adjacent two time points (at PIH 72 and on PID 14, with both P values <0.05). The differences in PLT of patients between all the adjacent time points in extremely severe burn group were statistically significant ( P<0.05). In the overall comparison of PT, TT, and FIB level of patients in the two groups at each time point, only the difference of main effect of time factor was statistically significant (with F values of 6.04, 8.45, and 32.90, respectively, all P values <0.05), and APTT and FIB level of patients in extremely severe burn group within PID 14 were higher than those in severe burn group. There were statistically significant differences in MA value, α angle, K value, and CI of patients in the two groups at each time point (with F values of 18.82, 11.38, 9.11, and 9.42, respectively, all P values <0.05). MA value was moderately correlated with PLT ( r=0.69, P<0.05), weakly correlated with TT and FIB level (with r values of -0.29 and 0.30 respectively, P<0.05), and very weakly correlated with D-dimer level ( r=-0.15, P<0.05); α angle was moderately correlated with PLT ( r=0.58, P<0.05), and weakly correlated with FIB level and TT (with r values of 0.26 and -0.29, respectively, P<0.05); R value was weakly correlated with APTT and FIB level (with r values of 0.24 and 0.31, respectively, P<0.05), and very weakly correlated with PT and TT (with r values of 0.16 and 0.14, respectively, P<0.05); K value was moderately correlated with PLT ( r=-0.59, P<0.05), and weakly correlated with FIB and TT (with r values of -0.29 and 0.32, respectively, P<0.05), and very weakly correlated with D-dimer level ( r=-0.15, P<0.05). Conclusions:Severe burn patients are already characterized with coagulation function changes in early stage, including insufficiency of coagulation function, enhanced platelet aggregation ability and enhanced FIB function. There is a certain correlation between conventional coagulation indexes and thromboelastogram indexes, but they cannot replace each other.

Objective: To understand physical activity status and its relation with cardiopulmonary endurance among Chinese children and adolescents, so as to provide reference for cardiopulmonary endurance improvement and intervention of Chinese children and adolescents. Methods: During September to November 2018, a stratified cluster sampling method was used to select 4 269 children and adolescents aged 7-18 years in six major regions of China, 20 m shuttle run test and physical activity were assessed. Results: Average duration for daily lowintensity physical activity among boys was (31.49±30.01) min, for moderate to vigorous physical activity (68.37±46.50) min. Average duration for low intensity physical activity among girls was (34.02±31.58) min, for moderate to vigorous physical activity was (63.02±44.91) min. The number of 20 m shuttle run test for boys reached ( 36.17 ±21.94) times, and the maximal oxygen uptake per minute was (44.51±5.05) mL/kg; the number of 20 m shuttle run test for girls reached (26.59±12.56) times, and the maximal oxygen uptake per minute was (41.99±5.29) mL/kg. There were statistically significant differences in the number of 20 m shuttle run test and maximal oxygen uptake across age groups in boys ( F= 589.37 , 152.79, P <0.01), as well as that in girls ( F=305.21, 1 032.46, P <0.01). The proportion of boys and girls who met moderate to vigorous physical activity standard was 49.24% and 42.92%, respectively. Linear regression analysis showed that there was a significant positive correlation between the duration of moderate to vigorous physical activity and maximal oxygen uptake ( β=0.11, P ＜ 0.01). Conclusion There is a significant correlation between moderate to vigorous physical activity with cardiorespiratory endurance among Chinese children and adolescents. Higher level of moderate to vigorous physical activity is important to help improve cardiopulmonary endurance among children and adolescents.

Objective: To explore age, gender, and regional differences in physical activity among children and adolescents in China, and to provide a scientific reference for enhancing physical activity promotion. Methods: A total of 4 269 children and adolescents aged 7 to 18 years were selected from six administrative regions of China (East China, Northwest China, North China, Central China, Southwest China and South China) using a stratified random cluster sampling method from September to December 2018. A questionnaire was administered to evaluate the physical activity level of Chinese children and adolescents aged 7 to 18. Results: The overall detection rate of MVPA insufficiency in children and adolescents in China was 53.8%, of which the detection rate of MVPA insufficiency was 50.8% among boys and 57.1% among girls. Gender differences were statistically significant ( χ 2= 17.10 , P <0.05). Among the different age groups, the lowest detection rate of MVPA among 10-12 year olds was 43.6%, whereas the highest rate among 16-18 year olds was 63.0%, with significant differences between gender ( χ 2=4.33, 30.79, P <0.05). The P 50 values of total physical activity(TPA), light intensity physical activity(LPA), moderate intensity physical activity(MPA), vigorous intensity physical activity(VPA), moderate to vigorous physical activity(MVPA) were 92.9,24.3,41.4,7.1 and 55.7 min/d , respectively. The P 50 values of physical exercise, housework activities, entertainment activities and transportation activities were 34.3 , 2.1, 2.3 and 30.0 min/d, respectively, and the difference in age groups was statistically significant( H =95.03, 74.99, 300.26 , 64.16, P <0.05). There was a statistically significant difference in the detection rate of insufficient MVPA among children and adolescents in different regions ( χ 2=83.91, P <0.05). The lowest rate was 44.0% in North China, and the highest was 65.9% in East China. Conclusion The detection rate of MVPA insufficiency among Chinese children and adolescents firstly decreased and then increased with age. Boys participated in higher levels of physical activity than girls.

Sepsis is defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection.It is considered a major cause of death and health loss worldwide.Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021, released in October 2021, included 93 total statements, which addressed screening and initial resuscitation, infection, hemodynamics, ventilation, additional therapies, and goals of care and long-term outcomes.This review interpreted the content ofthe guidelines and also analyzed the underlying issues.The guidelines provide a more accurate framework and guidance for the diagnosis and treatment of sepsis, and may also provide an opportunity to urge researchers in the field of sepsis worldwide to implement further individualized research.

Objective: To analyze the correlation between physical activity and physical fitness index of children and adolescents in China, so as to provide reference for physical activity and physical fitness promtion of children and adolescents. Methods: In September 12,2018, 4 269 students were selected by cluster sampling in east, northwest, north, central, southwest and South China, the test of standing long jump, grip strength, 50 m running, improved seat forward bend, 30 s sit ups, 20 s cross repeatedly, 20 m round trip running was completed. Results: In comparing the physical fitness index of children and adolescents with different levels of physical activity, the PFI values of the middle and high intensity physical activity (MVPA) groups of boys aged 10-12 and 16-18 years old were (0.46±3.58) (0.75±3.0), the value of PFI of the MVPA group were (-0.69±3.64) (-0.61±2.87), the difference was statistically significant ( t =0.04, 0.57, P >0.05). There was no significant difference in the values of PFI between the four age groups of the girls ( P <0.05). In comparison of physical activity status of children and adolescents in different physical ability grades, the time of MPA, VPA and physical exercise in healthy physical ability group was higher than that in unhealthy physical ability group ( Z =-2.04, -4.93, -7.09, P <0.05). Linear regression analysis showed that there was a positive correlation between daily MVPA, physical exercise and physical fitness index ( P <0.05). Conclusion Moderate and high intensity physical activity, that is, physical exercise, is positively correlated with physical fitness index. Therefore, it is particularly important for children and adolescents to engage in sufficient moderate and vigorous intensity physical activities.