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.

The classification of traditional Chinese medicine （TCM） syndromes is one of the core technical elements in the industry standard of Specification of Diagnosis and Therapeutic Effect Evaluation of Diseases and Syndromes in TCM. In the past，when clinical standards for TCM were formulated，the determination of TCM syndrome classification relied heavily on textbooks and expert experience，lacking systematic research. This approach thus failed to reflect the advancement and scientificity of the standards，thereby affecting their implementation and application. This article reviewed the presentation forms and technical methods of TCM syndrome classification，including the two-tier syndrome classification model with primary and secondary symptoms，as well as the application of modern literature research，ancient literature research，Delphi method，in-depth expert interviews，consensus conferences，and real-world research. When syndrome classification standards are developed，it is necessary to build upon modern literature research，adopt a mixed approach combining qualitative research and quantitative analysis results，and reach expert consensus through consensus conferences. Through systematic research，the scientificity，applicability，and coordination of TCM syndrome classification standards can be enhanced，providing guidance for the standardization of TCM.

Background: Carbohydrate antigen 72-4 (CA72-4) is generally recognized as a tumor marker of digestive system. However, elevated serum CA72-4 level is also evident in many benign diseases and healthy subjects, and its sensitivity in diagnosing malignant tumor is quite poor. Aims: To reassess the value of CA72-4 in tumor screening and diagnosis. Methods: Three cohorts were established in this study. Inpatients who underwent a serum CA72-4 measurement and had a definite final diagnosis were included into Cohort 1 (retrospective study). Inpatients with elevated serum CA72-4 level who had not been diagnosed as malignant tumor before admission were included into Cohort 2 (retrospective study). Individuals who underwent a serum CA72-4 measurement and willing to take a follow-up for at least 2 years were included into Cohort 3 (prospective study). Malignancies had been preliminarily excluded in all individuals in Cohort 3 before enrollment. Results: Among the 2 173 patients recruited in Cohort 1, the prevalence of positive serum CA72-4 was significantly higher in patients with malignancies than those without (16.4% vs. 7.4%, P<0.05). The sensitivity and specificity of CA72-4 for diagnosis of malignant tumor were 36.5% and 76.2%, respectively, at the cut-off value (2.955 U/mL) identified by ROC curve analysis. Among the 1 807 patients recruited in Cohort 2, most of the participants (76.5%) did not have malignancies. Serum CA72-4 level was associated with the histological classification, tumor differentiation and TNM staging of malignancies (P<0.05). Among the 376 individuals who underwent a follow-up for no less than 2 years in Cohort 3, elevated serum CA72-4 level did not increase the risk of malignant tumor (OR=1.268, 95% CI: 0.283-5.687). Conclusions: CA72-4 is not a sensitive marker for tumor screening, its value as an item in physical examination should be re-evaluated. In patients who had positive serum CA72-4 and malignant tumor was ruled out in initial examination, the necessity of long-term follow-up of serum CA72-4 needs to be discussed.

OBJECTIVE:To evaluate clinical efficacy of Angong niuhuang pill combined with chemical drug in the treatment of severe craniocerebral injury and its effect on the concentration of Mg2+ in peripheral blood,and to provide evidence-based reference in clinic.METHODS:Retrieved from Chinese Journal Full-text Database,China Science and Technology Journal Database,China Bxdxiology Medicine disc,Wanfang Database,Chinese Clinical Trial Registry,PubMed,Excerpta Media Database,The Cochrane Library,Web of Science,Clinical Trials,and related literatures of intemet searched by Google Scholar,randomized controlled trials (RCT) about Angong niuhuang pill combined with chemical drug (trial group) vs.chemical drug (control group) in the treatment of severe craniocerebral injury and its effects on the concentration of Mg2+ in peripheral blood were collected.After literature screening,data extraction,quality evaluation with modified Jadad scale,meta-analysis of Glasgow Coma Scale (GCS) scores and Mg2+ concentration in peripheral blood were conducted by using Rev Man 5.3 statistical software after 7 d of treatment.RESULTS:A total of 6 RCTs were included,involving 773 patients.Results of meta-analysis showed that GCS [MD=2.87,95％CI (1.64,4.10),P＜0.01] and Mg2+ concentration in peripheral blood [MD=0.11,95％CI(0.06,0.16),P＜0.01] of trial group were significantly higher than those of control group,with statistical significance.CONCLUSIONS:Therapeutic efficacy of Angong niuhuang pill combined with chemical drug is better than that of chemical drug alone in the treatment of severe craniocerebral injury,can improve clinical symptom and prognosis.

In the process of MPH graduates education in medical universities , there are three problems such as lack of initiative subjective of postgraduate, uneven level of tutors and monitoring defi-ciency of education. The main reasons are the low quality of MPH graduates, lack of quality consciousness for graduates education and graduates’ value tending to be utilitarian. Facing the problems, we suggest establishing guarantee mechanism for MPH graduate education quality, strengthening the tutors’ construc-tion and framing an eliminating system.

OBJECTIVETo evaluate the impacts of air temperature on years of life lost (YLL) among the residents in Guangzhou and Zhuhai, Guangdong province.

METHODSDaily mortality and meteorology data in Guangzhou and Zhuhai were collected, and distributed lag non-linear model (DLNM) was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature (0-1 days) and extreme low temperature (0-13 days) situation in Guangzhou and Zhuhai were analyzed respectively.

RESULTSThe average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day, while the cold effect reached the peak at 5(th) days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged ≥ 65 years than in people aged < 65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai.

CONCLUSIONThe effects of high and low temperatures on YLL were obvious, and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations.

Aged ; Air ; Cardiovascular Diseases ; epidemiology ; China ; epidemiology ; Extreme Cold ; adverse effects ; Extreme Heat ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Mortality, Premature ; Nonlinear Dynamics ; Respiratory Tract Diseases ; epidemiology ; Time Factors

Objective To evaluate the impacts of air temperature on years of life lost(YLL) among the residents in Guangzhou and Zhuhai,Guangdong province. Methods Daily mortality and meteorology data in Guangzhou and Zhuhai were collected,and distributed lag non-linear model (DLNM)was used to evaluate the cumulative and delayed effects of daily air temperature on YLL of total non-accident mortality. The accumulative effect of air temperature on mortality under the extreme high temperature(0-1 days)and extreme low temperature(0-13 days)situation in Guangzhou and Zhuhai were analyzed respectively. Results The average YLL was 1 928.0 in Guangzhou and 202.5 in Zhuhai. The exposure-response functions seemed to be non-linear. The hot effect seemed to be acute and reached the peak at the same day,while the cold effect reached the peak at 5th days and lasted for about two weeks. Low temperature had stronger gross effect than high temperature had. The cold effect among males was greater than that among females in Guangzhou. The hot/cold effect on YLL was greater in people aged ≥65 years than in people aged <65 years and in people suffering from respiratory disease than in people suffering from cardiovascular disease in both Guangzhou and Zhuhai. Conclusion The effects of high and low temperatures on YLL were obvious,and the impact of low temperature was greater. The elderly and people suffering from respiratory disease or cardiovascular disease are the vulnerable populations.

Objective To investigate the effects of supported employment(SE) on the vocational rehabilitation for schizophrenic rehabilitants.Methods 108 schizophrenic rehabilitants with stable conditions were recruited and randomly allocated into the control group and experimental group.Fifty-four cases in the control group received the general outpatient service and follow-up service with drug maintenance therapy and 54 cases in the experimental group received SE with drug maintenance therapy.At the baseline and the end of the sixth month,all of the 108 cases were assessed by the Positive and Negative Syndrome Scale (PANSS) and Work-related Social Skills Scale (WSSS) respectively.The competitive employment rate and average working days of the two groups were evaluated at the end of the sixth month.Results There was no significant difference in the total score of WSSS,and the total score of PANSS and its sub-scores on the Positive Scale,Negative Scale and General Psychopathological Scale betweeu the two groups at the baseline(P＞ 0.05).At the cnd of the sixth months,significant differences (P＜0.01 ～ 0.05) were found in the total score of WSSS,the sub-score of the Negative Scale,the competitive employment rate and the average working days((35.11 ± 12.71) d vs(20.15 ± 8.04) d) between the experimental and control groups.Conclusion SE can increase the employment rate of schizophrenic rehabilitants,improve their abilities to acquire and maintain competitive employment,and meanwhile relieve their negative symptoms.

Objective To explore the action mechanism and clinical significance of CD4+CD25+ regulatory T (Treg) cells in the development of atopic dermatitis (AD). Methods Peripheral blood mononuclear cells (PBMC) were obtained from 46 patients with AD and 20 normal human controls. Flow cytometry was performed to detect the number of CD4+CD25+ Treg cells, real-time fluorescence PCR assay to measure the Foxp3 mRNA level in PBMC, ELISA to determine the serum levels of IL-2, IL-4, IL-10 and IFN-γ. Results A statistical decrease was observed in the percentages of peripheral CD4+CD25+ Treg cells among CD3+ T cells and CD4+ T cells in AD patients compared with normal controls (t' = 3.775, 4.533, both P＜ 0.01 ), and in the percentage of peripheral CD4+CD25+ Treg cells among CD3+ T cells in patients with acute AD compared with those with chronic AD (t = 2.217, P ＜ 0.05), but no significant difference was noted between patients with acute AD and those with subacute AD or between those with subacute AD and those with chronic AD in the percentage of peripheral CD4+CD25+ Treg cells among CD3+ T cells (t = 1.558, 0.49, both P ＞ 0.05). The mRNA level of Foxp3 in PBMC from AD patients was statistically decreased compred with that from normal controls (z =-2.368, P ＜ 0.05 ). The count of CD4+CD25+ Treg cells was positively correlated with serum levels of IL-2 and IL-10 (r = 0.512, 0.494, both P ＜ 0.05), but had no significant correlation with serum levels of IL-4 and IFN-γ (r = -0.110, -0.237, both P ＞ 0.05). Conclusions In AD patients, there is a decrease in the count of CD4+CD25+ Treg cells and in the level of Foxp3 mRNA, which may suppress the proliferation of and secretion of Foxp3 mRNA by Th2 cells, lead to Th2 predominance, participate in the development of AD.

Objective To explore the role of mouse dermis-derived mesenchymal stem cells (mdMSC) on skin repair. Methods mdMSC and human dermal fibroblasts were isolated and identified. Human dermal fibroblasts were cultured alone or eoeultured with mdMSC in Transwell chambers with the density ratio of human dermal fibroblasts to mdMSC being 2/5, 1/1, and 2/1. On day 4 and 8 of culture, the expression levels of hydroxyproline and transforming growth factor-beta (TGF-beta) 1 were measured in the supematant of monoculture and coculture by alkaline hydrolysis and ELISA respectively. Results The level of hydro-xyproline was significantly higher in the supematants of coculture system with a density ratio of 2/5 and 1/1 than that in monoculture supematants of human dermal fibroblasts on day 8 (both P < 0.05). Elevated level of TGF-betal was observed in all coculture supematants on day 8 (all P < 0.01) and in the supernatants of coculture system with a density ratio of 1/1 on day 4 (P < 0.05). There was no significant correlation between the expression level of TGF-betal and hydroxyproline in the coculture supernatants (r = 0.108, P ＞ 0.05). Conclusion In vitro coculture with mdMSC can increase the production of hydroxyproline and TGF-betal by fibroblasts, which may be a mechanism underlying the facilitation of skin repair by mdMSC.