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@#Abstract: 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.
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This study was aimed to observe the clinical efficacy of Ju-Hong Tan-Ke (JHTK) liquid in the treatment of patients with anemofrigid (or mixing with damp) cough.A total of 70 patients with anemofrigid (or mixing with damp) cough admitted to Chinese medicine clinic in our hospital were selected and randomly divided into the treatment group (n =50) and the control group (n =20).Patients in the treatment group were treated with 2 JHTK liquid (Guangzhou Xiangxue Pharmaceutical Co.,Ltd.,20 ml),3 times a day.Two She-Dan Chen-Pi (SDCP) liquid (20 ml) was used in the control group,3 times a day.The treatment course was 1 week.Differences of the clinical efficacy of cough and expectoration symptoms between two groups after treatment were compared.The effect of JHTK liquid on different degrees of cough and expectoration was also compared.The results showed that the total effective rate of cough in the treatment group was 92.00％,which was obviously higher than 70.00％ of the control group with statistical difference (P＜ 0.05).The total effective rate of expectoration symptoms in the treatment group was 94.00％,which was obviously higher than 75.00％ of the control group with statistical difference (P＜0.05).The curative effects of JHTK liquid in the treatment of mild,moderate and severe cough were 90.00％,93.75％,and 87.50％,respectively.The curative effects of JHTK liquid on mild,moderate and severe expectoration were 100％,96.77％,and 80.00％,respectively.It was concluded that JHTK liquid can effectively improve cough and expectoration symptoms of patients with anemofrigid (or mixing with damp) cough,especially the clinical curative effect of mild and moderate cough with expectoration was obviously and the effect of severe cough and expectoration was excellent.Its curative effect was superior to SDCP liquid,which is worthy of clinical application.
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Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incompletely reversible airflow limitation and progressive course.The pathogenesis of COPD is complicated.Clinical symptoms include declining pulmonary function, airway and lung inflammation, cough, emaciation, low activity and so on.In the past, the medications for COPD treatment were mainly bronchodilators and anti-inflammatory drugs.With the better understanding of its pathogenesis, anti-oxidative drugs have also been used in the clinical treatment of COPD recently.This article reviews the development of drugs which include bronchodilators, anti-inflammatory drugs and anti-oxidative drugs for the therapy of COPD.
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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.
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BACKGROUND:The therapeutic effect of traditional Chinese drug on myocardial ischemia and reperfusion has been increasingly attached importance to. The tongxinluo, a Chinese paten drug taking insect medicine as its major gradients, has been achieved satisfactory effect in anti-myocardial ischemia clinicallyOBJECTIVE: To investigate the effect of tongxinluo on myocardial apoptosis induced by ischemic reperfusion.DESIGN:A randomized controlled trialSETTING: Department of Traditional Chinese Medicine (TCM) of the First Affiliated Hospital, Sun Yat-sen UniversityMATERIALS:The experiment was conducted from November to December 2002 at the Molecular Medicine Research Center of Sun Yat-sen University.METHODS:Totally 72 Kunming mice were at random divided into 6groups with 12 in each group: 2 g/kg tongxinluo, 1.5 g/kg tongxinluo, 1.0g/kg tongxinluo group (The mice were administrated by gavage, once a day, on the day 5, one hour after administration, pituitrin and nitroglycerin were in combination used for building the myocardial ischemic reperfusion model), isosorbide dinitrade group (The dose was 3.9 g/kg, and the rest treatment was the same as the above), model group and blank control group(Normal saline was taken as substitute for the drug). At the end of trial the myocardia of the mice were taken for investigating the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) of myocardia in mice with ischemic reperfusion, analyzing the myocardial apoptosis index, and determining the expression levels of apoptosis-relevant proteins bcl-2 and bax.MAIN OUTCOME MEASURES: [1] Comparison of SOD activity and MDA level in mice of each group. [2] Comparison of myocardial apoptosis and apoptosis relevant proteins.RESULTS:Totally 72 mice involved were good for the trial and no one died. [1] SOD activity and MDA level: Compared with the model and isosorbide dinitrade groups, SOD activity in 2 g/kg tongxinluo, 1.5 g/kg tongxinluo, 1.0 g/kg tongxinluo group was increased [( 1379.28±140.03 ),(1223.91 ±109.02), (1789.19 ±155.20), (2267.79 ±216.04), (2387.55±229.71 )nkat/L]; MDA level was decreased [(16.58±2.59), (20.40±2.66),(12.73±1.98), (9.65±2.03), (7.56±1.67)nmol/L], and the effect was increased as the dose was raised [2] myocardial apoptosis and apoptosis relevant proteins: Compared with the model and isosorbide dinitrade groups, the myocardial apoptosis index and Bax expression index in 2 g/kg tongxinluo,1.5 g/kg tongxinluo, 1.0 g/kg tongxinluo group were obviously decreased[(13.84±1.97)%, (11.56±1.43 )%, ( 334±0.96)%, (0.82±0.12 )%, (0.42±0.06)%;(17.44±6.18)%, (15.45±3.72)%, (10.85±2.73)%, (6.46±1.88)%, (5.57±1.49)% ]; Bcl-2 expression index was obviously increased [(6.22±0.50)%, (8.73 ±0.63)%, (11.38 ±1.38)%, (16.22 ±2.36)%, (19.45±2.92)%], and with a dose-effect relationship.CONCLUSION:Tangible capsule had the effects of. resisting oxygen free radical injury, anti-myocardial apoptosis and protecting ischemic reperfusion myocardial cells, and with a dose dependence.
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BACKGROUND: In the evaluation on the effects of intervention on the patients with angina pectoris,whether the quality of life is improved or not is a very important factor while the symptoms and physical signs are benefited.OBJECTIVE: To probe into the intervention effects of sini tang,the classic formula,on angina pectoris of coronary heart disease and compare the effects of simple Chinese herbs,western medicine and integrated traditional Chinese and western medicine on quality of life.DESIGN:Prospective observation and control study in which the patients with angina pectoris of coronary heart disease were taken as the objects.SETTING: Department of Traditional Chinese Medicine of a Hospital Affiliated to a University.PARTICIPANIT : The 88 cases in total were the patients with angina pectoris of coronary heart disease in the clinic of Department of Traditional Chinese Medicine of First Hospital Affiliated to Sun Yat-sen University from February to August 2003. Inclusion criteria: those compiled with "Guide Principles of Pharmaceutical Clinical Study in Cardiac Vascular System" and "Standards on Differentiation of Coronary Heart Disease with Chinese Medicine". Exclusion criteria: those complicated with various severe diseases. All the patients were randomized into sini tang group,isosrbide dinitrate group and allied medication group of 29,30 and 29 cases successively.METHODS: In sini tang group,isosrbide dinitrate group and allied medication group,sini tang,isosrbide dinitrate and sini tang allied with isosrbide dinitrate were prescribed successively. At the beginning and the end of treatment, it was to observe the attack frequency,condition, severity and persistent duration of angina pectoris and to record electrocardiogram (ECG).The evaluation on quality of life was carried on before and two weeks after medication with the unified inventory and determination device.MAIN OUTCOME MEASURES: Comparisons of therapeutic effect on angina pectoris control,ECG and evaluation on life quality in every group.RESULTS: Both isosrbide dinitrate and sini tang relieved remarkably angina pectoris, improved ECG and quality of life in physical symptoms, health pleasure and depression level(P<0.01) . The result of sini tang on improving the quality of life in above-mentioned three aspects was better than that of isosrbide dinitrate(P<0.01) . But the allied medication improved clinical therapeutic effects and quality of life (health pleasure and depression level) best(P<0.01).CONCLUSION: Sini tang benefits the improvement of quality of life of patients with angina pectoris. But during clinical medical intervention,the advantages of integrated traditional Chinese and western medicine should be adopted.