Structural optimization of lead compounds is a crucial step in drug discovery. One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules, thereby accelerating the molecular optimization process. Deep molecular diffusion generative models simulate a gradual process that creates novel, chemically feasible molecules from noise. However, the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules, leading to challenges in modifying the scaffold-based molecular structures, and creates limitations in the stability and diversity of the generated molecules. To address these challenges, we propose a deep molecular diffusion generative model, the three-dimensional (3D) equivariant diffusion-driven molecular generation (3D-EDiffMG) model. The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder (dual-SWLEE) is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions. Additionally, a gate multilayer perceptron (gMLP) block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies. The experimental results show that 3D-EDiffMG effectively generates unique, novel, stable, and diverse drug-like molecules, highlighting its potential for lead optimization and accelerating drug discovery.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.

Objective:To understand the status and influencing factors of the bowel function in patients with rectal cancer after sphincter-preserving surgery, and then to improve the patients′ quality of life.Methods:From January 2017 to April 2020, a total of 179 patients with rectal cancer after sphincter-preserving surgery in Sun Yat-sen University Cancer Center were selected as study subjects. General questionnaire and the scale about bowel function of patients with rectal cancer after sphincter-preserving surgery were used to investigate.Results:The total score of bowel function in patients with rectal cancer after sphincter-preserving surgery was (71.82±7.67), and the average score of all the items was (3.99 ± 0.43). In all dimensions of intestinal function, the average score of "defecation affected by diet" was the highest (4.39 ± 0.80), followed by "frequent and urgent defecation" (4.22 ± 0.49), and the average score of "defecation paresthesia" was the lowest (3.03 ± 0.67). Tumor distance from the anal border was the influencing factor of bowel function in patients with rectal cancer after sphincter-preserving surgery ( P<0.05). Conclusions:The bowel function of patients with rectal cancer after sphincter-preserving surgery was well, while the bowel function of patients with rectal cancer after sphincter-preserving surgery with the distance between the tumor and the lower edge of the anus <5.0 cm was relatively poor.

objective To explore the effect of application of cluster-based strategies on preventing the complication of fibrosclerosis of patients with systemic scleroderma.Methods A total of 59 patients with systemic scleroderma were randomly assigned to the experimental group (34 cases) and the control group (25 cases) during the period of hospitalization in our department.The experimental group took the cluster-based strategies after admission,including a gymnastics,two kinds of respiratory breathing,three kinds of habits,four kinds of protection to prevent the complication of fibrosclerosis.The control group received the conventional care procedures of dermatology.The skin stiffness,joint function,Raynaud's phenomenon and swallowing function were evaluated when patients were admitted and before discharge in two groups.The length of stay between the two groups was also compared.Results The skin stiffness,joint function,Raynaud's phenomenon and swallowing function scored (14.74±1.33),(7.06±0.69),(0.88±0.33),(0.54±0.21) in the experimental group,significantly better than those of the control group,(24.08±1.12),(13.48±0.77),(1.24±0.60),(0.96±0.34),P ＜ 0.01.The length of stay in the experimental group and the control group was (23.65±5.45),(32.00±6.56) days,t=-5.340,P ＜ 0.01.Conclusions Application of cluster-based strategies can be effective against the fibrosclerosis damage of patients with systemic scleroderma and reduce the occurrence of complications.

Objective To investigate pain heterogeneity in transfusion with different gestures in order to find the best gesture.Methods 80 cases were randomly selected and transfused in the back of the hand with three infusion gestures,which including horizontally laid hand with extended fingers for 20 min as control,horizontally laid hand with relaxed fist for 20 min and horizontally laid hand with fist for 20 min in time sequence.Mark-Gail method was used to assess the pain grade.Results Pain was enhanced in horizontally laid hand with relaxed fist group and horizontally laid hand with fist group when comparing with horizontally laid hand with extended fingers group.And pain was more stronger in horizontally laid hand with fist group than that of horizontally laid hand with relaxed fist group.Conclusions Transfusion with horizontally laid hand combining with extended fingers implicated minimum pain and was the best gesture.Horizontally laid hand with fist flat finger displayed the strongest pain and should be banned.

OBJECTIVE: To study the hospital infections caused by ESBLs-producing Escherichia coli and Kalispell.METHODS: Bacterial drug resistance of 460 stains of ESBLs-producing Escherichia coli and Kalispell pneumonia and the application of antibiotics in our hospital in 2005 were analyzed retrospectively.RESULTS: The infections caused by ESBLs-producing Escherichia coli and Kalispell pneumonia were more often found in department of respiratory diseases,ICU and neurosurgery patients,which were treated empirically predominantly with levofloxacin,followed by cefoperazone/sulbactam,but were treated mostly by carbapenems,levofloxacin,cefoperazone/sulbactam after the drug susceptibility test results were obtained.The drug combination was characterized predominantly by combined use of two kinds,at most 6 kinds in combination.CONCLUSION: In most of the cases the medication for infections caused by ESBLs-producing Escherichia coli and Kalispell pneumonia is effective and reasonable.However,in a few cases the application of antibiotics is irrational and nonstandard,which should be given fully attention.

Aim To design and synthesize new phenyloxyisobutyric acid analogues as antidiabetic compounds. Methods Eight new target compounds were synthesized by combination of lipophilic moieties and acidic moiety with nucleophilic replacement or Mitsunobu condensation. The eight compounds were confirmed by 1H NMR, 13C NMR, IR and MS. Results In vitro insulin-sensitizing activity (3T3-L1adipocyte) demonstrated, that the cultured glucose concentration of up-clear solution detected with GODpioglitazone, compounds A and B were added to the insulin-resistant system. Conclusion In vitro insulin-sensitizing activity of target compound A is in between that of rosiglitazone and pioglitazone, and activity of target compound B is slightly less than that of pioglitazone.

AIM: To study the compatible stability of cefepime with 0.5% metronidazole injection.　METHODS: Dual wavelength spectrophotometry and K-ratio spectrophotometry were described for the determination of cefepime with metronidazole injection during 6 h. 　RESULTS: There was no evident variation in content during 6 h at room temperature. The average recovery rates of cefepime and metronidazole were (100.9±0.4)% and (99.8±0.6)% (n=5).　CONCLUSION: The compatiblity of cefepime with metronidazole injection is stable. The method of using dual wavelength spectrophotometry and K-ratio spectrophotometry to determine the compatible stability of cefepime with metronidazole is simple, accurate and usable.

100MIC.The endotoxin could be released more and more with the time.CONCLUSION:It is reasonable to choose antibiotics to refer to the characteristics of the endotoxin release by germs.