Negative logarithm of the acid dissociation constant (pK _a) significantly influences the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of molecules and is a crucial indicator in drug research. Given the rapid and accurate characteristics of computational methods, their role in predicting drug properties is increasingly important. Although many pK _a prediction models currently exist, they often focus on enhancing model precision while neglecting interpretability. In this study, we present GraFpK _a, a pK _a prediction model using graph neural networks (GNNs) and molecular fingerprints. The results show that our acidic and basic models achieved mean absolute errors (MAEs) of 0.621 and 0.402, respectively, on the test set, demonstrating good predictive performance. Notably, to improve interpretability, GraFpK _a also incorporates Integrated Gradients (IGs), providing a clearer visual description of the atoms significantly affecting the pK _a values. The high reliability and interpretability of GraFpK _a ensure accurate pK _a predictions while also facilitating a deeper understanding of the relationship between molecular structure and pK _a values, making it a valuable tool in the field of pK _a prediction.

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Objective To investigate the clinical significance of CD7 expression in childhood acute myeloid leukemia(AML).Methods A retrospective analysis was performed on 60 children with AML admitted to Jiangxi Province Children's Hospital from October 2016 to December 2020.According to the results of immunophenotyping,the children were divided into CD7 positive(CD7+)group and CD7 negative(CD7-)group.The clinical characteristics,immunophenotype and treatment effect of the two groups were compared.Results Among 60 children with AML,18 cases were CD7+,and the positive rate was 30.00%,mainly M2 and M5,the expression rate of M2 was 55.56%,which was higher than that of other subtypes.The CD7+ group had significantly higher white blood cell count and bone marrow blast granulocyte count than the CD7-group(P<0.05).There were no significant differences in platelet count,hemoglobin,lactate dehydrogenase,creatinine and other laboratory indicators between the two groups(P>0.05).After 1 course of standard induction chemotherapy,the CD7+ group had a significantly lower complete remission rate than the CD7-group(P<0.05).There was no statistically significant difference(P>0.05)in the overall survival rate and disease free survival rate between the two groups of patients at 1 year and 2 years.Conclusion Compared with CD7-children,the peripheral white blood cell count and bone marrow blast cell count of CD7+ children were significantly higher,and the complete remission rate of induction chemotherapy was significantly lower.The expression of CD7 antigen has a significant predictive value for the poor prognosis of children with AML,which may provide new ideas for the treatment strategy of children with AML,and lay the foundation for further exploring the mechanism of CD7 in the development of AML.

OBJECTIVE: To investigate the early effectiveness of transiliac-transsacral screws internal fixation assisted by augmented reality navigation system HoloSight (hereinafter referred to as "computer navigation system") in the treatment of posterior pelvic ring injuries. METHODS: A retrospective analysis was made in the 41 patients with posterior pelvic ring injuries who had been treated surgically with transiliac-transsacral screws between June 2022 and June 2023. The patients were divided into navigation group (18 cases, using computer navigation system to assist screw implantation) and freehand group (23 cases, using C-arm X-ray fluoroscopy to guide screw implantation) according to the different methods of transiliac-transsacral screws placement. There was no significant difference in gender, age, body mass index, causes of injuries, Tile classification of pelvic fracture, days from injury to operation, usage of unlocking closed reduction technique between the two groups ( P>0.05). The time of screw implantation, the fluoroscopy times, the guide wire adjustment times of each screw, and the incidence of complications were recorded and compared between the two groups. The position of the transiliac-transsacral screw was scanned by CT within 2 days after operation, and the position of the screw was classified according to Gras standard. RESULTS: The operation was successfully completed in both groups. The time of screw implantation, the fluoroscopy times, and the guide wire adjustment times of each screw in the navigation group were significantly less than those in the freehand group ( P<0.05). There were 2 cases of incision infection in the freehand group, and the incision healed by first intention after active dressing change; there was no screw-related complication in the navigation group during operation and early period after operation; the difference in incidence of complications between the two groups (8.7% vs. 0) was not significant ( P=0.495). According to the Gras standard, the screw position of the navigation group was significantly better than that of the freehand group ( P<0.05). CONCLUSION Compared with the traditional freehand method, the computer navigation system assisted transiliac-transsacral screws internal fixation in the treatment of posterior pelvic ring injuries has advantages of improving the accuracy of screw implantation and reducing radiation damage and the time of screw implantation.
Humans ; Retrospective Studies ; Surgical Wound Infection ; Replantation ; Body Mass Index

【Objective】 To compare the clinical efficacy of percutaneous transforaminal endoscopic decompression （PEID） and percutaneous interlaminar endoscopic decompression （PETD） in the treatment of L5-S1 lateral recess stenosis. 【Methods】 We selected the patients in our center diagnosed with L5-S1 lateral recess stenosis from March 2018 to October 2019 and divided them into Group A and Group B according to the principle of prospective， single-blind， and randomized control （A： PETD； B： PEID）. The operation was performed by the same senior surgeon with mature spinal endoscopy technology. We recorded the basic information， operation duration， usage count of C-arm， hospital stay， VAS score and ODI index of lower back and lower limbs before operation and 3 days， 1 month， 1 year and the last follow-up after the operation， and the operative excellent and good rates （the last follow-up）. The angle of bony lateral recess was measured during pre- and postoperative CT. 【Results】 A total of 95 patients （A： n=48； B： n=47） successfully completed the operation and were followed up for at least 1 year. The two groups did not significantly differ in age， gender， hospital stay， or complication by lumbar intervertebral disc herniation， but PEID group had significantly shorter operation duration and fewer usage counts of C-arm （P<0.001）. VAS score of lower back and lower limbs， and ODI index were significantly reduced at 3 days，1 month， 1 year and the last follow-up after the operation， with no significant difference between the two groups at the same time； no statistical difference was found between the two groups in operative excellent and good rates at the last follow-up （P>0.05）. The postoperative bony side recess angle was significantly improved （P<0.05）， while there was no significant difference in either pre- or postoperative bony side recess angle between the two groups （P>0.05）. 【Conclusion】 Both PEID and PETD are effective strategies in the treatment of L5-S1 lateral recess stenosis and can achieve good clinical outcomes.

【Objective】 To investigate the effect of decompression technique with bone-chisel under percutaneous spinal endoscopy through transforaminal approach in elderly patients with unilateral lateral recess stenosis （ULLRS）. 【Methods】 We enrolled 46 old patients with ULLRS who underwent percutaneous spinal endoscopy through transforaminal approach assisted with bone-chisel technique from March 2017 to July 2019. The visual analogue scale （VAS） score of low back pain and leg pain， the Oswestry dysfunction index （ODI）， and the modified MacNab score before and after operation were obtained. We also recorded preoperative and postoperative sagittal diameter measured by computer tomography （CT） to evaluate decompression of the lateral recess. All the patients were followed up for at least 1 year for complications. 【Results】 All the 46 patients were followed up for 17 to 42 months. Dural tear occurred in one case， transient nerve root irritation in two cases， and there were no other complications. The low back pain VAS score， lower limb pain VAS score， and ODI index of all the patients were significantly improved in the last follow-up （P<0.05）. The results of the modified MacNab efficacy evaluation at the last follow-up revealed that the excellent and good rate was 91.3% （excellent in 38， good in 4， and fair in 4）. The sagittal diameter （mm） of the bony lateral recess 1 year after surgery increased by an average of 55.8%， which was significantly better than that before surgery （t=6.354， 4.22±1.25 vs. 2.71±0.57， P<0.001）. 【Conclusion】 Percutaneous spinal endoscopy through transforaminal foramen approach combined with bone-chisel technique is effective in treating ULLRS in elderly patients.

AIM: The aim of this research is to study the earlier enzyme activity changes of the diaphragm in diabetic rats. METHODS: An enzyme histochemical method was used to observe the changes in the enzyme activities of dehydrogenases,hydrolases and oxidases in 4th week diabetic rat diaphragm. RESULTS: The activites of enzymes including SDH(Succinate dehydrogenase),MDH(Malate dehydrogenase), GDH(Glutamate dehydrogenase), ICDH(Isocitrate dehydrogenase), NADHD(NADH diaphorase), G-6-PD(Glucose-6-phosphate dehydrogenase), ACP(Acid phosphatase) and ANAE(Acid ?-naphtyl acid esterase) were increased in diabetic diaphragm compared with the control. LDH (Lactate dehydrogenase)and CCO(Cytochrome oxidase) activities were decreased, whereas NADPHD(NADPH diaphorase) showed no changes in diabetic rats. Eleven kinds of enzyme were analysed with image analysis.Optical density (A) of SDH, MDH, GDH, ICDH, NADHD, G-6-PD, ACP and ANAE in diaphragm of diabetic rats were significantly higher than that of control rats (P0.05). CONCLUSION: Increase in the aerobic capacity, decrease in the glycolytic capacity, and disturbance of lipid and energy metabolism were found in diaphragm of 4th week diabetic rats.

Objective To investigate the effects of chloroquine on metabolism of insulin,glucose,lipids and expression of insulinase gene (EIG) in patients with type 2 diabetes mellitus.Methods Fasting plasma insulin (FINS),fasting plasma glucose (FPG),glycoslated hemoglobin (HbA1c),plasma lipids and lipoprotein,insulinase activity of erythrocytes (EIA) and EIG were determined in 30 patients with type 2 diabetes mellitus laking chloroquine for 14 day in dosage of 250mg twice daily,27 diabetic patients laking placebo and 20 normal subjects.Insulin sensitive index (ISI) were also calculated.Results Chloroquine caused a decrease in total plasma cholesterol,low density lipoprotein,EIA and EIG,and an increase in ISI,plasma high density lipoprotein and subclass 2.No change of these indices was observed in diabetic patients with placebo.Conclusion Chloroquine can ameliorate the dyslipidemia and insulin sensitivity of patients with type 2 diabetes mellitus.This may be due to a decrease in EIG,which may result in lowered degradation of insulin.