Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

BACKGROUND:Observational studies have suggested that statin drugs may have a protective effect on bone density,making them a potential treatment option for osteoporosis. OBJECTIVE:To evaluate the causal relationship between drug target-mediated lipid phenotypes and bone mineral density(BMD)using Mendelian randomization methods. METHODS:We obtained single nucleotide polymorphismsrelated to statin drugs and BMD data from the IEU Open GWAS database.The primary analysis method was the inverse variance weighted method,and we also used weighted median,simple median,weighted mode,and MR-Egger regression.We usedβ values and 95%confidence intervals(CI)to assess the causal relationship between statin drugs and BMD.Additionally,we conducted sensitivity analyses to validate the results,assessed heterogeneity using Cochran's Q test,examined for horizontal pleiotropy using the MR-Egger intercept test,and performed leave-one-out analyses to determine if individual or multiplesingle nucleotide polymorphism influenced the results. RESULTS AND CONCLUSION:There was a significant association between the statin target of action,3-hydroxy-3-methyl glutaryl coenzyme A reductase-mediated low-density lipoprotein cholesterol,and heel bone BMD(β=-0.086,95%CI:-0.117 to-0.055,P=5.42×10-8)and whole-body BMD(β=-0.193,95%CI:-0.288 to-0.098,P=7.35×10-5).The findings of this study support the protective effect of statin drugs on BMD.These findings not only deepen our understanding of the relationship between cholesterol-related genes and bone health but also reveal potential therapeutic targets for improving BMD.

Treponema pallidum(Tp),a common sexually transmitted pathogen,can infect the fetus via pla-cental vertical transmission,leading to congenital syphilis(CS).This infection results in adverse pregnancy outcomes,such as stillbirth,miscarriage,preterm birth,and fetal growth restriction.However,the exact pathogenesis remains un-clear.Studies indicate that patients with early syphilis primarily exhibit pro-inflammatory immune responses.The Tp has been proven to induce dysfunction in various immune cells and abnormal expression of cytokines,potentially disrupting im-mune tolerance homeostasis and leading to adverse pregnancy outcomes.Grounded in the current understanding of CS and maternal-fetal immunology by scholars both domestically and internationally,this paper provides a comprehensive review of the potential mechanisms of Tp interacting with the cells of the maternal-fetal interface,ultimately leading to adverse pregnancy outcomes.It summarizes the pathogenesis characteristics,clinical manifestations,and maternal-fetal immune responses of CS.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective To propose a topology-optimized design method for bone plates that effectively reduces stress concentration and improves bone healing compared with traditional topology-optimized method.Methods Based on the load constraints of a bone plate in a broken bone-splint system,an improved topology optimization method based on the load path was used to optimize the design of the bone plate structure.Subsequently,a bone regeneration simulation model based on bias strain was used to simulate the transverse fracture of the tibial tuberosity,and the force state,fixation stability,and healing performance of the optimized plate were evaluated based on data from the bone regeneration process.Results Using the optimized bone plate based on the load path optimization method,the maximum stresses of the bone plate were 55.68 MPa and 42.23 MPa at volume fractions f=0.55 and 0.65,respectively,which were reduced by 32.96％and 29.95％,respectively,compared with the optimized bone plate using the traditional topology optimization method.The average elastic moduli of the callus after the bone-healing process were 1 439.47 MPa and 1 355.71 MPa,respectively.These values were 145.86％and 131.06％higher than those of traditional bone plates,respectively.Conclusions In this study,the proposed improved topology optimization method based on the load path was used to optimize bone-plate structures.Compared to the bone plate obtained using the traditional topology optimization method,the optimized bone plate was more uniformly loaded and safer.The bone-healing performance was significantly improved compared to the traditional bone plate.These results provide a new method for the optimal design of internal fixation implants for fractures.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Objective:To explore the effect of gradual dural decompression(GDD)in preventing intraoperative encephalocele in severe traumatic brain injury (TBI).Methods:A retrospective case-control study was conducted to analyze the clinical data of 78 patients with severe TBI admitted to Affiliated Hospital of North Sichuan Medical College from January 2015 to October 2018, including 55 males and 23 females, aged 15-68 years with an average age of 38.2 years. Thirty-eight patients were treated by GDD (GDD group). During the operation, the hematoma was cleared by opening a window in the area with more hematoma, then gradually cleared in the area without opening a window. Finally, the dural "junction" was cut and the skull was closed quickly after covering the dural patch. The other 40 patients were operated by fast open dural (FOD) operation (FOD group). The incidence of intraoperative encephalocele, intracranial pressure data at the time, 24 hours, 72 hours and 7 days after operation, incidence of delayed intracranial hematoma and glasgow outcome score (GOS) at 3 months after operation were compared between the two groups.Results:All patients (except for 26 deaths) were followed up for 3-14 months, with an average of 8 months. None had intraoperative encephalocele in GDD group, compared to 8 patients in FOD group ( P<0.05). Intracranial pressure in GDD group was respective (18.4±3.6)mmHg, (20.4±4.0)mmHg, (27.7±4.6)mmHg and (28.3±4.5)mmHg at the time, 24 hours, 72 hours and 7 days after operation, showing no significant differences compared to FOD group [(19.1±3.4)mmHg, (20.9±3.9)mmHg, (27.0±3.5)mmHg, (27.6±3.4)mmHg, respectively] ( P>0.05). There was no significant difference in the incidence of delayed intracranial hematoma between the two groups [16% (6/38) in GDD group and 16% (5/32) in FOD group (except 8 cases of intraoperative encephalocele)] ( P>0.05). Three months after operation, the good rate of GOS score of GDD group was 61% (23/28) higher than that of FOD group [28% (11/40)], and the mortality rate of GDD group was 21% (8/38) lower than that of FOD group [45% (18/40)] ( P<0.05). There was no significant difference between the two groups in medium severe disability and plant survival rate ( P>0.05). Conclusions:For patients with severe TBI, compared with FOD, GDD is more effective in reducing the incidence of intraoperative encephalocele, improving the prognosis and decreasing mortality.

Objective: To investigate the current status of ICU nurses′ evaluation of clinical health work environment and its influence factor under the foundation of empowerment management model. Methods: This study included 162 ICU nurses from Renmin Hospital of Wuhan University. The Chinese version of the Essentials of Magnetism II was used to evaluate the healthy working environment and another two 0–10 single-item scales was used to evaluate job satisfaction and quality of care. Results: The total score of nurses on the healthy working environment was (183.75±1.56), and score of each dimensions were included medical relationship(2.83±0.43), support for training(2.88±0.05), autonomy of nursing work (2.98±0.03), nursing practical control(2.93±0.03), adequate nursing staff(2.83±0.33), colleagues′ clinical competence(3.37±0.04), nursing manager support(3.50±0.04), cultural values(3.48±0.04), the satisfaction of nursing work(8.12±0.14) and the quality of care evaluation(8.66±0.12) were higher. There were significant statistical difference in the evaluation of nurses′ healthy working environment on age, working years, education and level of authorization. The degree showed low level negative correlation degree and healthy working environment (r=-0.299, P=0.000), the level of authorization showed low level correlation degree and healthy working environment (r=0.236, P=0.003). The independent variable could explain 97.9% of the variation of the dependent variable, among which nursing manager support and cultural values and adequate nursing staff had a high explanatory power for the evaluation of healthy working environment. Conclusions ICU nurses have a higher evaluation of the healthy working environment. Nursing managers should be concerned about more support to different levels of nurses, pay attention to the needs of training, promote the harmonious development of doctor-nurse relationship, improve healthy working environment focuses on the process of nursing manager support and cultural values and adequate nursing staff,so to create a magnetic professional environment that will satisfy the nurses are helpful to improve the quality of care.