CB2-selective agonists have drawn attention in drug discovery, since CB2 becomes a promising target for the treatment of neuropathic pain without psychoactive or other CNS-related side effects. However, the lack of experimental data of the 3D structures of human cannabinoid receptors hampers the understanding of the binding modes between ligands and CB2 by traditional methods. In the present work, combinational molecular modeling studies including flexible docking, MD simulations and free energy calculations were performed to investigate the interaction modes and mechanism of CB2-unselective agonist CP55940 and CB2-selective agonist GW842166X, separately binding with the homology model of CB2 in a DPPC/TIP3P simulated membrane environment. The binding free energies calculated by MM-PBSA method give an explanation for the activity differences of the studied ligands. Binding free energies decomposition by MM-GBSA method shows that the van der Waals interaction is the dominant driving force during the binding process. Our MD simulations demonstrate that Phe197 could be a critical residue for the binding of CB2-selective agonists. Furthermore, by using the MD simulated binding conformer as a template, the 3D-QSAR studies were performed with the comparative molecular field analysis (CoMFA) approach on a set of GW842166X analogues. A combinational exploration of both CoMFA steric and potential contour maps for CB2 affinities and the MD studied interaction modes sheds light on the structural requirements for CB2 agonists and serves as a basis for the design of novel CB2 agonists.

Objective To explore the sensitivity regulatory mechanism of ziprasidone capsules on prolactin( PRL) and fast insulin( FINS) in male adolescents with episode schizophrenia.Methods According to inclusion and exclusion criteria, 52 adolescent males selected from January 2015 to March 2016 were confirmed the psychiatric treatment of schizophrenia in our hospital, their ages, ziprasidone capsule usage and suffering schizophrenia stage of disease, height, waist circumference, body weight, hip circumference, and in the morning fasting blood glucose, FINS and PRL content were recorded.Mathematical model were used to calculate QUICKIFINS sensitivity index, and in accordance with the classification criteria BMI, 52 male adolescents with schizophrenia were divided into normal group and overweight group.The correlation detection, and anthropometric parameters, PRL and FINS sensitivity parameters were analysed.Results PRL and FINS, QUICKI indicators were not correlated(r=0.153, P >0.05; r=-0.101, P >0.05) statistically significant; ziprasidone capsule dose has a positive correlation with FINS(r =0.376,P <0.05), and QUICKI negative indicators (r=-0.362,P<0.05); waist-hip ratio or fat content ratio has no correlation with FINS, QUICKI indicators, but BMI and FINS has a positive correlation (r=0.389,P<0.05) and QUICKI indicators with negative correlation(r=-0.413,P<0.05);PRL level between normal group and overweight group was not statistically significant, and levels of FINS in overweight group(10.89 ±8.23) mU/L was higher than the normal group(5.79 ±3.18) mU/L, the difference was statistically significant(P <0.05).QUICKI index between the two groups was statistically significant, and the overweight of FINS was sensitivity less than the normal group.Conclusion Ziprasidone capsule has no relationship with PRL and FINS resistance in the treatment of adolescent patients with schizophrenia, while body mass index correlated with FINS resistance, and ziprasidone capsule dose correlated with FINS resistance.

Objective:To evaluate the performance of our self-developed deep learning (DL) model which was designed to automatically classify the knee X-ray images into one non-surgical category and 4 surgical categories, including non-surgical knees (NSK), high tibial osteotomy (HTO), total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), and tibial plateau fracture fixation with an internal fixation plate (TPFF).Methods:The knee X-ray images were collected of the patients who had undergone knee joint surgery at Department of Orthopaedics, Fuzhou Second General Hospital from January 2017 to December 2022. On the Baidu EasyDL AI platform, a multi-class object recognition DL model was built using the You Only Look Once (YOLO) algorithm. The model was trained on a dataset of 1,281 knee anteroposterior X-ray images (including NSK, HTO, TKA, UKA, and TPFF) to generate a DL model which was able to automatically recognize and classify the knee X-ray images. The reliability of the model classification performance was evaluated by analyzing the 5 indicators [accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)] using a test set of 450 knee anteroposterior X-ray images with the above 5 categories. The receiver operating characteristic curve was plotted and the area under the curve (AUC) was calculated to further quantify the classification performance of the model.Results:In the test set, on the whole, the model achieved an accuracy of 97.0%, a sensitivity of 92.4%, a specificity of 98.1%, a PPV of 92.4%, and a NPV of 98.1%, an AUC of 0.947, indicating a high reliability in classifying various categories. The model showed a best performance for TKA, with the 5 indicators being 99.1%, 99.0%, 99.1%, 97.1% and 99.7%. The model showed a slightly lower sensitivity for TPFF and HTO (87.0% and 86.0%, respectively).Conclusion:A successful DL model has been developed which can automatically classify the knee X-ray images into non-surgical and surgical categories due to its satisfactory performance, particularly in accuracy and AUC.

Objective To evaluate the clinical application of early total care (ETC) for polytrauma patients combined with thoracolumbar fractures.Methods A retrospective case control study was conducted to analyze the clinical data of 137 polytrauma patients combined with thoracolumbar fractures admitted to the First Affiliated Hospital of Soochow University and the Third People's Hospital of Zhang,jiagang from January 2012 to October 2015.There were 90 males and 47 females,aged 26-69 years,with an average age of 48.2 years.The patients were divided into ETC group (n =59) and TMC group (n =78).In the ETC group,physicians from different departments evaluated the patients and developed individualized therapeutic regimens to allow the patients to undergo surgery at early stage after injury.The TMC group preferentially stabilized the patient's condition or transferred the patients to specialist treatment,and then the surgery was performed electively after the condition of the patient was stable.The ISS of the ETC group was (22.15 ± 9.28)points,and that of the TMC group was (23.37 ± 10.74) points.All patients underwent conventional posterior pedicle screw internal fixation.For patients with burst fracture and nerve injury,posterior spinal canal decompression was performed.The thoracolumbar injury classification and severity score (TLICS),spinal load sharing classification (LSC),preoperative and postoperative Glasgow coma score (GCS),Frankel classification,hospitalization time and postoperative complications were compared between the two groups.Results The TLICS scores of ETC group were significantly lower than those of TMC group (P ＜ 0.05) while the LSC scores showed no significant differences between the two groups (P ＞ 0.05).ETC group had shorter hospitalization time [(11.8 ± 3.7)days ∶ (17.5 ±4.5)days] and lower pressure ulcer incidence [(5％ ∶ 21％)] than the TMC group (P ＜ 0.05 or 0.01),but the former had significantly higher wound infection rate [(17％ ∶ 15％)] (P ＜ 0.05).There was no significant difference in pulmonary infection and deep venous thrombosis incidence between the two groups (P ＞ 0.05).No significant differences were found in the preoperative GCS scores between the two group (P ＞ 0.05) while the postoperative GCS scores of TMC group were higher than those of ETC group (P ＜ 0.01).Postoperative GCS scores in both groups were significantly higher than their preoperative GCS (P ＜ 0.05).The results of postoperative Frankel classification in the ETC group were as follows:Grade A in one patient,Grade B in one,Grade C in three,Grade D in four and Grade E in two patients,with an improvement rate of 82％.The results of postoperative Frankel classification in the TMC group were as follows:Grade A in three patients,Grade B in three,Grade C in three,Grade D in four and Grade E in four,with an improvement rate of 65％.Conclusions For polytrauma patients combined with thoracolumbar fractures,ETC can shorten hospitalization time,reduce the pressure ulcer incidence,and better facilitate the recovery of nerve function,yet with higher wound infection risk compared with TMC.TMC was preferred subjectively for patients with unstable thoracolumbar fractures and high TLICS.