Exploring the cause of the dual allosteric targeted inhibition attaching to allosteric sites enhancing SHP2 inhibition.

SHP2 is a protein tyrosine phosphatase (PTP) that can regulate the tyrosine phosphorylation level. Overexpression of SHP2 will promote the development of cancer diseases, so SHP2 has become one of the popular targets for the treatment of cancer. Studies have reported that both SHP099 and SHP844 are inhibitors of SHP2 and bind to different allosteric sites 1 and 2, respectively. Studies have shown that combining SHP099 with SHP844 will enhance pharmacological pathway inhibition in cells. This study uses molecular dynamic simulations to explore the dual allosteric targeted inhibition mechanism. The result shows that the residues THR108-TRP112 (allosteric site 1) move to LEU236-GLN245 (αB-αC link loop in PTP domain) , the residues of GLN79-GLN87 (allosteric site 2) get close to LEU262-GLN269 (αA-αB link loop in PTP domain) and HIS458-ARG465 (P-loop) come near to ARG501-THR507 (Q-loop) in SHP2-SHP099-SHP844 system, which makes the "inactive conformation" more stable and prevents the substrate from entering the catalytic site. Meanwhile, residue GLU110 (allosteric site 1), ARG265 (allosteric site 2), and ARG501 (Q-loop) are speculated to be the key residues that causing the SHP2 protein in auto-inhibition conformation. It is hoped that this study will provide clues for the development of the dual allosteric targeted inhibition of SHP2.

Analysis of influencing factors for outcomes of HIS use at three tertiary hospitals in Anhui / 中华医院管理杂志

Efficient use of the hospital information system can protect and promote the orderly operation of medical practice.The HIS usage effect by the medical staff is mainly affected by individual mastery of information technology,IS technical level and the organizational environment.A survey and analysis of these three factors were made at three tertiary hospitals in Anhui,and the results indicate personal command of information technology,technology and organizational impact to bear significant positive impacts on medical staff' use effect.Based on the results,the paper proposed countermeasures and suggestions on strengthening the HIS construction and enhancing medical staffs HIS use effect.

Analysis of predisposing factors of hematoma enlargement in spontaneous intracerebral hemorrhage / 中国医师杂志

Objective To investigate the main predisposing factors of hematoma enlargement in spontaneous intracerebral hemorrhage,reduce the early mortality,and improve clinical outcomes.Methods By a retrospective study of 268 patients,all patients underwent their first computed tomography (CT)scan within 24 hours of arrival and a second CT scan within 72 hours of admission.These predisposing factors were analyzed by means of univariate and multivariate logistic regression analyses.Results The patients occurred early hematoma enlargement were accounted for 27.99％ (75/268).Univariate analyses indicated that hematoma shape,midline shift,breaking into the ventricle,thrombin clotting time (TT),white blood cells,neutrophil percentage,serum creatinine,fasting plasma glucose (FPG),and Glasgow coma scale (GCS) were significantly different between the patients with or without hematoma enlargement (P ＜0.05).Furthermore,multivariate logistic regression analyses revealed that the following four factors were independently associated with hematoma enlargement:the midline shift [OR (95％ CI) =3.356 (1.251-8.999),P =0.000],the GCS score [OR (95 ％ CI) =0.745 (0.671-0.827),P =0.023],the FPG [OR (95％ CI) =3.022 (1.232-7.408),P =0.016],and the breaking into the ventricles [OR (95％ CI) =2.851(1.158-7.019),P =0.005].Conclusions The midline shift of brain CT scan,the GCS score,the FPG,and the breaking into the ventricles maybe the independent predisposing factors of hematoma enlargement.Therefore,timely review of CT scan and dynamic monitoring of peripheral blood biochemical indicators should be very important for further therapy.

Relationship of sub-health and alexithymia among medical students / 第三军医大学学报

P75 was the risk factor (PP50 were risk factors (P

A Study on the Mechanism of Integrity Educational for Medical Students from the Perspective of Socialist-Cored Values / 中国医学伦理学

Integrity education,as the main content of strengthening and improving ideological and political education of medical students,is an important part in building the socialist-cored value system and plays a key role in cultivating high-quality medical talents.This paper analyzes the connotations of integrity education from the perspective of socialist-cored value system,clarifies its demonstrations and expounds on the reasons for the lack of integrity among medical students.A deep understanding of integrity education is proposed in order to enhance students' cognition of integrity.Various strategies should be applied in its implementation process,and innovations should be brought forth in practice to achieve an effective long-term mechanism of integrity education.