OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective To evaluate the relationship between ceftazidime-avibactam(CAZ-AVI)blood concentrations and efficacy in critically ill patients and to investigate the factors influencing blood levels.Methods The CAZ-AVI trough concentrations(Cmin)were detected in 29 patients who received CAZ-AVI treatment for at least 48 hours.The clinical materials of the patients were collected together for retrospective analysis.Results The Cmin of ceftazidime(CAZ)and avibactam(AVI)were(50.95±5.17)and(7.52±0.96)mg·L-1 in the effective group and(31.16±7.03)and(5.37±1.32)mg·L-1 in the ineffective group,respectively.The Cmin of CAZ in the effective group was significantly higher than in the ineffective group(P<0.05),and there was no significant difference in AVI Cmin between the two groups(P>0.05).Spearman's correlation analysis showed that CAZ Cmin was positively correlated with clinical efficacy(P<0.05),and no correlation between AVI Cmin and clinical efficacy(P>0.05).The optimal CAZ Cmin threshold was 24.59 mg·L-1.Multiple linear regression analysis showed that age and creatinine clearance was significantly correlated with the Cmin of CAZ,and creatinine clearance was significantly correlated with AVI Cmin(P<0.05).Conclusions The Cmin of CAZ correlates with efficacy,and it may be more beneficial for clinical treatment to keep the concentration of CAZ-AVI always greater than the minimum inhibitory concentration during the dosing interval.The creatinine clearance should be fully considered when optimizing CAZ-AVI dosage in critically ill patients.

In recent decades, clinicians' research on the psychological distress of breast cancer patients mostly focuses on anxiety, depression and recurrence fear, and few researchers pay attention to the adverse effects of social constraints on breast cancer patients. This article briefly introduces the general situation of social constraints from the aspects of concept, characteristics, influencing factors and assessment tools, and summarizes the influence of social constraints on the psychological distress of breast cancer patients and intervention measures, in order to provide a theoretical basis for exploring effective intervention measures to help breast cancer patients who are psychologically distressed by social constraints.

Objective To explore the effects of family empowerment program on comprehensive care ability and care preparedness for main caregivers of patients with initial stroke.Methods A total of 64 main caregivers of patients with initial stroke were enrolled from a tertiary hospital in Hangzhou from January 2017 to July 2017,and assigned into the intervention group and the control group according to different wards,with 33 cases in the intervention group and 31 cases in the control group.Both groups received routine care,and the intervention group also received family empowerment program.The stroke caregivers' comprehensive care ability questionnaire and the Caregiver Preparedness Scale were used to evaluate the effects of the intervention.Results Before the intervention,there were no statistically significant differences in disease-related knowledge,daily and disease-related care skills,self-stress and health management,coping strategies,and total scores of comprehensive care ability,and caregiver preparedness scores between two groups(P＞0.05).After the intervention,the total scores and each dimension score of comprehensive care ability,and caregiver preparedness scores of two groups were significantly higher than those before the intervention,and the differences were statistically significant(P＜0.05).Conclusion Family empowerment program can effectively improve comprehensive care ability and care preparedness of main caregivers of patients with initial stroke,making the caregiver playing a positive role in the rehabilitation of stroke patients.

OBJECTIVETo explore the value of nutrition management in obese patients with type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG).

METHODSClinical data of 22 obese T2DM patients undergoing LSG from March 2013 to July 2015 in Fudan University Pudong Medical Center were collected. All the patients strictly followed the specialized instruction by nutritionists: diabetic and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation for promoting gastric emptying; fasting diet before postoperative ventilation; clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to 3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6 months after operation on time. Changes of body weight, waist circumference, hip circumference, body mass index(BMI), blood glucose indexes induding fasting blood glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and analyzed before and 1 week, 1, 3, 6 months after operation.

RESULTSThe average age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The duration of diabetes varied from 1 month to 15 years. Comorbidity included 12 patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease, 1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was performed successfully in all the patients and no severe complications and transference to laparotomy occurred. As compared to pre-operation, at 6 months after operation, the average body weight decreased from (103.9±20.2) kg to (80.9±12.6) kg (t=6.294, P=0.000), waist circumference from (118.6±13.8) cm to (96.4±8.0) cm (t=6.331, P=0.000), hip circumference from (116.9±12.6) cm to (104.0±7.7) cm (t=3.854, P=0.000), BMI from (36.2±5.9) kg/mto (27.9±3.5) kg/m(t=5.630, P=0.000), showing a decreasing trend over time. There was no underweight patient after 6 months follow-up. As compared to pre-operation, at 6 months after operation, the average FBG reduced from (7.4±1.4) mmol/L to (6.0±0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1±4.9) mmol/L to (7.5±2.2) mmol/L (t=7.026, P=0.000), FINS from (160.0±71.9) mIU/L to (43.8±20.8) mIU/L (t=7.259, P=0.000), 2-hour postprandial INS from (437.6±261.4) mIU/L to (140.5±104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1±0.6) μg/L to (0.7±0.3) μg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from (2.5±0.9) μg/L to (1.5±0.7) μg/L (t=3.865, P=0.000), HbAlc from (8.0±1.6)% to (5.9±0.6)% (t=5.953, P=0.000), showing a decreasing trend over time except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG of 16 patients returned to normal 3 months after the operation. Blood pressure and trigly ceride decreased obviously 6 months after operation compared to pre-operation with significant difference(P<0.05). At 6 months after operation, blood pressure of 8 comorbidity patients with high blood pressure became normal (8/12, 66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the menstruation of the menstrual disorder patient returned to normal 3 months and 1 month after the operation respectively.

CONCLUSIONAs for obese patients with T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body weight, and to obtain an ideal improvement of blood glucose and blood lipid levels.

Adolescent ; Adult ; Aged ; Bariatric Surgery ; Blood Glucose ; physiology ; Body Weights and Measures ; C-Peptide ; blood ; physiology ; Caloric Restriction ; Combined Modality Therapy ; Comorbidity ; Coronary Disease ; complications ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Diet Therapy ; methods ; Diet, Diabetic ; Endoscopy ; Fatty Liver ; complications ; surgery ; Female ; Food, Formulated ; Gastrectomy ; Glycated Hemoglobin A ; physiology ; Gout ; complications ; surgery ; Hashimoto Disease ; complications ; Humans ; Hypertension ; complications ; surgery ; Insulin ; blood ; physiology ; Lipids ; blood ; physiology ; Male ; Menstruation Disturbances ; complications ; surgery ; Middle Aged ; Obesity ; complications ; therapy ; Perioperative Care ; methods ; Thyroiditis ; complications ; Treatment Outcome ; Triglycerides ; blood ; physiology

Objective To understand the quality of sleeping in medical students, and provide a reference basis for designing sleep health management program for college students. Methods The survey was conducted at a medical college in Shanxi province with stratified random sampling and Pittsburgh Sleep Quality Index (PSQI) scale. Totally 210 individuals were enrolled, 199 completed the questionnaire, with a response rate of 93.5%. SPSS 21.0 statistical software was used for data analysis. Descriptive statistical analysis was carried out for socio-demographic data. Independent t-test, one-way analysis of variance and non-parametric test were used to compare the scores of PSQI between participants. Multiple stepwise linear regression was used to determine influencing factors of sleep quality. Results The average score of PSQI for the 199 medical students interviewed was (6.74±2.42), the incidence of sleep disorder was 50.25%, the overall sleep quality was not high. Learning pressure of medical student had statistically significant in PSQI (Completely unmatched, 5.14 ± 2.32, Mostly unmatched, 5.93 ± 2.73, Mostly matched, 6.70 ± 2.42, Absolutely matched, 7.39 ± 2.10, F=3.366, P=0.020), employment pressure of medical students in PSQI (Completely unmatched, 6.50 ± 0.71, Mostly unmatched, 6.80 ± 3.24, Mostly matched, 5.98 ± 2.14, Absolutely matched, 7.14 ± 2.35, F=3.134, P=0.027). Grade (β=-0.172, P<0.05) and learning pressure (β=0.210, P<0.01) were the main influence factors for students. Conclusion Sleep quality of medical students was not high, upper grade was worse than low grade, the incidence of sleep disorder had increasing trend as learning pressure and degree of employment pressure worsen.

Sarcopenia is common in chronic heart failure. The pathogenesis of chronic heart failure-related sarcopenia is complex and diverse. Resistance training, as the main intervention for chronic heart failure-related sarcopenia, is widely applicated as effective and safe therapy.

Objective To analyze the relationship between knowledge on cardiovascular disease prevention and ideal cardiovascular health behaviors and factors in community elderly. Methods From December, 2015 to May, 2016, totally 400 elderly in communities with-out overt cardiovascular disease were conveniently sampled. The level of knowledge on cardiovascular disease prevention was measured by self-designed cardiovascular disease prevention questionnaire. And each of the ideal cardiovascular health components was collected. Re-sults A total of 390 responses were valid. 13.85%community elderly were with high level of the knowledge. There were significant differ-ences in the distribution of cardiovascular health indexes among various leves of the knowledge groups (χ2>9.974, P<0.05), except choles-terol (P>0.05). The level of the knowledge was positively correlated with the scores of cardiovascular health behaviors and health factors (r>0.354, P<0.01). The cardiovascular health score, health behaviors score, health factors score and number of ideal cardiovascular health in-dexes were significantly different among various levels of the knowledge groups (F>8.961, P<0.001). Conclusion The level of knowledge on cardiovascular disease prevention was positively correlated with cardiovascular health behavior and health factors. The scores of cardio-vascular health score, health behaviors score and health factors increased with the improvement of knowledge on cardiovascular disease pre-vention.

Objective: To understand the molecular evolution characteristics of the nucleoprotein (N) genes and epidemiological feature of 118 rabies virus (RABV) strains isolated in Yunnan province, China from 2006 to 2015. Methods: The brain tissue samples from mad dogs, suspicious sick dogs, sick cow, and human brain tissue, saliva and CSF samples from rabies patients were collected in Yunnan province to detect the viral antigen by direct immunofluorescence assay (DFA). The viral RNA from positive samples was extracted. Coding region of N gene was amplified by RT-PCR and sequenced. The phylogenetic tree was constructed by Neighbor-Joining method of MEGA5.0 software. Results: The sequences of N genes of 91 RABV strains in Yunnan from 2012 to 2015 were obtained. With the sequences of N genes of 27 RABV strains in Yunnan from 2006 to 2011 and 29 RABV strains from Southeast Asian Countries, the phylogenetic analysis was performed. RABV strains in Yunnan were divided into clades YN-A (105 strains), YN-B (6 strains), YN-C (7 strains), which belonged to clades China-I, China-VI, China-II respectively. Clade YN-A was epidemic every year from 2006 to 2015, of them, 14 strains from 2006 to 2011 and 91 strains from 2012 to 2015 were distributed in 13 prefectures (cities) of Yunnan. Clades YN-B and YN-C were epidemic only from 2006 to 2010 and from 2008 to 2011 respectively. The regional distribution of clades YN-B and YN-C was limited. The strains of YN-A and YN-C were closely related to the strains of clades China-I and China-II from neighboring Sichuan, Guizhou, Guangxi and Hunan provinces. The strains of YN-B were closely related to the strains from Myanmar, Laos, Vietnam and Cambodia. Conclusions Three RABV clades with multiple transmission sources were identified in Yunnan. Clade YN-A was widely distributed in rabies endemic area in Yunnan from 2006 to 2015, and it has strong ability to spread as principal clade in Yunnan. Since 2012, clades YN-B and YN-C were not found again in Yunnan.

High-grade gliomas (HGG) are a group of malignant tumours with high recurrence rate, rapid progression, poor prognosis and short median survival. Patients suffer with severe symptoms after operation, which seriously affect the quality of life of patients. Palliative care is an important nursing measure to improve the quality of life of patients with malignant tumors. This paper reviews the current situation and research progress of palliative care in patients with advanced glioma at home and abroad, and provides the evidence and guidance for medical staff to carry out palliative care of patients with high grade glioma.