SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To explore the effect of workshop situational teaching in practice training of midwifery specialty.Methods:89 students in midwifery specialty were divided into observational group and control group. The control group was given traditional teaching, and the observational group was implemented with situational teaching based on workshop. The effect of teaching was investigated by skill assessment, Chinese version of self-rating scale of self-directed learning and practice teaching quality evaluation questionnaire. SPSS 23.0 was used for t test.Results:The scores of 6 practical skills and the total scores of students in the observational group were higher than those in the control group, and the difference was statistically significant ( P<0.01, P<0.05). Study initiative, learning behavior, learning strategies, learning evaluation, interpersonal skills and self-directed learning ability of students in the observational group were all higher than those in the control group, and the difference was statistically significant ( P<0.01, P<0.05).The evaluation of teaching quality of the observational group was "excellent" and was "good" in the control group. There was no statistically significant difference in the scores toward teaching attitude of the observational group compared with the control group ( P>0.05). The total scores of teaching content, teaching methods, teaching effects and practice teaching quality of the observational group were higher than those of the control group, and the difference was statistically significant ( P<0.01). Conclusions:The workshop situational teaching was helpful in promoting the transformation of students' theoratical knowledge to practice, stimulate students' independent learning ability and improve the quality of practice teaching.

Objective To evaluate the effect of of home-care orthopedic nursing platform in rehabilitation exercise of patients after knee replacement.Methods A total of 60 patients with knee joint replacement were randomly divided into experimental group (n =30) and control group (n =30).The control group adopted conventional nursing,while the experimental group was added home care platform for orthopedics.Joint function recovery (HSS score),quality of life score (SF-36) and daily living ability (Barthel index) between the two groups were compared on admission,and at 6 months after discharge.Results No statistical differences in culture and knowledge absorption and understanding ability were found between the two groups before intervention (P ＞ 0.05).After intervention,the score of knee function,quality of life and ability of daily living of the patients in the experimental group were significantly higher than that in the control group (P ＜ 0.01).Conclusion Home care platform of orthopedics provides a new extension nursing mode for patients after total knee arthroplasty.It is a scientific and reliable rehabilitation consultation platform,which significantly improves postoperative rehabilitation and quality of life.

Objective To evaluate the effect of of home-care orthopedic nursing platform in rehabilitation exercise of patients after knee replacement.Methods A total of 60 patients with knee joint replacement were randomly divided into experimental group (n =30) and control group (n =30).The control group adopted conventional nursing,while the experimental group was added home care platform for orthopedics.Joint function recovery (HSS score),quality of life score (SF-36) and daily living ability (Barthel index) between the two groups were compared on admission,and at 6 months after discharge.Results No statistical differences in culture and knowledge absorption and understanding ability were found between the two groups before intervention (P ＞ 0.05).After intervention,the score of knee function,quality of life and ability of daily living of the patients in the experimental group were significantly higher than that in the control group (P ＜ 0.01).Conclusion Home care platform of orthopedics provides a new extension nursing mode for patients after total knee arthroplasty.It is a scientific and reliable rehabilitation consultation platform,which significantly improves postoperative rehabilitation and quality of life.

Objective To explore the effects of systematic nursing intervention on calcium and phosphorus metabolism and pruritus in hemodialysis patients. Methods A total of 60 patients undergoing hemodialysis in the Department of Nephrology at Wuxi Second Hospital Affiliated to Nanjing Medical University from February to August 2017 were selected and divided into control group and observation group by random number method, with 30 cases in each group. The control group was given routine care. Dietary guidance, psychological care and comprehensive health education were implemented in the observation group on the basis of routine nursing. Diet, skin pruritus and calcium and phosphorus metabolism were compared between the two groups. Results The dietary compliance rate in the observation group (83.33%) was higher than that in the control group (60.00%) after the intervention, and the difference was statistically significant (P＜0.05). There was no significant difference in serum calcium levels between the two groups (P＞0.05). The differences in the total parathyroid hormone and serum phosphorus levels between the two groups were statistically significant (P＜ 0.05). The degree of pruritus, the distribution of the skin and the score of sleep disturbance in the observation group were significantly lower than those in the control group, with statistical difference (P＜0.05). Conclusions Systematic nursing plays a positive role in calcium and phosphorus metabolism and pruritus in hemodialysis patients and is worthy of promotion and application.

Objective · To design and synthesize a series of benzenesulfonamide derivatives, test their inhibitory activity to CDK2-cyclinA2 kinase, and investigate the structure-activity relationship. Methods · Virtual screening was executed via computer-aided drug design according to the ATP binding site in CDK2-cyclinA2 protein crystal. A series of benzenesulfonamide derivatives were designed and synthesized on the basis of the interaction modes between the lead compound and the CDK2-cyclinA2. The biological evaluation of compounds was made through the CDK2-cyclinA2 in-vitro kinase activity detection system. Results · Twenty-nine new benzenesulfonamide compounds were prepared, and their inhibitory activity to CDK2-cyclinA2 was elicited. WZ-026 had the highest inhibitory parameter, which half maximal inhibitory concentration (IC50) was 3.81 μmol/L. Conclusion · By multipurpose utilization of virtual screening, chemical synthesis, and biological activity test, a benzenesulfonamide compound WZ-026 was found, which has great inhibitory activity towards CDK2-cyclinA2. Preliminary structure-activity relationship of compounds was obtained.

OBJECTIVETo explore the influence of genetic and environmental factors on the executive function of twin children.

METHODSThe executive function of 122 twin pairs from Chongqing (aged from 6 to 18 years) were investigated with the perseverative errors of the Wisconsin Card Sorting Test. Structural equation modeling was performed to evaluate the effects of the additive genetic factors (A), dominance genetic latent factors (D) and individual specific environmental factors (E) on the executive functions.

RESULTSThe effects of D and E on perseverative errors were 0. 77 (95%CI: 0.65-0.84) and 0.23 (95%CI: 0.16-0.35), respectively. The probability of perseverative errors showed a significant negative correlation with family functioning and with the total GHQ-12 scores of the fathers and mothers (r:-0.335, -0.335, and -0.219, respectively, P<0.01). Perseverative errors were not significantly correlated with the parenting styles and stress life events.

CONCLUSIONPerseverative errors are influenced by a common dominance genetic latent factor and individual specific environmental factors, but the role of environmental factors such as family functioning and parental health can not be ignored.

Objective Using twins methods to explore the influence of genetic and environmental factor on Intelligence develop-ment of children and adolescent twins .Methods It was 190 pair of twins aged 6 to 18 who lived in Chongqing were recruited ,DNA were extracted from buccal mucosa and venous blood samples to identify zygosity .The intelligence was investigated by using the Wechsler Intelligence Scale for Children(C-WISC) ,the intrapair correlation coefficients of twins were compared and calculate the genetic degrees .Results The total IQ of children aged 6 to 18 heritability were 0 .63 ,Verbal IQ were 0 .44 ,Performance IQ were 0 .57 .The total IQ heritability of children aged 10 to 14 and 15 to 18 years(0 .78 ,0 .79) were higher than that of those aged from 6 to 9 years(0 .018) .Conclusion This study suggested the intelligence of children aged 6 to 18 affected by genetic and environment , and the older ,the more influence of genetic on intelligence development .

Objective Analyzing the impact of teachers' background characteristics on the Students' evaluation to improve the quality of teaching from the angle of the teachers professional development. Methods Based on the data of students' evaluation of teaching of Shanghai medical college of Fudan University from 2008 to 2011, the article analyzed the teachers' gender, age, job title, diploma, and other relevant background characteristics. Excell2007 was used to build dataset and the data was analyzed statistically by software of SPSS 11.0 and expressed with x±s. The statis-tical method of one-way analysis of variance was used to compare the teachers with different genders, education backgrounds, ages and professional titles, showing statistically significant difference (P<0.05). Results comparative analysis showed that no statistically significant differences existed in fac-ulty teaching evaluation scores among the teachers of different genders or different education back-grounds(P=0.613 9、0.891 0). There were however significant differences in teaching evaluation of teachers of diverse ages and professional ranks(P=0.017 3 and P=0.032 5). Conclusions According to the analysis results of faculty teaching evaluations, associate professors' teaching evaluation scores were lower than intermediate grade teachers', and the score of the teachers between the age of 41 to 45 was lower than that of the teachers between the age of 36 to 40. Therefore individual variations and various social backgrounds of teaching faculties should be taken into consideration and the corre-sponding countermeasures for the professional development of teachers should been put forward. In addition, the cultivation of new teachers, young and middle-aged teachers should be strengthened, and the proportion of teaching evaluation in the Performance Appraisal should be increased.

Objective To explore the influence of genetic and environmental factors on emotional and behavioral problems in children and adolescents using twins quantitative method. Methods One hundred fifty-six twins pairs, aged from 6 to 18, were included in the present study. The parental version of the strengths and difficulties questionnaire (SDQ)was used to evaluate their emotional and behavioral problems. The DNA test of twin zygosity was conducted using DNA extracted from buccal mucosa or venous blood samples. The influence of genetic and environmental factors on emo-tional and behavioral problems was analyzed using structural equation modeling(SEM). Results Shared environment and special environment had impact on emotional symptoms and their contribution to the total variance of emotional symp- tom was 0.42 and 0.58, respectively. Prosocial behavior was mainly affected by shared environment and the contribution of shared environment to the total variance of prosocial behavior was 0.89. Genetic factors had greater influence on hyperac-tivity/attention deficit and the contribution of genetic factors to the total variance was 0.62. Shared environment had more influence on conduct disorder and the contribution of shared environment to total variance was 0.56. Heredity, shared envi-ronment and special environment had impact on peer problems and their contribution to the total variance was 0.24, 0.33 and 0.43, respectively. Conclusion In child and adolescent period, emotional symptoms are only affected by environ-ment, while behavior problems are affected by the combination of heredity and environment. Different behavior problems are affected by different genetic and environmental factors.