Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.

Objective:To explore the application effect of traditional Chinese medicine comprehensive nursing on elderly patients with coronary heart disease(qi stagnation and blood stasis type) constipation.Methods:A total of 126 elderly patients with coronary heart disease (qi stagnation and blood stasis type) constipation were divided into the control group and the experimental group by random digits table method, 63 cases each; the control group received routine nursing, and the experimental group was given traditional Chinese medicine comprehensive nursing; comparing the two groups of patients defecation, mental state, recurrence rate, and nursing satisfaction.Results:There was no significant difference in defecation frequency, each defecation time, defecation smoothness score, fecal trait score, fall inflated score, and self-Rating Anxiety Scale (SAS) score( P >0.05). After one month of nursing, defecation frequency, each defecation time, defecation smoothness score, fecal trait score, fall inflated score, and SAS score were (4.09±0.86) times/week, (5.12±1.24) min/time, (2.57±0.39) points, (1.53±0.31) points, (0.97±0.21) points, (49.27±4.15)points in the experimental group, (3.12±0.61) times/week, (6.87±1.52) min/time, (2.59±0.36) points, (2.02±0.44) points, (1.29±0.27) points, (54.42±6.01) points in the control group, the differences were significant ( t values were -6.638-7.081, all P<0.05). Within 1 month after nursing, the recurrence rate of constipation in the experimental group (14.3%, 9/63) was lower than that in the control group (74.6%, 47/63) , and the satisfaction rate of the experimental group (98.4%, 62/63) was higher than that in the control group (69.8%, 44/63) , the differences were significant(× 2 values were 46.414, 19.257, P<0.05). Conclusions:Traditional Chinese medicine comprehensive care for elderly patients with coronary heart disease (qi stagnation and blood stasis type) constipation can significantly improve their defecation and psychological state, and can reduce the recurrence rate and improve the patient's satisfaction with nursing, which deserves further clinical application and research.

0bjective To translate and revise the Assessment of Interprofessional Team Collaboration Scale (AITCS) into Chinese, then to evaluate the reliability and validity of the Chinese version of AITCS. Methods The Chinese version of AITCS was translated from the original one, back-translated and adjusted for cultural adaptation. The reliability and validity were tested among 288 nurses, 81 physicians, 25 respiratory therapists, 10 physical therapists and 3 nutritionists from a tertiary hospital in Hangzhou using convenience sampling. Results The average of scale-level content validity index was 0.98, unanimity of scale-level content validity index was 0.84 and item-level content validity index was 0.89-1.00. Exploratory factor analysis extracted three common factors,which explained 61.427% of the total variance,and each item had high factor loading quality (>0.4). The correlations coefficients between each dimension score and the total score ranged from 0.801 to 0.898 (P<0.05),and the correlations coefficients between each dimension score ranged from 0.607 to 0.698 (P<0.05). The Cronbach α of AITCS was 0.909, split-half reliability was 0.835 and test-retest reliability was 0.763. Conclusion The Chinese version of the AITCS has been proved to be reliable and valid. It is a valuable tool for evaluating interprofessional team collaboration among the health professional providers in mainland China.

Objective: To analyze the resting energy expenditure and optimal energy supply in different age groups of critically ill children on mechanical ventilation in pediatric intensive care unit (PICU). Methods: Patients on mechanical ventilation hospitalized in PICU of Beijing Children's Hospital from March 2015 to March 2016 were enrolled prospectively. Resting energy expenditure of patients was calculated by US Med Graphic company critical care management (CCM) energy metabolism test system after mechanical ventilation. Patients were divided into three groups:<3 years, 3-10 years, and >10 years. The relationship between the measured and predictive resting energy expenditure was analyzed with correlation analysis; while the metabolism status and the optimal energy supply in different age groups were analyzed with chi square test and variance analysis. Results: A total of 102 patients were enrolled, the measured resting energy expenditure all correlated with predictive resting energy expenditure in different age groups (<3 years (r=0.3, P=0.0) ; 3~10 years (r=0.6, P=0.0) ;>10 years (r=0.5, P=0.0) ) . A total of 40 cases in < 3 years group, including: 14 cases of low metabolism (35%), 14 cases of normal metabolism (35%), and 12 cases of high metabolism (30%); 45 cases in 3-10 years group, including: 22 cases of low metabolism (49%), 19 cases of normal metabolism (42%), 4 cases of high metabolism (9%); 17 cases in>10 years group, including: 12 cases of low metabolism (71%), 4 cases of normal metabolism (23%), 1 case of high metabolism (6%). Metabolism status showed significant differences between different age groups (χ²=11.30, P<0.01, r=-0.01). Infants had higher metabolic status, which lessened with aging. The total average actual energy requirement was (210±84) kJ/ (kg⋅d) . There were significant differences in actual energy requirement between age groups (F=46.57, P<0.001), with (277±77) kJ/ (kg⋅d) in<3 years group, (184±53) kJ/ (kg⋅d) in 3-10 years group, and (120±30) kJ/ (kg⋅d) in>10 years group. Conclusion The resting energy metabolism of the critically ill children on mechanical ventilation is negatively related to the age. The actual energy requirement should be calculated according to different ages.

Objective To evaluate the efficacy and experience of Q-switched laser with small light spot in the treatment of melasma.Methods Forty-six patients with melasma were emolled in study.Subjects received total of forty-six patients treatment with 1064 nm Q switched laser at one month intervals.Light spot of 3-4 nm were used.Results Forty-six patients completed the trial.The physician evaluation showed that 50％ of patients achieved 90％ to 100％ clearance,and 89.1％ patients achieved 60％ to 90％ clearance.Side effects was minimal and all the patients tolerated the treatment well.Conclusions Small light-spot and low-energy 1064 nm Q Switched laser is substantially effective and highly safe for the treatment of melasma.

Objective To analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.

Objective To investigate the morphological changes of the head,body and tail of the hippocampus in patients with Alzheimer's disease (AD).Methods Totally 30 AD (AD group),30 mild cognition impairment (MCI) patients (MCI group) and 30 normal old persons (normal control group) underwent brain MR scan.Based on the MR images,the head,body and tail of the hippocampus were segmented and the volume was measured.The difference of the volume in total,head,body and tail of hippocampus in AD group,MCI group and normal control group were compared.The correlation between hippocampal volume and the scores of neurological assessment scale was analyzed.Results The left total,head,body and tail volume were greater than those of the right side in 3 groups (all P＜0.05).For the comparison of total volume of left and right sides among the 3 groups,AD group was less than normal control group (both P＜0.01) and MCI group (both P＜0.05),MCI group was less than normal control group (both P＜0.05).Compared with the normal control group,the head,body and tail volume of hippocampus of both sides were decreased in AD group (all P＜0.05) and the volume of left head,body and right head of hippocampus in MCI group were decreased (all P＜0.05).Both sides hippocampus's head and body volume of AD group were less than those of MCI group (both P＜0.05).The scores of minimum mental state examination (MMSE) were positively correlated with the total and the head,body,tail volume of bilateral hippocampus.Except volume of left tail,there were negative correlations between the scores of activities of daily living (ADL),clinical dementia rating (CDR) and the volume of total and head,body,tail of bilateral hippocampus,which were positively correlated with Montreal cognitive assessment (MoCA) score.Conclusion The volume of bilateral hippocampus was significantly reduced in AD patients.The head of hippocampal volume was significantly reduced and the body and tail was not obvious.

Purpose To explore an automatic measurement method to replace the manual segmentation of hippocampal volume and brain structure by comparing the relevance and consistency between Freesurfer,as well as voxel based morphometry software (VBM8),and manual measurement of hippocampal volume,respectively.Materials and Methods Totally 67 young subjects (aged 20-40 years) and 75 elderly subjects (aged 60-80 years) were collected separately.After the whole brain MRI scan,the volume of the hippocampus was obtained by manual segmentation,importing to Freesurfer and VBM8 software respectively.Pearson correlation analysis and intraclass correlation coefficient (ICC) were used to statistically analyze the correlation of Freesurfer and VBM with manual measurement.Meanwhile,Bland-Altman scatter plot was used to reflect the consistency.Results Freesurfer and VBM were both highly related with manual measurement.The left and right r values of Freesurfer and VBM were 0.633,0.679 and 0.666,0.703,respectively in the young group,and 0.627,0.765 and 0.663,0.708,respectively in the elderly group;while ICC results showed an obvious difference.The value measured by Freesurfer in young group (ICC=0.377,0.502) was larger than that in the elderly group (ICC=0.307,0.459).However,on the whole,ICC VBM was larger than ICC Freesurfer and right hippocampal volume was larger than left one.The Bland-Altman diagram showed that the consistency of VBM with manual measurement was better than that of Freesurfer.Conclusion Freesurfer can be applied locally on the measurement of hippocampal volume in young subjects.VBM is more accurate than Freesurfer in replacing manual segmentation for measurement of adult hippocampal volume and for volume measurements used in hippocampus related clinical diseases or needed in experiments.

Purpose To study the hemodynamic changes of kidney interlobar artery in children with type 1 diabetes, and to explore the clinical value of the color Doppler ultrasound in diabetic nephropathy during the incubation period. Materials and Methods The study was performed in 52 children with type 1 diabetes and in 51 age-matched healthy children as control group. The resistance index (RI) of interlobar artery was measured with color Doppler ultrasonography, and the clinical data and laboratory indicators were analyzed. Results The left kidney RI, right kidney RI and average RI were all significantly higher in children with diabetes than in age-matched healthy group (P<0.01). The mean RI were correlated positively with (HbA1c) (r=0.96, P<0.01) and diabetes duration (r=0.31, P<0.01), respectively. Fasting blood glucose, glycated hemoglobin, and glomerular filtration rate were significantly higher in children with diabetes than in age-matched healthy group (P<0.01). Conclusion The RI of interlobar artery increases in children with type 1 diabetes. Early changes of renal hemodynamics in children with type 1 diabetes are detectable with Doppler sonography, and have certain value in early diagnosis of diabetic nephropathy.

OBJECTIVETo examine the oral health status among the orphan children and adolescents of Chongqing and assist in planning of the oral health programs.

METHODSAccording to the third national oral health investigation of epidemiology, the dental caries, gingival bleeding and calculus was examined among 317 orphan living in Chongqing, by cluster sampling. The statistical software SPSS 17.0 was used for the data analysis.

RESULTSIn primary and permanent teeth, the prevalence of dental caries and mean DMFT (dmft) were found to be 50.00%, 1.94 +/- 2.81 and 39.53%, 0.90 +/- 1.38. There were no significant difference between female and male (P>0.05). But there was significant difference of the prevalence of permanent tooth caries between the age group under 12 (include 12) and above 12 (P < 0.05). It was also found that 35.25% of the orphan children and adolescents had caries in the first permanent molar, and there was significant difference between female and male (P < 0.05). Neither of the caries teeth above was treated nor the healthy teeth were sealed. The prevalence rate of gingival bleeding was 78.22%, and the calculus rate was 67.66%.

CONCLUSIONThe oral status of the orphan is poor, and this community has experienced a low utilization of preventive or therapeutic oral health services. In the future work, orphans should be considered as a priority group when make plans for oral health care.

Adolescent ; Child ; Child, Preschool ; China ; DMF Index ; Dental Caries ; Dentition, Permanent ; Female ; Health Status ; Humans ; Male ; Molar ; Oral Health ; Prevalence