Objective: To develop a new series of hydroxy ethylamine (HEA) BACE1 inhibitors with nitrogen heterocyclic moiety at N-terminal and find new N-terminal moiety for enhancing BACE1 inhibition activity. Methods: New HEA compounds with nitrogen heterocyclic moiety at N-terminal were synthesized and evaluated as BACE1 inhibitors,with (-)-epigallocatechin-3-gallate EGCG as a positive control. Results: All new compounds were characterized by 1H NMR and ESI-MS. Evaluation of BACE1 inhibition activity showed that the compound I6 with indole moiety at N-terminal had BACE1 inhibition activity. Conclusion: The results suggested that the indole moiety at N-terminal interact with S2 pocket of BACE1 and be favorable for enhancing BACE1 inhibition activity, Thus, the indole moiety at N-terminal can be used as lead structure for further finding more effient BACE1 inhibitors.

0.05).Conclusion There is no significant correlation between ACE gene polymorphism and type 2 diabetic nephropathy.

Retinitis pigmentosa (RP) is a large group of common hereditary eye diseases with highlyheterogeneous genetic background. Over forty genes with diverse functionalities are associated with RP and they include a set of ubiquitously expressed genes. These include five genes involved in the precursor messenger RNA( premRNA) splicing. Recent progress in disease gene identification for RP has established the involvement of pre-mRNA splicing as one important mechanism in the disease etiology and has shed light on the splicing process itself, a fundamental biological process. To this date, studies in this field have been focused on two major issues. First, how do the mutations of the adRP associated splicing factors (adRP-SF) affect the splicing function? Second, how do the mutations in these ubiquitously expressed genes lead to specific retinopathy? The two topics fit with the two continuous important steps of the disease pathogenesis. Recently, researchers have made a dramatic progress in the first topic. The identification of the SNRNP200 gene,the fifth adRP-SF and its relevant functional study has shown significance to the progress in the study of RP. Numerous investigations are also being carried out in addressing the second issue.Generation of a variety of models led to a better description of the pathological process of the disease. However, in respect to the key pathogenic mechanism,researchers are still puzzled with a number of confusing questions. In this commentary,the results from the latest investigations were summarized, and in particular,the difficulties in studying the molecular mechanism by which the pre-mRNA splicing deficiency causes RP were detailed.

Background Nomal binocular vision is achieved through accommodation and vergence.Anisometropia is associated with abnormal visual development,but its impact on accommodation and vergence is unknown.This study is helpful to make a reaonable correction plan for anisometropia.Objective This clinical study was to examine the binocular vision function in myopic anisometropia and evaluate the influence of myopic anisometropia on binocular vision function.Methods Seventy subjects with myopic anisometropia ≥ 1.0 D were recruited in Tianjin Eye Hospital and Tianjin Vocational Institute from 2006 to 2009.The subjects were assigned to the low anisometropia group with the 1.0 D ≤ spherical equivalent difference ＜ 2.5 D and the moderate and high anisometropia group with spherical equivalent difference ≥2.5D,and other 35 individuals with spherical equivalent difference ＜ 1.0 D were enrolled as the without anisometropia group.Binocular vision function parameters were examined in all the individuals,including comprehensive refractometer to check the diopter,Worth 4 dot to examine the binocular vision function,different distance of vertical fusional amplitudes,accommodative convergence/accommodation (AC/A) and stereoscopic vision.Written informed consent was obtained from each subject prior to the study.Results After anisometropia was completely corrected,the normal rate of Worth 4 dot examination was 94.3％,80.0％ and 60.0％ in the without anisometropia group,low anisometropia group,moderate and high anisometropia group,respectively,showing a statistical difference among groups (x2 =12.137,P＜0.05),and the normal rate of 4 dot was less,and that of 5 dot was higher in the moderate and high anisometropia group compared with the without anisometropia group and low anisometropia group (P＜0.05).No significant difference was found in the normal rate for phoria of distance among the three groups (x2 =4.489,P=0.344).The normal rate for near phoria of distance was 65.7％,42.9％ and 37.1％ in the without anisometropia group,low anisometropia group,moderate and high anisometropia group,respectively,with significant difference among them (x2 =6.045,P＜0.05).The normal rate of stereopsis was 91.4％,77.1％ and 54.3％ in the without anisometropia group,low anisometropia group,moderate and high anisometropia group,respectively,which was statistically different among groups (x2 =12.863,P =0.002),and that in the moderate and high anisometropia group was significant declined in comparison with the without anisometropia group (x2 =12.208,P ＜ 0.05).The difference of distance phoria,AC/A,negative relative accommodation (NRA),positive relative accommodation (PRA),accommodation amplitude and binocular accommodative lag were statistically different among groups (P＞0.05).Conclusions The normal rate of the stereopsis,Worth 4 dot and the phoria of near distance are decreased with the increase of anisometropia,but other ocular motor parameters are normal in anisometropic subject.

Objective To evaluate the clinical efficacy of percutaneous vertebroplasty (PVP) for patients with fresh osteoporotic vertebral compression fracture (OVCF).Methods From February 2010 to November 2011,103 patients with fresh OVCF were assigned to receive either PVP or conservative treatment according to their choice or the choice of surgeons.There were no significant differences between the 2 groups regarding general clinical data (P ＞ 0.05).The pain was scored at pre-treatment,1,4,12,24 and 48 weeks post-treatment in all the patients.The vertebral re-fractures were recorded in both groups at follow-ups.The 2 groups were compared in terms of postoperative pain relief and risk of re-fracture.Results The overall pain relief at 1,4 and 12 post-treatment in the PVP group was significantly greater than in the conservative treatment group (P ＜ 0.05).The pain relief at night at 1,4 and 12 post-treatment was significantly greater in the PVP group than in the conservative treatment group (P ＜ 0.05).At one year post-treatment,7 vertebral re-fractures were observed in the PVP group (18.4％,7/38) and 12 ones in the conservative treatment group (20.3％,12/59),with no significant difference between the 2 groups in the risk of re-fracture (Hazard ratio =0.909,95％ CI:O.36 ～ 2.29,P =0.841).Conclusion Compared with conservative treatment,PVP may significantly reduce the pain for patients with fresh OVCF but does not increase the risk of vertebral re-fracture.

Objective To explore the main inhalational and alimentary allergens which triggers allergic asthma in children in Suzhou area.Methods The serum specific aspiration allergens were detected with enzyme-linked immunosorbent assay(ELISA) in 119 children with bronchial asthma,including 7 kinds of common inhalational allergens.The 6 kinds of alimentary allergens test was conducted in 65 children.Results The total inhalational allergens positive rate of the subject was 75.63%(90/119).The highest rate was dust mite 49.58%(59/119),then was house dust 21.02%(25/119),animal hair 19.33%(23/119).The positive rate of aspiration allergens increased with the patient′s age and showed a positive correlation.Positive rate of food allergens was 49.23%(32/65).Of them,the highest rate was fish 20.0%(13 cases),then was lobster and claw 16.92%(11 cases),egg 12.31%(8 cases).Conclusions Inhalational allergens are the main allergens in children with asthma in Suzhou district.The positive rate of aspiration allergens increases with the patient′s age.The most common allergen is dust mite.The allergen test plays a clinically significant and advisable role in treatment and prognosis in bronchial asthma in children.

Objective To investigate effects of driving fatigue on auditory involuntary attention.Method Between-groups design was used.The control group included 13 taxi drivers after adequate rest while the fatigue group included 13 taxi drivers who had been driving for 10 h.Auditory oddball pattern was adopted.The standard stimulus was 800 Hz,probability 80%;target stimulus was 1 000 Hz,probability 10%;novel stimulus was sound generated by computer or other sound,probability 10%.Subjects were asked to press the mouse upon hearing the target sound.Result The distribution of P3a was mainly around the frontal-central area of the subjects in control group;the amplitude of P3a was evidently lowered in subjects after driving fatigue.Conclusion The ability of auditory involuntary attention declines after driving fatigue.

Artificial femoral head replacement is commonly performed in elderly patients with femoral neck fracture. However, the patients are always complicated by other diseases and their major organ functions are low, which increases risks of anesthesia and replacement. The anesthesia methods for artificial femoral head replacement include epidural anesthesia, combined spinal-epidural anesthesia, and general anesthesia. Respiratory system and nervous system complications, bleeding and transfusion complications, deep venous thrombosis and lung embolism, and bone cement-associate complications are common complications in anesthesia for femoral head replacement. Therefore, appropriate anesthesia pattern, rigid monitoring, and proper treatment can reduce anesthesia risks.

Background Rhodopsin (RHO) gene is the most common disease gene for autosomal dominant retinitis pigmentosa (adRP),one of the main pathogenesis is that misfolded mutant RHO proteins accumulate in the endoplasmic reticulum and cause endoplasmic reticulum stress (ERS).Objective This study aimed to determine the genetic basis for a consanguineous Chinese Han adRP family.Methods This study procedure complied with Helsinki Declaration.All participants in the family were investigated under the informed consent.Regular ocular examination was performed on the patients in this family.Next-generation sequencing (NGS) was carried out to screen the mutations in 189 genes associated with hereditary retinal diseases (HRDs).After being analyzed and filtered,variations detected by NGS were validated by Sanger sequencing and evaluating of pathogenicity.The wild-type RHOWT and mutant RHOP53Rwere cloned into the vector pEGFP-N1.Then the two plasmids were transfected into adult retinal pigmentosa epithelium cell line(ARPE19) and human embryo kidney 293 line (HEK293) to observe the location of rhodopsin-GFP fusion protein in cells,and the expression of ERS related protein XBP1 in the cells was detected by quantitative-PCR and Western blot.Results This family included 5 generations with the typical adRP characteristics.Genetic analysis identified a heterozygous variation,p.P53R in RHO gene,which was fully cosegregated in the family.Wild-type RHOWT-GFP fusion proteins showed the green fluorescence on the endoplasmic reticulum and cytomembrane,but the misfolded mutant RHO-GFP fusion protein gathered only in endoplasmic reticulum.Compared to wild-type RHOWT,the XBP1 was activated and increased by (1.28 ±0.09) fold.The introns of 26 bases in XBP1 mRNA were removed in the HEK293 cells with mutant RHO-GFP fusion protein,and the expression of XBP1 was stronger in the HEK293 cells with mutant RHO-GFP than that in HEK293 cells with wild type RHO-GFP and cells with blank pEGFP-N1 plasmid.Conclusions Heterozygous variant RHO p.P53R is very likely the pathogenical mutation in the adRP family.The RHOP53R mutant rhodopsin protein can not be delivery effectively from the endoplasmic reticulum to the cell membrane,and these proteins accumulate in the endoplasmic reticulum,which causes ERS.

A methodology named immunoscorehas been proposed in recent years.It has been demonstrated to be a prognostic factor superior to the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC)TNMclassification.Over the past few years,it has gained a forefront posi-tion in colorectal cancer.It has the advantages of simple operation,low cost and high accuracy,and it is nee-ded for individual therapy.However,it still has its limitations.