In order to solve the difficucties of renaturation and immunogenicity of new bifunctional fusion protein GAD,inclusion bodies of GAD were modified by PEG-maleimide.Conformational changes of the modified GAD were compared by circular dichroism and tryptophan fluorescence spectroscopy.The biological activity was verified by oral glucose tolerance test and lipid scavenging.The results showed that PEG-maleimide completed the specific-point modification of GAD,and improved its refolding efficiency.The secondary and tertiary structures of mPEGylated GAD were consistent with that of GAD.PEG-GAD has significant hypoglycemic and lipid-lowering effects (P ＜0.001) with longer half life in vivo and lower immunogenicity (P ＜0.01).This study provides effective strategies for the development of strongly hydrophobic peptide drugs.

Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight=3.29, RMS=0.53, total cost-null cost=62.75, Correl=0.93, Config=19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.

Objective:To explore the cytogenetic characteristics of hypospadias in children by karyotype analysis.Methods:From June 2008 to May 2018, 45 children with hypospadias in Tianjin Children's Hospital had cytogenetic abnormalities. Their median age was 10 months(range 3 hours to 5 years old). Of the 45 cases, 20 were proximal hypospadias, 1 was middle hypospadias. All 24 cases had varying degrees of genitourinary malformations. Among them, 15 cases had unilateral or bilateral cryptorchidism, 5 cases had scrotal division, 3 cases had penile scrotal transposition, 3 cases had small penis, 3 cases had indirect inguinal hernia, 1 case had repeated urethra, 1 case had hydrocele and 1 case had concealed penis. To the other systemic malformations, there was 1 with cleft lip and palate and 1 with congenital heart disease. G-banding karyotype analysis of peripheral blood lymphocytes was performed in all 45 cases.Results:Among the 45 cases of hypospadias with abnormal karyotypes, with an abnormal rate of 14.0%, 28 cases (62.22%) had sex chromosome abnormalities, including (47, XXY), (46, XX/47, XXY), (45, X0/47, XYY), etc. Sexual inversion occurred in 8 cases (17.78%), all of which were 46, XX. There were 4 autosomal abnormalities (8.89%), including (46, XY, 9p+ ), (46, XY, 10p+ ) and (46, XY, 1q+ ). Chromosome polymorphism was found in 4 cases (8.89%), including [46, XY, inv(9)] and [46, XY, 16qh+ ], and the equilibrium translocation of 1 case (2.22%) was [45, XY, -21, -22, + t(21; 22)]. Among the 45 cases, 8 sex reversal children with (46, XX) chromosome karyotype were all proximal hypospadias.Conclusions:Children with hypospadias may be associated with chromosomal karyotype abnormalities, including sex chromosomal abnormalities, autosomal abnormalities, chromosome polymorphism and balanced translocation. Among them, sex chromosome abnormality was the most common and balanced translocation was the least.

OBJECTIVE To explore the origin and morphological features of small supernumerary marker chromosomes (sSMCs) in Turner syndrome. METHODS For 5 cases of Turner syndrome with a sSMC identified by conventional G-banding, dual-color fluorescence in situ hybridization (FISH) was applied to explore their origin and morphological features. RESULTS Among the 5 cases, 3 have derived from the X chromosome, which included 2 ring chromosomes and 1 centric minute. For the 2 sSMCs derived from the Y chromosome, 1 was ring or isodicentric chromosome, while the other was an isodicentric chromosome. CONCLUSION The sSMCs found in Turner syndrome have almost all derived from sex chromosomes. The majority of sSMCs derived from the X chromosome will form ring chromosomes, while a minority will form centric minute. While most sSMC derived from Y chromosome may exist as isodicentric chromosomes, and a small number may exist as rings. For Turner syndrome patients with sSMCs, dual-color FISH may be used to delineate their origins to facilitate genetic counseling and selection of clinical regime.

Air ; analysis ; Air Pollutants, Occupational ; analysis ; Chromatography, Gas ; methods ; Environmental Monitoring ; methods ; Toluene ; analogs & derivatives ; analysis ; Workplace

Objective To study the relationships between the standing balance and walking ability of hemiplegic stroke survivors.Methods Eighty-eight post-stroke hemiplegic patients who could walk independently for more than 10 metres were selected into a patient group,while 88 healthy counterparts were recruited into a control group.Descriptors of the gait and balance function of both groups were collected using a gait and balance training and evahuation apparatus (Model:AL-600).The gait parameters were step width,walking speed,step length asymmetry (SLA),swing time asymmetry (SWTA) and stand time asymmetry (STA).The balance parameters studied were total trajectory length of the center of plantar pressure (COPD),the average left and right deviation of the center of plantar pressure (COPD-X) and the average anterio-posterior deviation of the center of plantar pressure (COPD-Y).Differences in indexes of gait and balance function between the two groups were analyzed using t-tests,and the relationships between the gait and balance indicators were analyzed using Pearson correlation coefficients.Results The walking speed,step width,COPD,COPD-X,COPD-Y,SLA,SWTA and STA of the patient group [(37.64± 18.29)cm/s,(14.45±4.17)cm,(66.75±29.04)cm,(2.04±1.41)cm,(2.48±1.28)cm,(1.30±0.46),(1.65±0.67) and (1.18±0.16),respectively] all increased significantly more compared to the control group [(90.76±14.72)cm/s,(8.70±2.62) cm,(27.84±6.54) cm,(1.30±0.53) cm,(1.68±0.40) cm,(1.07±0.06),(1.07±0.08) and (1.05±0.06),respectively],though the walking speed was significantly slower than that in the control group (P＜0.05).The patient group's average COPD-X showed slightly and moderately negative correlation with their walking speed,step width,SLA and SWTA (P＜0.05).COPD-Y was weakly related with step width (P＜0.05).Conclusion The standing balance of hemiplegic patients after stroke is related to their walking speed,step width and gait asymmetry.Especially significant correlation is observed between standing balance parameters such as COPD-X and gait parameters.

Objective To investigate plasma level of soluble intercellular adhesion molecule-1 (sICAM-1)and soluble E-slectin (sES) in patients with Keshan disease (KD) accompanied by hypertension,and to further their relation to systolic blood pressure (SBP),diastolic blood pressure (DBP) and ejection fraction (EF) of left ventricle.Methods Patients with Keshan disease investigated in 2007 in Fuyu County,Heilongjiang Province were divided into two groups according to whether they were accompanied by hypertension or not:KDP group (n =17),the patients were diagnosed as Keshan disease accompanied by hypertension;KDN group (n =14),the patients were only diagnosed as Keshan disease.Healthy volunteers lived in the same area as the patients were included in the control group (CON group,n =10).The clinical data (such as age,sex and past medical history),SBP and DBP were recorded.EF was detected by echocardiography.Plasma sICAM-1 and sES concentrations were measured by ABC-enzyme-linked immunosorbent assay technique.Results Plasma level of sICAM-1 in the subjects was significantly elevated in KDP group as compared with that in CON group and KDN group [(399.84 ± 99.06) vs (323.06 ± 61.27) μg/L,P ＜0.05;(399.84 ± 99.06) vs (268.27 ± 72.88) μg/L,P ＜ 0.01].However,there was no statistical significance in plasma sICAM-1 between the KDN group and control group (P ＞ 0.05).The difference of plasma sES between the control group,KDN group and KDP group did not reach statistical significance [(76.31 ± 23.17),(72.26 ± 20.15) and (90.21 ± 19.21) μg/L,F =3.236,P ＞ 0.05].As compared with the KDN group,SBP and DBP were obviously higher in KDP group [(169 ± 27) and (121 ± 10) mmHg,(102 ± 17) and (81 ± 6) mmHg,1 mmHg =0.133 kPa,F =6.376,4.300,all P ＜ 0.01],and EF was not significantly increased [(58 ± 14)％ and (55 ± 14)％,F =0.789,P ＞ 0.05].Furthermore,correlation analysis showed plasma sICAM-1 was positively correlated with SBP (r =0.540 6,P ＜ 0.01)and DBP (r =0.461 2,P ＜ 0.01),but not with EF of left ventricle in subjects whir Keshan disease (r =0.073 4,P ＞0.05).Conclusion These data shows slCAM-1 may play a role in the development of Keshan disease accompanied by hypertension,providing an potential index for its risk assessment.

Objective To explore the correlation between plantar pressure and walking function in hemiplegic stroke patients.Methods Thirty hemiplegic patients with stroke (a hemiplegic group) and thirty age-matched healthy persons (a control group) were recruited.Gait and balance function training and assessment system (model:AL-600) were used to quantify the walking velocity,peak plantar pressure at heel-strike and push-off periods and displacement of center of pressure (DCOP) of all subjects during walking.The asymmetry of gait was calculated.Two independent sample t-test were used to compare the walking velocity,peak plantar pressure and DCOP for the two groups.Pearson correlation coefficients were applied to analyze the correlation between the walking velocity and peak plantar pressure and DCOP.Results The walking velocity,the peak plantar pressure at heel-strike and push-off periods and DCOP of the hemiplegic group were significantly lower than the control group.In the hemiplegic group,the asymmetry of peak plantar pressure and DCOPx significantly increased,while that of DCOPy became bigger without significant difference.Moreover,the walking capacity of the hemiplegic group was positively correlated with the peak plantar pressure and DCOP.Conclusion Among hemiplegic stroke patients,both the peak plantar pressure at heel-strike and push-off periods lower in a way.Their capacity of weight transfer decreases,which is closely related to their walking velocity.

At 2:28 p.m. local time on 12 May, 2008, the Wenchuan earthquake struck with a magnitude of 8.0. After the earthquake, 1364 injured persons, including 732 women and 632 men, were admitted to Deyang People's Hospital. The ages of the injured persons ranged from 0.2 years to 102 years (mean, 42.5 years). Of all injured persons, 4.65% aged under 7 years, 13.84% between 7 and 18 years, 39.57% between 19 and 45 years, 24.48% between 46 and 65 years, and 17.46% above 65 years. A total of 1713 injuries were found in all the injured persons, and the predominant injuries were found in limbs, body surface, head and chest. The incidence of the multiple injuries was 23.64%. Eighteen persons with abdominal injuries received operation. Prompt, accurate and systematic evaluation of the injury is necessary in raising the rescue efficiency. Treating the injured persons according to a classification optimizes the usage of the limited medical resources. Early definitive operation is crucial in rescuing the lives of the injured persons, and the treatment should be applied within 24 hours after the earthquake, then the emphasis of the rescue work should shift to helping orthopedic surgeons with operation and debridement.

Objective To evaluate the targeted killing of malignant melanoma cells by aclarubicin liposomes conjugated with vascular endothelial growth factor(ADM-VEGF-SSL)in vitro.Metheds To detect the binding abilitv of liposomes to malignant melanoma(MM)cells,the human malignant melanoma cell line A375 was cultured in the presence of ADM-VEGF-3H-SSL or ADM-3H-SSL for 2 days followed by the detection of radioactivity of these cells.Then.A375 cells were cultured with various concentrations(0.01,0.1,1,10,100 mol/L)of ADM-VEGF-SSL,ADM-SSL or free ADM for 48 hours in the 48-hour cytotoxity test,or for 0.5 hour followed by another 48-hour culture in drug-free medium in the 0.5-hour cytotoxity test.After that,MTT assay was used to detect the survival rate of these cells.Results ADM-VEGF-SSL could specifically bind to and kill A375 cells.The binding rate of ADM-VEGF-SSL was 2.15 folds as high as that of ADM-SSL.The survival rate of A375 cells after being treated with ADM-VEGF-SSL for 48 hour was similar to that with flee ADM(P＞0.05).but lower than that with ADM-SSL(P＜0.05),while the survival rate of melanocytes treated with ADM-VEGF-SSL was higher than that with free ADM or ADM-SSL(both P＜0.05).As shown by the 0.5-hour cytotoxity test.shortening the treatment course did not attenuate the effect of ADM-VEGF-SSL on A375 cells.Conclusions ADM-VEGF-SSL can specifically recognize A375 cells.efficiently deliver adriamycin into tumor cells,markedly inhibit the proliferation of A375 cells,and eventually,a targeted kill of these cells is realized.