Objective Alzheimer's disease(AD) is a common and devastating disease and there is no readily available biomarker to aid diagnosis or to monitor disease progression. This study is to further understand the pathogenesis of Alzheimer's disease and seek new biomarkers for AD. Methods AD rats made by Aβ1-40 were assessed using the Morris water maze method. Sera of two groups were collected and albumin, IgG and sodium chloride were removed from the serum before concentration. Two-dimensional electrophoresis(2-DE) was performed on serum protein. Altered proteins were identified by matrix assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS). Results Compared with untreated samples, 10 altered proteins were found through 2-DE and all of them were down-regulated of which 2 were identified by MALDI-TOF-MS to be plasma retinol-binding protein precursor and complement component 4, gene 2 (C4b). Conclusion C4b may be the biomarker of AD and it may be helpful to understand the pathogenesis of AD.

Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

Objective To prospectively investigate the characteristics and correlative influential factors for the changes in pulmonary artery hypertension (PAH)in chronic kidney disease (CKD) patients without end-stage renal disease.Methods Complete clinical and laboratory data of 133 outpatients without ESRD (CKD stage 2,3 and 4)in Beijing Hospital between January 2012 and January 2013 were retrospectively analyzed.Pulmonary artery systolic pressure(PASP)was assessed by echocardiography according to the guideline from the American Society of Echocardiography in 2010,and PASP more than 35 mmHg(1 mmHg=0.133 kPa)was diagnosed as PAH.Results PAH was found in twelve(9.0 ％) patients,including 7 females and 5 males,with mean age(82.9 ± 5.4 years).The prevalence of PAH was 2.3％,10.9％ and 17.6％ in the patients of CKD stage 2,3 and 4(P＜ 0.05) respectively.PASP could be calculated in 67 patients in whom tricuspid regurgitation was present.The mean PASP was (27.1 ± 5.4) mmHg,(31.0 ± 8.3) mmHg and (37.3 ± 13.8) mmHg in patients with CKD stage 2,3 and 4,respectively(P ＜ 0.05).Body mass index(BMI),eGFR and BUN showed significant differences between PAH group and non-PAH group with statistical significance (P＜0.05).Multivariate logistic regression analysis revealed that the lower BMI and the higher stage of CKD were independent risk factors for PAH (P ＜ 0.05).Conclusions PAH is not a rare complication in the CKD patients without end-stage renal disease.The incidence of PAH is significantly associated with lower BMI and the higher stage of CKD.Doppler echocardiography should be performed periodically to detect PAH in CKD patients in order to improve the prognosis of these patients.

Objective Predicting protein structural class is the basis for predicting protein spatial structure,so it is important to improve the prediction accuracy of protein structural class.Methods We proposed 3-state and 8-state Hidden Markov model (HMM),and applied these HMMs to the prediction of protein structural class,respectively.We evaluated their accuracy on two different datasets through the rigorous jackknife cross-validation test.Results Prediction ability of 8-state HMM and 3-state HMM to all α class were excellent,the prediction accuracy of 3-state HMM even reached above 95％.Compared with Chou data set,the prediction accuracy of Zhou data set for all β class and α/β class of was improved,while overall prediction accuracy increased by 2％.Conclusion HMM is an effective method to predict protein structural class.

The on-line monitor for the changes in the content of baicalin in Scutellariae Radix formula particles during the extraction process was conducted by using near infrared spectroscopy (NIR). High performance liquid chromatography (HPLC) was used as a reference method. Kennard-Stone (KS) was used to divide sample sets, so as to compare different pretreatment methods. The synergy interval partial least squares (SiPLS) was used to screen out modeling wave band to establish partial least-squares models. The relative error method was applied to predict forecast set samples of Scutellariae Radix in three extraction phases. The results showed that the model established by Savitzky-Golay smoothing with 11 points (SG11 points) was the best, with the root mean square with cross validation (RMSECV), root mean square error of correction (RMSEC) and root mean square error of prediction (RMSEP) of baicalin of 0.092 7, 0.134 4 and 0.114 8, respectively, the determination coefficient R2 of greater than 0.99, and the relative error of baicalin content of less than 5%. This indicates that the on-line near infrared reflectance spectroscopy could be applied in on-line monitor and quality control of the extraction process of Scutellariae Radix formula particles.
Automation ; methods ; Drugs, Chinese Herbal ; chemistry ; standards ; Quality Control ; Scutellaria baicalensis ; chemistry ; Spectroscopy, Near-Infrared ; methods

Objective To explore pre-attentive information processing in undergraduate students with major depressive disorder(MDD) indexed by auditory mismatch negativity (MMN) and provide scientific theory basis for the diagnosis of MDD.Methods In the deviant-standard reverse oddball paradigm with deviant stimulus presentation probability of 20％,duration auditory MMN was obtained in 17 MDD university students and 17 gender-/age-matched healthy undergraduate students.All data were analyzed by statistics means of repeated measurement of F test.Results The amplitudes of 150 ms MMN over the frontal-central area were smaller in MDD undergraduate students((-0.34± 1.24) μV) than those in healthy undergraduate students ((-1.07± 1.55) μV,F=24.318,P=0.000).The 50 ms MMN did not differ between MDD students ((-1.96± 1.14) μV) and healthy undergraduate students ((-1.23 ± 1.97) μV,F =0.089,P =0.767).Conclusion Pre-attentive auditory information processing is impaired in MDD undergraduate students.

Objective To investigate the growth curve,breeding rate,and blood physiological and biochemical parameters in Npc1 gene mutant mice (Npc1-/-) for providing theoretical evidence in research on Niemann-Pick disease type C1 (NPC1) patient.Methods 1) The body mass of Npc1-/-,Npc1+/-,and Npc1+/+ mice (n=120;60♀,60♂) was measured from 0 to 77 days;(2) As Npc1-/-mice were born only by the mating Npc1+/-mice,the breeding rate of Npc1+/-mice was counted here from the 1st to 4th generation;(3) The blood physiological and biochemical parameters were measured on both Npc1-/-and Npc1+/+ mice at 60 days.Results 1) Compared with the wild type controls,the body weight of Npc1-/-mice was progressively increased up to 7 weeks and then decreased,and died around 11 weeks.The body weight of the Npc1+/-and Npc1+/+ mice was increased as time went on.After 4 weeks,the male mice showed a higher weight gain than the females;(2) The generations of Npc1+/-mice had no significant difference in mating-parturition interval,litter size,weaning litter and the number of male and female (P>0.05),but the weaning rate of the 2nd generation was significantly higher than that of the 1st generation (P<0.05);(3) The hematological parameters showed a significant difference only in mean corpuscular hemoglobin (MCH) and mean peroxidase index (MPXI) between the Npc1-/-and Npc1+/+ mice (P<0.05).No significant difference was found in other hematological parameters (P>0.05).Among the biochemical parameters,aspartate aminotransferase (AST),glucose (GLU),lactate dehydrogenase (LDH),potassium (K) and copper (Cu) had a significant difference between the Npc1-/-and Npc1+/+ mice (P<0.05).Conclusions 1) The growth curves of Npc1-/-,Npc1+/-,and Npc1+/+ mice are different due to different genotype and sex;(2) The reproduction rates of Npc1+/-mice have no significant difference among different generations;(3) The blood physiological parameters (MCH,MPXI) and biochemical parameters (UREA,AST,GLU,LDH,K,Cu) are significantly different between Npc1-/-and Npc1+/+ mice.

Objective To investigate the rates of undernutrition and nutritional risks of surgical pa-tients with pancreatic tumors .Methods Totally 121 surgical patients with pancreatic tumors from Depart-ment of Surgery Beijing Hospital were enrolled in a prospective study during January 2014 to December 2015 . Patients were divided into two groups:the pancreatic cancer group ( n=90 ) and other pancreatic tumor group ( n=31 ) .Nutritional Risk Screening 2002 was used to assess the nutritional status .Other data including an-thropometric measure, body composition, blood biochemistry and clinical outcome were collected and ana-lyzed.Results Among 121 patients, the mean age was ( 61.9 ±13.6 ) years, the mean body mass index was ( 23.20 ±2.95) kg/m2 , the mean mid-upper circumference was ( 28.8 ±3.5 ) cm, the mean muscle weight was (44.6 ±7.4) kg, and the mean fat mass was (16.8 ±7.6) kg .There was no significantly differ-ence in anthropometric measurement results and body compositions between two groups ( all P>0.05 ) .In the pancreatic cancer group, albumin [ (39.0 ±4.7) g/L vs. (42.3 ±2.9) g/L, P<0.001], total protein [ (62.8 ±6.2) g/L vs.(66.3 ±2.9) g/L, P<0.001], and prealbumin [ (136.1 ±85.4) mg/L vs. (197.8 ±112.6 ) mg/L, P=0.011 ] were significantly lower than those in the other pancreatic tumor group and a higher fasting blood-glucose [ (6.45 ±2.47) mmol/L vs.(4.95 ±0.79) mmol/L, P<0.011] was found.Among all patients , the rates of undernutrition and nutritional risk were 4.1% and 78.5%, and the pancreatic cancer group had a higher rate of nutritional risk (91.1% vs.38.7%,χ2 =36.525, P<0.001). Conclusion In this prospective study , surgical patients with pancreatic cancer have a high incidence of nutri -tional risk, with low protein level and abnormal glucose metabolism .

AIM:To investigate the renal function and pathological changes in Npc1 mutant ( Npc1-/-) mice. METHODS:Different genotypes of Niemann-Pick disease type C1 (Npc1) mice were identified by PCR.Subsequently, the renal function of Npc1-/-and Npc1 +/+mice at postnatal day 60 ( P60) was evaluated by measuring the activity and con-tent of important indicators in the serum including ALT , AST, LDH, urea, UA and Cr.Furthermore,β-galactosidase stai-ning and Masson staining were performed to examine the aging and fibrosis of the renal tissues , respectively .RESULTS:Compared with the Npc1 +/+mice, the body weight and kidney weight had a significant reduction ( P<0.01) in the Npc1-/-mice.The results of hepatic and renal functions showed that the activities of ALT , AST and LDH, and contents of urea, UA and Cr had marked increases (P<0.05) in the Npc1-/-mice.Moreover, the results of senescence-associatedβ-galacto-sidase staining in the renal tissues demonstrated accelerated aging in the Npc1-/-mice (P<0.01), and these results were confirmed by Masson staining, which clearly showed the formation of collagen fibers (P<0.01).CONCLUSION:Muta-tion of the Npc1 gene results in abnormal lipid metabolism , which accelerates kidney senescence by promoting fibrosis in the renal tissue and subsequently causes reduction in renal function .

0.05).Conclusion Febrile seizures seldomly cause severe neurological damage.