Investigation of simvastatin and its related substances was carried out using a reversed phase ultra performance liquid chromatography/tandem mass spectrometry method. The identification of impurities in simvastatin was performed with a triple-quadrupole mass spectrometer, with an electrospray ionization (ESI) source in the negative/positive ion mode. A total of 12 compounds were characterized in commercial samples, among which 2 impurities had never been reported. All the impurities were deduced based on the MS fragment pathways of simvastatin and the biosynthetic pathway of lovastatin. This work provides very useful information for quality control of simvastatin.
Chromatography, High Pressure Liquid ; Chromatography, Reverse-Phase ; Drug Contamination ; Hypolipidemic Agents ; chemistry ; Quality Control ; Simvastatin ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry

OBJECTIVETo explore the scavenging action of tenuigenin (TEN) on intracerebral amyloid β protein (Aβ) aggregation and the abnormal phosphorylated tau protein and its mechanism in Alzheimer's disease (AD) rats' brain.

METHODSAβ1-40 was injected into the right CA1 region hippocampus to establish the AD model. Successfully modeled rats were divided into the model group, the low, middle, high TEN group. Rats were administered with TEN (18.5, 37.0, 74.0 mg/kg) by gastrogavage. Besides, a sham-operation group was set up. Expression levels of Aβ1-40 and Tau p-Ser262 were detected by immunohistochemistry. Expression levels of ubiquitin (Ub) and Ub-protein ligase E3 were measured by Western blotting.The content of 26S proteasome was detected by ELISA.

RESULTSImmunohistochemical results showed that the number of Aβ and Tau p-Ser262 positively reacted neurons significantly increased in model group, when compared with the sham-operation group (P < 0.01). Results of Western blot showed expression levels of ubiquitinated protein were up-regulated and those of Ub-protein ligase E3 were down-regulated in the model group (P < 0.01). ELISA results showed that the content of 26S proteasome significantly decreased in AD rats' brain (P < 0.01). Compared with the model group, expression levels of Aβ1-40, Tau p-Ser262, and Ub significantly decreased; expression levels of Ub-protein ligase E3 apparently increased; the content of 26S proteasome significantly increased in each TEN treatment group (P < 0.05, P < 0.01). Best effect was shown in 37.0 mg/kg and 74.0 mg/kg TEN groups.

CONCLUSIONSUb proteasome pathway (UPP) participated in the occurrence of AD. TEN could obviously reduce intracere- bral Aβ1-40 accumulation and abnormal tau phosphorylation.

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Neurons ; metabolism ; Phosphorylation ; Proteasome Endopeptidase Complex ; metabolism ; Rats ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitins

OBJECTIVETo examine the protective effect of Ginkgo biloba leaf extract (GbE) on learning and memory deficit induced by aluminum chloride (AlCl(3)), and explore its mechanisms.

METHODSThe rat models with learning and memory deficit were induced by administering via gastrogavage and drinking of AlCl(3) solution. And the model rats were treated with GbE at the dose of 50, 100, 200 mg/kg every day for 2 months accompanied with drinking of AlCl(3) solution, respectively. Their abilities of spatial learning and memory were tested by Morris water maze, and the acetylcholinesterase (AChE) activity in serum was assayed with chemical method, the AChE expression in hippocampus was observed by immunohistochemistry assay, and then quantitative analysis was done by BI 2000 image analysis system.

RESULTSLearning and memory deficit of rats could be induced by AlCl(3) solution (P < 0.01), and AChE expressions in rats hippocampus were increased (P < 0.01); GbE ameliorated learning and memory deficit and reduced AChE expression in rats hippocampus in a dose-dependent manner, while GbE significantly increased serum AChE activity at the dose of 200 mg/kg each day (P < 0.05).

CONCLUSIONGbE can ameliorate learning and memory deficit induced by AlCl(3), which may be due to its inhibition of the AChE expression in hippocampus.

Acetylcholinesterase ; metabolism ; Aluminum Compounds ; toxicity ; Animals ; Chlorides ; toxicity ; Dose-Response Relationship, Drug ; Ginkgo biloba ; Hippocampus ; enzymology ; Immunohistochemistry ; Male ; Maze Learning ; drug effects ; Memory Disorders ; chemically induced ; prevention & control ; Neuroprotective Agents ; therapeutic use ; Phytotherapy ; Plant Extracts ; therapeutic use ; Plant Leaves ; Plant Structures ; Rats ; Rats, Wistar ; Reaction Time

Background Sirius system,a new Scheimpflug camera combined with Placido topography,improved the capability of imaging the anterior eye segment significantly.However,the study of assessing the repeatability and agreement between Sirius and Pentacam is still lack up to now.Objective This study was to evaluate the repeatability and agreement of the anterior ocular segment measuring parameters by Sirius and Pentacam in myopia received laser in situ keratomileusis (LASIK).Methods Thirty-five myopic eyes of 35 patients received LASIK were included in School of Optometry and Ophthalmology Eye Hospital from 2010 May through 2010 July.Corneal power flat keratometry (Kf),step keratometry (Ks),mean keratometry (Km),thinnest corneal thickness(TCT),the location of TCT,anterior chamber depth (ACD) and anterior chamber volume (ACV) were measured by Sirius and Pentacam in all the eyes,respectively.The repeatability of the measuring results were evaluated using intraclass correlation coefficients (ICC) and Cronbach's coefficient alpha (CoA),and the agreement of measuring parameters between Sirius and Pentacam was analyzed using Bland-Altman plot.Results Both Sirius and Pentacam demonstrated high intraobserver repeatability,with all ICC and CoA more than 0.90.No significant differences were found in Kf values and Ks values between the two methods (t =-1.533,-1.750,P＞0.05).Km value was (39.14 ± 1.95) D by Sirius measurement,which was sígnificantly higher than (39.05 ± 1.91) D by Pentacam measurement (t =3.572,P =0.001).The TCT was (457.6 ± 40.9) μm by Sirius method,showing a significant reduce in comparison with (465.4±37.5) μm of Pentacam method (t =-6.689,P＜0.001).A positive correlation was seen in the TCT between the two methods (r=0.988,P＜0.001).The Bland-Alrman plots showed the 95％ CI-21 μm to 6 pm in the TCT value between the two devices.Pairwise comparison of the location of TCT measurements showed significant differences between the two devices (t =-4.132,-5.696,P＜0.001),with a good correlation (r=0.751,0.775) and the 95％ CI (-0.36-0.17 mm,-0.35-0.12 mm).A very good agreement was seen in ACD between the two devices (-0.02-0.12 mm),but the agreement result was not very well in the ACV between the two devices with the 95％ CI (-27.70-6.20 mm3).Conclusions Sirius and Pentacam measurements for anterior ocular segment parameters have a very good repeatability in post-LASIK eyes.In addition,good agreement results are exhibited in corneal power,TCT and ACD between Sirius and Pentacam with an acceptable maximal different value between them.Sirius and Pentacam can be used interchangeably in clinical examination.However,the two devices can not interchangeably for ACV measurement and TCT location.

?AIM: To study the association of the single nucleotide polymorphism ( SNP) rs1157699 in the calcitonin receptor-like receptor ( CRLR ) gene with primary angle closure ( PAC) in a Han Chinese population.?METHODS: All samples, involved 232 PAC cases and 306 controls, were obtained from an epidemiologic survey conducted in Funing, Jiangsu Province, China. Genotyping were carried out by TaqMan-MGB probe using the real time quantitative polymerase chain reaction system to study the relationship between SNP of rs1157699 in CRLR gene and PAC.?RESULTS: The prevalence of CRLRrs1157699 genotype was 67.4%, 30.0%, 2.6% for CC, CT, TT in cases, and 71.3%, 27.0%, 1.7% in controls respectively.There was no difference between the two groups in the distribution of genotype and allele frequencies of rs1157699 (P>0.05).?CONCLUSION:Our results do not support a significant role for rs1157699 in CRLR with PAC.

Background Biometry of the anterior ocular segment parameter is very important for the diagnosis and treatment of glaucoma and ocular injury as well as measurement of intraocular lens(IOL).Objective This study was to compare the differences in the anterior chamber depth(ACD) and the central corneal thickness (CCT) between Sirius and Pentacam and evaluate the agreement of these two measurement methods.Methods The ACD and the CCT of 38 right eyes from 38 health volunteers aged 23- 32 years were measured with both Pentacam and Sirius.Three times of measurement were pedormed on each eye for each method to obtain the average values.The repeatability and agreement from each method were assessed as intraclass correlation coefficient( ICC ) and coefficient of variation(CV) and the agreement between these two methods were evaluated using Bland-Altman mode.ResultsThe mean ACD value was( 3.18±0.21 ) mm from Pentacam with the ICC 0.995 and CV 0.066.The mean ACD value from Sirius was (3.22 ±0.21 )mm with the ICC 0.996 and CV 0.065.The difference value in ACD between two methods was 0.04 mm,showing a significant difference( t =-6.225,P＜0.05 ) and a positive correlation (r=0.977) between two methods.The 95％ limit of agreement was( -0.04-0.13)mm within 1 standard difference (SD) of the mean value( ±0.21mm),which was acceptable for clinical measurement.The CCT was( 535±33 )μm from Pentacam with the ICC 0.994 and CV 0.062.The CCT was(537±36)pm from Sirius with the ICC 0.999 and CV 0.067.The difference value in the CCT between two methods was about 2 μm,presenting a in significant difference ( t =1.771,P＞0.05 ) and positive correlation ( r =0.985 ).The 95 ％ limit of agreement was ( - 11.64-15.65 ) μm within 1 SD of the mean value( ±34.27 pm),which was acceptable for clinical measurement.ConclusionsSirius and Pentacam show good agreement in the measurement of ACD and CCT.The two methods offer an alternative choice for the biological measurement of the anterior ocular segment.

Objective To study the gene mutation of a Chinese family with Alport syndrome and to perform preimplantation genetic diagnosis before embryo implantation.Methods Next generation sequence analysis was done for checking COL4A3,COL4A4 and COL4A5 genes in the Alport syndrome family members.Array comparative genomic hybridization(CGH) was used to detect the embryos.Results A mutation c.2605G ＞ A was found and identified in COL4A5 gene of all of the Alport syndrome patients in the family,but COL4A3 and COL4A3 genes were normal in all of the detected people.After searching for the mutation database,the mutation c.2605G ＞ A of COL4A5 gene was related to the X-linked dominant Alport syndrome.Three embryos were detected by using the preimplantation genetic diagnosis.Among these embryos,there were two male and one female.One of the male embryos was chromosomal aneuploidy,which was 45,XY,-16 and the other was normal.This normal embryo was implanted,and after 20 weeks the prenatal amniocentesis diagnosis approved that the fetus was normal.Conclusions The mutation of COL4A5 gene (c.2605 G ＞ A) is the cause of Alport syndrome in this family,which indicates that next generation sequence analysis proves to be an accurate and rapid method to detect Alport syndrome disease.Meanwhile array CGH can be used to reduce birth rates as a useful preimplantation genetic diagnosis method.

Background Axial length and anterior chamber depth are important parameters for the calculation of diopter of intraocular lens ( IOL ). Objective This study was to investigate and compare the measuring outcomes of axial length and anterior chamber depth with IOLMaster,Axis- Ⅱ A-scan and ODM 1000A sonograph.Methods This a observational study.Axial length and anterior chamber depth were measured in 83 eyes of 48 patients with IOLMaster,Axis-Ⅱ A-scan and ODM 1000A sonograph by the same operator.The measuring results were compared among the three methods.Results The axial length were(25.79±0.85) mm,(25.72± 0.82 )mm and ( 26.00 ±0.83 )mm respectively with Axis- Ⅱ,ODM 1000A sonograph and IOLMaster.The difference between Axis-Ⅱ and DM 1000A sonograph was (0.07 ± 0.35 )mm without statistical difference between them (t=1.711,P =0.091 ).The difference of axial length between IOLMaster and DM 1000A sonograph was ( 0.27 ±0.29) mm with a statistical difference between them ( t =-8.570,P =0.000 ).The difference between IOLMaster and Axis- Ⅱ was (0.21 ±0.32 ) mm and showed a statistical difference ( t =- 5.931,P ＜ 0.01 ).The positive correlations were found in the axial length values by the each other comparison among the three instruments( r=0.916,0.938,0.928,P＜0.01 ).The anterior chamber depth values were ( 3.81 ±0.21 ) mm,( 3.84 ±0.25 ) mm and ( 3.83 ±0.18 )mm respectively with Axis-Ⅱ,0DM 1000A sonograph and IOLMaster.The difference of anterior chamber depth between Axis- Ⅱ and DM 1000A was (0.03 ±0.17 ) mm without statistical difference between them ( t =- 1.324,P =0.189 ).The difference in the anterior chamber depth between IOLMaster and DM 1000A was (0.01 ±0.15 ) mm and that between IOLMaster and Axis-Ⅱ was( 0.01 ±0.12)mm without any statistical differences among them (t =0.815,P=0.417 ;t=-0.900,P=0.371 ).The high correlation between anterior chamber depth measurements were found by the each other comparison in the three instruments ( r =0.735,0.813,0.823,P ＜ 0.01 ).Conclusions ODM 1000A sonograph can provide precise axial length and anterior chamber depth values.However,ODM 1000Asonograph can not substitute for IOLMaster in the measurement of the anterior chamber depth and axial length.

Background Clinical research showed that the corneal endothelial cell density value from different corneal specula microscopies exist diversity.The relevant literature of SP02,Tomey EM-3000 and SP3000P is still seldom up to now. Objective This research was to assess the repeatability of endothelial cell density measurements by SP02,Tomey EM-3000 and SP3000P respectively and the agreement among 3 kinds of endothelial microscopes.MethodsFifty-four healthy volunteers with the age 17-38 years old were included this research.The written informed consent was obtained from each subject before examination.The corneal endothelial cell densities in the right eyes were analyzed with SP02,Tomey EM-3000 and SP3000P respectively for 3 times under the automatic mode,and the analytical procedure of SP3000P measurement were divided into automatic mode SP3000P (A) and manual correction modes SP3000P( M).The repeatability of each specula microscopy was analyzed by calculating the intraclass correlation coefficients (ICC) and coefficient of variation ( CV ),and the 95％ confidence intervals and plotting Bland-Altman graphs were used to analyze the agreement among these methods.ResultsThe mean corneal endothelial cell densities in the population ＜24 years were significantly higher than the ones ≥ 24 years (t =3.692,P＜0.05 ),but no statistical difference was found between different gender ( t =0.335,P =0.739 ).The mean corneal endothelial cell densities were ( 3058 ± 260 ),( 2954 ± 229 ),( 2668 ± 258 ),( 2734 ± 268 ) cell/mm2 ; the ICCs were 0.957,0.940,0.972 and 0.972 and the CV were 0.063,0.061,0.056,0.058 for SP02,Tomey EM-3000,SP3000P (A) and SP3000P ( M ) respectively.The 95％ confidence intervals were ( - 100.8 - 306.8 ),( 162.6 - 617.4 ),( 109.9-494.1 ) and ( -0.6 - 132.6 ) cell/mm2 for between SP02 and Tomey EM-3000,SP3000P ( A ) and SP02,SP3000P(A) and Tomey EM-3000,SP3000P(A) and SP 3000P(M) respectively.ConclusionsSP02,Tomey EM-3000 and SP3000P(A) have good repeatability in the measurement of corneal endothelial cell density,however the outcome is different.Therefore,it is not interchangeable for the detection of corneal endothelial cell density.The differences of corneal endothelial cell density obtained from these instruments shall be paid high attention for their differences.SP3000P(A) and SP3000P(M) can be used interehangeably and SP3000P(A) is a preferable choice due to its convenience and quickness.

Objective　To investigate the drug resistance of Enterobacter cloacae isolated from blood samples in 75 member units of the Bacterial Drug Resistance Monitoring Network in Hebei, 2016- 2021, so as to provide a basis for rational drug use in clinic. Methods　WHONET 5.6 software was used to retrospectively analyze drug susceptibility of Enterobacter cloacae isolated from 32 secondary hospitals and 43 tertiary hospitals. SPSS19.0 software was used for statistical analysis. Results After removing the duplicate strains, 1 225 strains of E. cloacae were isolated from blood samples of 75 hospitals during 6 years, including 157 strains from secondary hospitals and 1 068 strains from tertiary hospitals. In this study, the resistance of Enterobacter cloacae to 16 kinds of antibiotics was analyzed. The drug resistance rates to cefuroxime (52.4%-67.8%), piperacillin (27.4%-31.2%), ceftazidime (27.8%-35.5%), ceftriaxone (29.5%-45.0%), aztreonam (22.2%-32.3%), cotrimoxazole (21.6%-28.7%) were higher; the resistance rates to amikacin and tobramycin were lower than 15.0%. The resistance rates to imipenem and meropenem were 3.6%-12.3% and 5.1%-11.4%, respectively. The resistance rate to ciprofloxacin in tertiary hospitals was 22.4%, and the resistance rate to cotrimoxazole was 23.9%. Except for these two antimicrobials, the resistance rates to other antimicrobial drugs in tertiary hospitals were higher than that in secondary hospitals. A total of 121 carbapenem-resistant Enterobacter cloacae strains were detected in the past 6 years, with an increasing detection rate (χ2trend=6.305, P=0.012). Conclusions　Enterobacter cloacae has great differences in antimicrobial resistance to different antibiotics, and is sensitive to carbapenems. The drug resistance in tertiary hospitals is generally higher than that in secondary hospitals. Drug resistance monitoring and drug resistance mechanism research should be strengthened to better guide clinical drug use and curb the rise of drug resistance.