Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.

Objective To evaluate the bioequivalence of lamivudine tenofovir tablets in Chinese healthy volunteers.Methods A randomized,open,single-dose,two-period,double-crossover drug trial design was conducted.24 subjects were randomly divided into two groups,and administered orally one tablet of test preparation or one tablet of each reference preparation per period under fasting and fed condition respectively.The concentrations of lamivudine and tenofovir in plasma were determined by HPLC-MS/MS.The pharmacokinetic parameters were calculated and the bioequivalence was compared by non-compartment model of WinNonlin 7.0 program.Results The pharmacokinetic parameters of test and reference preparations after fasting oral administration:lamivudine Cmax were(2 777.74±702.55)and(2 985.00±979.23)ng·mL-1,AUC0-t were(11 977.14±2 550.67)and(12 450.22±2 336.41)ng·h·mL-1,AUC0-∞ were(12 177.69±2 526.02)and(12 660.98±2 333.30)ng·h·mL-1,respectively;tenofovir Cmax were(316.72±63.79)and(301.46±79.82)ng·mL-1,AUC0-t were(2 584.72±619.04)and(2 474.94±636.05)ng·h·mL-1,AUC0-∞ were(2 789.87±701.97)and(2 666.35±676.21)ng·h·mL-1,respectively.The pharmacokinetic parameters of test and reference preparations after fed oral administration:lamivudine Cmax were(2 079.46±583.92)and(2 084.28±517.59)ng·mL-1,AUC0-t were(10 628.86±1 751.63)and(10 573.70±2 059.54)ng·h·mL-1,AUC0-∞ were(10 827.86±1 734.39)and(10 791.93±2 098.91)ng·h·mL-1,respectively;tenofovir Cmax were(286.97±85.91)and(271.79±63.64)ng·mL-1,AUC0-t were(3 087.01±707.76)and(3 023.48±612.46)ng·h·mL-1,AUC0-∞ were(3 307.08±746.76)and(3 221.56±672.44)ng·h·mL-1,respectively.The statistical results of the 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t and AUC0-∞(test preparation/reference preparation)were all within the equivalent range of 80.00％-125.00％.Conclusion The test and reference preparations of lamivudine tenofovir tablets were bioequivalent in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVETo investigate the expression of phosphoglycerate kinase 1 (PGK1) and its prognostic value in endometrial carcinoma (EC).

METHODSThe expression of PGK1 was detected immunohistochemically in 30 normal endometrium and 130 EC specimens. The relationship between PGK1 protein expression and the clinicopathological features of the patients was evaluated.

RESULTSImmunohistochemical analysis revealed low PGK1 expression in 55.4% (72/130) and high PGK1 expression in 44.6% (58/130) of the EC specimens, as compared with the rates of 90% (27/30) and 10% (3/30) in normal endometrium, respectively (P<0.001). PGK1 expression was significantly correlated with FIGO stage (P<0.001), histological grade (P=0.002) and lymph node metastasis (P<0.001). Kaplan-Meier survival analysis indicated that patients with a high PGK1 expression had a shorter overall survival rate than those with a low PGK1 expression (P<0.001). Multivariate analysis showed that a high PGK1 expression was not the independent predictor of the prognosis of EC (P=0.077).

CONCLUSIONA high expression of PGK1 is associated with aggressive and metastatic behaviors of EC, and detection of PGK1 provides assistance in evaluating the prognosis of patients with EC.

Objective: To study the effects of glucagon-like peptide-1(GLP-1) analogues on kidney function and kidney ultrastructure in type 2 diabetic rats. Methods: Twenty-eight SPF level male SD rats were randomly divided into control groups (normal control group and diabetic control group) and GLP-1 analogues Exenatide intervention groups(normal intervention group and diabetic intervention group). The effects of Exenatide intervention on glucose, lipid metabolism, kidney function and kidney ultrastructure were observed. Results: Fasting glucose, fasting insulin, insulin sensitivity index, insulin resistance index, lipid profile, 24-hours microalbuminuria, serum creatinine and blood urea nitrogen of Exenatide intervention group were much better than those of corresponding control groups. Through electron microscopy, glomerular mesangial cell in diabetic control group proliferated, basement membrane thickened, while glomerular mesangial cell in diabetic intervention group did not proliferate, basement membrane mildly thickened. Conclusion: GLP-1 analogues can improve kidney function of diabetic rats. Maybe it is connected with improving kidney ultrastructure.

To characterize long-term nonprogressors (LTNPs) and viremia controllers (VCs), infected with HIV-1 through contaminated blood donation or transfusion between 1992 and 1996 in Henan, China. LTNPs and VCs were defined by CD4+T lymphocyte (CD4) count and viral load (VL). Of 29,294 patients infected with HIV-1 via contaminated blood donation or transfusion that had conducted for more than 20 years, 92 were LTNPs/VCs. There were 70 LTNPs (0.24%), 43 VCs (0.15%), and 48 LTNPs+VCs- (0.16%). VCs had a significantly lower CD4 nadir, compared to LTNPs and LTNPs+VCs-, and no significant differences for the highest VL and HIV-1 DNA. Cases P4 and P5 were LTNPs, while their VL reached approximately 4.3 log copies/mL. P6 was a VC, but with CD4 < 500 cells/μL constantly. Data from the LTNPs/VCs cohort provided valuable information, future research is needed.

Objective To design and develop an online training and evaluation system for parasitic pathogen recognition. Methods The system was based on a Parasitic Diseases Specimen Image Digitization Construction Database by using MYSQL 5.0 as the system of database development software,and PHP 5 as the interface development language. It was mainly used for on-line training and evaluation of parasitic pathology diagnostic techniques. Results The system interface was designed simple, flexible,and easy to operate for medical staff. It enabled full day and 24 hours accessible to online training study and evaluation. Thus,the system broke the time and space constraints of the traditional training models. Conclusion The system provides a shared platform for the professional training of parasitic diseases,and a reference for other training tasks.

OBJECTIVETo analyze the expression of MAP2K4 and vimentin in human endometrial carcinoma (EC) and their association with the clinicopathological features and prognosis of the patients.

METHODSMAP2K4 and vimentin expressions were detected immunohistochemically in paraffin-embedded tissue sections from 128 patients with EC, and the correlation of MAP2K4 and vimentin expressions with the clinicopathological factors of the patients was analyzed.

RESULTSMAP2K4 and vimentin proteins were positively expressed in 49 (38.3%) and 83 (64.8%) of the patients, respectively. A positive expression of MAP2K4 was negatively correlated with FIGO stage of the tumor (P=0.010) and lymph node status (P=0.016); a positive expression of vimentin was positively correlated with FIGO stage of the tumor (P=0.025), histological grades (P=0.017), depth of myometrial invasion (P=0.044) and lymph node status (P=0.032). MAP2K4 was inversely associated with vimentin expression in EC(r=-0.598, P<0.001). Patients positive for MAP2K4 tended to have a higher overall survival rate (P=0.002), and those positive for vimentin tended to have a lower overall survival rate (P=0.007); patients positive for MAP2K4 but negative for vimentin had the longest survival time, while those negative for MAP2K4 and positive for vimentin had lowest survival rate (P=0.004).

CONCLUSIONDetection of MAP2K4 and vimentin might help in early diagnosis and prognostic evaluation of patients with EC.

Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; MAP Kinase Kinase 4 ; metabolism ; Prognosis ; Survival Rate ; Vimentin ; metabolism

OBJECTIVETo classify colorectal carcinoma (CRC) by TNM staging integrated with the gene expression profile and copy number variation (CNV).

METHODSProfile data of gene expression and CNV of CRC were downloaded from public database and processed with batch bias adjustment, quartile normalization, missing value estimation and feature filtration. The processed profiles of mRNA and CNV were introduced into the codes of Bayesian consensus clustering (BCC) method and were used to calculate the subclasses of CRC. With the follow-up information of disease free survival of CRC patients, the prognostic values of the subclasses was investigated and the software of function enrichment analysis was employed to discover the major pathway signaling to each interesting subclass. All statistic analyses were performed under R-3.0.1 environment or by using SPSS 16.0 software.

RESULTSProfile data of gene expression and corresponding CNV from 335 CRC patients with TNM stage Ⅱ-Ⅲ and followed-up information were obtained. After feature filtering, the profiles contained 1578 probes of mRNA and 345 location of CNV. Four CRC subclasses were identified by the integrative analysis with BCC, and the concordances of BCC subclasses and each of gene-based subclasses (Cramer's V=0.49), CNV-based subclasses (Cramer's V=0.51) and Marisa's subclasses (Cramer's V=0.32) were statistically significant (Ps<0.001). Among BCC subclasses, BCC-I had a favorable prognosis, while BCC-Ⅳ had more unfavorable prognosis. The differences of prognosis were significant among BCC-I, BCC-(Ⅱ+Ⅲ) and BCC-Ⅳ with an overall log-rank P<0.001. The top enriched function was DNA damage and repair signaling when BCC-I compared to BCC-Ⅳ, and the new subgroups classified by the genes associated with enriched signaling had the better prognostic value than BCC subclasses but both of them were significantly correlated (Cramer's V=0.39, P<0.001).

CONCLUSIONBCC method is effective to integrate multi-type genomic data for molecular classification of colorectal carcinoma, and the BCC-Ⅳ subclass has poor prognosis, which may be associated with the decreased repairing function of DNA damage.

Colorectal Neoplasms ; classification ; genetics ; pathology ; DNA Copy Number Variations ; Gene Expression Profiling ; Humans ; Neoplasm Recurrence, Local ; Postoperative Period ; Prognosis ; Transcriptome

OBJECTIVETo investigate the prevalence and distribution of hepatitis C virus (HCV) genotypes in Henan province in 2012.

METHODSA total of 32 203 permanent residents (1 to 74 years old) in Henan were recruited using multi-stage random samping method from March to June 2012. All participants were asked to complete a questionnaire to collect demographic information, past medical history and the exposure history of risk factors. A blood sample of 5 ml was collected at the same time. The condition of anti-HCV and HCV RNA was determined through the ELISA test and nested RT-PCR. HCV RNA positive samples were further subject to the nonstructural protein 5 region (NS5B) gene amplification and sequencing. The sequence was amplified for the phylogenetic tree and genetic analysis. The differences of the positive rate of anti-HCV and HCV RNA and the HCV genetic subtype distribution in different respondents'characteristics were analyzed.

RESULTSAmong 32 203 subjects, the overall positive rate of anti-HCV and HCV RNA were 0.48% (153/32 203) and 0.24% (78/32 203), in which men were 0.42% (65/15 634), and 0.23% (36/15 634), and women were 0.53% (88/16 569) and 0.25% (42/16 596). The differences between men and women were not statistically significant (χ(2) values were 2.26, 0.18, respectively, both P values > 0.05). The results of NS5B genotyping and molecular evolution analysis showed that there were six subtypes in the 71 HCV RNA positive samples.In those six subtypes, the proportion of genotypes 1b, 6a, 3a, 2a, 3b and 1a were 56.3% (40/71), 19.7% (14/71), 11.3% (8/71), 8.5% (6/71), 2.8% (2/71) and 1.4% (1/71), respectively. The HCV genetic subtypes of infestor were mainly present with two branches of 1b and 6a, and the two subtypes Bootstrap values were 0.95.

CONCLUSIONThe prevalence of HCV infection was high in Henan. The major HCV genotypes in patients with HCV infection were 1b and 6a.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C ; epidemiology ; virology ; Humans ; Infant ; Male ; Middle Aged ; Phylogeny ; RNA, Viral ; genetics ; Sequence Analysis, DNA ; Young Adult

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.
Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; enzymology ; pathology ; Cell Line, Tumor ; Enzyme Activation ; drug effects ; Esophageal Neoplasms ; drug therapy ; enzymology ; pathology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; metabolism ; Humans ; Mitogen-Activated Protein Kinase Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-raf ; antagonists & inhibitors ; metabolism ; Signal Transduction ; drug effects ; ras Proteins ; antagonists & inhibitors ; metabolism