To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL) than that of the normal group, indicating the increase in absorption in rats in the pathological state by reducing the clearance rate. The method is accurate and sensitive and so can be used to determine the plasma concentrations of the eight active ingredients in Maxing Shigan decoction. RSV pneumonia-infected rats absorbed more ingredients in Maxing Shigan decoction.
Animals ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacokinetics ; Male ; Pneumonia, Viral ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Respiratory Syncytial Virus Infections ; drug therapy ; metabolism ; Tandem Mass Spectrometry

Objectives：This study was designed to investigate the clinical pathological characteristics of malignant lymphoepithelial lesion(MLEL) of salivary glands and the relationship with EBV（ Epstein-Barr Virus） . Methods：In situ hybridization and immunohistochemical methods were used to detect EBERs (EBV-encoded small RNAs), latent membrane protein 1 (LMP1), EBNA2(EB nuclear antigen-2), and ZEBRA (Z EBV replication activator) in paraffin embedded tissues of 41 MLEL cases. Results：(1)Forty cases of MLEL showed staining with EBERs. Positive rate of EBERs by in situ hybridization in 41 cases of MLEL was 97.56％ . (2)LMP1 expression was detected in 75.6％ (31/41), positive rate of ZEBRA was 2.5％ (1/41), no EBNA2 was found (0/20). Conclusion：EBV might play an important role in pathogenesis of MLEL.

Objective To investigate the genetic etiologies in the 0 -3 years old infants with hearing loss and to analyze the interaction between genetics and environmental factors. Methods Total of 130 infants were performed detailed audiological evaluation as well as the detection of the popular deafness gene mutations in GJB2 gene, SLC26A4 and mtDNAI2SrRNA. Of them, 84 cases were performed the computer tomography or magnetic resonance imaging examinations. Results Of the 130 cases, 54 infants were diagnosed as large vestibular aqueduct syndrome, while seven of 130 were as auditory neuropathy and the others were diagnosed as sensorineural hearing loss. Considering of the risks of etiologies for hearing loss, 85 of them had the experiences of the high risk factors at birth(65.4% ,85/130), while 23 of them had the exposure of aminoglycoside antibiotics, and 13 had the family history background as well as two eases were from the consanguineous families. In the causative genes screening, 42 infants were caused by the mutations of SLC26A4 gene (32.3%), but 14 infants found the mutations in GJB2 gene (4.6%), and no infants carried the mutation in mtDNA 12SrRNA 1555G and 1494T points in our studies. Conclusions In our studies, about 36. 9% infants hearing loss cases can be found the mutations in SLC26A4 and GJB2 genes. It is essential to put the idea into the hearing evaluation combined with genetic testing for the diagnoses of heating loss. It is also helpful for exploring the etiologies of hearing loss and performing the target genetic consulting for decreasing the prevalence of deafness in the future.

OBJECTIVEThe purpose of this study was to investigate the clinical significance of THY1 protein expression in epithelial ovarian cancer.

METHODSImmunohistochemistry (IHC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were used to detect the protein expression of THY1, Ki67 and cell apoptosis in 76 epithelial ovarian cancers by tissue microarray. The correlation between THY1 expression and patients' clinical features was analyzed.

RESULTSOf the 76 epithelial ovarian cancer samples, 64 were informative for IHC and TUNEL assays and 42 (65.6%) among them showed down-regulated/loss expression of THY1 protein. A significant positive correlation of THY1 protein expression with clinical stage and distant metastasis was observed in this ovarian cancer cohort (P < 0.05). The more advanced the tumor stage, the more frequency of loss expression of THY1 protein. In addition, the mean positive rate of Ki67 staining in tumors with down-regulated/loss expression of THY1 was 33.7% +/- 3.5%, significantly higher than that in the tumors with normal expression of THY1 (17.3% +/- 6.1%, P = 0.0027). However, no significant correlation was observed between THY1 protein expression and tumor cell apoptosis as well as patients' survival in this series (P > 0.05).

CONCLUSIONDown-regulated/loss expression of THY1 protein in epithelial ovarian cancer is significantly correlated with cancer cell proliferation and metastasis in the epithelial ovarian cancer, and it may be used as one of the new molecular biomarkers to predict the disease progression in patients.

Adult ; Aged ; Apoptosis ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Down-Regulation ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen ; metabolism ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Ovarian Neoplasms ; metabolism ; pathology ; Survival Rate ; Thy-1 Antigens ; metabolism

Objective To investigate the current situation of health promoting behaviours among the maintenance hemodialysis patients(MHD) and explore the related factors of health promoting behaviours among the MHD patients. Methods A total of 120 MHD patients were investigated with a set of questionnaires, including demographic data, Health-promoting Lifestyle Profile (HPLP), Self Rated Abilities for health Practices Scales (SRAS), Short Form 36 Health survey Questionnaire (SF-36) and Social Support Rating Scale (SSRS). Results The mean score of overall health-promoting lifestyles was 63.18, which was significantly positively correlated with demographic characteristics, education and economic status. The health promotion behaviors was positively correlated with self-efficacy of health behaviours, perceived health status and social support. Conclusions The health-promoting behaviours among the MHD patients is at medium level. Better health promoting are found among the MHD patients with higher education and better economic status. Better health promoting behaviours are found among the MHD patients with high self-efficacy of health behaviours,better perceived health status and more social support.

Objective To estimate correlation between phonetically balanced maximum(PB max)and pure tone auditory threshold in auditory neuropathy(AN)patients.nethods 0ne hundred and six ANpatients were identified using multipie criteria including PB max,a metric for speech recognition,pure tone auditory threshold.acoustic emission test.distortion products otoacoustic emission(DPOAE) and auditory brainstem response(ABR).SPSS statistical software was used to estimate the Pearson's correlation between PB max and pure tone auditory threshold and to test whether pure tone auditory threshold,or auditory configuration had a significant impact on PB max.Results Even the patients had the same or similar values for pure tone auditory threshold or auditory configuration.varied values of PB max were found in two hundreds and twelve ears for 106 patients.Analysis of the data for 106 patients revealed a negative correlation(r=-0.602,P<0.01) between PB max and pure tone auditory threshold,i.e.hearing loss at a mild relates to a lower PB max.By using analysis of variance(ANOVA)method,it Was found that both pure tone auditory threshold and auditory configuration had a significant(P<0.01)impact on the patients' PB max.Conclusions This analysis implicated the promise and potential of pure tone auditory threshold and auditory configuration for predicting PB max of the AN patients,and improving the diagnosis of AN.

OBJECTIVETo analyze the correlation between prognosis and p53 expression in primary lesion and the surgical margin of laryngeal squamous cell carcinoma (SCC) as an indication of postoperative radiotherapy.

METHODSSixty-seven laryngeal SCC with pathological negative margin were analyzed retrospectively. Immunohistochemical method was used to detect the expression of p53.

RESULTSThe p53 positive rates in the primary tumor and the surgical margin were 19.4% (13/67) and 50.7% (34/67). In p53 positive primary tumor group, the survival rate was higher in patients who received postoperative radiotherapy than those without (60.6% vs 20.0%, P = 0.000 5) and the recurrent rate was just the reverse (42.1% vs 93.3%, P = 0.002), though these differences were not significant in p53 negative primary tumor group (87.5% vs 94.1%, P = 0.409 6; 25.0% vs 5.9%, P = 0.175). The recurrent rate and survival rate between patients with and without postoperative radiotherapy did not show any significant difference either in p53 positive surgical margin group (47.4% vs 20.0%, P = 0.378 1; 62.5% vs 80.0%, P = 1.0) or p53 negative ones (84.9% vs 66.6%, P = 0.074 3; 20.6% vs 40.7%, P = 0.248).

CONCLUSIONPostoperative radiotherapy should be given to patients with p53 positive primary laryngeal cancer. But those who are pathologically margin negative but p53 positive should not be taken, at least for the present, as candidates for postoperative radiotherapy.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; chemistry ; mortality ; radiotherapy ; Female ; Humans ; Laryngeal Neoplasms ; chemistry ; mortality ; radiotherapy ; Male ; Middle Aged ; Survival Rate ; Tumor Suppressor Protein p53 ; analysis

Background: The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis. Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein–Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan–Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. Results: Of the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor micro-environment was negatively correlated with C-Myc expression (r = ? 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P < 0.01). Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expres-sion in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.

OBJECTIVETo study the clinicopathologic features of various types of mature T-cell and natural killer (NK)/T-cell lymphoma in Guangdong, China, with respect to the 2008 WHO classification of lymphoid neoplasms.

METHODSEleven hundred and thirty-seven (1137) cases of mature T-cell or NK/T-cell lymphoma diagnosed during the period from 2002 to 2006 in Guangzhou area were retrieved. The clinical data, histologic features and immunohistochemical findings were reviewed by a panel of experienced hematopathologists. Additional immunostaining was performed if indicated. The cases were re-classified according to the 2008 WHO classification of lymphoid neoplasms.

RESULTSNine hundred and sixty-three (963) cases fulfilled the diagnostic criteria of mature T-cell or NK/T-cell lymphoma and accounted for 20.1% of all cases of lymphoma encountered during the same period (963/4801). A predominance of extranodal involvement was noted in 644 cases (66.9%), while 319 cases (33.1%) showed mainly nodal disease. The prevalence of various lymphoma subtypes was as follows: peripheral T-cell lymphoma, unspecified (PTCL, NOS) 293 cases (30.4%), extranodal NK/T-cell lymphoma, nasal type 281 cases (29.2%), anaplastic large cell lymphoma (ALCL) 198 cases (20.6%), and angioimmunoblastic T-cell lymphoma (AILT) 46 cases (4.8%). The male-to-female ratio was 1.99. The median age of the patients was 44 years, with the peak age of PTCL, NOS, extranodal NK/T-cell lymphoma, nasal type and AILT being 55 to 64 years, 25 to 54 years and 65 to 74 years, respectively. ALK-positive ALCL occurred more frequently in young age, while the ALK-negative ALCL cases occurred mainly in the elderly.

CONCLUSIONSExtranodal lesions predominate in mature T-cell and NK/T-cell lymphomas occurring in Guangzhou area. There is a male predominance and the overall incidence shows no increasing trend with age of the patient. The peak age of various subtypes however varies. The most common subtype was PTCL, NOS, followed by extranodal NK/T-cell lymphoma, nasal type, ALCL and AILT. The relatively frequent occurrence of extranodal NK/T-cell lymphoma, nasal type in Guangdong area is likely associated with the high incidence of Epstein-Barr virus infection there.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; Epstein-Barr Virus Infections ; Female ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; virology ; Infant ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; virology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; virology ; Lymphoma, T-Cell ; classification ; metabolism ; pathology ; virology ; Lymphoma, T-Cell, Peripheral ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Protein-Tyrosine Kinases ; metabolism ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Sex Factors ; World Health Organization ; Young Adult

BACKGROUND AND OBJECTIVEExpression of Skp2 was related with the prognosis of several tumors. However, there was no intensive study on the relationship between Skp2 and extranodal NK/T cell lymphoma. This study was to explore the role of Skp2 in extranodal NK/T cell lymphoma.

METHODSThe clinicopathological data of 39 patients with extranodal NK/T cell lymphoma were analyzed. The expression of Skp2 was examined by immunohistochemistry on formalin fixed, paraffin embedded tissue sections.

RESULTSAmong the patients with high expression of Skp2, complete remission (CR) rate was only 14.3% (2/14). However, CR rate among the patients with low expression of Skp2 was 68.0% (17/25). Significant difference was shown between these two groups (P < 0.001). In the group of low expression, the median overall survival (OS) was 85.59 months (95% CI: 35.83 135.34 months), the 1 and 2 year OS rates were 81% and 71%, respectively. However, in the group of high expression, the median OS was only 9.73 months (95% CI: 2.05-17.40 months), the 1 and 2 year OS rates were 42% and 14%, respectively. There was statistical difference between these two groups (P < 0.001). Multivariate analysis showed that Skp2 expression (P <0.001), LDH (P = 0.026) and ECOG PS (P = 0.003) were dependent prognostic factors of extranodal NK/T cell lymphoma.

CONCLUSIONHigh expression of Skp2 is an independent unfavorite adverse prognostic factor of extranodal NK/T cell lymphoma.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase ; blood ; Lymphoma, Extranodal NK-T-Cell ; drug therapy ; metabolism ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; Remission Induction ; S-Phase Kinase-Associated Proteins ; metabolism ; Survival Rate ; Young Adult