This study was aimed to explore if the intracellular transportation direction of von Willebrand factor-cleaving protease (ADAMTS13, vWF-CP) after synthesis is determined by the carboxyl terminal TSP2-8CUB1+2 domains of ADAMTS13 and to decipher the relationship between the structure and function of ADAMTS13. The recombinant plasmids pcDNA3.1-ADAMTS13 and pcDNA3.1-delTSP2-8CUB1+2 ADAMTS13 were introduced into Madin-Darby canine kidney cells (MDCK) by lipofectamine-mediated DNA transfection. Positive cell clones gained after antibiotic-screening were grown on 6-well transwell filter units with a zeolite membrane in the middle layer. The conditioned culture media in both apical and basolateral wells were collected when cells reached confluency and the tight cell monolayer formed. ADAMTS13 proteases in the conditioned media were determined by Western blot, and the direction of ADAMTS13 secretion in polarized cells was comparatively analyzed. The results showed that Madin-Darby canine kidney cells stably expressing wild-type ADAMTS13 were grown on 6-well transwell filter units, then ADAMTS13 protease was only determined in the apical area of the transwell filter units by Western blot, but the recombinant ADAMTS13 protease was determined both in the apical and basolateral area of cells in the group of expressing TSP2-8CUB-1+2 domain-deleted ADAMTS13. It is concluded that the metalloprotease ADAMTS13 is sorted apically in polarized cells, and the carboxyl-terminal TSP2-8 and CUB1+2 domains of ADAMTS13 are important for the direction of ADAMTS13 protease transportation in the cells after being synthesized.
ADAM Proteins ; biosynthesis ; ADAMTS13 Protein ; Animals ; Dogs ; Madin Darby Canine Kidney Cells ; Plasmids ; Protein Interaction Domains and Motifs ; Protein Transport ; genetics ; Transfection ; von Willebrand Factor ; genetics ; metabolism ; secretion

OBJECTIVETo investigate the early efficacy of nedaplatin combined with megestrol in concurrent chemoradiotherapy for advanced cervical cancer.

METHODSForty-two cases of cervical cancer (FIGO IIb to IVa) were divided randomly into two groups: radiotherapy alone (21 cases) and radiation plus chemotherapy (Nedaplatin) group. The same radiotherapy was given to the two groups. Patients of the RT + C group received nedaplatin 30 mg/m2 in intravenous drip infusion once weekly on day 1, for 4 to 5 weeks, and megestrol 160 mg orally every day during the radiation therapy.

RESULTSThe early outcome: the complete remission rate was 81.0% and partial remission rate was 19.0% in the RT + C group, significantly better than the CR (38.1%) and PR (42.9%) in the RT group. The 1-year survival rates in the two groups were 100% (21/21) and 81.0% (17/21), respectively, with a significant difference between the two groups (P<0.05).

CONCLUSIONSThe combination of nedaplatin and megestrol with concurrent chemoradiotherapy can improve the early outcome of advanced cervical cancer, with somewhat increased but tolerable adverse effects.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Adult ; Alopecia ; chemically induced ; Anemia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brachytherapy ; Chemoradiotherapy ; adverse effects ; Diarrhea ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Iridium Radioisotopes ; therapeutic use ; Leukopenia ; chemically induced ; Megestrol ; administration & dosage ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Particle Accelerators ; Radiotherapy, High-Energy ; Remission Induction ; Survival Rate ; Thrombocytopenia ; chemically induced ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; radiotherapy

In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease (PD),201 PD patients were enrolled and underwent extensive clinical evaluations.Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index (PSQI),and the Epworth Sleepiness Scale (ESS).It was found that poor sleep quality (77.11％) and excessive daytime sleepiness (32.34％) were commonly seen in PD patients and positively correlated with disease severity.Then 70 out of the 201 PD patients and 70 age-and sex-matched controls underwent a polysomnographic recording.The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed.The results showed that sleep efficiency (SE) was significantly decreased (P＜0.01),and sleep latency (SL) and the arousal index (AI) were increased (P＜0.05) in the PD group as compared with those in the control group.SE and total sleep time (TST) were positively correlated with the Hoehn and Yahr (H&Y) stage.There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group (P＜0.05).Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder,which may be correlated with the disease severity.Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

OBJECTIVETo investigate the survival rate and prognostic factors of laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy.

METHODSOne hundred and sixty-seven laryngeal carcinoma cases with no surgery, radiotherapy or chemotherapy were analyzed retrospectively. Survival rates were calculated by Kaplan-Meier product-limit method. With univariate analysis, comparisons among/between groups were performed using Log-rank test. Multivariate analysis was carried out using Cox proportional hazard model.

RESULTSOverall survival time was (16.0 ± 1.4) months (x(-) ± s), overall 1- and 2-year survival rates were 56.4% and 26.5%, respectively. No patient survived over 5 years in these cases who had been diagnosed more than 5 years (except for those who lost). Univariate analysis showed that primary site, pathological grade, T-stage, N-stage and clinical stage were significant prognostic factors for the survival of the patients (P < 0.05). The survival rates of laryngeal carcinoma whether with tracheotomy were no statistically significant (P > 0.05). Multivariate analysis showed survival rates statistically correlated with T stage and N stage (hazard ratio were 1.812 and 1.557, P < 0.05).

CONCLUSIONSThe development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgical such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological grade, T-stage, N-stage and clinical stage, and of them, T-stage and N-stage are the independent prognostic factors.

Adult ; Aged ; Aged, 80 and over ; Carcinoma ; mortality ; pathology ; Factor Analysis, Statistical ; Female ; Humans ; Laryngeal Neoplasms ; mortality ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate