Pololike kinase 1(Plk1)contain an Nterminal Ser/Thr kinase catalytic domain and a Cterminal region that contains two poloboxes.As a key regulator of multiple steps during cell cycle across eukaryotic species,many proteins interact with Plk1.Plk1 is highly expressed in malignant cells and serves as a negative prognostic marker in specific human cancer types.Plk1 is a potential target for cancer therapy.Some novel smallmolecule inhibitors of pololike kinase 1 provide novel opportunities for cancerdrug discovery,such as BI 2536,ON01910.

Objective To explore the quality of life (QOL) and its influential factors among patients with 3 major rheumatic diseases. Methods A total of 216 patients with rheumatic diseases (84 patients with systemic lu- pus erythematosus, SLE, 83 with rheumatoid arthritis, RA, and 49 with ankylosing spondylitis, AS) were recruited. The information with regard to their quality of life, sociopsychological factors and the evaluation of disease activity were obtained by using the medical outcomes study short form-36 (SF-36) and clinic documents. Results Patients with rheumatic diseases scored significantly lower with each subscale of SF-36 as compared to those of a healthy popu- lation in China (P

OBJECTIVETo explore the clinical effect of Tripterygiitotorum (T II) combined with prednisone in treating patients with myasthenia gravis (MG) and the changes of immune function after treatment.

METHODSSixty-eight patients with MG were randomly divided into two groups, the 36 patients in the treated group were treated with T II plus prednisone and the 32 in the control group were treated with prednisone alone. The therapeutic effect, serum interleukin-6 (IL-6) and peripheral B lymphocyte levels were observed.

RESULTSThe therapeutic effect in the treated group was significantly higher than that in the control group (P < 0.05). There were significant decrease in serum IL-6 and peripheral B lymphocyte in both groups after treatment (P < 0.05), with the decrements more significant in the treated group (P < 0.05).

CONCLUSIONThe therapy of T II plus prednisone is superior to that of prednisone alone in treating MG, it has a more potent effect of immunosuppression.

Adolescent ; Adult ; B-Lymphocyte Subsets ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glycosides ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Interleukin-6 ; blood ; Male ; Middle Aged ; Myasthenia Gravis ; blood ; drug therapy ; Phytotherapy ; Prednisone ; therapeutic use ; Tripterygium ; chemistry

OBJECTIVETo evaluate the sequential fecal occult blood test (SFOBT) program for the screening of colorectal cancer and elucidate the prevalence of colorectal cancer in Wuhan area.

METHODSAt 19 screening sites, 63,961 residents were recruited as target population according to random cluster and stratified sampling for four years (between 2005 and 2008). Residents aged over 40 years old received SFOBT. Those with positive SFOBT underwent colonoscopy.

RESULTSThe target population was 63,961. There were 25,837 people whose age was over 40. Finally, 7784 participants received the SFOBT screening, with a medium age of 56 years old. The positive rate of SFOBT was 12.3% (956 persons). Of the 956 persons, 240 participants underwent colonoscopy. Colorectal cancer was found in 14 cases (6.5%), gastric cancer in 2 cases (0.9%), colorectal adenoma in 53 cases(24.8%), colorectal inflammation in 80 cases (37.3%) and hemorrhoids in 65 cases (30.4%).

CONCLUSIONSThe prevalence of colorectal cancer is relatively high in Wuhan area. The SFOBT is available and feasible in screening early changes of colorectal cancer.

Adult ; Aged ; China ; epidemiology ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; epidemiology ; prevention & control ; Female ; Humans ; Male ; Mass Screening ; methods ; Middle Aged ; Occult Blood ; Population Surveillance ; methods ; Prevalence

Kv4.3 channel is present in many mammalian tissues, predominantly in the heart and central nervous system. Its currents are transient, characterized by rapid activation and inactivation. In the hearts of most mammals, it is responsible for repolarization of the action potential of ventricular myocytes and is important in the regulation of the heart rate. Because of its central role in this important physiological process, Kv4.3 channel is a promising target for anti-arrhythmic drug development. Jingzhaotoxin-V (JZTX-V) is a novel peptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. Whole-cell patch clamp recording showed that it partly blocked the transient outward potassium channels in dorsal root ganglion neurons of adult rats with an IC(50) value of 52.3 nmol/L. To investigate the effect of JZTX-V on Kv4.3 channel, JZTX-V was synthesized using the solid-phase chemical synthesis and separated by reverse phase high performance liquid chromatography (HPLC). The purity was tested by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MOLDI-TOF mass spectrometry). Two-electrode voltage-clamp technique was used to characterize the action of JZTX-V on Kv4.3 channels expressed in Xenopus laevis oocytes. As a result, JZTX-V displayed fast kinetics of inhibition and recovery from inactivation. Furthermore, it could inhibit Kv4.3 channel current in a time- and concentration-dependent manner with an IC(50) value of 425.1 nmol/L. The application of JZTX-V affected the activation and inactivation characteristics of Kv4.3 channel and caused a shift of the current-voltage relationship curve and the steady-state inactivation curve to depolarizing direction by approximately 29 mV and 10 mV, respectively. So we deduced that JZTX-V is a gating modifier toxin of Kv4.3 channel. Present findings should be helpful to develop JZTX-V into a molecular probe and drug candidate targeting to Kv4.3 channel in the myocardium.
Animals ; Ganglia, Spinal ; cytology ; Neurons ; drug effects ; Neurotoxins ; pharmacology ; Oocytes ; Patch-Clamp Techniques ; Peptides ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Rats ; Shal Potassium Channels ; metabolism ; Spider Venoms ; pharmacology ; Xenopus laevis

BACKGROUNDThere are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events.

METHODSAll consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups.

RESULTSNine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3-8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group.

CONCLUSIONSDuring a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.

Aged ; Coronary Artery Bypass ; Coronary Artery Disease ; physiopathology ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Stroke Volume

OBJECTIVETo explore the situation of smoking behavior among the students of middle school in Beijing, Hangzhou, Wuhan and Urumchi and to analyze the relationship between smoking behavior and several unhealthy behaviors together with psychological troubles to provide evidence in developing an early intervention plan.

METHODSThe National Health Education Institute (NHEI) of Chinese Center for Disease Control and Prevention (CDC) provided relevant data on all middle schools in the 4 cities and then U.S. CDC randomly sampled 100 common middle schools from them with a special sampling process. The core questionnaire developed by the experts from WHO and other countries was used in the survey among 9015 sampled students.

RESULTSAmong all the sampled students, 29.4% of them had ever attempted cigarettes smoking while 6.6% of them tried tobacco in the 30 days before survey, 27.0% of the students with smoking behavior began smoking at the age of 9 or younger, 31.8% had learned how to refuse smoking from school education. The students with smoking behavior were more likely to drink alcohol, use drugs, bully others, be injured, miss classes, and have some psychological troubles than those without smoking behavior.

CONCLUSIONThere were increasing trends noticed on the incidence of attempt and smoking cigarettes. Smoking was closely related to other unhealthy behaviors and psychological troubles. Comprehensive education activities on "no-smoking" should be implemented as early as possible among adolescents, as well as to promote training on life skills.

Adolescent ; Adolescent Behavior ; Child ; China ; epidemiology ; Health Behavior ; Humans ; Incidence ; Mental Disorders ; Smoking ; epidemiology ; Students ; psychology ; Substance-Related Disorders

OBJECTIVETo filtrate breast cancer resistance protein (BCRP)-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance.

METHODSMTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography (HPLC) assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immunohistochemistry (IHC) were employed to investigate the BCRP expression in breast cancer tissue specimens.

RESULTSMTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil (5-Fu) (P<0.05, n=3) in the cell model, while HPLC assay indicated that the intracellular retention dose of 5-Fu was significantly correlated with the expression of BCRP (r=-0.897, P<0.05, n=3). A total of 140 breast cancer tissue specimens were collected. BCRP-positive expression was detected in forty-seven specimens by both RT-PCR and IHC. As shown by MTT assay subsequently, the resistance index (RI) of 47 BCRP-positive breast cancer tissue specimens to 5-Fu was 7-12 times as high as that of adjacent normal tissue samples. BCRP expression was related to 5-Fu resistance (R2=0.8124, P<0.01).

CONCLUSIONResistance to 5-Fu can be mediated by BCRP. Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.

ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Adult ; Antimetabolites, Antineoplastic ; pharmacology ; Chromatography, High Pressure Liquid ; Drug Resistance, Neoplasm ; Female ; Fluorouracil ; pharmacology ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD).

METHODSA total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed.

RESULTSThe 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01).

CONCLUSIONKA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Aged ; Angina Pectoris ; drug therapy ; Coronary Disease ; drug therapy ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Oils, Volatile ; therapeutic use ; Phytotherapy

OBJECTIVETo evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma.

METHODSTotally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy.

RESULTSOf the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group.

CONCLUSIONThis phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.

Adult ; Aged ; Antibodies, Monoclonal ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; pathology ; therapy ; Combined Modality Therapy ; Female ; Fever ; etiology ; Humans ; Hypotension ; etiology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Quality of Life ; Radiotherapy ; adverse effects ; methods ; Receptor, Epidermal Growth Factor ; immunology ; Remission Induction