Animals ; Drugs, Chinese Herbal ; pharmacology ; PC12 Cells ; Patch-Clamp Techniques ; Potassium Channels, Voltage-Gated ; drug effects ; physiology ; Rats

Objective To explore the effects of valsartan and MEK1/2 inhibitor U0126 on atrial fibrosis and connexin40 (Cx40) remodeling in rats treated with isopreterenol (ISO).Methods 32 male SD rats were randomly divided into control group (A),ISO (5 mg · kg-1 · d-1 for7 days) + DMSO group (B),ISO + U0126 (0.5 mg · kg-1 · d-1 for 28 days) group (C,U0126 was dissolved in DMSO),ISO +valsartan (30 mg · kg-1 · d-1 for 28 days) + DMSO group (D).Rats were sacrificed after 28 days.The AngⅡ content in myocardial tissue was measured by radioimmunoassay,P-MEK1/2,P-ERK1/2 and Cx40 was detected by immunohistochemistry,atrial fibrosis was determined on HE and Masson stained heart sections.Results The content of Ang Ⅱ was significantly higher in group B,C and D compared with group A [ (368.243 ±6.283 ) ng/L,( 357.175 ± 5.944 ) ng/L,( 359.908 ± 2.496 ) ng/L vs ( 250.380 ± 4.261 )ng/L,P ＜0.01 ] ; the degree of atrial fibrosis was significantly lower in group C and D compared with group B [CVF(10.260 ±0.525)％,(10.238 ±0.524)％ vs (78.710 ± 1.587)％,P＜0.01 ] while there was no atrial fibrosis in group A [ CVF(9.025 ± 0.456)％ ] ; the expression of P-MEK1/2 and P-ERK1/2 was significantly upregulated in group B compared with group A ( P-MEK1/2:0.311 ± 0.007 vs 0.203 ± 0.009,P ＜0.01 ; P-ERK1/2:0.259 ±0.003 vs 0.173 ±0.006,P ＜0.01 ) and significantly lower in group C and D compared with group B (P-MEK1/2:0.212 ± 0.004,0.213 ± 0.005 vs 0.311 ± 0.007,P ＜0.01,P-ERK1/2:0.178 ±0.004,0.175 ±0.007 vs 0.259 ±0.003,P ＜0.01 ).The content of Cx40 was obviously reduced and the distribution of Cx40 was disordered in group B compared with A (0.199 ±0.007 vs 0.241 ±0.004,P＜0.01) which could be partly reversed in group C and D ( 0.239 ±0.037,0.235 ±0.006 vs 0.199 ± 0.007,P ＜ 0.01 ).All parameters in group C and D were similar ( P ＞ 0.05 ).Conclusion The chronically elevated Ang Ⅱ content in myocardium may be related to atrial fibrosis and Cx40 remodeling in this model,valsartan and U0126 were equivalent on attenuating atrial fibrosis and Cx40 remodeling by inhibiting ERK pathways at different levels.

Objective To investigate the impact of age on patients with metabolic syndrome (MS) and normal persons. Methods Data was gathered from 8280 persons including 4873 males and 3407 females who were randomly selected. All subjects were devided into normal group and MS group. According to the interval of ten years, the subjects were devided into seven age groups, to calculate the difference of impaired fasting glycaemia (IFG) between patients with diabetes mellitus (DM) and normal people, as well as the related portions. Results (1) The risk of IFG and DM appeared to be different among age groups among the target subjects as well as in the normal and the MS groups (P<0.05). (2) Among the whole subjects, the overall prevalence of IFG was increasing with age. The prevalence of DM had an increasing trend with age augment in 20-79 years group, whereas a decreasing trend appeared in people over 80 years of age. (3) For normal persons, the prevalence of IFG and DM were all increasing with age augment in 20-79 years group, and then decreasing with age augment in the over-80-years group. (4)For MS patients, the prevalence of IFG had an increasing trend with age augment in 20-69 years group, whereas a decreasing trend appeared in people over 70 years of age. There was no tendency of variation with age augment in DM.Conclusions (1) For normal persons, high prevalence rates of IFG and DM were correlated to age augment, especially in senior persons. (2) For MS patients, high prevalence of IFG was also correlated to age augment, but no association between prevalence of DM and age augment was seen. (3)Age from 70 to 79 years appeared to be in high risk with MS.

OBJECTIVETo investigate the toxicity of copper on MES23.5 dopaminergic cells and the probable mechanisms involved in this process.

METHODSMES23.5 dopaminergic cells were selected as our experimental model. [3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide] (MTT) assay was used to detect the influence of copper on the cell viability. The semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blotting and the high performance liquid chromatography-electrochemical detection (HPLC-ECD) have been used to detect the tyrosine hydroxlase (TH) mRNA and protein expression and the dopamine content in MES23.5 cells. The flow cytometry have been used to detect the changes of mitochondrial transmembrane potential.

RESULTS100 and 200 mumol/L copper had no effect on the MES23.5 cell viability, whereas 400 and 800 mumol/L of copper could decrease the cell viability (P < 0.01). Treating cells with 200 mumol/L copper for 24 h decreased the TH mRNA expression, the TH expression and the dopamine content compared with the control (P < 0.01, P < 0.01, P < 0.05, respectively). Besides, the mitochondrial transmembrane potential also decreased with the treatment of 200 mumol/L copper for 24 h (P < 0.01).

CONCLUSIONCopper could exert the toxic effects on MES23.5 dopaminergic cells and decrease the cell function. The dysfunction of mitochondria may be the mechanism of this toxicity effect.

Animals ; Cell Survival ; drug effects ; genetics ; Cells, Cultured ; Copper ; metabolism ; toxicity ; Dopamine ; biosynthesis ; Dose-Response Relationship, Drug ; Hybridomas ; Membrane Potential, Mitochondrial ; drug effects ; genetics ; Mice ; Mitochondria ; drug effects ; metabolism ; pathology ; Nerve Degeneration ; chemically induced ; metabolism ; physiopathology ; Neurons ; drug effects ; metabolism ; pathology ; Neurotoxins ; toxicity ; Oxidative Stress ; drug effects ; physiology ; Parkinson Disease ; etiology ; metabolism ; physiopathology ; RNA, Messenger ; drug effects ; metabolism ; Rats ; Tyrosine 3-Monooxygenase ; drug effects ; genetics ; metabolism

Objective To compare the expression of CD 49f splicing isoforms in different human stem cells and colon cancer cell lines , and construct lentiviral vectors overexpressing specific isoform .Methods The expression of CD49f isoforms in different cells was detected by RT-PCR and real-time PCR.The lentiviral vectors overexpressing CD49f isoforms were constructed by molecular cloning method .The overexpression of CD49f in colon cancer cell line HT29 was confirmed by FCM, Western blot and real-time PCR, the invasive ability was examined by transwell assay.Results CD49f splicing isoform B was highly expressed in H 9 human embryonic stem cell line , while iso-form A expressed in epithelial cells .Both isoform A and B were expressed in mesenchymal cells .CD49f isoforms A and B were also expressed in colorectal cancer cell lines , while HT29 and HCT116 showed higher expression of iso-form A than isoform B , HCT8 and LoVo showed higher expression of isoform B than isoform A .Overexpression of CD49f isoform B greatly increased the invasive ability of HT 29 cells, while isoform A showed no effect .Conclusions The expressions of CD49f splicing isoforms A and B in different types of cells are significantly different , which sug-gests that CD49f isoforms play different biological functions in cells .

Objective To evaluate the clinical safety and efficacy of GuidezillaTM guide extension catheter during complex coronary percutaneous coronary intervention(PCI). Methods A total of 13 patients were included in the studywho presented with complex coronary lesions during PCI. Stents or balloons could not be delivered to these complex lesions with conventional approach and GuidezillaTM guide extension catheters were used. Results Among these 13 patients,there were 7 CTO lesions,7 calcified lesions, 6 tortuous lesions,8 diffuse lesions,8 distal lesions and 8 lesions with pre-existing stents. PCI success rate was 100% .In one patient,GuidezillaTM guide extension catheter was obstructed which were relieved after stent implantation. There was no major adverse cardiac event(MACE) during follow-up.Conclusions The GuidezillaTM guide extension catheter was safe and effective for PCI of complex coronary artery lesions.

Objective To explore the effects of glutamine (Gln) induced heat shock protein 70 (Hsp70) overexpression on atrial fibrosis and connexin43 remodeling in isoprenaline(ISO) treated rats and related mechanisms.Methods Forty male SD rats were randomly divided into five groups (n =8 each group):control group,DMSO group,ISO5 mg · kg-1 · d-1 group (Fibrosis group),ISO5 mg· kg-1 ·d-1 +Ala-Gln0.75 mg· kg-1 ·d-1 group(Intervention group) and ISO 5 mg·kg-1 ·d-1 +QUE 100 mg·kg-1 ·d-1 +Ala-Gln0.75 mg· kg-1 · d-1 +DMSO group(QUE group).Rats were killed after7 d.The Ang Ⅱ expression in myocardial tissue was detected by radioimmunoassay; myocardial fibrosis was observed by HE staining.Collagen volume fractions were quantified by Masson staining and as the indicators of atrial fibrosis.The expressions of Hsp70,p-JNK1/2/3,c-Jun and Cx43 were determined with immunohistochemical method.Results Ang Ⅱ content was similar between the control group[(68.51 ± 10.76) pg/L] and DMSO [(71.47±11.49) pg/L] group (P＞ 0.05),and significantly increased in fibrosis group[(211.25 ±49.49)pg/L],intervention group[(185.32 ± 54.85) pg/L] and QUE[(189.90 ± 42.12) pg/L] group (P ＜ 0.01 vs.control group).Atrial fibrosis was significantly higher in the fibrosis group [(29.485 ± 9.966)％] and QUE group[(25.060 ±8.581)％] but not in the intervention group[(7.861 ± 1.867)％]compared to control group [(6.842 ± 1.674) ％] and DMSO group [(7.108 ± 1.343) ％].The expression of Hsp70 was similar among the control group (0.160 ± 0.023),DMSO group (0.163 ± 0.022),fibrosis group(0.166 ±0.028) and QUE(0.168 ±0.027) group (P ＞0.05) while significantly upregulated in the intervention group (0.215 ± 0.018) (P ＜ 0.01 vs.control group).The expressions of p-JNK1/2/3 and c-Jun were similar between control group(0.151 ±0.016;0.163 ±0.022) and DMSO group(0.154 ±0.021 ;0.164 ± 0.024) (P ＞ 0.05),while significantly upregulated in fibrosis group (0.202 ± 0.025 ; 0.254 ± 0.044) and QU E group (0.196 ± 0.024 ; 0.251 ± 0.027) (P ＜ 0.01 vs.control group) but not in intervention group(0.160 ±0.025 ; 0.168 ±0.024) were not changed obviously(P ＞0.05 vs.control group).The content of Cx43 was similar between control group and DMSO group(0.231 ± 0.035 vs.0.220 ± 0.032,P ＞ 0.05),and was linearly distributed in intercalated disc of the cardiomyocytes,however,the content of Cx43 was significantly reduced(P ＜ 0.01)and the Cx43 distribution was disordered in fibrosis group(0.163 ± 0.013) and QUE group(0.165 ± 0.024),while these changes were not found in intervention group.Conclusion Glutamine could reduce the atrial fibrosis and Cx43 remodeling in isoprenaline-treated rats by up-regulating Hsp70 and inhibiting JNK signaling pathway activation through down-regulating p-JNK1/2/3 and c-Jun expression.

OBJECTIVESTo determine the prevalence of cancer-related anemia and iron deficiency anemia (IDA) in patients with gastric and colorectal cancer in North of China.

METHODSA cross-sectional study of 262 inpatients diagnosed with gastric or colorectal cancer admitted to eight general hospitals in Beijing from August 2009 to December 2009 was performed. The blood samples were took on the day after admission and the seventh day after operation for the tests of hemoglobin, serum iron and ferritin. The morbidity of cancer-related anemia and IDA before and after the surgery was also compared respectively.

RESULTSThe preoperative morbidity of cancer-related anemia was 36.6% in 131 patients with gastric cancer, and the morbidity of IDA was 52.1%. The mean age of the anemic patients was higher than that in cases without anemia [(62 ± 11) yrs vs. (57 ± 12) yrs, P < 0.05]; the postoperative morbidity of IDA increased to 72.6% (P < 0.05). In the 131 cases with colorectal cancer, the preoperative incidence of cancer-related anemia and IDA was 37.4% and 61.2%, respectively. About 45% of the cases with anemia had a tumor in the right colon. Postoperative incidence of IDA was significantly higher than that before the surgery (76.7%, P < 0.05). Only 10.3% of the anemic patients were treated with chalybeate therapy before surgical procedures, and the proportion was 22.7% after the operation. More than 50% of anemic patient received blood transfusion.

CONCLUSIONSCancer-related anemia is a common clinical manifestation in patients with gastrointestinal cancer, and anemia occurs more frequently in elder and patients with right colon tumor. The treatment to cancer-related anemia is insufficient and a systematic therapy is needed to be established.

Adult ; Aged ; Aged, 80 and over ; Anemia ; complications ; epidemiology ; Colorectal Neoplasms ; complications ; surgery ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Perioperative Period ; Stomach Neoplasms ; complications ; surgery

OBJECTIVETo study hepatitis C virus (HCV) transmission through different modes of sharing injection equipment and sexual behavior among injecting drug users (IDUs) in Liangshan of Sichuan province.

METHODSA community-based survey was conducted to investigate past and current demographic data, injection equipment sharing patterns and sexual behavior of IDUs. Blood samples were also taken to test for HCV. The survey was conducted between Nov 8 and Nov 29, 2002. 379 subjects were screened through outreach recruitment and peer informing. SPSS (11.5) was used for data analysis.

RESULTSHCV prevalence was 71.0% (269/379). Needles or syringes sharing in the past three months and past syphilis infection were strongly associated with HCV transmission after univariate analysis using chi-square test. Trend analysis indicated that HCV infection rate increased along with the increase of needles or syringes sharing, sharing of rinse water and the number of peers sharing the equipments. Data from multivariate logistic regression showed that sharing of needles or syringes and history of syphilis infection were significantly associated with HCV transmission. No significant difference was found between HCV infection and sexual behavior after univariate analysis using chi-square test.

CONCLUSIONFurther sero-epidemiological prospective cohort studies should be conducted to clarify the relationship between different modes of sharing injection equipment, sexual behavior and HCV infection.

Adult ; China ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepacivirus ; immunology ; Hepatitis C ; blood ; transmission ; Humans ; Injections, Intravenous ; adverse effects ; Logistic Models ; Male ; Multivariate Analysis ; Needle Sharing ; adverse effects ; Sexual Behavior ; Sexually Transmitted Diseases, Viral ; blood ; Surveys and Questionnaires

This study was aimed to investigate the effects of low frequency and power ultrasound combined with adriamycin on apoptosis of drug-resistant leukemia cell line K562/A02 in vitro, to find out the parameters of optimal exposure, and to explore the possible mechanism reversing drug-resistance of K562/A02 cells. The K562/A02 cells in logarithmic growth phase were used in experiments. The experiments were divided into 4 groups: group control, group adriamycin (A02) alone, group ultrasound (US) alone and group A02+US. The trypan blue dye exclusion test and MTT assay were used to determine the cell viability; Wright's staining was used to detect the apoptosis; the flow cytometry was used to analyze the drug concentration, and the scanning electron microscopy was used to observe the changes of cell surface. The results showed that the significant differences in cell viability, intracellular adriamycin concentration and changes of cell membrane were found between ultrasound-treated and untreated cells in the presence of various concentration of adriamycin. The exposure to ultrasound at 20 kHZ, 0.25 W/cm2 for 60 seconds could obviously decrease LC50 of adriamycin to K562/A02 cells, while the exposure to ultrasound at 20 kHZ, 0.05 W/cm2 for 60 seconds could kill K562/A02 cells at once. After being treated by low frequency ultrasound, the small holes with diameter about 1-2 microm in the cell surface appeared. The ultrasound increased the adriamycin concentration in the cells, accelerated the formation of apoptotic bodies, and promoted apoptosis of adriamycin-resistant cells. It is concluded that the ultrasound at optimal parameters enhances inhibitory effect of adriamycin on drug-resistant cell line, thereby reverses drug-resistance of drug-resistant cell line through sound-hole effect in tumor cells resulting from ultrasound induced cavitation.
Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; K562 Cells ; Ultrasonics