1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; pharmacology ; Animals ; Cardiomyopathy, Hypertrophic ; drug therapy ; metabolism ; Connexin 43 ; metabolism ; Disease Models, Animal ; Male ; Myocardium ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the correlation of the deleted azoospermia (DAZ) gene copy related to gr/gr and b2/b3 deletions in the AZFc region with male spermatogenic impairment.

METHODSThis study included 121 infertile men with different de- grees of spermatogenic impairment and 95 healthy donors from the sperm bank. Using PCR, PCR-RFLP, and Y chromosome specific sequence tagged sites (STS) , we analyzed the association of DAZ gene copy deletions related to gr/gr and b2/b3 deletions in the AZFc region with spermatogenic impairment.

RESULTSThere were 15 cases of gr/gr deletion (12. 40% ) and 6 cases of b2/b3 deletion (4.96%) in the infertility group as compared with 13 cases of gr/gr deletion (13.68%) and 1 case of b2/b3 deletion (1.05%) in the control. Analysis of the DAZ-specific single nucleotide variant (SNV) loci revealed 11 gr/gr-DAZI/DAZ2 deletions (9.09%), 4 gr/gr-DAZ3/DAZ4 deletions (3.31%), and 6 b2/b3-DAZ1/DAZ2 deletions (4.96%) in the infertile men in comparison with 3 gr/ gr-DAZ1/DAZ2 deletions (3.16%), 10 gr/gr-DAZ3/DAZ4 deletions (10.53%), and 1 b2/b3- DAZ3/DAZ4 deletion (1.05%) in the control.

CONCLUSIONPartial deletions of gr/gr and b2/b3 exist in both healthy men and male patients with different degrees of spermatogenic impairment and cannot be considered as a risk factor for spermatogenesis impairment. However, deletions of different DAZ duplicons in gr/gr and b2/b3 deletions have different effects on spermatogenesis. DAZ1/DAZ2 instead of DAZ3/DAZ4 deletions might be associated with spermatogenesis impairment.

Deleted in Azoospermia 1 Protein ; Gene Deletion ; Gene Dosage ; Humans ; Male ; RNA-Binding Proteins ; genetics ; Spermatogenesis ; genetics

OBJECTIVETo study the effect of C21 steroidal glycoside (CSG) from the root of Cynanchum auriculatum from Jiangsu on D-galactose (D-gal) induced aging model mice.

METHODD-gal aging mouse model was established by cervicodorsal region subcutaneous injection with D-gal once a day for eight successive weeks. The mice in the normal control group (NCG, non-modeled) and the model control group (MCG, modeled but untreated) were treated with 1% CMC-Na. The model mice in the low, middle and high-dose CSG and Vitamin E treated groups were treated with a dose of (10, 20, 40, 100 mg x kg(-1) per day, respectively. The SOD activity, MDA content and telomerase activity in serum, heart, liver and brain tissues of mice were measured.

RESULTCSG could obviously increase the SOD activity and decrease the MDA level in serum, heart, liver and brain tissues in D-gal aging mice (P < 0.01). There was no significant difference between three CSG treated groups and Vitamin E treated groups. In comparison of telomerase activity between MCG and the treated groups, it was shown that there was a significant increase in serum in middle and high dose group, and in heart tissues in CSG and Vit E treated groups, but was not in liver and brain tissue.

CONCLUSIONThis study demonstrates that CSG can antagonize free radical injury, increase the SOD activity and decrease the MDA content of serum, heart, liver and brain in D-gal aging mice, and increase the telomerase activity in serum and heart tissues but not in liver and brain tissue.

Aging ; drug effects ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Cynanchum ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Galactose ; toxicity ; Glycosides ; isolation & purification ; pharmacology ; Liver ; drug effects ; metabolism ; Male ; Malondialdehyde ; blood ; metabolism ; Mice ; Mice, Inbred ICR ; Myocardium ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Steroids ; isolation & purification ; pharmacology ; Superoxide Dismutase ; blood ; metabolism ; Telomerase ; metabolism

Objective To investigate the occurrence of new cretinism cases and the prevalence of endemic goiter, and the reason of lower coverage rate of iodized salt in the iodine deficiency disorders(IDD) high-risk areas of China, so as to put forward target prevention measures for these areas. Methods A hundred and one counties from 11 provinces(autonomous regions, municipality), such as Tibet, Qinghai, Xinjiang, Gansu, Ningxia, Sichuan, Hainan, Chongqing, Yunnan, Guangxi, Inner Mongolia, were chosen into the survey by simple random sampling. In the counties of high risk, typical sampling principle was used. In the selected townships, searching for new cretinism cases were carried out in the children under 10 years old, the thyroid volume of children aged 8-10 years old were determined by B-ultrasonography methods and their urinary iodine (UI) were determined by As3-Ce<'4+> catalytic spectrophotometry, the intelligence quotient(IQ) values of children aged 8-10 years old were measured by the combined Raven Test in China. In the household survey, the housewives were asked to fill in the questionnaire, the iodized salt coverage rates and the UI levels of child-bearing age women were investigated, the salt iodine content was determined using self-quantitative kit. Epi Info software was used to analyze the determination results. Results In the 101 high-risk counties, 249 were diagnosed as new cretinism cases from 4122 suspected cases searched. The goiter rate of children aged 8-10 years old by B-ultrasound was 8.28% (4434/53 541), 44 counties had goiter rates in the range of 5%-20%, 5 counties had goiter rates in the range of 20%-30%, and 3 counties had goiter rates of 30%. The mean IQ of children was 85.44, and the percentage of IQ value less than 70 was 16.52%(8713/52 745). The median urinary iodine(MUI) of children was 154.69 μg/L, the percentage of UI less than 50 μg/L was 17.26% (9069/52 558). Twenty-five counties had a MUI of children less than 100 μg/L. The MUI of housewives was 107.14 μg/L, the percentage of UI less than 50 μg/L was 27.50% (3722/13 534). MUI of housewives in 46 counties were less than 100.0 μg/L. The coverage rate of iodized salt at household level was 77.85%(13 150/16 891). The coverage rate of iodized salt was 52.80%(1585/3002), 44.72% (631/1411) and 72.82% (1850/2506) in Tibet, Hainan and Qinghai, respectively. More than 10% residents of Tibet, Sichuan, Hainan, Gansu and Qinghai complained that iodized salt was not convenient to buy. There were 71.39%(7652/10 719) of observed people ate crude salt. The average price of crude salt price(0.30-1.20 Yuan/kg) was lower than iodized salt(1.20-3.00 Yuan/kg). Conclusions In these IDD high-risk areas, the risk of endemic goiter and cretinism prevalence is threatening. The IDD monitoring should be carried out successively in these high-risk areas. The prevention measures, increasing iodized salt coverage rate and establishing the sustainable mechanism for eliminating IDD should be strengthened. Emergent iodine fortification measure for high risk region people should be implemented as soon as possible, a long term effective mechanism of eliminating IDD should be established.

Objective To explore the expression and clinical significance of CCAAT-enhancer-binding proteins (C/EBPα) in colon cancer tissues.Methods The expression level of C/EBPoα in colon cancer tissues and corresponding non-tumor normal tissues of 41 colon cancer patients was detected by Western blot.The correlation between the expression of C/EBPoα and clinicopathological parameters of colon cancer and survival rate of prognosis were statistically analyzed.Results In 41 cases of normal tissue adjacent to carcinoma,low expression of C/EBPeα appeared only 2 cases,high expression 39 cases,low expression rate was only 4.88％;and in 41 cases of colon cancer,C/EBP low expression appeared 32 cases,high expression only 9 cases,low expression rate was 78.05％.Compared with normal adjacent tissues,the expression of C/EBP in colon cancer was down regulated (P＜0.05).In 41 cases of colon cancer,independent of C/EBPα expression and colon cancer,cancer size,sex,age and histological classification of colon cancer clinical pathological parameters (P ＞ 0.05),but tumor node metastasis (TNM) and colon cancer staging was closely related (P ＜ 0.05).The median survival times in low expression and high expression groups were 31.5 and 54.2 months,with significant difference(P ＜0.05).Conclusion The low expression of C/EBPα in colon cancer has a close relationship with TMN staging and survival rate of prognosis,which has a great significance on early diagnosis and targeted therapy of colon cancer in the future.

OBJECTIVESTo investigate role of hypoxia inducible factor 1 (HIF-1) in the transcriptional activation of heat shock protein 70-2 (HSP70-2) in hepatocellular carcinoma (HCC) cells under hypoxic conditions.

METHODSHCC cells were exposed to reduced oxygen atmosphere (1% O2), or treated with YC-1 or HIF-1 alpha siRNA, the expression of HIF-1 alpha and HSP70-2 were detected by Western blot analysis. Serial deletions of the HSPA2 promoter were cloned in the reporter pGL3-Basic plasmid. These reporter plasmids were co-transfected with HIF-1 alpha siRNA, and the promoter activities were detected with the dual luciferase assay.

RESULTSWestern blot analysis showed that both HIF-1 alpha and HSP70-2 proteins were strongly increased after HCC cells were exposed to hypoxic conditions (1% O2) for 6 h, and the expression level of HSP70-2 was increased in a time-dependent manner. Treatment of HepG2 cells with YC-1 or HIF-1 alpha siRNA significantly inhibited the expression of HIF-1 alpha and HSP70-2. In silico analysis of the HSP70-2 promoter using the Gene2 Promoter software revealed the presence of two putative hypoxic response element (HRE) consensus at -446bp (HRE1) and -238bp (HRE2). Depletion of promoter sequence between -653 and -385 led to a dramatic reduction of promoter activity, whereas further deletion to position -201 did not reduce the activity further. These data suggested that HRE1 plays an important role in hypoxia-induced activation of the HSPA2 promoter. Site-directed mutagenesis further confirmed these results. Mutation of HRE1 but not of HRE2 abrogated the sensitivity of the HSP70-2 promoter to hypoxia.

CONCLUSIONSHSP70-2 expression is up-regulated in response to hypoxia and a HIF-1 binding site (HRE1) in the HSP70-2 promoter is involved in this response.

Base Sequence ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Hypoxia ; Gene Expression Regulation, Neoplastic ; HSP70 Heat-Shock Proteins ; genetics ; metabolism ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1 ; genetics ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Molecular Sequence Data ; Plasmids ; genetics ; Promoter Regions, Genetic ; RNA, Small Interfering ; genetics ; Transfection ; Up-Regulation

Objective: To explore the relationship between ABO blood group and acute non-ST-segment elevation myocardial infarction (NSTEMI) occurrence. Methods: Our research included 2 groups: NSTEMI group, 1039 relevant patients treated in Anzhen hospital from 2013-01 to 2014-12 were retrospectively enrolled; Control group, 1039 subjects with normal coronary artery which was confirmed by coronary angiography. The Baseline condition including age, previous disease history and ABO blood group was studied. Logistic regression model was used to conduct single and multivariate analysis. Results: In NSTEMI group and Control group, blood type A was 287/1039 (27.6％) vs 259 (24.9％), type B was 345 (33.3％) vs 356 (34.3％), type AB was 102 (9.8％) vs 114 (11.0％) and type O was 305 (29.4％) vs 310 (29.8％), ABO blood group distribution for A and non-A, B and non-B, AB and non-AB blood group, O and non-O had no statistic meaning between 2 groups, P>0.05. Logistic regression analysis indicated that with adjusted risk factors of MI such as age, gender, hypertension, diabetes, hyperlipemia, cerebrovascular disease and smoking, the patients with blood types A, B and AB had the similar risk for NSTEMI occurrence than type O patients; there was no relationship between ABO blood group and NSTEMI occurrence. Conclusion: ABO blood group had no relationship to NSTEMI occurrence.

Speckle tracking echocardiography (STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge (G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group (n=10), mild trans-aortic banding (TAB) group (n=14) and severe TAB group (n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening (FS), left ventricular (LV) mass, and left ventricular end diastolic diameter (LVEDD) (P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures (P>0.05 for both). STE analysis revealed that longitudinal strain (LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups (P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group (P<0.05). Radial strain (RS) and circumferential strain (CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group (P<0.05 for both) from the postoperative week 1 (P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6 (P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.
Animals ; Cardiomegaly ; physiopathology ; Disease Models, Animal ; Echocardiography ; methods ; Heart Failure ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL

Objective To investigate the efficacy of telbivudine blocking the spread of hepatitis B virus in intrauterine. Methods Collecting 64 cases of pregnant women who receive treatment in Hangzhou Sixth People's hospital between November 2007-June 2009,which are divided into control group (36 cases)and treatment group (28 eases). Two groups of pregnant women intramuscular HBIG 200IU each one times during pregnancy 28, 32 and 36 weeks. Pregnant women of treatment simultaneously oral telbivudine tabels,600 mg/d. To observe the HBV DNA load and HBsAg levels in newborns of two groups. Results HBsAgpositive rate is 30.56% (11/36) in newborns of the treatment group, which is 7. 14% (2/28) in control group. The difference is statistically significant between two groups ( χ2 = 3. 985, P = 0. 046 ). HBV DNA positive rate is 1 16.67% (6/36) in newborns of control group, which is 0 in treatment group. The difference is statistically significant between two groups ( P ＜ 0.05 ). All pregnant women and newborns do not appear adverse reactions during the treatment. Conclusion HBV blocking rate of treatment group is significantly higher than control group. The results suggest that telbivudine can reduce the risk of HBV vertical transmission to a certain extent.

Objective To explore the effect of aspirin(ASP) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inducer TIC10 on apoptosis and autophagy of cervical cancer Siha and HeLa cells. Methods HPV16 positive squamous carcinoma Siha cells and HPV18 positive cervical adenocarcinoma HeLa cells were selected as research objects. Two cell lines were treated with ASP,TIC10 or two drugs combination. The effects of ASP and TIC10 on cell proliferation were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,cell migration ability was detected by cell scratch assay,cell clone formation ability was detected by plate clone formation assay,and the levels of cleaved Caspase-3/8,LC3A/B,Beclin1 were detected by Western Blot. Results The MTT showed that the proliferations of Siha and HeLa cells were inhibited by APS in a concentration dependent manner (all P < 0. 01). After treated with TIC10 combined with ASP for 48 h,the cell proliferation inhibition rates of Siha and HeLa cells were higher than thosetreated with TIC10 alone (all P < 0. 01). After treated with TIC10 or ASP for 24 h, the migration rates of Siha and He- La cells in the experimental groups [ASP: (19. 61 ± 1. 17) ％,(23. 75 ± 0. 78) ％; TIC10: (16. 89 ± 1. 47) ％,(20. 59 ± 2. 01) ％]were lower than those of control group [(41. 18 ± 2. 01) ％,(40. 83 ± 3. 77) ％],all P < 0. 01. After two weeks of treatmentof ASP and TIC10,the CFE(colony-forming efficiency) rates of Siha and HeLa cells in the experimental groups [ASP: (24. 93 ± 2. 12) ％, (26. 47 ± 3. 30) ％, TIC10: (17. 33 ± 1. 50) ％,(19. 13 ± 4. 99) ％]were lower than those of control group [(69. 60 ± 3. 54) ％,(68. 40 ± 4. 20) ％],all P < 0. 01. Western blot assays showed that the expression of cleaved Caspase-3/8 and autophagy related protein LC3A/B,Beclin1 were higher than those of control group (all P < 0. 01). Conclusion ASP increases cervical cancer cells apoptosis with TRAIL inducer TIC10 through autophagy enhancement.