Objective : To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo- lar epithelial interstitial transformation (EMT) and its related signaling pathways . Methods : Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin ( E-cad) , alpha-smooth muscle actin ( α- SMA) and Collagen I (Col I) in the process of EMT induced by TGF-β1 . LncSIL interacting proteins were ana- lyzed by RNA pulldown . Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2 (EZH2) and its downstream factors P21 and cyclin-de- pendent kinase 6 (CDK6) . Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression . Results: After lncSIL silencing , the expression of α-SMA and Col I increased , the expression of E-cad decreased . RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL , and the expression of EZH2 increased after silencing lncSIL , the expression of EZH2 downstream gene P21 decreased , CDK6 increased . Flow cytometry showed that the number of cells in S phase significantly increased . When lncSIL was overexpressed , the expression of EZH2 and CDK6 was down-regulated , the expression of P21 was up-regulated , and the number of S phase cells significantly decreased . Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen- chymal transition by negatively regulating EZH2/P21 /CDK6 signaling pathway to inhibit cell cycle progression .

Objective: To observe the platinum drugs resistance effect of N-acetyltransferase 10 (NAT10) overexpression in breast cancer cell line and elucidate the underlining mechanisms. Methods: The experiment was divided into wild-type (MCF-7 wild-type cells without any treatment) group, NAT10 overexpression group (H-NAT10 plasmid transfected into MCF-7 cells) and NAT10 knockdown group (SH-NAT10 plasmid transfected into MCF-7 cells). The invasion was detected by Transwell array, the interaction between NAT10 and PARP1 was detected by co-immunoprecipitation. The impact of NAT10 overexpression or knockdown on the acetylation level of PARP1 and its half-life was also determined. Immunostaining and IP array were used to detect the recruitment of DNA damage repair protein by acetylated PARP1. Flow cytometry was used to detect the cell apoptosis. Results: Transwell invasion assay showed that the number of cell invasion was 483.00±46.90 in the NAT10 overexpression group, 469.00±40.50 in the NAT10 knockdown group, and 445.00±35.50 in the MCF-7 wild-type cells, and the differences were not statistically significant (P>0.05). In the presence of 10 μmol/L oxaliplatin, the number of cell invasion was 502.00±45.60 in the NAT10 overexpression group and 105.00±20.50 in the NAT10 knockdown group, both statistically significant (P<0.05) compared with 219.00±31.50 in wild-type cells. In the presence of 10 μmol/L oxaliplatin, NAT10 overexpression enhanced the binding of PARP1 to NAT10 compared with wild-type cells, whereas the use of the NAT10 inhibitor Remodelin inhibited the mutual binding of the two. Overexpression of NAT10 induced PARP1 acetylation followed by increased PARP1 binding to XRCC1, and knockdown of NAT10 expression reduced PARP1 binding to XRCC1. Overexpression of NAT10 enhanced PARP1 binding to LIG3, while knockdown of NAT10 expression decreased PARP1 binding to LIG3. In 10 μmol/L oxaliplatin-treated cells, the γH2AX expression level was 0.38±0.02 in NAT10 overexpressing cells and 1.36±0.15 in NAT10 knockdown cells, both statistically significant (P<0.05) compared with 1.00±0.00 in wild-type cells. In 10 μmol/L oxaliplatin treated cells, the apoptosis rate was (6.54±0.68)% in the NAT10 overexpression group and (12.98±2.54)% in the NAT10 knockdown group, both of which were statistically significant (P<0.05) compared with (9.67±0.37)% in wild-type cells. Conclusion: NAT10 overexpression enhances the binding of NAT10 to PARP1 and promotes the acetylation of PARP1, which in turn prolongs the half-life of PARP1, thus enhancing PARP1 recruitment of DNA damage repair related proteins to the damage sites, promoting DNA damage repair and ultimately the survival of breast cancer cells.
Breast Neoplasms/enzymology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Female ; Humans ; MCF-7 Cells ; N-Terminal Acetyltransferases/metabolism* ; Organoplatinum Compounds/pharmacology* ; Oxaliplatin/pharmacology* ; X-ray Repair Cross Complementing Protein 1

Objective: To explore the association between dust exposure and the incidence of hypertension in male coal miners. Methods: Using the method of retrospective cohort study,a hypertension cohort of colliery in Henan Province was established in January 2006. From 2006 to 2017,all the male coal miners in a colliery who were exposed to dust were selected into the exposure group including tunneling, mining,auxiliary and combining workers, and workers from administrative logistics departments who were not exposed to dust were selected into the control group. The eligible participants should satisfy following conditions: working more than one year, with clear and complete record of occupation change, and with complete archives and reliable diagnosis of occupational health surveillance. The exclusion criteria of participants were with hypertension at the baseline of study or with heart,liver,kidney diseases and malignant tumors. A total of 12 647 participants were enrolled in this study (11 663 in the exposure group and 984 in the control group). The follow-up period was from January 2006 to December 2017,with a total follow-up of 89 259.75 person-years. Questionnaires and physical measurements were used to collect general demographic characteristics, occupational exposure history and occupational health surveillance data of all participants. The Cox proportional hazards regression model was used to estimate the association between the dust exposure and the incidence of hypertension. Results: During the follow-up period, 2 549 new-onset hypertension patients were identified with an incidence density of hypertension about 2 855.71 per 100 000 person-years. The incidence density of hypertension was 2 967.58 per 100 000 person-years in the exposure group, and 1 643.85 per 100 000 person-years in the control group. The results of multivariate Cox proportional hazards regression model showed that after the adjustment of marriage, age, smoking, alcohol drinking and body mass index,the risk of hypertension was higher in the exposure group compared with the control group (HR=1.692, 95%CI: 1.410-2.032). Further analysis showed that compared with workers from administrative logistics departments,the risk of hypertension in tunneling,mining and auxiliary working was 1.629(1.345-1.973),1.677(1.374-2.046) and 1.782(1.475-2.151),respectively. Conclusion Dust exposure may increase the risk of hypertension in male coal miners.

Objective: To investigate the prevalence and influencing factors of lower respiratory tract disease. Methods: The health physical examination data of 4000 coal dust exposed workers who had physical examination in the Institute of Occupational Disease Prevention and Treatment in 2016 were collected and analyzed with SPSS 20.0 software. Results: Out of the 4000 coal workers, the Prevalence rate of pulmonary tuberculosis, chronic bronchitis, CWP were 1.00% (40/4000) , 0.63% (25/4000) , 0.43% (17/4000) . 17 coal workers suffered from coal workers. The prevalence of workers both exposed to silicon and coal dust was 1.15% (2/174) , which was higher than that of other the job type. The prevalence of CWP among age groups, length of service and occupational category were found significant difference (P<0.05) , raising with the increase of duration of dust exposure and age increasing (χ²_trend=17.171, 5.344, P<0.05) . The prevalence of emphysema and chronic bronchitis between different working years and different ages are all statistically significant (P<0.05) , increasing with duration of dust exposure (χ²_trend=9.906, 10.118, P<0.05) . Conclusion The prevalence rate of CWP is not high, and closely related with duration of dust exposure and dust species. The prevalence of lower respiratory tract disease is higher in the tunneling and mining workers and raising with the duration of dust exposure.

Objective To explore the ischemic myocardial perfusion and viability.Methods Ten successful pigs with myocardial infarction model underwent MRI first-pass myocardial perfusion examinations preoperatively and 24 hours,72 hours and one week postoperation.After MRI examinations,the experimental pigs were executed and the samples underwent TTC staining and pathological examination.Results The preoperative myocardial perfusion in the all of the 10 pigs was nomal,but there were myocardial perfusion decrease and defects in 8 experimental pigs after operation,the perfusion curves in the area with perfusion defects had no obvious peak,but there was gradual increase in the end of the performance.The perfusion peak of the area with perfusion decrease was lower than that of normal inferior and lateral myocardial wall(P＜0.05) and the peak perfusion time was delayed compared with that of normal inferior and lateral myocardial wall (P＜0.05).There was myocardial necrosis in the perfusion defects areas that was certified by TTC staining and pathological examination.The intersititial edema and myocardial degeneration could be seen in the perfusion reduced areas.Conclusion MRI fist-pass myocardial perfusion imaging combined with perfusion curve analysis can evaluate the perfusion changes of the regional myocardial microcirculation.

Objective To assess the frequency of different subtype of spinocerebellar ataxias (SCAs) in Chinese Han population. Methods The nueleotide repeat mutations of SCA1, SCA2, SCA3/ MJD, SCA6, SCAT, SCA8, SCA10, SCA12, SCA17 and dentatorubral-pallidoluysian atrophy (DRPLA) were detected by the polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis (PAGE), Southern blot, recombinant DNA technology by T-vector cloning and direct sequencing technique in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 families with autosomal dominant SCA (AD-SCA) and 196 sporadic cases. Results Among the 363 AD-SCA families, 15 families (4. 13%) were positive for SCA1, 26 (7. 16%) for SCA2, 187 (51.52%) for SCA3/MJD, 6 (1.65%) for SCA6, 7 (1.93%) for SCA7, 1 (0. 28%) for SCA12 and 1 (0. 28%) positive for SCA17; 120(33. 06%) were negative for all the tested SCAs. There were 2 (1.02%) SCAI, 3 (1.53%) SCA2, 15 (7. 65%) SCA3/MJD, 3 (1.53%) SCA6 and 173 (88.27%) not identified in the 196 sporadic SCA patients. None of the SCA8, SCA10 and DRPLA mutation was found. Conclusions SCA3/MJD is a substantially common subtype of AD-SCAs and sporadic SCA in Chinese Han patients with SCAs, subsequently followed by SCA2, SCA1, SCAT and SCA6; SCA12 and SCA17 are uncommon subtypes, while SCA8, SCA10, and DRPLA are rare, if not absent. SCA17 subtype was initially identified in mailand China. Some other genes might be causative in those unidentified AD-SCA pedigrees, and other etiological factors besides genetic cause might contribute for those sporadic cases.

Objective To explore the influence of social network on the quality of life of elderly stroke patients in communities. Methods The general situation questionnaire, the stroke impact scale ( SIS) and social network scale for the elderly were used to investigate the community elderly stroke patients. Results The total score of social network was(39. 82±5. 87). The scores of social participation,social con-tact and social support were(11. 79±1. 61),(14. 90±3. 31) and (13. 13±3. 19). Results of univariate a-nalysis showed there were statistically significant differences ( P<0. 05) in quality of life among stroke pa-tients of different ages (F=7. 803),educational level (F=2. 664),family income (F=4. 754),smoking (F=5. 467),alcohol consumption (F=7. 058),physical exercise (F=10. 393),body mass index (t=4. 841) and hypertension (t=-2. 862). Multiple linear regression results showed that 3 times or more exercises per week ( B=5. 689),normal body mass index (B=6. 613),high degree of social support (B=0. 710),social partici-pation (B=1. 421) and social contact (B=1. 372) were protective factors for the quality of life of stroke pa-tients. Age 80 years and above (B=-10. 426),frequent smoking (B=-9. 005),frequent drinking (B=-8. 419) and hypertension ( B=-5. 224) were risk factors for quality of life. Conclusion The elderly stroke patients should quit smoking and alcohol,strengthen exercise,maintain a normal body mass index and avoid overweight and obesity in daily life. While promoting health-related behaviors,more attention should be paid to the promotion effect of social network on treatment,rehabilitation and overall quality of life of stroke patients.

OBJECTIVETo investigate the CAG trinucleotide repeat expansion in spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, 12, and 17 from Chinese Han.

METHODSThe pathological CAG triplet repeat expansions of the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA12 and SCA17 genes were analyzed in a cohort of 559 Mainland Chinese patients affected by spinocerebellar ataxia, including 363 probands from families with autosomal dominant SCA and 196 sporadic cases. Polymerase chain reaction, agarose gel electrophoresis, recombinant DNA technology by T-vector cloning and direct sequencing were performed to detect the CAG-repeat number of abnormal allele.

RESULTSAmong the 559 SCA patients, twenty-three were positive for SCA1, the ranges of expanded CAG repeats were from 39 to 60 (mean:51.09+/-4.88); thirty-two were positive for SCA2, the ranges of expanded CAG repeats were from 36 to 51 (mean:40.34+/-4.40); three hundred and five were positive for SCA3/MJD, the ranges of expanded CAG repeats were from 49 to 86 (mean:73.84+/-5.07); nine were positive for SCA6, the ranges of expanded CAG repeats were from 23 to 29 (mean:25.56+/-1.94); twenty-seven were positive for SCA7, the ranges of expanded CAG repeats were from 38 to 71(mean:58.22+/-10.90); three were positive for SCA12, the ranges of expanded CAG repeats were from 51 to 52 (mean:51.33+/-0.58); and finally, two were positive for SCA17, the range of expanded CAG repeats were from 53 to 55 (mean:54.00+/-1.41).

CONCLUSIONThe 39 CAG repeats of SCA1, 49 CAG repeats of SCA3 and 51 CAG repeats of SCA12 are all the shortest known causative expanded alleles, while the 86 CAG repeats of SCA3/MJD is the largest full expanded allele that has never been reported. Furthermore, it is the first report of SCA17 subtype in Mainland Chinese and first research that established the abnormal reference standard of CAG repeat number of different subtypes of SCA in Chinese Han.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Ataxin-7 ; Ataxins ; Base Sequence ; Child ; Child, Preschool ; Cohort Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Nerve Tissue Proteins ; genetics ; Protein Phosphatase 2 ; genetics ; Spinocerebellar Ataxias ; ethnology ; genetics ; Trinucleotide Repeat Expansion ; Young Adult

OBJECTIVETo study pantothenate kinase 2 (PANK2) gene mutations in Chinese patients with Hallervorden-Spatz syndrome (HSS).

METHODSPANK2 gene mutations were detected by PCR, DNA sequence analyses, restriction enzyme digestion and PCR-single strand conformation polymorphism in 5 patients, 3 unaffected family members and 51 unrelated healthy persons.

RESULTSNovel compound heterozygous PANK2 gene mutations, A803G and T1172A, in exons 3 and 5, respectively, were found in one patient. At the same time, 3 types of single nucleotide polymorphisms, -38 t>a in 5'-UTR, IVS1+42 c>a and G77C in exon 1, were confirmed; among them, -38 t>a, IVS1+42 c>a, were first reported.

CONCLUSIONPANK2 gene mutations can cause HSS in Chinese patients.

Adolescent ; Adult ; Base Sequence ; Child ; China ; DNA Mutational Analysis ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pantothenate Kinase-Associated Neurodegeneration ; genetics ; Pedigree ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Young Adult

OBJECTIVETo study the effect of down-regulation of histone deacetylase 2 (HDAC2) expression on cell proliferation and cell cycle in cervical carcinoma cell lines HeLa.

METHODSHDAC2 siRNA and control siRNA were transfected to HeLa cells. CCK-8 and flow cytometry were used to analyze the changes of cell proliferation and cell cycle, respectively. Western blot was employed to detect the changes of cell proliferation and cell cycle-related proteins.

RESULTSHDAC2 siRNA significantly down-regulated the expression of HDAC2 protein in HeLa cells, resulting in marked inhibition of cell proliferation. In addition, the percentage of cells in G(0)/G(1) phase in HDAC2 siRNA group (63.3% ± 2.0%) was significantly higher than that in untreated group (29.3% ± 1.7%) or control siRNA group (29.4% ± 1.7%), F = 354.181, P = 0.000. Furthermore, Western blot demonstrated that down-regulation of HDAC2 expression decreased the expression of cyclin D1, cyclin E and CDK2 proteins but increased the expression of p21 protein.

CONCLUSIONSDown-regulation of HDAC2 expression mediates proliferation inhibition and cell cycle arrest. It is associated with decrease in cyclin D1, cyclin E and CDK2 protein expression and increase in p21 protein expression.

Cell Cycle ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Cyclin-Dependent Kinase 2 ; metabolism ; Down-Regulation ; HeLa Cells ; Histone Deacetylase 2 ; genetics ; metabolism ; Humans ; Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins p21(ras) ; metabolism ; RNA, Small Interfering ; genetics ; Transfection