Objective:To determine the clinicopathological significance of the DNA methyltransferase 3B (DNMT3B)overexpression in endometrial carcinomas and to evaluate its correlation with hormone re-ceptor status.Methods:Immunohistochemistry was performed to assess the expression of DNMT3B and hormone receptors in 104 endometrial carcinomas.Results:DNMT3B overexpression occurred frequently in endometrioid carcinoma (EC,54.8%)more than in nonendometrioid carcinoma (NEC,30.0%) with statistical significance (P =0.028).Furthermore,there was a trend that EC with worse clinico-pathological variables and shorter survival had a higher DNMT3B expression,and the correlation between DNMT3B and tumor grade reached statistical significance (P =0.019).A negative correlation between DNMT3B and estrogen receptor (ER)or progesterone receptor (PR)expression was found in EC. NMT3B overexpression occurred frequently in the ER or PR negative subgroups (78.9%,86.7%)more than in the positive subgroups (47.7%,47.8%)with statistical significance (P =0.016,P =0.006). In addition,the DNMT3B overexpression increased in tumors with both ER and PR negative expression (92.9%,P =0.002).However,no such correlation was found in NEC (P >0.05).Sequence analyses demonstrated multiple ER and PR binding sites in the promoter regions of DNMT3B gene.Conclusion:This study showed that the expression of DNMT3B in EC and NEC was different.DNMT3B overexpres-sion in EC was associated with the worse clinicopathological variables and might have predictive value. The methylation status of EC and NEC maybe different.In addition,in EC,DNMT3B overexpression negatively correlated with ER or PR expression.In NEC,the correlation between DNMT3B and ER or PR status was not present.

Lynch syndrome is an autosomal dominant genetic disease characterized by the early onset of colon cancer, endometrial cancer and other tumors caused by a genetic mutation within DNA mismatch repair (MMR) genes.A small subgroup (approximately 3% -5%) of endometrial cancer and colorectal cancer is related to Lynch syndrome .Identification of these patients in clinical practice will be of great benefit to the relatives and patients themselves .We reported two cases, and reviewed the literature and clinical diagnostic guideline.MMR protein was lost in the tumors.Meanwhile the two cases had different clinicopathological characteristics.Together with the literature, our findings may suggest that the MMR protein expression, associated molecular alterations and clinicopathological features and biological behavior of endometrial cancer and colorectal cancer related to Lynch syndrome are different .Thus the algorithm for detection the patients at highest risk is different .To detect the MMR loss by immunohisto-chemistry is a practicalscreening method.

Objective To explore the impact of polysomy of chromosome 17 on the interpretation of human epidermal growth factor receptor 2 (HER2) status and its clinical significance in breast cancers. Methods Clincopathological data of 338 breast cancer patients were collected, and the association of clinicopathological characteristics with polysomy of chromosome 17 was analyzed.Based on the American Society of Clinical Oncology /College of American Pathologists updated recommendations of HER2 testing in breast cancer in 2013, the relationships between the copy number of centromeres on chromosome 17 (CEP17) and HER2 status, other important biological markers and clincopathological features of breast cancer were analyzed statistically.Results Immunohistochemical examination revealed that among the 338 breast cancer cases, there were 9 (2.7%) HER2-negative cases, 309 (91.4%) HER2-equivocal cases, and 20 (5.9%) HER2-positive cases.The FISH analysis showed that there were 226 (66.9%) HER2-negative cases, 13 (3.8%) HER2-equivocal cases, and 99 (29.3%) HER2-positive cases.Among the 338 breast cancer patients, 42 (12.4%) cases were identified as chromosome 17 polysomy (polysomy 17), 291 (86.1 %) cases were chromosome 17 disomy, and 5 (1.3%) cases were chromosome 17 monosomy.Polysomy 17 showed significant correlation with the intensity of HER2 protein expression (P =0.046).The HER2 FISH results and HER2 gene copy number of polysomy 17 cases showed significant differences from the non-polysomy 17 cases (P<0.001).There were no significant differences of HER2/CEP17 ratio between the polysomy 17 and non-polysomy 17 groups (P=0.930).Polysomy 17 cases showed a significant relationship with tumor grading and Ki -67 index (P<0.05), but not with the age of patient, tumor size, lymph node metastasis, ER and PR expressions, and effect evaluation of neoadjuvant chemotherapy ( P >0.05). Co nclusi ons In the breast cancer with polysomy of chromosome 17, assessment of the absolute copy number of HER2 signals is even more important, and the HER2/CEP17 ratio and HER2 protein expression levels should be comprehensively evaluated together.

Objective To study the clinical significance of PI3Kp110αexpression in breast cancer. Methods The expressions of PI3Kp110α, HER2, PTEN, p?Akt and Ki?67 in invasive ductal carcinoma ( IDC ) , adjacent ductal carcinoma in situ ( DCIS ) and normal breast tissue were detected by immunohistochemistry in 102 cases of breast cancer. The expression of PI3Kp110α in IDC was compared with those in DCIS and normal breast tissues. Correlations between expression of PI3Kp110αand expression of HER2, PTEN, p?Akt and Ki?67 index in IDC were analyzed. Correlation between expression of PI3Kp110αand stage of IDC was studied as well. Results In the normal breast tissues, there were 97 cases (95.1%) with low level and 5 cases (4.9%) with high level expression of PI3Kp110α. In the DCIS tissues, there were 67 cases ( 65. 7%) with low level and 35 cases ( 34. 3%) with high level expression of PI3Kp110α. In the IDC tissues, there were 14 cases (13.7%) with low level and 88 cases (86.3%) with high level expression of PI3Kp110α. The difference between expression of PI3Kp110α in normal breast tissue, DCIS and IDC was significant ( P<0. 001 ) . In the IDC tissues, expression of PI3Kp110α was negatively correlated with expression of HER2 ( rs=-0.213,P=0.032) and PTEN ( rs=-0.197,P=0.047) , while was not significantly correlated with expression of p?Akt ( P=0.119) and Ki?67 index ( P=0.636) . In contrast, expressions of HER?2 and p?Akt were positively correlated with Ki?67 index ( P=0. 001, P=0.035), while expression of HER2 was not correlated with p?Akt (P=0.177). Expression of PI3Kp110αwas negatively correlated with T stage and TNM stage (P=0.003, P=0.016), while not correlated with N stage and M stage(both P>0.05). Expression of HER?2 was positively correlated with T stage (P=0.037), while not correlated with N stage, M stage and TNM stage ( P>0. 05 for all ) . Neither Ki?67 index nor expression of PTEN and p?Akt (P=0.194) were correlated with T stage, N stage, M stage and TNM stage. Conclusions Expression of PI3Kp110α plays an important role in oncogenesis and development of breast cancer. Based on the fact that expression of PI3Kp110αis negatively correlated with expression of HER2 and PTEN and with T stage and TNM stage, we may conclude that increased expression of PI3Kp110αis another independent pathway in breast cancer development, and breast cancer patients with high expression of PI3Kp110α may have a better prognosis.

Objective To explore the impact of polysomy of chromosome 17 on the interpretation of human epidermal growth factor receptor 2 (HER2) status and its clinical significance in breast cancers. Methods Clincopathological data of 338 breast cancer patients were collected, and the association of clinicopathological characteristics with polysomy of chromosome 17 was analyzed.Based on the American Society of Clinical Oncology /College of American Pathologists updated recommendations of HER2 testing in breast cancer in 2013, the relationships between the copy number of centromeres on chromosome 17 (CEP17) and HER2 status, other important biological markers and clincopathological features of breast cancer were analyzed statistically.Results Immunohistochemical examination revealed that among the 338 breast cancer cases, there were 9 (2.7%) HER2-negative cases, 309 (91.4%) HER2-equivocal cases, and 20 (5.9%) HER2-positive cases.The FISH analysis showed that there were 226 (66.9%) HER2-negative cases, 13 (3.8%) HER2-equivocal cases, and 99 (29.3%) HER2-positive cases.Among the 338 breast cancer patients, 42 (12.4%) cases were identified as chromosome 17 polysomy (polysomy 17), 291 (86.1 %) cases were chromosome 17 disomy, and 5 (1.3%) cases were chromosome 17 monosomy.Polysomy 17 showed significant correlation with the intensity of HER2 protein expression (P =0.046).The HER2 FISH results and HER2 gene copy number of polysomy 17 cases showed significant differences from the non-polysomy 17 cases (P<0.001).There were no significant differences of HER2/CEP17 ratio between the polysomy 17 and non-polysomy 17 groups (P=0.930).Polysomy 17 cases showed a significant relationship with tumor grading and Ki -67 index (P<0.05), but not with the age of patient, tumor size, lymph node metastasis, ER and PR expressions, and effect evaluation of neoadjuvant chemotherapy ( P >0.05). Co nclusi ons In the breast cancer with polysomy of chromosome 17, assessment of the absolute copy number of HER2 signals is even more important, and the HER2/CEP17 ratio and HER2 protein expression levels should be comprehensively evaluated together.

Objective To study the clinical significance of PI3Kp110αexpression in breast cancer. Methods The expressions of PI3Kp110α, HER2, PTEN, p?Akt and Ki?67 in invasive ductal carcinoma ( IDC ) , adjacent ductal carcinoma in situ ( DCIS ) and normal breast tissue were detected by immunohistochemistry in 102 cases of breast cancer. The expression of PI3Kp110α in IDC was compared with those in DCIS and normal breast tissues. Correlations between expression of PI3Kp110αand expression of HER2, PTEN, p?Akt and Ki?67 index in IDC were analyzed. Correlation between expression of PI3Kp110αand stage of IDC was studied as well. Results In the normal breast tissues, there were 97 cases (95.1%) with low level and 5 cases (4.9%) with high level expression of PI3Kp110α. In the DCIS tissues, there were 67 cases ( 65. 7%) with low level and 35 cases ( 34. 3%) with high level expression of PI3Kp110α. In the IDC tissues, there were 14 cases (13.7%) with low level and 88 cases (86.3%) with high level expression of PI3Kp110α. The difference between expression of PI3Kp110α in normal breast tissue, DCIS and IDC was significant ( P<0. 001 ) . In the IDC tissues, expression of PI3Kp110α was negatively correlated with expression of HER2 ( rs=-0.213,P=0.032) and PTEN ( rs=-0.197,P=0.047) , while was not significantly correlated with expression of p?Akt ( P=0.119) and Ki?67 index ( P=0.636) . In contrast, expressions of HER?2 and p?Akt were positively correlated with Ki?67 index ( P=0. 001, P=0.035), while expression of HER2 was not correlated with p?Akt (P=0.177). Expression of PI3Kp110αwas negatively correlated with T stage and TNM stage (P=0.003, P=0.016), while not correlated with N stage and M stage(both P>0.05). Expression of HER?2 was positively correlated with T stage (P=0.037), while not correlated with N stage, M stage and TNM stage ( P>0. 05 for all ) . Neither Ki?67 index nor expression of PTEN and p?Akt (P=0.194) were correlated with T stage, N stage, M stage and TNM stage. Conclusions Expression of PI3Kp110α plays an important role in oncogenesis and development of breast cancer. Based on the fact that expression of PI3Kp110αis negatively correlated with expression of HER2 and PTEN and with T stage and TNM stage, we may conclude that increased expression of PI3Kp110αis another independent pathway in breast cancer development, and breast cancer patients with high expression of PI3Kp110α may have a better prognosis.

Objective:To study whether cisplatin may induce apoptosis in the pericytes of cochlear stria vascularis and underlying mechanisms.Methods:Twenty male C57BL/6J mice aged 6-8 weeks were divided into control group and a cisplatin group. Primary cultured mouse cochlear vascular peristriatal cells were identified and divided into control group, cisplatin group, and N-acetylcysteine+cisplatin group. Auditory brainstem response (ABR) was used to detect hearing in mice. Hematoxylin eosin (HE) staining was used to observe morphological changes in the stria vascularis of the cochlea. The total superoxide dismutase (SOD) activity test kit (WST-1 method) and thiobarbituric acid (TBA) method were used to detect SOD activity and Malondialdehyde (MDA) content, respectively. DCFH-DA fluorescence probe was used to detect the content of reactive oxygen species in peripheral cells. Hoechst 33 342 and flow cytometry were used to detect the apoptosis rate of pericytes. Immunofluorescence technology was used to detect the distribution and expression of apoptosis related proteins in pericytes of cochlear stria vascularis. Immunohistochemistry and Western blotting (WB) were used to detect the expression of apoptosis-and mitochondrial-related proteins. Mito SOX TM-red and JC-1 were used to detect the mitochondrial function of pericytes. Evans blue staining was used to observe the permeability of the blood labyrinth barrier (BLB). Statistical analysis was conducted using SPSS 18.0 software. Results:Compared with the control group, the cisplatin group significantly increased in the hearing threshold ( t=4.72, P<0.01), Ⅰ-wave latency ( t=12.25, P<0.05), and the levels of oxidative stress in the cochlea and pericytes ( t=38.34, P<0.01), and also cisplatin caused disorder and contraction of the cochlear stria vascularis structure, increased BLB permeability [Evans blue leakage (1.08±0.42) AU vs (0.55±0.23) AU, t=4.64, P<0.05], with a statistically significant difference, enhanced the expressions of apoptotic proteins c-Caspase-3 ( t=5.01, P<0.01) and Bax ( t=6.33, P<0.01) in the peristriatal cells of cochlear blood vessels in mice treated with cisplatin increased. And cisplatin can induce apoptosis of primary cultured pericytes and up-regulate the expression of c-Caspase-3 and Bax ( P<0.05). The NAC+cisplatin group partially reversed cisplatin-induced pericyte apoptosis ( P<0.05). Cisplatin caused damage to the mitochondrial function of peripheral cells, and induced the release of apoptosis-inducing factor (AIF) and cytochrome C (cyt-c) into the cytoplasm ( P<0.05). The NAC+cisplatin group partially reversed cisplatin induced pericyte apoptosis ( P<0.05) and mitochondrial damage ( P<0.05). Conclusion:Cisplatin can increase the level of oxidative stress in the cochlea and cause mitochondrial pathway apoptosis in C57BL/6J mouse cochlear vascular peristriatal cells.

Objective:Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer.Methods:Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer.Results:A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer ( P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95% CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95% CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95% CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95% CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele( OR=3.35,95% CI:2.10-5.34, P<0.001). Conclusion:There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

Background Shoemaking industry workers are prone to work-related musculoskeletal disorders (WMSDs) due to long-term awkward postures during the work process. There is little research on the prevalence and influencing factors of WMSDs in the knee region of this industry, and it should be taken seriously. Objective To estimate the prevalence of work-related knee pain among shoemaking workers and analyze the related influencing factors. Methods A total of 6982 shoemaking workers were selected from 26 shoemaking factories in Guangdong, Hubei, Fujian, Chongqing, Shandong, Zhejiang, and Jingxi by convenience sampling. Prevalence of work-related knee pain in past year, demographic characteristics, occupational related factors, and work posture were collected by a cross-sectional survey using the electronic version of Musculoskeletal Disorder Questionnaire. Logistic regression analysis was used to analyze the influencing factors that may lead to work-related knee pain. Results This survey collected 6982 valid questionnaires with a recovery rate of 98.3%. The prevalence of work-related knee pain of shoemaking workers in the past 12 months was 13.0% (908/6982). According to the results of logistic regression analysis, compared with workers with less than 5 years of service, workers with 5-10 years of service (OR=1.21, 95%CI: 1.02, 1.45) and more than 10 years (1.53, 95%CI: 1.27, 1.83) showed a higher risk of knee WMSDs; sometimes, often and very frequent (reference : rarely or never) long-term standing (OR=1.33, 95%CI: 1.08, 1.64; OR=2.67, 95%CI: 2.10, 3.39; OR=2.75, 95%CI: 2.08, 3.63) and sometimes, often and very frequent (reference: rarely or never) long-term squatting or kneeling (OR=1.80, 95%CI: 1.47, 2.21; OR=2.43, 95%CI: 1.58, 3.75; OR=3.22, 95%CI: 1.66, 6.24) increased the risk of knee pain: long-term bending (OR=1.59, 95%CI: 1.34, 1.89) and often repeated movement of lower limbs and ankles (OR=1.48, 95%CI: 1.25, 1.75) were also risk factors for knee WMSDs among shoemaking industry workers (P<0.05). Adequate rest time (OR=0.58, 95%CI: 0.49, 0.68) and able to stretch or change leg posture (OR=0.75, 95%CI: 0.64, 0.88) reduced the risk of knee WMSDs (P<0.05). Conclusion In the shoemaking industry, length of service and awkward postures are risk factors for knee pain. The shoemaking enterprises should ensure that workers have sufficient rest time, reduce long-term standing, squatting, kneeling, and bending postures, as well as lower limbs repetition in order to reduce the occurrence of knee WMSDs of workers.