[The relationship between homocysteine, coagulation dysfunction and breast cancer risk].

Objective: To investigate the correlation of homocysteine (HCY) and coagulation function index with the risk of breast cancer and its clinicopathological characteristics. Methods: The HCY, coagulation function test index, and clinicopathological information of female breast cancer patients (333 cases) treated in Tianjin Medical University Cancer Hospital from January 2018 to December 2018 were collected, and female patients with benign breast (225 cases) were selected during the same period for the control group. The t-test was used to compare measurement data with normal distribution, D-Dimer data were distributed discreetly and described by median, non-parametric Mann-Whitney U test was used to compare the two groups. The chi-square test was used to compare enumeration data, and the Logistic regression analysis was used for the risk analysis. Results: The levels of HCY, fibrinogen (Fbg), protein C (PC), and median D-Dimer (D-D) in peripheral blood of breast cancer patients group [(13.26±5.24) µmol/L, (2.61±0.83) g/L, (117.55±19.67)%, and 269.68 ng/ml, respectively] were higher than those in the control group [(11.58±0.69) µmol/L, (2.49±0.49) g/L, (113.42±19.82)% and 246.98 ng/ml, respectively, P<0.05]. The prothrombin time (PT), PT(INR), α2-antiplasmin (α2-AP) levels [(10.19±0.63) s, 0.91±0.07 and (110.64±13.93)%, respectively] were lower than those in the control group [(10.58±0.65) s, 0.93±0.01 and (123.81±14.77) %, P<0.05]. The serum levels of PC and median D-D in premenopausal breast cancer patients [(112.57±17.86)% and 242.01 ng/ml, respectively] were higher than those in the control group [(105.31±22.31)% and 214.75 ng/ml, respectively, P<0.05]. The levels of PT(INR), α2-AP [0.91±0.07 and (111.29±12.54)%, respectively] were lower than those of the control group[0.98±0.15 and (120.17±16.35)%, respectively, P<0.05]. The levels of HCY and median D-D in postmenopausal breast cancer patients [(14.25±5.76) µmol/L and 347.53 ng/ml, respectively] were higher than those in the control group [(11.67±2.38) µmol/L and 328.28 ng/ml, P<0.05]. The levels of PT, PT(INR), antithrombin Ⅲ (AT-Ⅲ), α2-AP levels [(10.18±0.66) s, 0.87±0.09, (97.30±12.84)% and (110.13±14.96)%] were lower than those in the control group [(10.38±0.61) s, 0.90±0.08, (102.89±9.12)%, and (127.05±12.38)%, respectively, P<0.05]. The levels of α2-AP and median D-D in T2-4 stage breast cancer patients [(111.69±14.41)% and 289.25 ng/ml, respectively] were higher than those in Tis-1 stage patients [(108.05±12.37)% and 253.49 ng/ml, respectively, P<0.05]. The levels of PT, PT (INR), Fbg, AT-Ⅲ, α2-AP, median D-D [(10.62±0.63) s, 0.95±0.06, (3.04±1.52) g/L, (103.21±9.45)%, (118.72±14.77)% and 331.33 ng/ml, respectively] in breast cancer patients with lymph node metastasis were higher than those of patients without lymph node metastasis [(10.42±0.58) s, 0.93±0.06, (2.52±0.54) g/L, (95.20±13.63)%, (106.91±13.13)% and 263.38 ng/ml, respectively, P<0.05]. In non-menopausal breast cancer patients, the level of HCY [(12.63±4.41) µmol/L] in patients with T2-4 stage was higher than that of patients with Tis-1 stage [(10.70±3.49) µmol/L, P=0.010], and the level of thrombin time [(19.35±0.90) s] of patients with T2-4 stage was lower than that of patients with Tis-1 stage [(19.79±1.23) s, P=0.015]. The levels of PT(INR), Fbg, AT-Ⅲ, α2-AP [0.97±0.56, (3.37±2.34) g/L, (102.38±8.77)% and (120.95±14.06)%] in patients with lymph node metastasis were higher than those of patients without lymph node metastasis [0.94±0.05, (2.36±0.48) g/L, (94.56±14.37)% and (109.51±11.46)%, respectively, P<0.05]. Among postmenopausal breast cancer patients, the levels of AT-Ⅲ and α2-AP in T2-4 stage patients [(98.48±11.80)% and (111.84±15.35)%, respectively] were higher than those in patients with the Tis-1 stage [(94.12±14.98)% and (105.49±12.89)%, respectively, P<0.05]. The levels of AT-Ⅲ and α2-AP in N1-3 stage patients [(103.74±9.94)% and (117.29±15.23)%] were higher than those in N0 stage patients [(95.75±13.01)% and (108.39±14.42)%, P<0.05]. Conclusions: HCY and abnormal coagulation function are related to the risk of breast cancer, T stage and lymph node metastasis in breast cancer patients.

[Survey on tobacco use and associated factors in population in Shandong province, 2016-2017].

Objective: To understand the status of tobacco use and related influencing factors in population in Shandong province. Methods: Stratified multi-stage cluster sampling was used to select respondents from 216 villages (communities) of 36 districts (counties) in Shandong province. Influencing factors on smoking were analyzed by logistic regression model. Results: The adequate sample size was 6 271 participants. After complex weighted, the current smoking prevalence was 23.93%,45.58% in males and 1.18% in females. The Public's smoking rates varied widely among different groups in the population. 45-64 age group had the highest smoking rate (25.07%). Smoking rates were substantially different in education levels, with the highest in junior high school (28.94%). The rate was higher in the rural area (24.98%) than that in the urban areas (23.08%). The average daily smoking rate was 20.23%. The average age of initiating smoking was 21.21 years. The average daily cigarette intake was 16.31 cigarettes. Among all the former and current smokers, the quitting rate was 20.79%. Multiple logistic regression model analysis showed that gender, age, occupation, region, and health knowledge score were correlated with smoking behavior. The current smoking rate of men was much higher than that of women (OR=49.625, 95%CI: 37.832-65.093). The current smoking rate in 45-64 age group was higher than that in the 15-24 age group (OR=1.830, 95%CI: 1.048-3.194). The current smoking rate of medical (OR=0.403, 95%CI: 0.187-0.866) and retired personnel (OR=0.648, 95%CI: 0.481-0.873) were lower than those engaging in agriculture, forestry, animal husbandry and the fishery ,respectively. The prevalence of residents living in the central part showed lower rate on current smoking than that in the eastern region (OR=0.724, 95%CI: 0.606-0.865). The current smoking prevalence of smoke hazard in 1-3 score group was higher than that in the group with 4-6 score (OR=1.432, 95%CI: 1.240-1.654). Conclusions: Smoking rate in adults in Shandong remained stable and at a high level. Comprehensive intervention measures such as tobacco control and health education should be carried out to reduce the smoking rate.

[Study on the relationship between smoking behavior and health literacy among grade 4-6 primary students in Shandong province].

Objective: To investigate the associations between smoking and literacy on health among 4-6 grade primary school students. Methods: A questionnaire survey was conducted to research on health literacy and smoking among 4-6 grade pupils in Shandong province, through a multi-stage stratified cluster random sampling method. Sociodemographic characteristics, health literacy level and smoking rate were collected from respondents. Binary logistic regression analysis was used to evaluate the association of smoking and health literacy. Results: A total of 9 240 questionnaires were distributed, with the rate of valid response as 99.7%. The current smoking rate of the students was 2.6%, on higher in boys (3.1%) than in girls (2.0%). 60.8% of 4-6 grade students were found to have adequate health literacy level. Levels of literacy health in both boy and girl school students appeared 56.7% and 64.9%, respectively. Results indicated that health literacy in smokers (14.4%) was lower than that in non-smokers (62.0%). Results from the binary logistic regression analysis showed that the independent influencing factors would include grade, father's education level, economic situation of the family, self-assessment on the school record and literacy on health (P<0.01). After controlling the other independent variables, the smoking rate was 8.62 (1/0.116) times in students with low literacy level on health, than those with high literacy level. Conclusions: Literacy on health was significantly associated with smoking in the 4-6 grade pupils of Shandong province.

Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC.

The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and cell lines compared with the normal liver tissues and cell lines. The MTT and colony formation assays demonstrated that overexpressing EPS8L3 enhances, while silencing reduces the proliferation of HCC cells. Further experiments illustrated that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but inhibits the transcriptional activity of FOXO1. Besides, colony formation assay demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3-silenced cells, suggesting that EPS8L3 might promote proliferation by hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1 transcriptional activity. Our results provide new view between EPS8L3 and progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic target for HCC.

[Clinicopathological and ultrasound characteristics of extranodal extension in metastatic papillary thyroid carcinoma patients].

Objective: To explore clinicopathological and ultrasound characteristics of extranodal extension in metastatic papillary thyroid carcinoma patients. Methods: 176 patients with papillary thyroid carcinoma who were diagnosed in Tianjin Medical University Cancer Institute and Hospital between March 2011 and March 2016 were identified and recruited in the study. Among the 176 patients, 59 patients were diagnosed with regional lymph nodes metastasis accompanied with extranodal extension (extranodal extension positive group), 117 patients were regional lymph nodes metastasis without extranodal extension (extranodal extension negative group). The clinicopathological and ultrasound characteristics between extranodal extension positive group and extranodal extension negative group were also discussed in this article. Results: 59 patients were diagnosed with regional lymph nodes metastasis accompanied with extranodal extension (extranodal extension positive group). Single lymph node region of extranodal extension was identified in 40 patients, while 19 patients were confirmed with more than 2 regions of extranodal extension. The most frequent extranodal extension were detected in region Ⅵ lymph nodes(32 cases), following by Ⅲ(25 cases), Ⅳ(16 cases), Ⅱ(11 cases). In the aspect of ultrasound characteristics, metastatic papillary thyroid carcinoma with extranodal extension showed a higher incidence of node matting[13.6%(8/59) vs 3.4%(4/117), P=0.022], micro-calcification[66.1%(39/59) vs 46.2%(54/117), P=0.016], cystic[28.8%(17/59) vs 12.8%(15/117), P=0.013], aspect ratio(L/S)<2[88.1%(52/59) vs 75.2%(88/117), P=0.032] and larger diameter(1.95±1.01 cm vs 1.63±0.94 cm, P=0.028). Logistic multivariate analysis demonstrated that node matting (P=0.025) and cystic (P=0.026) were independent risk factors for extranodal extension. Conclusion: Node matting, micro-calcification, cystic, aspect(L/T)>2 and larger diameter were associated with extranodal extension in metastatic papillary thyroid carcinoma patients, especially node matting and cystic, which might help topre-operative ultrasound diagnosis of extranodal extension.

[A case of congenital cyst of epiglottis caused by severe upper respiratory tract obstruction].

The main clinical manifestations were respiratory distress，perioral cyanosis and Upper respiratory obstruction symptoms.The epiglottis opened by laryngoscope,can see a gray white semi elliptical sacs.Clinical diagnosis:congenital cyst of epiglottis.

Validation of associations between ESR1 variants and breast cancer risk in Chinese cohorts.

Estrogen receptor-a (ER) protein plays a key role in breast carcinogenesis, and common genetic variants in the corresponding gene locus have been associated with breast cancer risk in different populations. Here, we analyzed estrogen receptor 1 (ESR1) associations in two hospital-based studies of patients from the south of China. Three single-nucleotide polymorphisms (SNPs; rs3757318, rs2046210, and rs3734805) in ESR1 were selected from previous genome-wide association study results and were genotyped using the Sequenom MassARRAY® iPLEX System in 845 breast cancer patients and 882 healthy controls. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Stratified analyses according to the status of ER and progesterone receptor (PR) were also performed. Of the three SNPs, rs3757318 did not pass the Hardy-Weinberg equilibrium test and was excluded from the subsequent analysis. The other two SNPs (rs2046210 and rs3734805) were strongly associated with susceptibility to breast cancer. Allele T of rs2046210 and allele C of rs3734805 were risk alleles and the adjusted ORs were 1.348 (95%CI = 1.172-1.550, P = 0.0001) and 1.319 (95%CI = 1.144-1.522, P = 0.0001), respectively. Furthermore, the risk allele of rs2046210 gave negative results for ER and PR expression in an immunohistochemical test, with ORs of 0.602 (95%CI = 0.384-0.944, P = 0.027) and 0.532 (95%CI = 0.338-0.837, P = 0.006), respectively. Our study further supports associations between rs2046210 and rs3734805 and breast cancer risk in Chinese women.

Protein-protein interaction between ezrin and p65 in human breast cancer cells.

Our study aimed to investigate the co-localization and protein-protein interactions between ezrin and p65 in human breast cancer cells. Liquid chromatography-mass spectrometry (LCMS) was used to uncover novel protein interactions with ezrin in MDA-MB-231 cells. Endogenous co-immunoprecipitation was used to validate protein-protein interactions between ezrin and p65 in MDA-MB-231. Exogenous interactions between ezrin and p65 were validated in MDA-MB-231 cells via Flag-ezrin and HA-p65 co-transfection and followed by co-immunoprecipitation. Immunofluorescence staining was used to visualize ezrin and p65 co-localization in MDA-MB-231. LCMS results showed that there were 1000 proteins interacting with ezrin in MDA-MB-231 cells. Ezrin and p65 interactions were confirmed with both endogenous and exogenous methods. We were also able to visualize ezrin and p65 co-localization in MDA-MB-231. In summary, we found protein-protein interactions between Ezrin and p65 in human breast cancer cells.

Association analysis of colorectal cancer susceptibility variants with gastric cancer in a Chinese Han population.

Evidence suggests that some genetic variants are risk factors for both colorectal cancer (CRC) and gastric cancer (GC). Thus, we selected 12 reported single nucleotide polymorphisms (SNPs) from genome-wide association studies of CRC and conducted this case-control study to assess the associations between these SNPs and the risk for GC in a southern Chinese population. All SNPs were genotyped in 249 individuals with GC and 292 healthy population-matched subjects using the Sequenom MassArray iPLEX System. Association analyses based on the c2 test and binary logistic regression were performed to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. A stratified analysis by gender was also performed. Borderline significant associations were observed for rs4444235 (P = 0.070) and rs10411210 (P = 0.084), both fitting the overdominant model. The rs4444235 CT genotype showed a protective effect (OR = 0.72, 95%CI = 0.50-1.03), while the rs10411210 CT genotype was a risk factor (OR = 1.40, 95%CI = 0.96-2.05) as compared with the CC+TT genotype. In the female subgroup, the rs6983267 GT genotype (compared with TT, OR = 2.31, 95%CI = 1.07-4.99) and the rs10505477 CT genotype (compared with TT, OR = 2.36, 95%CI = 1.09-5.11) significantly increased the risk for GC. No significant association was detected for the other SNPs. These results provide evidence that known genetic variants associated with CRC risk may also confer risk for GC.

Homology-based cloning and expression analysis of Rf genes encoding PPR-containing proteins in tobacco.

As a model plant, mechanisms of the cytoplasmic male sterility/restoration of fertility (CMS/Rf) system in tobacco are seldom studied. Using Rf gene sequences from other Solanaceae plants and the draft genome of Nicotiana benthamiana, degenerate primers were designed to amplify the cDNA pool of N. tomentosiformis. In total, six possible Rf sequences were identified, two of which contained base-deletion mutations. The other four were intact open reading frames, of which NtomPPR5 harbored a 3-pentatricopeptide repeat (PPR) motif deletion. Structure analysis revealed that they all encoded a PPR-containing protein with putative mitochondrial targeting signals at their N-terminus, and they all belong to the P subfamily. Phylogenetic analysis showed that all of the Rf-coding PPRs clustered together, and recent duplication events might have occurred in tobacco after the divergence of the species. Quantitative reverse transcription polymerase chain reaction analysis demonstrated that the NtomRfs were expressed in all tissues of N. tomentosiformis and (CMS) K326, although the expression levels varied with gene, organ, and developmental stage. Furthermore, the expression levels of Rf sequences in K326 were lower than those in CMS K326. The molecular basis of the CMS/Rf system in tobacco requires further investigation.

Genetic variants on 17q21 are associated with asthma in a Han Chinese population.

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.

Prevalence of thyroid diseases in Nevada counties with respect to perchlorate in drinking water.

Perchlorate is well-known to inhibit the uptake of iodine by the thyroid and has been shown to do so at doses in the milligrams-per-day range and higher. Perchlorate has been found in the water supply of Clark County (Las Vegas), Nevada, at 4 to 24 micrograms/L (parts per billion) and may provide exposure dosages in the tens of micrograms per day. An analysis of the Medicaid database from Nevada was undertaken to determine whether an increase in the prevalence of any thyroid disease was associated with that level of perchlorate content. The prevalence of persons being seen for thyroid disease or for specific thyroid diseases (goiter, nodule, thyrotoxicosis, congenital hypothyroidism, acquired hypothyroidism, thyroiditis, and other thyroid disorders) and for thyroid cancer among the Medicaid-eligible population of each county was calculated for the 2-year period 1997 to 1998. The prevalences in Clark County were compared with those in Washoe County (i.e., Reno), the second most populous county in the state, and with those for the rest of the state. There was no evidence of an increased rate of thyroid disease (or of any specific thyroid disease) associated with perchlorate exposure. Generally, the prevalences in the metropolitan parts of the state were lower than for the rest of the state, particularly for acquired hypothyroidism. This analysis found no evidence that perchlorate-containing drinking water at the given level increased the prevalence of acquired hypothyroidism or of any other thyroid condition.

A role for E2F1 in the induction of ARF, p53, and apoptosis during thymic negative selection.

E2F transcriptional activity controls the expression of many of the genes required for G1 to S phase progression. E2F1, one member of the E2F family, plays an important role in the induction of apoptosis. We have examined the role of the E2F1 transcription factor in apoptosis during T-cell maturation in the thymus. We show that E2F1 is required for the apoptosis of autoimmune immature T cells during thymic negative selection in vivo. This T-cell receptor-mediated apoptosis coincides with the E2F1-dependent increase of p19-ARF mRNA and p53 protein levels. In contrast, E2F1 is not required for the induction of apoptosis by glucocorticoids or DNA damage. These results demonstrate a specific role for E2F1, which triggers a pathway leading to ARF and p53 induction, in a physiological apoptosis pathway that is uncoupled from a normal proliferative event.

[Comparative study of applying tiaoxue yisui recipe and SSL regimen in treating infantile chronic aplastic anemia and analysis of its therapeutical mechanism].

OBJECTIVE: To explore the effective method in treating infantile chronic aplastic anemia (ICAA) by using traditional Chinese medicine (TCM). METHODS: Seventy-eight cases of ICAA were observed, 48 of them were treated with Tiaoxue Yisui recipe (treated group), 30 cases were treated with SSL regimen (control group). RESULTS: The remission rate and total effective rate in treated group were 52.08% and 81.25% respectively, they were higher than those in control group (P < 0.05). After one year treatment the ratio of hemopoietic and non-hemopoietic cells in treated group was higher than that in control group (P < 0.05). The number of megakaryocyte in treated group was more than those in control group (P < 0.05). CONCLUSION: Tiaoxue Yisui recipe could improve the quality of the patient's life. The therapeutical mechanism of the Tiaoxue Yisui recipe might promote the proliferation of hemopoietic stem cells and regulate the immune function.