Expression and Clinical Relevance of uPA and ET-1 in Non-small Cell Lung Cancer

Background and objective uPA and ET-1 proteins have been reported to be up-regulated in some of human cancers. The aim of this study is to investigate the alteration and clinical relevance of uPA and ET-1 protein levels in non-small cell lung cancer (NSCLC). Methods Expressions of uPA and ET-1 protein were detected in 155 cases of NSCLC with tissue microarrays and immunohistochemistry (TMA-IHC) technique. The correlations between the alteration of the two proteins and clinicopathological parameters were analyzed. Results Negative/weak, moderate and high expression of uPA were observed in 12.3%, 64.4% and 23.3% of squamous cell carcinomas, in 12.2%, 53.7% and 34.1% of adenocarcinomas, and in 12.3%, 58.7% and 29.0% of all cases. ET-1 presented negative/weak, moderate and high expression in 2.7%, 42.5% and 54.8% of squamous cell carcinomas, in 11.0%, 30.5% and 58.5% of adenocarcinomas, and in 7.1%, 36.1% and 56.8% of all cases. Simultaneously high expression of uPA and ET-1 were found in adenocarcinomas without lymph node metastasis (P=0.017). Adenocarcinoma patients with high expression of uPA or with high expression of both ET-1 and uPA had the longer survival time (P=0.007 and 0.016). Conclusion Detection of uPA and ET-1 protein levels might contribute to the prognosis evaluation of NSCLC

Research on optimal coil configuration scheme of insulator relay WPT system

This paper presents the optimized structure of the multi-relay coils insulator of WPT system. With the rapid development of the smart grid, on-line monitoring devices in the transmission tower have been widely used. However, the power supply problem has become an important bottleneck in the development of transmission tower intelligent sensing technology. Hence, the multi-relay coils wireless power transfer technology has been proposed to supply for the tower monitoring equipment in this paper. Compared with traditional multi-relay coils, the effects of the number, arrangement position and turns of relay coils on the performance of WPT system are further explored. The simulation results show that the operation performance of WPT can be significantly improved by optimizing the coil arrangement position and turns. Moreover, there are multiple configuration schemes that the design indexes of the system could be achieved. The experiment results show that in the 110 kV high-voltage transmission with the insulator length of 1.015 m, the transmitting power and efficiency of the WPT system could be increased to 1.81 W and 60.11% respectively by parameters optimization, which ensures the continuous and stable work of the monitoring equipment

Causal effects of potential risk factors on postpartum depression: a Mendelian randomization study

BackgroundPostpartum depression (PPD) is a type of depressive episode related to parents after childbirth, which causes a variety of symptoms not only for parents but also affects the development of children. The causal relationship between potential risk factors and PPD remains comprehensively elucidated.MethodsLinkage disequilibrium score regression (LDSC) analysis was conducted to screen the heritability of each instrumental variant (IV) and to calculate the genetic correlations between effective causal factors and PPD. To search for the causal effect of multiple potential risk factors on the incidence of PPD, random effects of the inverse variance weighted (IVW) method were applied. Sensitivity analyses, including weighted median, MR-Egger regression, Cochrane’s Q test, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), were performed to detect potential Mendelian randomization (MR) assumption violations. Multivariable MR (MVMR) was conducted to control potential multicollinearity.ResultsA total of 40 potential risk factors were investigated in this study. LDSC regression analysis reported a significant genetic correlation of potential traits with PPD. MR analysis showed that higher body mass index (BMI) (Benjamini and Hochberg (BH) corrected p = 0.05), major depression (MD) (BH corrected p = 5.04E-19), and schizophrenia (SCZ) (BH corrected p = 1.64E-05) were associated with the increased risk of PPD, whereas increased age at first birth (BH corrected p = 2.11E-04), older age at first sexual intercourse (BH corrected p = 3.02E-15), increased average total household income before tax (BH corrected p = 4.57E-02), and increased years of schooling (BH corrected p = 1.47E-11) led to a decreased probability of PPD. MVMR analysis suggested that MD (p = 3.25E-08) and older age at first birth (p = 8.18E-04) were still associated with an increased risk of PPD.ConclusionIn our MR study, we found multiple risk factors, including MD and younger age at first birth, to be deleterious causal risk factors for PPD

Relaxation of the one child policy and trends in caesarean section rates and birth outcomes in China between 2012 and 2016: observational study of nearly seven million health facility births.

OBJECTIVE: To examine how the relaxation of the one child policy and policies to reduce caesarean section rates might have affected trends over time in caesarean section rates and perinatal and pregnancy related mortality in China. DESIGN: Observational study. SETTING: China's National Maternal Near Miss Surveillance System (NMNMSS). PARTICIPANTS: 6 838 582 births at 28 completed weeks or more of gestation or birth weight ≥1000 g in 438 hospitals in the NMNMSS between 2012 and 2016. MAIN OUTCOME MEASURES: Obstetric risk was defined using a modified Robson classification. The main outcome measures were changes in parity and age distributions and relative frequency of each Robson group, crude and adjusted trends over time in caesarean section rates within each risk category (using Poisson regression with a robust variance estimator), and trends in perinatal and pregnancy related mortality over time. RESULTS: Caesarean section rates declined steadily between 2012 and 2016 (crude relative risk 0.91, 95% confidence interval 0.89 to 0.93), reaching an overall hospital based rate of 41.1% in 2016. The relaxation of the one child policy was associated with an increase in the proportion of multiparous births (from 34.1% in 2012 to 46.7% in 2016), and births in women with a uterine scar nearly doubled (from 9.8% to 17.7% of all births). Taking account of these changes, the decline in caesarean sections was amplified over time (adjusted relative risk 0.82, 95% confidence interval 0.81 to 0.84). Caesarean sections declined noticeably in nulliparous women (0.75, 0.73 to 0.77) but also declined in multiparous women without a uterine scar (0.65, 0.62 to 0.77). The decrease in caesarean section rates was most pronounced in hospitals with the highest rates in 2012, consistent with the government's policy of targeting hospitals with the highest rates. Perinatal mortality declined from 10.1 to 7.2 per 1000 births over the same period (0.87, 0.83 to 0.91), and there was no change in pregnancy related mortality over time. CONCLUSIONS: China is the only country that has succeeded in reverting the rising trends in caesarean sections. China's success is remarkable given that the changes in obstetric risk associated with the relaxation of the one child policy would have led to an increase in the need for caesarean sections. China's experience suggests that change is possible when strategies are comprehensive and deal with the system level factors that underpin overuse as well as the various incentives at work during a clinical encounter

Sociodemographic and obstetric characteristics of stillbirths in China: a census of nearly 4 million health facility births between 2012 and 2014

Background Very little is known about the burden and determinants of stillbirths in China. We used data from a national surveillance system for health facility births to compute a stillbirth rate representative of all facility births in China and to explore sociodemographic and obstetric factors associated with variation in the stillbirth rate. Methods We used data from China’s National Maternal Near Miss Surveillance System between Jan 1, 2012, and Dec 31, 2014, which covers 441 hospitals in 326 urban districts and rural counties. The surveillance aimed to enumerate all maternal deaths and near misses in health facilities, and collected data prospectively for all pregnant or post-partum women admitted to the obstetric department. We restricted the analysis to births of 28 or more completed weeks of gestation or 1000 g or heavier birthweight. We examined the strength of association between sociodemographic characteristics, gestational age, and obstetric complications and stillbirths using logistic regression, taking account of the sampling strategy and clustering of births within hospitals and in cases of more than one birth per woman. Findings There were 3 956 836 births and 37 855 stillbirths, giving a stillbirth rate of 8·8 per 1000 births (95% CI 8·8–8·9). The stillbirth rate was particularly high for women younger than 15 years of age (59·9 stillbirths per 1000 births), those who had not sought antenatal care (38·3 per 1000), the unmarried (32·5 per 1000), those with no education (26·9 per 1000), or those who had had four or more births (23·2 per 1000). A high proportion (29 319 [78·2%] of 37 514) of stillbirths occurred at gestational ages of younger than 37 weeks, and about two thirds (24 787 [66·1%] of 37 514) were in women without any maternal complication at the time of birth. Of babies born at normal gestations (37–41 weeks), maternal complications substantially increased the risk of stillbirth (odds ratio comparing antepartum or intrapartum complications with no complication 3·96 [95% CI 3·66–4·29]), but only a small proportion (1638 [4·4%] of 37 514) of stillbirths fell into this group. Interpretation Our analysis of nearly 4 million births in 441 health facilities in China suggests a stillbirth rate of 8·8 per 1000 births between 2012 and 2014. Stillbirths do not feature in the Chinese Government’s 5 year plans and most information systems do not include stillbirths. The Government need to start paying attention to stillbirths and invest strategically in antenatal care, particularly for the most disadvantaged women, including the very young, unmarried, and illiterate, and those at high parity

Identification of Novel Biallelic TLE6 Variants in Female Infertility With Preimplantation Embryonic Lethality

Preimplantation embryonic lethality is a rare cause of primary female infertility. It has been reported that variants in the transducin-like enhancer of split 6 (TLE6) gene can lead to preimplantation embryonic lethality. However, the incidence of TLE6 variants in patients with preimplantation embryonic lethality is not fully understood. In this study, we identified four patients carrying novel biallelic TLE6 variants in a cohort of 28 patients with preimplantation embryonic lethality by whole-exome sequencing and bioinformatics analysis, accounting for 14.29% (4/28) of the cohort. Immunofluorescence showed that the TLE6 levels in oocytes from patients were much lower than in normal control oocytes, suggesting that the variants result in the lower expression of the TLE6 protein in oocytes. In addition, a retrospective analysis showed that the four patients underwent a total of nine failures of in vitro fertilization and intracytoplasmic sperm injection attempts, and one of them became pregnant on the first attempt using donated oocytes. Our study extends the genetic spectrum of female infertility caused by variants in TLE6 and further confirms previously reported findings that TLE6 plays an essential role in early embryonic development. In such case, oocyte donation may be the preferred treatment

Preventable maternal mortality: Geographic/rural-urban differences and associated factors from the population-based maternal mortality surveillance system in China

<p>Abstract</p> <p>Background</p> <p>Most maternal deaths in developing countries can be prevented. China is among the 13 countries with the most maternal deaths; however, there has been a marked decrease in the maternal mortality ratio (MMR) over the last 3 decades. China's reduction in the MMR has contributed significantly to the global decline of the MMR. This study examined the geographic and rural-urban differences, time trends and related factors in preventable maternal deaths in China during 1996-2005, with the aim of providing reliable evidence for effective interventions.</p> <p>Methods</p> <p>Data were retrieved from the population-based maternal mortality surveillance system in China. Each death was reviewed by three committees to determine whether it was avoidable. The preventable maternal mortality ratio (PMMR), the ratios of PMMR (risk ratio, RR) and 95% confidence intervals (CI) were used to analyze regional disparities (coastal, inland and remote regions) and rural-urban variations. Time trends in the MMR, along with underlying causes and associated factors of death, were also analysed.</p> <p>Results</p> <p>Overall, 86.1% of maternal mortality was preventable. The RR of preventable maternal mortality adjusted by region was 2.79 (95% CI 2.42-3.21) and 2.38 (95% CI: 2.01-2.81) in rural areas compared to urban areas during the 1996-2000 and 2001-2005 periods, respectively. Meanwhile, the RR was the highest in remote areas, which was 4.80(95%CI: 4.10-5.61) and 4.74(95%CI: 3.86-5.83) times as much as that of coastal areas. Obstetric haemorrhage accounted for over 50% of preventable deaths during the 2001-2005 period. Insufficient information about pregnancy among women in remote areas and out-of-date knowledge and skills of health professionals and substandard obstetric services in coastal regions were the factors frequently associated with MMR.</p> <p>Conclusions</p> <p>Preventable maternal mortality and the distribution of its associated factors in China revealed obvious regional differences. The PMMR was higher in underdeveloped regions. In future interventions in remote and inland areas, more emphasis should be placed on improving women's ability to utilize healthcare services, enhancing the service capability of health institutions, and increasing the accessibility of obstetric services. These approaches will effectively lower PMMR in those regions and narrow the gap among the different regions.</p

Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity

Aurora-A is a serine/threonine protein kinase and plays an important role in the control of mitotic progression. Dysregulated expression of Aurora-A impairs centrosome separation and maturation, which lead to disrupted cell cycle progression and tumorigenesis. However, the molecular mechanism by which Aurora-A causes cell malignant transformation remains to be further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpression of Aurora-A suppressed transcription activity of AP-2α, a tumor suppressor that is often downregulated in variety of tumors, and inhibited expression of AP-2α-regulated downstream genes. These array-based observations were further confirmed by microwell colorimetric TF assay and luciferase reporter assay. Downregulated transcription activity of AP-2α by Aurora-A was found to be associated with reduced AP-2α protein stability, which appeared to be mediated by Aurora-A enhanced ubiquitin-dependent proteasomal degradation of AP-2α protein. Interestingly, Aurora-A-mediated AP-2α degradation was likely dependent Aurora-A kinase activity since inhibition of Aurora-A kinase activity was able to rescue Aurora-A-induced degradation of AP-2α. Moreover, we defined a physical interaction between Aurora-A and AP-2α, and such interaction might bridge the suppressive effect of Aurora-A on AP-2α protein stability. These findings provide new insights into molecular mechanism by which Aurora-A acts as an oncogenic molecule in tumor occurrence and malignant development