Molecular mechanisms involved in the growth of human uterine leiomyomas

Human uterine leiomyomas (fibroids) are benign neoplasms arising from uterine smooth muscle cells, and are suggested to be sex steroid dependent. The aim of this study was to investigate the molecular mechanisms by which sex steroids, mainly estrogen and progesterone, influence the growth of Ieiomyomas. The first study investigated cell proliferation and apoptosis in both leiomyoma and myometrial cells during the menstrual cycle to determine if a growth advantage existed for leiomyomas. Leiomyoma cells had significantly higher mitotic activity than myometrial cells in the secretory phase compared with the proliferative phase of the menstrual cycle, suggesting that progesterone is important for cell proliferation in leiomyomas. Apoptosis in leiomyomas is related to the function of Bcl-2 family proteins and was explored in the second study. The expression of Bcl-2 in leiomyomas was stronger than in myometrium both in the proliferative and secretory phases of the menstrual cycle. Bax immunostaining was also higher in leiomyomas than in myometrium and decreased after menopause, however the expression of other proteins in this family (Bak, Bcl-x and Mcl-1) was very diverse. In the third study we investigated expression of the progesterone receptor (PR) and local growth factor insulin-like growth factor (IGF-I). There were significant differences in mRNA and protein expression of PR and IGF-I in both myometrium and leiomyomas proliferative phase tissue compared with tissue after gonadotropin releasing hormone agonist (GnRHa) treatment. In situ hybridization revealed that IGF-I mRNA in the myometrium and leiomyomas was located in areas where the smooth muscle cells were dominant. Using representational difference analysis (RDA) of cDNA in the fourth study, we identified five candidate genes, latent transforming growth factor binding protein 2 (LT13P2), zinc finger protein (ZFP 185), tomoregulin, cellular retinoid acid binding protein 1 (CRABP1) and pregnancy-associated plasma protein A (PAPPA) with higher expression in leiomyomas than in myometrium, suggesting a potential role as growth promoters in leiomyomas. In the final study we analyzed the expression of approximately 3000 genes affected by estrogen in the rat uterus by using cDNA-microarray. Five interesting genes were putatively estrogen-responsive in the uterus, including Fas-activated serine/threonine kinase (FAST), CD24, thymosin beta4, follistatin-related protein (FSRP) and thy-1 protein. We hypothesize that the Fas/Fas-L pathway and CD24 may be important during the cellular processes in the uterus influenced by estrogen. Gene expression profiling provides a unique opportunity for understanding the molecular mechanisms of estrogen actions in uterus. In conclusion, there exists a selective growth advantage for leiomyomas involving a complex of factors regulated by the sex steroid hormones whose actions are very universe

Do the outstanding comments of regulatory reviewers for approved IPOs serve as a valuation signal for investors?

ABSTRACTSince 2015, the China Securities Regulatory Commission (CSRC) has disclosed initial public offering (IPO) companies’ review outcomes and hearing questions. For 15% of the companies that pass the IPO screening process, the CSRC also discloses some of their hearing questions that require further disclosure and clarification after the IPO screening process (termed outstanding comments herein). A company passing the vote means that it has received general approval from the majority of review experts. However, outstanding comments also reflect that some review experts have remaining concerns about the IPO applicant. Results show that approved IPO companies with outstanding comments perform significantly worse than those without outstanding comments both before and after listing, suggesting that outstanding comments serve as a signal of a stock’s valuation. Moreover, investors (particularly institutional ones) appear to perceive the signal of outstanding comments, as they react more negatively around the listing date of such companies

Bifurcation and chaos analysis of a pretensioned moving printed electronic laminated membrane considering aerothermoelasticity

The bifurcation and chaotic motion characteristics are studied for a roll-to-roll flexible printed electronic laminated membrane subjected to initial tension in a steady temperature field. First, an aerodynamic model of the moving membrane is established by using an improved Newton's law for internal friction. Based on von Karman's large deflection theory, a nonlinear vibration differential equation is derived for the laminated membrane under multiple physical fields using Hamilton's principle and solved numerically using the fourth-order Runge-Kutta method. The effects of the temperature, air resistance and other parameters on the nonlinear vibration of the membrane are analyzed by using the bifurcation diagram, Lyapunov exponent diagram and corresponding phase diagram, Poincaré diagram and time history diagram. The results show that the membrane exhibits abundant chaos and bifurcation phenomena under a coupling field. The parameters of the membrane can be varied to control the nonlinear vibration characteristics. This study provides theoretical guidance for improving the transmission stability of electronic membranes and realizing high-precision overprinting

The etiology of community-acquired pneumonia among children under 5 years of age in mainland China, 2001–2015: A systematic review

Background: The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 y and provide evidence for further cost-effectiveness analyses for vaccine development, diagnostic strategies and empirical treatments. Methods: The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained by searching PubMed, Embase, Web-of Science, and the Chinese databases Wanfang Data and China National Knowledge Infrastructure. All CAP etiological studies on children under 5 y of age from China published in Chinese and English between the years of 2001 and 2015 were included. A total of 48 studies were included in the final review, comprising 100 151 hospitalized children with CAP episodes. Heterogeneity and the percentage of variation between studies was analyzed based on Q statistic and I2 indices, respectively. Random effect models were used to calculate the weighted average rate in all analyses. Results: The most frequently detected bacterial agents were Klebsiella pneumoniae (5.4%), Streptococcus pneumoniae (5.2%), Escherichia coli (5.2%), Staphylococcus aureus (3.9%), Haemophilus influenza (3.6%) and Haemophilus parainfluenzae (3.3%). The most frequently detected viruses were human rhinovirus (20.3%, in just 2 studies), respiratory syncytial virus (RSV, 17.3%), human bocavirus (9.9%), parainfluenza virus (5.8%), human metapneumovirus (3.9%) and influenza (3.5%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were identified in 9.5% and 2.9%, respectively, of children under 5 y of age with CAP. Conclusion: This article provides the most comprehensive analysis to date of the factors contributing to CAP in children under 5 y of age. S. pneumoniae, H. influenzae and influenza were the most common vaccine-preventable diseases in children. Corresponding, vaccines should be introduced into Chinese immunization programs, and further economic evaluations should be conducted. RSV is common in Chinese children and preventative measures could have a substantial impact on public health. These data also have major implications for diagnostic strategies and empirical treatments