Objective To investigate the effect of steroid receptor coactivator family in initiation, development, treatment and prognosis of breast cancer. Methods The literatures in recent years which have related to the effect of steroid receptor coactivators in breast cancer are reviewed. Results Steroid receptor coactivators are essential for several kinds of steroid hormones binding to steroid receptors, so they are important accessory factors that induce the initiation, development and recurrence of breast cancer, and predictive factors that estimate the prognosis of breast cancer. Conclusion Inhibition of the expression and signaling pathway of steroid receptor coactivators may be effective for breast cancer prevention and treatment.
【摘要】 目的 观察在不同剂量乙醇作用下大鼠下丘脑和脊髓神经细胞P物质的表达情况和扫描电子显微镜（SEM）下神经细胞的形态学变化，探讨乙醇作用下大鼠行为学改变的相关机制。 方法 通过福尔马林实验观察大鼠在不同剂量乙醇及时间作用下行为学的改变；采用免疫组织化学技术检测不同剂量乙醇作用下大鼠脊髓和下丘脑神经细胞中P物质的表达，通过扫描电子显微镜观察神经细胞的形态学变化。 结果 乙醇灌胃后0～2 h大鼠舔足次数有不同程度的变化，组间比较差异有统计学意义（Plt;0.05），灌胃2 h大鼠下丘脑和脊髓P物质表达程度与乙醇剂量有相关关系，扫描电子显微镜下各组大鼠的神经细胞形态学变化显著。 结论 急性乙醇中毒可引起大鼠对疼痛反应的变化，其程度与乙醇剂量和作用时间有关，大鼠下丘脑和脊髓神经细胞中P物质的表达强度与乙醇剂量和作用时间有关。【Abstract】 Objective To observe the expression of substance P(SP)in the hypothalamus and spinal cord nerve cells of rats with different concentrations of ethanol, and to observe the morphological changes of nerve cells by scanning electron microscopic(SEM) for elucidating the mechanism of ethological changes effected with ethanol. Methods Ethological changes were detected through the formalin test; SP expressions in the hypothalamus and the spinal cord were evaluated with immunohistochemistry technology, and the morphological changes of nerve cells were observed by SEM. Results The frequency of licking foot changed when the rats were gavaged with different concentrations of ethanol among zero to two hours, the difference between two groups was statistical signifcant (Plt;0.05). The expression level of SP and the morphological changes of nerve cells in hypothalamus and spinal cord had relationship with the ethanol concentration. Conclusions Acute alcoholism could cause pain dysfunction in rats. The frequency of licking foot of rats is correlated to the role of the time closely. The expression intensity of SP in the hypothalamus and the spinal cord nerve cells are correlated to the concentration of ethanol closely.
ObjectiveTo summarize the remodeling of cholesterol metabolism in the occurrence and progression of pancreatic ductal adenocarcinoma (PDAC), and to review the research progress on targeted cholesterol metabolism in the treatment of PDAC. MethodRelevant literatures on cholesterol metabolism in the occurrence, development, and diagnosis and treatment of PDAC in recent years were searched and reviewed. ResultsMetabolites of PDAC tumor cells affected the expression of oncogenes or tumor suppressor genes. Signaling regulation within tumor cells affects cholesterol metabolism, characterized by increased de novo cholesterol synthesis and esterification, and reduced efflux. Tumor cells also regulated tumor immune microenvironment or tumor stroma formation through cholesterol metabolism. Inhibiting cholesterol metabolism could suppress the proliferation, invasion and migration of PDAC tumor cells, and combination therapy targeting cholesterol metabolism had a synergistic anti-PDAC effect. ConclusionsRemodeling of cholesterol metabolism occurs in both PDAC tumor cells and the tumor microenvironment, and is closely related to the occurrence, development, invasion, metastasis, and treatment response of PDAC. Targeting cholesterol metabolism or combined application with chemotherapy drugs can have anticancer effects. However, more research is needed to support the translation of cholesterol metabolism regulation into clinical treatment applications.
Objectives To investigate the correlation between blood total cholesterol (TC) and prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL) and to provide references for clinical treatment and prognosis assessment. Methods We included 232 ISSNHL patients with total deafness in Wenzhou Central Hospital from June 2015 to March 2017 using a prospective cohort design. Recording information including age, gender, hypertension, diabetes mellitus, vertigo, level of blood total cholesterol (TC), level of triglyceride (TG), level of low-density lipoprotein (LDL-C) and LDL/HDL ratio (LDL-C/HDL-C) were collected. Correlation between the prognosis of ISSNHL and blood total cholesterol were analyzed by univariable and multivariable logistic regression analysis. Results The clinical effective rate of patients with TC ranging from 5.2 mmol/L to 6.2 mmol/L was higher than that of patients with TC lower than 5.2 mmol/L (univariable: RR=6.49, 95%CI 3.16 to 13.30, P<0.001; multivariable-adjusted covariates: RR=6.15, 95%CI 2.66 to 14.3,P<0.001) with significant difference. No significant difference was found between patients with TC lower than 5.2 mmol/L and patients with TC higher than 6.2 mmol/L (univariable: RR=1.02, 95%CI 0.52 to 2.00,P=0.960; multivariable-adjusted covariates: RR=1.61, 95%CI 0.55 to 4.73, P=0.386). Gender-specific analysis showed for both male and female groups, the effective rates of patients with TC ranging from 5.2 mmol/L to 6.2 mmol/L were significantly higher than those of patients with TC lower than 5.2 mmol/L. There was no significant difference between patients with TC lower than 5.2 mmol/L and patients with TC higher than 6.2 mmol/L (P>0.05) in either male group or female group. Conclusion The current study suggests that patients with levels of TC ranging from 5.2 mmol/L to 6.2 mmol/L predicts the best prognosis.
ObjectiveTo analyze the effects of miR-451a on the proliferation and apoptosis of human pancreatic cancer BxPc3 cells, and to explore its molecular mechanisms.MethodsThe liposome transfection mimics of miR-451a were established in the BxPc3 cells, which were used as the research objects, and different concentrations (25, 50, 100 and 200 μmol/L) of miR-451a and blank control group were set up respectively. The expression of miR-451a mRNA in the BxPc3 cells after the transfection was detected by the qRT-PCR method. The effects of miR-451a at different concentrations on the proliferation, cell clone number, cell cycle and apoptosis, and the expressions of the macrophage migration inhibitory factor (MIF), calcium binding protein 39 (CAB39), phosphorylated phosphatidylinositol-3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) proteins in the BxPc3 cells were detected by the MTT assay, plate cloning assay, flow cytometry, and Western blot, respectively.ResultsThe expressions of miR-451a mRNA in the transfected BxPc3 cells were significantly higher than in the blank control BxPc3 cells (P<0.050). The miR-451a could inhibit the proliferation of BxPc3 cells in a time- and concentration-dependent manner significantly (P<0.050), block the differentiation of BxPc3 cells in the G0/G1 phase, and induce the apoptosis with a concentration-dependent manner (P<0.050). The expressions of MIF, CAB39, p-PI3K, and p-AKT proteins in the BxPc3 cells were down-regulated with a concentration-dependent manner (P<0.050).ConclusionFrom results of this study, miR-451a could inhibit proliferation and induce apoptosis of BxPc3 cells in a concentration-dependent manner, and its mechanisms might be related to inhibition of PI3K/AKT signaling pathway.
ObjectiveTo systematically review the efficacy of peginterferon alpha (PEG-IFNα) initially combined with lamivudine (LAM) or adefovir (ADV) in treatment of HBeAg-positive chronic hepatitis B (CHB) patients. MethodsWe electronically searched databases including The Cochrane Library (Issue 11, 2014), PubMed, CBM, CNKI, VIP, and WanFang Data from inception to December 2014, to collect randomized controlled trials (RCTs) about PEG-IFNα initially combined with LAM or ADV for HBeAg-positive CHB. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 11 RCTs involving 2031 patients were included. The results of meta-analysis showed that: After 48 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus ADV group was significantly higher than that of the PEG-IFNα monotherapy group (8.6% vs. 0%, OR=7.73, 95%CI 1.53 to 39.05, P=0.01) or the ADV monotherapy group (8.5% vs. 0%, OR=7.75, 95%CI 1.07 to 56.23, P=0.04); and the HBsAg seroclearance rate in the combination therapy group was significantly higher than that of the ADV monotherapy group (10.5% vs. 1.2%, OR=5.56, 95%CI to 2.14 to 14.47, P=0.0004). After 52 weeks of treatment, the HBsAg seroconversion rate of the PEG-IFNα plus LAM group was significantly higher than that of the PEG-IFNα monotherapy group (11.6% vs. 5.6%, OR=2.21, 95%CI 1.04 to 4.72, P=0.04). After 26 weeks of follow-up, no significant differences were found between the combination therapy group and the PEG-IFNα monotherapy group in HBsAg seroclearance rate and HBsAg seroconversion rate (all P values >0.05). ConclusionCurrent evidence shows that, compared with PEG-IFNα, LAM, or ADV monotherapy, PEG-IFNα plus LAM or ADV could improve the HBsAg seroclearance or seroconversion rate after 48-52 weeks of treatment for HBeAg-positive CHB, but this effect is still limited. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To assess the rationale for including rifampicin150/isoniazid75/ethambuto/275mg fixed dose, combination oral tablets/3-FDC R150H75E275/ in the WHO Model List of Essential Medicines (WHO EML) for treatment of category II tuberculosis (TB II) and to provide evidence for the updating of national guidelines. Methods We searched Chinese Biomedical Database (CBM, 1978 to 2006), The Cochrane Library, Issue 4, 2006, the Database of Abstracts of Reviews of Effects (1994 to 2006, the Centre for Reviews and Dissemination website), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), BIOSIS Previews (1997 to 2006), websites for grey literature and the references of studies. We applied inclusion and exclusion criteria in assessing the studies we found and eligible studies were graded following an assessment of their quality. Results Thirty-six randomized controlled trials, 4 controlled clinical trials, 11 descriptive studies and 5 WHO/national guidelines were included. Rifampicin (R), isoniazid (H) and ethambutol (E) were used in the ccontinuation phase (CP) of TB II in guidelines of WHO and high tuberculosis (TB) burden countries, but the course of treatment and dosage regimens varied. R, H and E were also widely used in conditions of pulmonary tuberculosis (PTB), extrapulmonary tuberculosis (EPTB) and pulmonary diseases caused by nontuberculous mycobacteria (NTM).Conclusions It is recommended that FDC RHE be included in WHO EML for the treatment of TB II.The suggested dosage ratio of RHE is 1:1:2, which needs to be adjusted based on more solid clinical evidence. High quality clinical studies and systematic reviews on the effectiveness, safety, economics and applicability of WHO and national guidelines and their outcomes in high TB burden countries are needed to guide their updating, promote rational resource allocation and improve cost effectiveness. Alternative drugs or drug combinations with good profile of effectiveness, safety, economics, and applicability for the prevention and treatment of drug-resistant tuberculosis are also needed to be developed.