Background and purpose:The prognosis of ovarian cancer is poor and the diagnosis is relatively late. It is needed to search for early diagnosis and treatment for ovarian cancer. This study investigated the expression of serum miRNAs in patients with malignancy or benign ovarian tumor preoperativey and analyzed its correlation with clinicopathological progress and prognostic features of epithelial ovarian cancer.Methods:Forty-eight miRNAs which have been reported to be related to ovarian cancer were ordered. The differential expression of 48 miRNAs in the serum of patients with malignant or benign epithelial ovarian tumors was detected by TaqMan low density array. The differentially expressed miRNAs were further confirmed by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). The relationship between the expression level of selected miRNA and clinical clinicopathological factors, progress and prognosis were analyzed.Results:TaqMan low density array and further RTFQ-PCR showed that only miR-125b was sig-nificantly increased in 135 ovarian cancer patients as compared with 38 individuals with benign tumor. The expression of miR-125b was higher in early stage patients than that in advanced stage patients (P=0.039). The patients without residual tumor expressed more miR-125b than patients with residual tumor (P=0.013). The high level of miR-125b was signifi-cantly correlated with longer progress free survival (PFS) (P=0.003), but not correlated with overall survival (OS) (P=0.069). Conclusion:MiR-125b may play an important role in the pathogenesis of epithelial ovarian cancer and prognosis. It may be a potential gene to predict the recurrence of epithelial ovarian cancer, but the change of gene expression at different stages and its underlying mechanism need further research.

Objective To observe the effect of short-term treatment with metfbrmin on psychological distress and metabolic feature in patients with polycystic ovary syndrome(PCOS).Methods Ninety women were diagnosed as cases of PCOS based on the 2003 Rotterdam criteria.These patients were divided into three groups:group A,consisted of 26 subjects treated with mefformin only; group B,36 cases treated with metformin plus Dane-35 ; and group C,28 cases treated with placebo and Dane-35.The treatment was carried out for 3 months.Clinical and metabolic parameters were observed.The psychological distress was evaluated by the hospital anxiety and depression scale(HAD scale).Results Compared with group C,patients in group A and B showed significantly lower body mass index(BMI),waist circumference (WC),waist-hip ratio (WHR),serum fasting insulin,homeostasis model assessment for insulin resistance (HOMA-IR),total cholesterol (TC),triglyceride (TG),low density lipoproteincholesterol(LDL-C) levels as well as anxiety and depression scores,but higher high density lipoprotein-cholesterol (HDL-C) levels (all P＜0.05).Compared with group A,patients in Group B had significantly higher WC,WHR,and LDL-C levels(all P＜O.05).No significant differences in BMI,TG,HDL-C,anxiety and depression scores were found between group A and B (all P＞0.05).In group A,a positive correlation was found between the changes of metabolic feature (BMI,WHR,and HOMA-IR) and the changes of anxiety and depression scores (all P ＜0.05).Conclusion Short-term treatment with metformin will benefit patients with polycystic ovary syndrome,regarding psychological distress and metabolic features.

Hematopoietic Stem Cells ; Histone-Lysine N-Methyltransferase ; Histones ; Humans ; Leukemia ; pathology

OBJECTIVE To investigate the role of TLR4 signaling pathway in secretory otitis media of rats.METHODS Rats SOM models were made by infusing FS and LPS to the middle otocysts. The rats were killed separately at the 3rd, 5th, 7th, 9th,11th and13th day(5 rats each time). And then the expressions of TLR4, iNOS, IL-8mRNA of middle ear mucosae were detected. NF-?B was also detected through the method of immunohistochemistry. RESULTS The expressions of TLR4mRNA, iNOS and IL-8mRNA in middle ear mucosae of SOM group were significantly higher than that of control group. Immunohistochemistry method showed that the activation of NF-?B in middle ear mucosae was obviously increased in SOM. CONCLUSION The expression of TLR4 was obviously increased in SOM and it activates the NF-?B, promotes the expression of downstream IL-8. That maybe the mechanism which cause SOM.

OBJECTIVE TNF- related apoptosis- inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors. However, most breast cancer cells are resistant to TRAIL- induced apoptosis. Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance. METHODS To identify modulators of TRAIL-induced apoptosis, we carried out a genome wide siRNA screen. To validate the screening result, we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model. Finally, we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy. RESULTS We unexpectedly identified androgen receptor (AR) to be responsible for TRAIL resistance. While AR is classically viewed as the key factor in prostate cancer progression, we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple- negative breast cancers (TNBC) that are highly aggressive with poor prognosis. Importantly, breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance. AR overexpression in MDA- MB- 231 and MDA- MB- 436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis. AR overexpression also induced TRAIL resistance in breast tumors in vivo. Further, we observed an upregulation of the TRAIL receptor, death receptor 5 (DR5) in breast cancer cells, following the removal or inhibition of AR by its antagonists Casodex and MDV3100. Treatment with AR antagonists also enhanced TRAIL- induced breast cancer cell apoptosis. CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis, in part, by suppressing DR5 expression, and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.

Objective To investigate the value and clinical significance of congenital heart diseases (CHD)detection in twins.Methods A total of 1103 twins were included in this study(127 twins were at high risk for CHD).The fetal hearts were scanned by ultrasound using Yagel's heart examination method. Autopsies were done when the pregnancy was terminated.And blood samples from fetal hearts or umbilical veins were used to evaluate fetal chromosomes.A close follow-up was conducted for normal heart cases and another heart examination was done within three months after birth.Results(1)12 twins(1.09%,12/ 1103)had CHD.Among them,4 cases were from the high risk for CHD group(33.3%,4/12),and 8 cases(66.7%,8/12)were from the low risk pregnancy group.(2)Two twins suffered from the same CHD (one pair were both TOF,and the other pair were both rhabdomyoma).One pair of twins had different abnormalities(one baby was TOF,and the other was duodenal atresia with a normal heart).All three pairs of twins chose termination and autopsies were conducted.Unanimous conclusions between prenatal ultrasound and autopsy were obtained.Nine twins were CHD in one baby and a normal heart in the other baby.Seven of them had the same conclusion after delivery.(3)Two twins with CHD were found with fetal abnormal chromosome.(4)1091 cases were not found having any abnormality,however,one fetus from one twin pair was diagnosed with ventricular septal defect(VSD)with abnormal chromosome after birth,and one fetus from another twin pair had patency of ductus arteriosus after birth.(5)The sensitivity of Yagel's heart examination was 82.4% and specificity was 100% in twins.Conclusion Yagel's heart examination is an effective and time-saving method to scan fetal hearts in twins.

Objective To explore the effect of Fas/FasL pathway on fluoride.induced apoptosis in hurnan neumbla8toma SH-SY5Y cells.Methods The cell survival rate,percentage of apoptosis,and mRNA expression levels of Fas and FasL were measured respectively after the SH-SY5Y cells were exposed to O(control),20,40,80 mg/L sodium nuoride(NaF)for 24 hours/n vitro.Furthermore,the changes of the percentage of apoptosis and mRNA expression levels of Fas and FasL in 40 mg/L NaF-treated groups incubated with activaling or neutralizing anti-Fas antibody(CH11 or ZB4)also observed respectively.Results Compared with the control group(100.00%), the cell surval rates in 40,80 mg/L NaF-treated groups[(84.63±2.57)%,(69.04±5.63)%]were significandy lower(P<0.01).The percentage of apoptosis in 40,80 mg/L NaF.treated groups[(8.54±1.95)%.(17.94±2.71)%]were higher(P<0.05)than thal in the control group[(3.32±1.33)%],and increased with the dose of NaF.NaF could up-regulate Fas and FasL mRNA expression,and increased the Fas/β-actin [40 ms/L group (0.94±0.51),80 mg/L group(0.99±0.12)]and FasL/β-actin[40 mg/L group(0.96±0.42),80 mg/L group(0.99±0.24)] ratio,compared with the control[Eas/β-actin(0.50±0.33),FasL/β-actin(0.58±0.23)],both the difference had 8tatistical significances (P<0.05).NaF and CH I 1 had a synergisfic effect on apoptosis and mRNA expression levels of Fas and FasLL(F=32.89,18.46,.14.69,P<0.01)while NaF and ZB4 had an antagonistic effect (F=5.73,24.26,10.17,P<0.05 or<0.01).Conclusion NaF exposure can cause apoptosis in SH-Y5Y cells,and the Fas/FasL pmhway may play an important role in NaF-induced apoptosis.

To study the effect of Fuzheng Huayu recipe (FZHY) on five types of isozymes of cytochrome P450 (CYP450) of normal and liver fibrosis rats by using the cocktail probe method. Dimethylnitrosamine ( DMN) was injected to induce the liver fibrosis model. After the tail vein injection with Cocktail probe solutions prepared with five CYP450s probe substrates (phenacetin-CYP1A2, omeprazole-CYP2C9, tolbutamide-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A4), the plasma concentrations of the five probe substrates were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by PK solutions 2. After the oral administration with FZHY, normal rats given phenacetin, omeprazole, tolbutamide and dextromethorphan showed increase in AUC(0-t) and decrease in CL to varying degrees, indicating that FZHY obviously inhibited the activities of CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in normal rats, but with no obvious effect on the activity of CYP3A4. After the oral administration with FZHY, liver fibrosis rats treated with CYP2C9 showed the significant increase in AUC(0-t) and significant decrease in Vd, hut with no obvious changes in the pharmacokinetic parameters of other four types of prove substances, suggesting that FZHY could significantly inhibit the activity of CYP2C9 in rats but had no effect on the activities of CYP1A2, CYP2C19, CYP2D6 and CYP3A4. The changes in the activity of CYP450 isozymes in liver fibrosis rats may be the reason for FZHY's different effects on CYP450 isozymes in normal and liver fibrosis rats.
Animals ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; pharmacokinetics ; Humans ; Isoenzymes ; genetics ; metabolism ; Liver Cirrhosis ; drug therapy ; enzymology ; genetics ; Male ; Mass Spectrometry ; Rats ; Rats, Wistar

Emodin is an effective active ingredient extracted from Chinese herbal medicine, which has the function of antimicrobial, anti-inflammatory, antioxidant and scavenging oxygen free radicals, inhibiting platelet aggregation, improving microcirculation, protecting various organs and tissues as well as a wide range of anti-tumor effect. Primary biliary gallbladder is a common malignant tumor resection rate and lack of effective adjuvant treatment. It has been confirmed that emodin has broad spectrum antitumor effect, whereas, whether it has curative effect in the treatment of gallbladder carcinoma there is no reliable clinical trials confirmed that its resistance to gallbladder carcinoma function needs further experimental research. In this review, we report the research progress of emodin anti-gallbladder carcinoma.
Animals ; Antineoplastic Agents ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Emodin ; therapeutic use ; Gallbladder ; drug effects ; Gallbladder Neoplasms ; drug therapy ; Humans

PI3K/AKT/mTOR signaling pathway plays an essential role in the growth, proliferation and survival of various type of cells and also hematopoietic stem cells (HSC). Aberrant activation of PI3K/AKT/mTOR signaling pathway leads to exhaustion of HSC, while the inhibition of PI3K/AKT/mTOR signaling pathway results in blocking of B cell differentiation. This article reviews the latest advances on the role of key components involved in the PI3K/AKT/mTOR signaling pathway, including PI3K, AKT, mTOR, FoxO and GSK-3 in HSC.
Hematopoietic Stem Cells ; Humans ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; metabolism