Objective To determine levels of nuclear factor (NF)-κB, interleukin (IL)-10, and visfatin in adipocytes treated by different degrees of intermittent hypoxia (IH), and to investigate the mechanism of IH leading to insulin resistance (IR). Methods The cell model of intermittent hypoxia/re-oxygenation (IH/ROX) in obstructive sleep apnea (OSA) was established. Differentiation mature 3T3-L1 adipocytes, were randomly divided into 10 groups including four different-frequency intermittent hypoxia groups(IH1-4, fixed intermittent hypoxia scheme for 1.5%O2 45 s and then re-oxygen 21%O2 for 2 min 15 s, 4 min 15 s, 5 min 45 s and 8 min 45 s, 60 times circulation), and their normal oxygen control groups (SC1-4, instead each IH group 1.5%O2 to 21%O2, the rest groups were treated as same as IH group), continuous hypoxia group (CH, 10%O2 for 6 h) and normal oxygen control group (CC, 21%O2 for 6 h). ELISA method was used to determine the levels of IL-10 and visfatin in the supematant of adipocytes. Western blot method was used to determine the protein levels of NF-κB p65 and visfatin. Real-time PCR method was used to determine the mRNA levels of IL-10 and visfatin. Results The protein and mRNA expressions of IL-10 were significantly lower in IH group and CH group than those of control groups (P<0.01). The levels of NF-κB p65 protein were significantly increased in IH group and CH group than those of control group. The protein and mRNA expressions of visfatin were significantly higher in IH1, IH2 and CH groups than those of control group (P<0.01). Conclusion As a prominent feature of OSA pathophysiology, IH may take part in insulin resistance of OSA patients by abnormally secreting NF-κB, IL-10 and visfatin in adipocytes.

Obstructive sleep apnea (OSA) is characterized by repeated intermittent hypoxia (IH), hypercapnia, sleep fragmentation and intrathoracic pressure change. IH is related to the clinical pathophysiological processes of hypertension, atherosclerosis, coronary heart disease, arrhythmia, stroke, heart failure and sudden death. IH from OSA can lead to metabol-ic dysregulation, endothelial dysfunction, systemic inflammation, oxidative stress and the change of nerve body fluids, which has been shown to increase the risk of cardiovascular diseases. This study mainly describes the pathogenesis of IH leading to the various cardiovascular diseases.

Humans ; Occupational Exposure ; Occupational Health ; Risk Factors ; Sanitation

5-Flucytosine (5-FC) could be changed to 5-fluorouracil (5-FU) by cytosine deaminase (CD), the latter is able to kill cancer cells. However, there is no efficient method to deliver the CD gene into the tumor cells, which hampers the application of the suicide gene system. In this experiment, for the first time, the NDV has been utilized as a vector to deliver the CD gene into the cancer cells, the virus can infect the cancer cells specifically, replicate and assemble, while the cytosine deaminase is expressed. Then the CD converts the prodrug 5-FC into 5-FU to achieve the purpose of inhibiting tumor. Firstly, the whole genome of E. coli JM109 was extracted, and the CD gene was obtained by cloning method. Then the CD and IRES-EGFP were ligated into the pEE12.4 expression vector to become a recombinant pEE12.4IE-CD eukaryotic expression plasmid. The human liver cancer cells were transfected with the plasmid. The cells were treated with different concentrations of 5-FC, MTT method was used to determine the killing effect of CD/5-FC system on the human liver cancer cells. The cell deaths were 18.07%, 42.98% and 62.20% respectively when the concentrations of prodrug were at 10, 20 and 30 mmol x L(-1). In 5-FC acute toxicity experiment, Kunming mice were injected with different concentrations of 5-FC at intervals of 1:0.5. The LD50 of 5-FC through iv injection was determined by improved Karber's method, the LD50 was 507 mg x kg(-1) and the 95% confidence limit was 374-695 mg x kg(-1). According to the maximum LD0 dose of the LD50, the maximum safe dose was 200 mg x kg(-1). Body weight and clinic symptoms of the experimental animals were observed. These results laid the foundation to verify the antitumor effect and safety of CD/5-FC system in animal models. The CD gene was ligated into the NDV (rClone30) carrier, then the tumor-bearing animal was established to perform the tumor inhibiting experiment. The result showed that the recombinant rClone30-CD/5-FC system has a high antitumor activity in vivo. To summarize, CD gene has been cloned and its bioactivity has been confirmed in the mammalian cells. It is the first time in this study to utilize the recombinant NDV to deliver the CD gene into the tumor cells; our result proves the rClone30-CD/5-FC system is a potential method for cancer therapy.

Transcriptional regulation is one of the major regulations in plant adventious shoot regeneration, but the exact mechanism remains unclear. In our study, the RNA-seq technology based on the IlluminaHiSeq 2000 sequencing platform was used to identify differentially expressed transcription factor (TF) encoding genes during callus formation stage and adventious shoot regeneration stage between wild type and adventious shoot formation defective mutant be1-3 and during the transition from dedifferentiation to redifferentiation stage in wildtype WS. Results show that 155 TFs were differentially expressed between be1-3 mutant and wild type during callus formation, of which 97 genes were up-regulated, and 58 genes were down-regulated; and that 68 genes were differentially expressed during redifferentiation stage, with 40 genes up-regulated and 28 genes down-regulated; whereas at the transition stage from dedifferentiation to redifferention in WS wild type explants, a total of 231 differentially expressed TF genes were identified, including 160 up-regualted genes and 71 down-regulated genes. Among these TF genes, the adventious shoot related transcription factor 1 (ART1) gene encoding a MYB-related (v-myb avian myeloblastosis viral oncogene homolog) TF, was up-regulated 3 217 folds, and was the highest up-regulated gene during be1-3 callus formation. Over expression of the ART1 gene caused defects in callus formation and shoot regeneration and inhibited seedling growth, indicating that the ART1 gene is a negative regulator of callus formation and shoot regeneration. This work not only enriches our knowledge about the transcriptional regulation mechanism of adventious shoot regeneration, but also provides valuable information on candidate TF genes associated with adventious shoot regeneration for future research.
Arabidopsis ; growth & development ; Arabidopsis Proteins ; physiology ; Gene Expression Regulation, Plant ; Genes, Plant ; Plant Shoots ; growth & development ; RNA ; Regeneration ; Seedlings ; growth & development ; Transcription Factors ; physiology ; Up-Regulation

Objective To evaluate the effect of dexmedetomidine and tramadol on perioperative insulin resistance in patients undergoing radical resection of rectal carcinoma.Methods Sixty ASA I or II patients undergo-ing radical resection of rectal carcinoma were randomly divided into 3 groups(n =20 each):dexmedetomidine group (group D),tramadol group(group T),control group(group C).Group D was given dexmedetomidine intravenously at 1μg/kg 15min before induction of anesthesia followed by a continuous infusion of 0.5μg·kg -1 ·h -1 until the abdo-men was closed,and group T was given tramadol intravenously at 1.5mg/kg 15min before induction of anesthesia fol-lowed by a continuous infusion of 0.5mg·kg -1 ·h -1 until the abdomen was closed,whereas group C received the same volume of normal saline.Venous blood samples were taken at 30min before anesthesia induction(T1 ),1 h after the beginning of the operation(T2 ),1h after operation(T3 ),24h after operation(T4 )for determination of blood con-centrations of glucose(BG),insulin(INS),interleukin -6 (IL -6),tumor necrosis factor -α(TNF -α).Insulin resistance(HOMA -IR)and insulin sensitivity index(QUICKI)were calculated.The numbers of patients with PONV were studied respectively.Results The serum IL -6,TNF -α,BG,INS concentrations and HOMA -IR were signifi-cantly lower while ISI was significantly higher in both group D[t =7.71,3.37,8.78,8.73,11.45,2.82(T2 ),3.04, 2.95,12.75,10.73,16.09,2.92(T3 ),11.26,2.45,11.40,5.10,14.5,2.51(T4 ),all P <0.05]and group T[t =3.02,2.59,2.93,7.76,6.32,2.03(T2 ),8.78,2.27,4.14,8.83,7.68,2.12(T3 ),6.10,2.05,3.71,2.35,7.12, 2.09(T4 ),all P <0.05]at T2 ,T3 and T4 than those in group C.The serum TNF -αconcentration and HOMA -IR were significantly lower while ISI was significantly higher in group D[t =6.68,4.58,2.05 (T2 ),9.01,6.66,2.23 (T3 ),7.54,5.5,2.02(T4 ),all P <0.05]at T2 ,T3 and T4 than those in group T.The numbers of patients with PONV were significantly higher in group T than those in group D and group C (χ2 =26.13,18.75,all P <0.05 ). Conclusion Both dexmedetomidine and tramadol can attenuate perioperative insulin resistance in patients undergo-ing Radical Resection of Rectal Carcinoma,and the decrease the consentrations of IL -6 and TNF -αmay be involved in the mechanism.The roles of prevention of perioperative insulin resistance in dexmedetomidine group are superior to tramadol group.The incidence of PONV is less in a dexmedetomidine group than that in a tramadol group.

Purpose To investigate the expression of EZH2 and p53 protein in breast cancer and to analyze their relationship with the clinical pathologic characteristics and prognosis. Methods The expression of EZH2 and p53 protein were detected by immunohisto-chemical method in 50 cases of breast adenosis tissues, 92 cases of breast invasive lobular carcinoma ( ILC) and 200 cases of breast in-vasive ductal carcinoma ( IDC) , and their correlation was also analyzed. Results There was no statistical significance of EZH2 be-tween ILC and IDC (P>0. 016 7), while its expression in breast adenosis tissues was lower than that in ILC and IDC (P<0. 016 7). In breast cancer the expression of EZH2 protein were not correlated with patient age, menopausal status, histological types, and pTNM stage. In contrast, its expression correlated with the tumor size, lymph node metastasis, molecular subtype, survival status and p53 (P<0. 05). There was no statistical significance of p53 between ILC and breast adenosis tissues (P>0. 016 7), while its expression in IDC was higher than that in ILC and breast adenosis tissues (P<0. 016 7). Its expression had no related to patient age, menopausal status, tumor size, lymph node metastasis in breast cancer, but related to histological types, pTNM stage, molecular subtype and sur-vival status (P<0. 05). The Kaplan-Meier survival analysis showed the expression of EZH2 and p53 had correlated with disease-free and overall survival rates of breast cancer (P<0. 05). Multivariate COX regression analysis showed that the expression of EZH2 and p53 were independent affecting factors to breast cancer patients. Conclusion The expression of EZH2 and p53 protein increase in the breast adenosis, ILC and IDC gradually, and they have positive correlation. The expression levels of EZH2 and p53 protein have im-portant value to evaluate the prognosis of breast cancer patients.

Fibroblast growth factor-21 (FGF-21) is an important metabolism regulator, however, whether FGF-21 has effects on cardiovascular remains unclear. In this study, H2O2-induced injury in H9c2 cells was used as a cell model, the anti-apoptosis potential and mechanism of FGF-21 against oxidative injury were evaluated by MTT assay, flow cytometry assay and real-time PCR. The results showed that FGF-21 could increase the cell survival of H2O2-induced injury in H9c2 cells and prevent H9c2 cells from oxidative stress-induced apoptosis. Furthermore, FGF-21 can elevate SOD activity and regulate Bcl-2/Bax expression in H9c2 cells. The results suggest that FGF-21 have protective effect against the H2O2-induced apoptosis in H9c2 cells.

Purpose To investigate the clinicopathological characteristics and the survival outcomes of invasive lobular carcinoma. Methods A retrospective analysis of 98 patients with invasive lobular carcinoma and 530 invasive carcinoma of no special type was performed in order to observe the histological features and the clinical outcomes of invasive lobular carcinoma. Results Median follow-up was 68. 5 months for invasive lobular carcinoma and 67 months for invasive carcinoma of no special type. Invasive lobular carcinoma presented with a larger tumor size, more histopathological grade 2 tumors, increased rate of hormonal receptor positivity, human epider-mal growth factor 2 (HER-2) negativity, and had a lower proliferative index as compared to invasive carcinoma of no special type, more frequently presented with the luminal A subtype (P<0. 001). The classical invasive lobular carcinoma presented with a smaller tumor size, to have a lower histological grade and proliferative index compared to the non-classic type, and more frequently presented with the luminal A subtype, whereas the non-classic invasive lobular carcinoma patients more frequently presented with the luminal B, HER-2 overexpression, or triple negative subtype (P=0. 035). A statistically significant difference in the outcome was observed at un-ivariate analysis for patients with non-classic for disease-free survival (P=0. 043) and for overall survival (P=0. 048), as compared with patients with classical invasive lobular carcinoma. The disease-free survival difference between the invasive lobular carcinoma and the invasive carcinoma of no special type was not significant (P=0. 537), and the overall survival rates were not statistically different between the two groups (P=0. 397). A statistically significant difference of overall survival was observed at multivariate analysis for patients with HER-2 positive and triple negative subtypes versus patients with luminal A invasive lobular carcinoma (P=0. 015, P=0. 016) . Conclusions The outcome of invasive lobular carcinoma is significantly correlated with histological and immunohistochemi-cally defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley (SD) rats were fed with high-fructose (10%) water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups: model control, FGF21 0.25, 0.1 and 0.05 micromol x kg(-1) x d(-1) groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure (SBP) was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test (OGTT) and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [(122.2 +/- 3.5) mmHg, P < 0.01] after 4-week treatment, whereas, SBP of untreated (model control) rats maintained a high level [(142.5 +/- 4.5) mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at (130 +/- 4.5) mmHg vs. (143 +/- 5.5) mmHg for model control (P < 0.01). FGF21 treatment groups improved serum lipids obviously, total cholesterol (TC) and triglyceride (TG) levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [(7.32 +/- 0.11), (7.24 +/- 0.13), (6.94 +/- 0.08) vs. (6.56 +/- 0.19) micromol x L(-1), P < 0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF21 significantly ameliorates blood pressure in fructose-induced hypertension model by relieving insulin resistance. This finding provides a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of essential hypertension.