Objective To upregulate Notch signaling in cancer cells by overexpression of active part of Notch1 and to examine the proliferation of the cells. Methods Four cancer cell lines were infected with retrovirus recombined with sequence encoding active part of Notch1.CBF-1 reporter plasmid was used to detect Notch signaling and proliferation assay was carried out by MTS method.Cell cycle analysis was synchronously conducted. Results The overexpression of the active part of Notch1 induced upregulation of Notch signaling,led to growth inhibition in Hela and HepG2 cell lines and growth boost in BGC-823 cell lines,while had no effect on Chang cell lines. Conclusion The upregulation of Notch signaling can exert various effects on different cancer cell lines which is critical to the gene therapy for cancers.

Objective To study the activity of the survivin gene promoter in several tumor cell lines and evaluate the possible application of this promoter in tumor gene therapy. Methods ①The expressions of survivin gene in A549,MDA-MB231 and HepG2 cell lines were detected by RT-PCR and Western blotting.②Tumor cells(A549,MDA-MB231,HepG2) were transiently transfected by reporter plasmids containing different length of survivin promoter using lipofectamine.And 48 h later,the level of reporter gene expression was analyzed.Results There were different levels of survivin expression in A549,MDA-MB231 and HepG2 cell lines.Transient transfection assay approved that pLuc-surP-987,pLuc-surP-596,pLuc-surP-269 and pLuc-surP-158 showed high activity and 269 bp survivin promoter demonstrated the highest activity. Conclusion In transcriptional level,survivin promoter can activate the reporter gene in several tumor cell lines.It is a potential candidate promoter in tumor gene therapy.

OBJECTIVE:To observe the effect of Pipers hancei extract on the atherosclerosis of rabbits fed with high lipid food and to discuss its mechanism of action.METHODS:The rabbits were divided into high lipid group,Pipers hancei groups (high,medium and low dose groups),which were fed with high lipid food for 3 weeks before administered with medicine or normal saline,12 weeks later,the blood lipid,pathological changes of aortic plaque and lesion of coronary artery,serum superoxide dismutase (SOD)activity and serum malondialdehyde (MDA)activity were determined,in which a control group was established.RESULTS:Compared with the high lipid group,the levels of serum total cholesterol (TC),triglycerides (TG)and low density lipoprotein (LDL)have been significantly decreased for the high dose Pipers hancei group(P

BACKGROUNDNumerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFα) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes.

METHODSPeripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 µg/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 µg/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37°C, and quantitative determination of TNFα, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 µmol/L, 1 µmol/L, 0.1 µmol/L, 0.01 µol/L and 0.001 µmol/L) or dimethyl sulfoxide at 37°C for 10 minutes, and then stimulated with LPS or PMA, protein concentrations of p44.42, IKBα, P38 and Jun NH2-terminal kinase were determined by Western blotting. Cyclic adenosine-3',5'-monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech).

RESULTSY316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and therefore appeared to mediate its effects on TNF by acting at an early point in the signaling cascade induced in response to LPS. There was no effect of Y316 on cAMP levels either alone or in the presence of LPS.

CONCLUSIONSY316 appears to be a small molecule inhibiting TNF production, which may act via a novel mechanism. Identification of the target of Y316 may lead to the development of alternative strategies for achieving selective cytokine inhibition.

Anti-Inflammatory Agents ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Interleukin-1 ; antagonists & inhibitors ; biosynthesis ; Interleukin-6 ; antagonists & inhibitors ; biosynthesis ; Lipopolysaccharides ; pharmacology ; Monocytes ; drug effects ; immunology ; Phosphorylation ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; biosynthesis

Animals ; Blotting, Western ; Cell Differentiation ; drug effects ; Embryonic Stem Cells ; cytology ; enzymology ; Isoenzymes ; analysis ; Mice ; Neurons ; enzymology ; Protein Kinase C ; analysis ; Tretinoin ; pharmacology

OBJECTIVETo analyze the long-term results after the correction of the paralytic ectropion in leprosy.

METHODSSeventy-four patients with 115 paralytic ectropion eyes after leprosy were treated with the surgical procedures included medial canthoplasty, medial canthal tendon plication, lateral tarsal strip, medial canthal resection, lateral canthoplasty, and lid shortening. The results were evaluated with the follow-ups from 2 to 4 years.

RESULTSThe eye-redness was reduced from 93 to 40 while the epiphora from 107 eyes (24 mild, 36 moderate and 47 severe) to 90 (40 mild, 32 moderate and 18 severe). The mean lid gap in mild eye closure was reduced from 6.8 mm to 5.3 mm and the cornea lesion was reduced from 53 to 36. The results were excellent in 18 eyes (15.7%), good in 45 eyes (39.1%), fair in 41 eyes (35.7%) and poor in 11 eyes (9.6%). However, the mean visual acuity remained same pre- and postoperatively.

CONCLUSIONSSurgical correction of ectropion is helpful for cornea protection and could improve the signs and symptoms of the eyes such as epiphora and red [abstract truncated].

Adult ; Aged ; Aged, 80 and over ; Ectropion ; surgery ; Eyelids ; abnormalities ; surgery ; Facial Paralysis ; etiology ; surgery ; Female ; Humans ; Leprosy ; complications ; surgery ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Treatment Outcome

OBJECTIVETo investigate the feasibility and safety of modified quadruple stapling technique in radical proximal gastrectomy for gastric carcinoma.

METHODSMedical records of 55 consecutive patients who underwent radical proximal gastrectomy for gastric cancer were analyzed retrospectively. Twenty-eight patients (modified group) undergoing modified quadruple stapling technique were compared to 27 patients (traditional group) who underwent traditional approach during the same period.

RESULTSThere was no perioperative mortality. All the patients had negative pathological resection margin. The mean operative time in the modified group was significantly shorter than that in the traditional group [(158±31) min vs. (195±42) min, P<0.05]. There were no immediate complications such as stricture, bleeding or leakage at the anastomosis, gastroparesis, and wound infection. Postoperative recovery did not differ between the two groups (P>0.05). During the follow-up (range: 3 months-2 years), 2 (7.1%) patients in the modified group and 2 (7.4%) in the traditional group developed reflux esophagitis (P>0.05) and anastomotic inflammation occurred in 2 cases (7.1%) for the modified group and 8 (29.6%) for the traditional group (P<0.05).

CONCLUSIONModified quadruple stapling technique is a feasible and safe method in radical proximal gastrectomy.

Anastomosis, Surgical ; methods ; Chi-Square Distribution ; Follow-Up Studies ; Humans ; Retrospective Studies ; Stomach Neoplasms ; surgery

A total of 108 subjects were enrolled in this study, including 21 healthy subjects(control group), 34 non-obese patients with polycystic ovary syndrome [PCOS1 group, body mass index(BMI)<25 kg/m²], 32 obese patients with PCOS(PCOS2 group, BMI≥25 kg/m²), and 21 simple obese patients whose age and BMI matched with PCOS2(OB group). BMI, waist-hip ratio(WHR), fasting plasma glucose(FPG), postprandial 2h plasma glucose(2hPG), HbA_1C, fasting insulin(FINS), postprandial 2h insulin(2hINS), sex hormones, and lipid parameters were determined. The status of insulin resistance was assessed by homeostasis model assessment for insulin resistant index(HOMA-IR)and insulin sensitivity index(ISI). Levels of plasma galectin-3 and interleukin-6(IL-6)were detected by ELISA. The results showed that the plasma level of galectin-3 was significantly higher in PCOS group than those in control and OB groups(all P<0.05). Moreover, the level of galectin-3 was also higher in OB group compared with control group, while galectin-3 level in PCOS2 group was higher than that in PCOS1 group(all P<0.05). After adjusted by age, BMI, and WHR, correlation analysis showed that the level of galectin-3 was positively correlated with FPG, 2hPG, FINS, HOMA-IR, highly-sensitive C-reactive protein, and IL-6, while negatively correlated with ISI. A multiple linear regression analysis revealed that the plasma galectin-3 concentration was independently associated with IL-6, HOMA-IR, and BMI(all P<0.05). These data suggest that plasma galectin-3 is closely associated with glucose metabolism, chronic inflammation, and insulin resistance, which may be involved in the pathogenesis of PCOS. (Chin J Endocrinol Metab, 2018, 34: 578-582)

Objective To study the effects of ubenimex on immunocyte functions of mice.Methods Antitumor activity of ubenimex was observed in implanted H22 mice.The killing activity of NK cells to target cell YAC-1, phagocytosis of peritoneal macrophage and the secretion of mac -rophage NO effect were carried out with CCK method , neutral red colori-metric method and Griess method , respectively.Lymphocyte proliferation test was done by stimulating methods in vitro and in vivo.Tumor associated macrophages(TAMs)and myeloid derived suppressor cells (MDSCs) in pe-ripheral blood and T lymphocytes , B lymphocytes and NK cell in spleen were determined by flow cytometry method.Results The 20 mg· kg-1 of ubenimex could depress the growth of H 22 and its tumor inhibitory rate was 41.71%.The killing activity of NK cells was increased by 56.5%.The 10μg· mL-1 of ubenimex significantly enhanced secretion of macrophage NO effect (P<0.01) and it also enhanced phagocytosis of peritoneal mac-rophage (P<0.05) at concentration of 100μg· mL-1.Besides the lym-phocyte proliferation was also strengthened (P<0.05).The number of T lymphocytes and CD 8+T cell in spleen was increased obviously ( P<0.01 or P<0.05).Ubenimex could adjust the number of TAMs and MDSCs in peripheral blood to normal level.Conclusion Ubenimex has antitumor growth activity through enhances non -specific immunity and specific immunity and suppresses the tumor associated cell.

BACKGROUNDThere are few reports of quantitative and qualitative measuring of left main coronary artery (LMCA) plaques by multislice computed tomography coronary angiography (MSCTA), especially when compared with intravascular ultrasound (IVUS) as reference standard. The aim of this study was to evaluate the use of 64-MSCTA in the diagnosis of LMCA disease, and the accuracy of MSCTA in the quantitative and qualitative assessment of the LMCA lesion as compared with IVUS.

METHODSA total of 91 patients (53 men, 38 women, mean age (64.78 +/- 9.19) years) were examined by 64-MSCTA and IVUS. Compared with the IVUS, the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the MSCTA on the diagnosis of LMCA diseases were calculated. Also, kappa index (kappa) for the agreement between MSCTA and IVUS was calculated. Minimal lumen area (MLA), external elastic membrane cross-sectional area (EEM-CSA) and plaque burden were measured by two blinded and independent operators on MSCTA cross-sectional reconstruction and compared with the parameters measured from IVUS by manually tracing. The CT value of soft, fibrous and calcific plaques was measured using IVUS classification of the plaques.

RESULTSThe sensitivity, specificity, PPV and NPV of MSCTA for detecting LMCA plaques were 93.1%, 84.2%, 95.7%, 76.2%, respectively. Kappa index (kappa = 0.744, P < 0.001) indicated excellent agreement between MSCTA and IVUS. The Pearson index between MLA on IVUS and MLA on MSCTA was 0.815 (P < 0.01). The Pearson index of plaque burden and EEM-CSA between IVUS and MSCTA was 0.736 and 0.740 respectively (both P < 0.01). The CT value of soft plaque, fibrous plaque and calcific plaque compared with IVUS were (52.52 +/- 15.71) HU, (108.32 +/- 43.44) HU and (604.16 +/- 377.67) HU (P < 0.001). Receiver operating characteristic curve analysis of CT value of non-calcific plaques for predicting soft plaques showed the cutpoint was 54.35 HU, with a sensitivity of 83.3% and specificity of 94.4%.

CONCLUSIONSSixty-four section MSCTA is an effective diagnostic tool for the detection of LMCA plaques with higher sensitivity and specificity. The correlation of quantitative and qualitative analysis between MSCTA and IVUS was excellent. The CT value of plaques can help the diagnosis of plaque composition.

Adult ; Aged ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Tomography, Spiral Computed ; methods ; Ultrasonography