FLIP is a protein containing death domain.Human beings have three subtypes of c-FLIPL,c-FLIPs and c-FLIPR,which can inhibit the apoptosis of a variety of tumor cells.c-FLIPL plays a dual role in the apoptotic signal.The expression level of FLIP not only decides the opening and closing of the apoptosis pathway but also achieve the conversion of cells in the apeptotic signaling and proliferative signaling pathway.The regulation of FLIP's expression is a multi-layered,involving multiple signaling pathways.FLIP will probably become an attractive death receptor signaling target of therapy.

Objective To investigate the association between glucose metabolism status and brachial-ankle pulse wave velocity(baPWV)in Chinese patients with coronary artery disease(CAD).Methods baPWV values were measured in 198 CAD patients.Plasma glncose,serum lipids,hsCRP and other baseline data were obtained in all the patients.According to the glucose level,the participants were divided into 3 groups:normal glucose tolerance(NGT)group,impaired glucose regulation(IGR)group and diabetes mellitus(DM)group.ResultsbaPWV values in the DM group(1807±381)cm/s were significantly higher than those in the NGT group[(1615±248)cm/s,P=0.000]and IGR group[(1674±277)cm/s.P=0.035].Multiple stepwise linear regression analyses indicated that higher baPWv values were associated with aging and hsCRP levels in 198 patients.In DM group,higher baPWV values were independently associated with aging and HbA1 C levels.Conclusions In patients with coronary artery disease.baPWV values increase with different glucose metabolism status from NGT to IGR then DM.baPWV values in the patients with DM were significantly higher than those in the other two groups.Glycemic control may ameliorate arterial stiffness.

Objective To evaluate the results of thoracic endovascular aortic repair (TEVAR) for chronic type B aortic dissection.Methods From September 2005 to January 2013,30 patients with chronic type B aortic dissection received TEVAR.All patients were followed for 2-90 months [mean (33 ±25) months].Results All of the procedures finally achieved technical success.However,during TEVAR,there were transient endoleaks in 8 patients including type Ⅰ endoleaks in 3 patients,type Ⅱ endoleaks in 5 patients and persistent endoleaks in 3 patients which are type Ⅳ endoleaks.Type Ⅰ and type Ⅱ endoleaks were successfully managed during the procedures.There was no mortality or major complication during the perioperative period.Three patients died during follow-up:one patient died of carcinoma of the colon and two patients died of the complications of secondary interventions related to aortic dissection.Totally there were seven patients receiving secondary interventions.The Kaplan Meier actuarial survival curve showed a 5-year survival rate of 87.9％ and the 5-year survival rate without secondary intervention was 72.8％.Conclusions Early and midterm results showed that TEVAR was effective in treating chronic type B aortic dissection.

Objective:To observe the clinical efficacy of Yi Jin Jing (Sinew-transforming Qigong Exercises) for primary osteoporosis in the elderly.Methods:Eighty old patients with primary osteoporosis were randomized into a Yi Jin Jing group and a medication group,40 cases in each group.The Yi Jin Jing group was intervened by Yi Jin Jing (Sinew-transforming Qigong Exercises) training,while the medication group was intervened by oral administration of alendronate sodium tablet.Prior to and after 6-month intervention,the bone mineral density (BMD) of the proximal femur,visual analog scale (VAS) and activities of daily living (ADL) were estimated.Results:There were no significant differences in the BMD of the proximal femur,and VAS and ADL scores between the two groups before the intervention (P＞0.05).After 6-month intervention,the above items all improved significantly in both groups (both P＜0.01);the improvements in VAS and ADL scores in Yi Jin Jing group were more significant than those in the medication group (P＜0.01),while the between-group difference in the BMD of the proximal femur was statistically insignificant (P＞0.05).Conclusion:Practice of Yi Jin Jing (Sinew-transforming Qigong Exercises) can effectively ameliorate the BMD in the elderly with primary osteoporosis,and it can reduce the pain and improve ADL,with a better general effect compared to oral administration of alendronate sodium tablet.

Objective To understand the mycoplasma pneumoniae(MP) infection degree in community children by testing specific IgM antibodies against MP in different age bracket group in Shanghai Meilong area. Methods Using random sampling method, blood specimens of 1 817 children from kindergartens and primary or junior high schools in Meilong area were obtained. Children were from 2 to 15 years old, 969 males, 848 females. The specimens were tested for IgM antibodies against MP using with gelatin particle agglutination test. The data were statistically analyzed using with ?2 test. Results Five hundred and fifty-nine (30.7%) IgM antibodies against MP were positive from 1 817 blood specimens. The positive percentages were 27.34% and 34.66% for males and females, which had significant difference(?2=11.383 P=0.001). The higher percentage was detected from kindergarten children than primary and junior high school children(P=0). The positive percentages of anti-mycoplasma IgM had no significant differences between different kindergartens and primary schools(P=0.526,0.232). On the contrary, between different junior high schools, there were siginificant differences (?2=9.825 P=0.002). Conclusions MP is an important pathogenic mycoplasma cause for respiratory tract infections in Meilong area. It is relative to childhood asthma. The prevention and cure of MP infection for children shall be paid more attention.

The aims of this research were to constitute and evaluate one targeting anticancer co-delivery system for both micro-molecularchemotherapeutic drugs(docetaxel, DTX)and small interfering RNA(siRNA)expressed by COX-2. The nanoparticles composed of poly(D, L-lactide-co-glycolide)(PLGA)bearing disulfide-linkaged reducible polyethyleneimine(PEIss)covered by hyaluronic acid(HA). Meanwhile, HA-PEI-PLGA nanoparticles were prepared as control. Firstly, the solvent evaporation was used to the particles which exhibited a core-shell structure with a uniform size of 150-200 nm. The cumulative drug release in two kinds of PBS media(pH 7. 4 and pH 5. 0)during 72 hours indicated that DTX-loaded nanoparticles had sustained-release effect within 24 hours. The cumulative release of DTX of HRPSP NPs in PBS pH 5. 0 was 10%-25% more than that in PBS pH 7. 4, which demonstrated that favored release of DTX from nanoparticles could be achieved in acidic tumor microenvironment. Then, the highest transfection efficiency was observed after 14-16 h incubation at N/P ratio of 40/1. Following the saturation of CD44 receptor, the mean fluorescence intensity of HRPSP NPs from the cells decreased drastically in the case of saturation with free HA before. However, there existed no significance in the fluorescence of RPSP NPs between the cells with and without saturation with free HA, which indicated the nanoparticles′ targeting potential toward tumor cells. In the Western blot, the relative silencing efficiency of Bcl-2, bax, capase-3 and COX-2 mRNAprotein was calculated. In comparison to the control group, the silence efficiencies of bax and capase-3 were both significantly increased while that of Bcl-2 was evidently reduced, particularly in siCOX-2/HRPSP NPs group(P< 0. 01). The similar results were obtained in the silence efficiency of COX-2 protein in which the COX-2 quantity on mRNA and protein decreased. The results suggest that the nanoparticles could achieve the synergistic effect on the combinatorial delivery of siRNA and lipophilic anti-tumor drugs.

BACKGROUNDThe down-regulation of constitutive nitric oxide synthase (cNOS) and up-regulation of inducible nitric oxide synthase (iNOS) are associated with the allergen-provocated airway hyperresponsiveness (AHR). This study aimed to determine whether their alteration also plays an important role in the AHR induced by lipopolysaccharide (LPS).

METHODSHartley male guinea pigs, weighing between 250 g and 350 g, were injected with LPS at a dose of 1 mg/kg every 24 hours for three days. A non-selective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), or a selective inducible NOS inhibitor, aminoguanidine (AG), were used thirty minutes before each injection of LPS. Airway reactions, nitric oxide (NO) production and inflammatory changes were detected 24 hours after the last dose of LPS.

RESULTSAG significantly decreased the NO production in the bronchoalveolar lavage fluid (BALF) and sharply reduced the intensity of bronchoconstriction to histamine challenge. L-NAME also significantly decreased the NO production in the BALF, but had no effect on airway reactions or, perhaps, a tendency to enhance the intensity of AHR.

CONCLUSIONSThe data suggest that inducible NOS contributes to the AHR induced by repetitive intraperitoneal LPS, and constitutive NOS was also involved.

Airway Resistance ; drug effects ; Animals ; Bronchial Hyperreactivity ; chemically induced ; Enzyme Inhibitors ; pharmacology ; Guanidines ; pharmacology ; Guinea Pigs ; Lipopolysaccharides ; toxicity ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase ; antagonists & inhibitors ; physiology

OBJECTIVEIn order to provide a reliable basis for the diagnosis and treatment of autoimmune hepatitis (AIH) and its overlap syndrome, we investigated the clinical, immunological characteristics of and the therapeutic methods for AIH and AIH-primary biliary cirrhosis (PBC) overlap syndrome.

METHODSOne hundred seven patients (77 with AIH and 30 with AIH-PBC overlap syndrome) were enrolled in the study. Their clinical manifestations, serum liver function tests (LFTs) findings, serum immunoglobulins, liver histopathological changes and their responsiveness to the therapies were investigated.

RESULTSThe age distribution of AIH patients showed a single peak during their fifties and their main clinical manifestations were malaise, abdominal distension, anorexia and jaundice. Serum gamma globulin and IgG were significantly higher than their normal levels. 74% of the patients were positive for anti-nuclear antibody (ANA), 32% of the patients were positive for anti-smooth muscle antibody (AMA), and over 50% of the patients suffered from concurrent extrahepatic autoimmune diseases. The main histological changes in the liver biopsies were interface hepatitis (65%), lobular hepatitis and rosette formation of liver cells. Bridging necrosis was observed in severe AIH cases. In the AIH-PBC overlap syndrome patients, the levels of serum ALT, AST, GGT, ALP and incidences of ANA and AMA/AMA-M2 were all significantly higher than those of the AIH group. After treating AIH patients with prednisolone and azathioprine (Aza), complete response was seen in 42 cases (70%), sustained response was seen in 26 cases (43%). Sixteen cases had relapses after the withdrawal of the treatment or prednisolone dosage was reduced lower than 10 mg/d. The cases having normal serum ALT, AST, gamma-globulin and IgG levels after treatment were still responding to the reduced prednisolone dosage of 5-10 mg/d without azathioprine added. After combination with ursodeoxycholic acid (UDCA) treatment, the liver function tests (AST, ALT, TBil) of AIH-PBC overlap syndrome patients also significantly improved compared to those before the treatment (P<0.01).

CONCLUSIONAIH and AIH-PBC overlap syndrome are not rare in our clinics. Their diagnoses should be based on the clinical presentations, biochemical and immunological indices and liver histological changes. In AIH cases, once their AST, ALT, gamma-globulin and IgG levels return to normal, the prednisolone dosage can be maintained at 5-10 mg/d and Aza can even be withdrawn. Good improvement for patients with AIH-PBC overlap syndrome can be obtained with UDCA and immunosuppression treatment.

Female ; Hepatitis, Autoimmune ; diagnosis ; drug therapy ; Humans ; Liver Cirrhosis, Biliary ; diagnosis ; drug therapy ; Male ; Middle Aged ; Prognosis ; Syndrome

Objective To probe into the pre-operative design and the operative approach dealing with anastomotic vein and superior sagittal sinus in patients with large meningiomas in the sagittal sinus and falx cerebri. Methods Thirty-five patients with large meningiomas in the sagittal sinus and falx cerebri, admitted to our hospital from January 2001 to December 2010, were chosen; their clinical data were analyzed retrospectively. The resection of the tumors by microsurgery (total or subtotal resection) was performed and intraoperative effective management of the sagittal sinus and falx cerebri was done. Results Resection was performed in these 35 patients, including Simpson grade Ⅰ in 21(60.0％), grade Ⅱ in 12 (34.2％), and grade Ⅲ in 2 (5.7％). Skull defect was noted in 5 patients. Unilateral　paralysis of limbs (muscle strength grade Ⅰ-Ⅳ) in 5; paralysis of both lower extremities (muscle strength grade Ⅰ-Ⅱ) in 1; good results were achieved after 1-6 months of hyperbaric oxygen, acupuncture and physiotherapy. During the follow-up period for 6 to 24 months, the tumor recurred in 2 with Simpson Ⅲstage resection (5.7％). Conclusion Designing a detailed pre-operative design according to the MRI,MRA, DSA and CTA, application of microsurgical techniques, avoidance of damage to the cerebral cortex and veins of central suleus and protection of the sagittal sinus are important factors that increase the success rate of surgical resection, reduce complications, prevent the tumor recurrence and improve the survival outcome in patients with parasagittal meningiomas.

Colorectal cancer (CRC) is one of the malignant tumors with the highest incidence and mortality in the world. The pathogenic mechanism of CRC has not been fully elucidated until now. Ubiquitination plays an important role in CRC development, and its effects mainly depend on E3 ubiquitin ligases, which could modify substrate proteins by ubiquitination, in turn altering their activity or mediating ubiquitin-proteasome degradation. Here research progress of the regulatory roles of RING (really interesting new gene) type and HECT(homologous to E6AP C-terminus) type E3 ubiquitin ligases in CRC cell proliferation, apoptosis, migration, invasion and chemotherapy sensitivity as well as targeted inhibitors of these E3 ligases are reviewed, providing new clues for the study of pathogenesis and targeted therapy of CRC.