BACKGROUND:Osteoarthritis,often accompanied by cartilage abnormal signal transduction,suggesting that intracellular signal transduction may play an important role in osteoarthritis genesis and development.OBJECTIVE:To review recent advances in the research of Notch signaling pathway,and explore the mechanisms of chondrogenic differentiation of bone marrow mesenchymal stem cells and its role in cartilage development and chondrogenesis.To analysis the role of dysregulated Notch signaling in the development of osteoarthritis.METHODS:Pubmed was undertaken to identify the relevant articles published from March 1919 to February 2009 with the key words of"Notch signaling pathway,osteoarthritis,chondrocytes,chondrogenesis,bone marrow stem cells"in English.Simultaneously,CNKI Database was searched for relevant articles published from February 2004 to September 2008 with the key words of"Notch signaling pathway,osteoarthritis,chondrocytes,chondrogenesis,bone marrow stem cells"in Chinese Articles with the Notch signaling pathway-related research,Notch signaling pathway of bone marrow-derived mesenchymal stem cells,differentiation of cartilage relative to the mechanism studies,and the Notch signaling pathway disorders and osteoarthritis research were included,Reproducibility articles were excluded Development regulation of articular cartilage and cartilage cell proliferation were considered as evaluation indexes.RESULTS AND CONCLUSION:Of 632 articles retrieved,30 were included in our study according to the inclusive and exclusive criteria.The Notch pathway is a highly consewed signaling mechanism involved in many processes determining cell fate during development and maintenance of homeostasis of mature tissues in the adult organism.Activation of Notch occurs following Notch receptor/ligand engagement upon cell-cell contact,which initiates translocation of the Notch intracellular domain to the nucleus and activation of target genes.It has been demonstrated that the Notch signaling plays an important role in regulating articular cartilage development and chondrocyte proliferation and differentiation In recent studies abnormality of notch signaling was also found in disease,which suggests that notch signaling is involved in osteoarthritis initiation and development.Further study of the specific mechanism of notch signaling in the initiation and development of osteoarthritis will enable us to develop targeted approaches in the treatment of osteoarthritis,thus bring more strategies in the future treatment of osteoarthritis.

Objective To understand the status and influencing factors of benefit finding in patients with cancer.Methods 350 patients with cancer were collected with convenience sampling method from two Jiangsu hospitals.All patients received a questionnaire survey.Multiple linear regression analysis was used to analyze the influencing factors of benefit finding in patients with cancer.Results (1) The score of benefit finding in patients with cancer was statistically significant in different frequency of physical exercise (F=8.37,P=0.00),different character (F=3.04,P=0.04) and different educational level (F=2.91,P=0.03).(2) There was a positive correlation between benefit finding(78.53± 10.50) and communication with physicians(7.27±2.19),medical coping(43.48±4.50),optimism(17.33±2.24) and social support(44.81±3.91)(r=0.31,0.35,0.29,0.23,all P＜0.05) in patients with cancer.The benefit finding in patients with cancer was negatively correlated with depression(8.59± 1.83) (r=-0.37,P＜0.05).(3) Multiple linear regression analysis results showed that medical coping modes-confrontation,objectively social support and utilization,physical exercise,depression,communication with physicians and character were the factors influencing benefit finding in patients with cancer(△R2 =28％,P＜ 0.05;△R2 =5.5％,P＜ 0.05;△R2 =3.1％,P＜ 0.05;△R2 =1.9％,P＜0.05;△R2 =1.7％,P＜0.05;△R2 =1.0％,P＜0.05;△R2 =1.1％ P＜0.05),which explained 42.0％ of the total variance.Conclusion Medical coping modes-confrontation,objectively social support and utilization,physical exercise,depression,communication with physicians and character are the factors influencing benefit finding in patients with cancer.

Objective: To investigate the effect of medication on left ventricular myocardial matrix remodeling in neuroendocrine hypertensive rats and the mechanism and inhibitive method thereof. Methods: A neuroendocrine hypertensive model was established with adult Wistar rat. A total of 34 rats were randomly divided into four groups: parzosin (Hα), cilazapril (Hace), pentoxifylline(Hptx) and hypertensive control group(Hc). Ten normal-tensive Wistar rats were used as normal control (Nc). The systemic blood pressure, serum procollagen type Ⅲ level, serum TNF-α level, collagen volume fraction(CVF) were detected. Results: In Hace group, systolic pressure, left ventricular weight, the levels of serum procollagen type III and TNF-α were all reduced obviously compared to those in Hc group(P < 0.05). In Hα group, the systolic pressure and left ventricular weight were reduced obviously compared to those in Hc group(P < 0.05), however, the levels of serum procollagen type III and TNF-α were higher than those of Nc group(P < 0.05). In group Hptx, the systolic pressure and left ventricular weight were not decreased, while the levels of serum procollagen typeⅢ,TNF-α and CVF were reduced to normal levels. Conclusion:The angiotensin coverting enzyme inhibitor is the effective agent to reverse myocardial fibrosis, which can be achieved mostly by the inhibition of AngⅡ. Pentoxifylline may inhibit and reverse myocardial fibrosis which correlated with inhibiting TNF-α.

Objective:To investigate the changes of left ventricular mass index(LVMI),plasma brain natriuretic peptide (BNP),interJeukin-6(IL-6)and interleukin-10(IL-10)in patients with congestive heart failure(CHF),and their values in risk stratification and prognostic evaluation of CHF thereof.Methods:Ninety-five patients with CHF in accordance with 2001ACC/AHA guidelines were enrolled and stratified as stage A(n=21),B(n=23),C(n=31)and D(n=20).The levels of plasma BNP,IL-6 and IL-10 were measured and compaired with those in 20 healthy subjects(control group).The patients were followed up every three months in two years.The end point was the rehospitalization and the cardiac death.Results:(1)The level of LVMI increased early in patients with CHF at stage B.(2)The plasma BNP levels were initially elevated in CHF patients at stage B,and the concentrations of BNP closely paralleled disease severity.(3)The levels of plasma IL-6 and IL-10 were increased,and the ratio of IL-10/IL-6 was decreased,with the progression of CHF at stage C and D.The plasma BNP level was positively correlated with the levels of IL-6 and IL-10.(4)The new CHF stratification was surperior to NYHA functional classification in regard to CHF prognosis prediction.(5)Multivariate COX regression analysis showed the levels of BNP and IL-6 were the independent risk factors in prognostic evaluation(P＜0.01,P=0.026).(6)Patients in high-risk groups stratified by the combination of BNP and stage classification had obviously higher end point events rate.Conclusion:(1)LVMI was a better marker for the evaluation of left ventrieular remodeling.(2)The intrinsic mechanism of CHF progression was inflammatory reaction deterioration.(3)BNP was a good marker in predicting onset and prognosis of CHF.The combination of BNP and the stage classification could improve the prognostic evaluation in patients with CHF.

Objective: Enriching secoiridoid glycoside in Gentiana manshurica kitag. Methods: Gentiana manshurica kitag. was extracted with 70% EtOH by cold macerating and purified with AB 8 macroreticular resin. Results: The content of gentiopicrin in the extract is 28.69%. Conclusion: AB 8 macroreticular resin fits in purification of water soluble secoiridoid glycoside in Gentiana manshurica kitag.

Objective:To introduce a 2-stage treatment protocol for the management of temporomandibular joint ankylosis with sec-ondary deformities in adults.Methods:24 adult patients (9 males and 15 female)(30 joints)at the average age of 26.1 years un-derwent TMJ reconstruction as the initial surgery,followed by orthodontic treatment and correction of secondary deformities as the sec-ond surgery.Clinical outcome was assessed based on maximal incisal opening,radiography and medical photography.Results:Skele-tal deformities were significantly improved in all patients,satisfactory occlusion was achieved with the orthodontic treatment,average maximal incisal opening increased from 3.4 mm to 32.5 mm(P <0.05).Conclusion:The 2-stage treatment protocol is an effective approach for management of TMJ ankylosis with secondary deformities in adult patients.

An ultra-high performance liquid chromatography-tandem mass spectrometry ( UHPLC-MS/MS ) method was developed and validated for the simultaneous determination of 9 kinds of trace endocrine disrupting chemicals in biological samples using ultrasonic-assisted extraction followed by purification with gel permeation chromatography ( GPC) and silica gel columns. The sample extracts were purified by Bio beads S-X3 GPC columns with cyclohexane/ethyl acetate (1:1, V/V) as mobile phase, and the target compounds were eluted in the fraction of 12-28 mL retention volume. Electrospray ionization source operated in positive mode and atmospheric pressure chemical ionization source operated in negative mode were used for mass spectrometric detection. Data acquisition was carried out in multiple reaction monitoring mode. Recoveries were predominately within 65 . 2%-118 . 0%. Method quantification limits were 0 . 1-9 . 7 ng/g dw ( dry weight ) . This method was successfully applied to the analysis of the target endocrine disrupting chemicals in carps collected from the Pearl River. with the exception of carbanilide and triclocarban, the rest analytes were detected in fish tissue samples, with the concentrations varied within the range of 0. 1-22. 6 ng/g dw.

Objective To study the dynamic changes of injury and apoptosis of liver induced by lipid metabolic disturbance in the rats with diabetes mellitus and their correlation with the expressions of sterol regulatory element binding protein-1c(SREBP-1c)and c-Jun N-terminal kinase(JNK).Methods Experimental animals were randomly divided into 4 groups:diabetesgroup(n=64)induced by high-carbohydrate and high-fat diet plus intra-peritoneal streptozeotocin(STZ)injection,normal control(n=37)fed regular diet and receiving citric buffer solution injection,STZ group(n=42)fed regular diet and receiving STZ injection,high gluaxeard fat group(n =37)receiving citric buffer solution injection.Body weight,liver weight,fasting plasma glucose(FPG),fasting insulin(FINS),triglyceride(TG),total cholesterole(TC),alanine transaminase(ALT),asparate transaminase(AST)were detected at various time intervals.The changes of liver histopathology and ultrastructure were observed by ES and Sudan Ⅲ stanings,transmission electrom microscope.The expressions of SREBP-1c and JNK mRNAs and proteins were determined by real time-PCR methods.Apoptosis was analyzed by flow cytometry.Results The diabetic rats showed much lower body weight(P＜0.05)and higher liver weight than controls,STZ group and high-carbohydrate and fat group(P＜0.05),while showed higher levels(P＜0.05)of serum FPG,FINS,TG,TC,ALT,AST.Diabetic rats exhibited fatty degeneration of liver cells accompanied by inflammatory infiltration and fibrosis.Organelle structures were more disturbed and apoptosis was more obviou along with longer course of disease.The expressions of SREBP-1c,JNK proteins and mRNA were significantly enhanced.The rats fed high-carbohydrate and fat diet also showed similar liver lesions and enhanced SREBP-1c,J NK proteins and mRNA expressions but not as severe as in diabetes group Conclusions Insulin resistance and high blood glucose may induce diabetic hepatopathy.The high expressions of JNK and SREBP-1c may play important roles in liver lipid metabolism disorders and cell apoptosis.

Objective To study the roles of abnormal expressions of Caspase-8 and protein kinase C(PKC)-β of cardiomyocytes in the development of the apoptosis of cardiomyocyte in diabetic rat. Methods Rats were divided into 4 groups:(1)normal control (NC, n=37),(2)rats given STZ injection and normal diet(STZ,n= 42), (3) rats fed with high fat and high sngar ( HFS, n= 37), (4)rats given STZ injection and high fat and high sugar diet (type 2 DM, n=64). Plasma glucose, insulin and lipids were detected. At the end of experiment, the animals were sacrificed, and their hearts were examined. Pathological changes were observed and the expressions of Caspase-8, PKC-β mRNA were determined by real time-PCR method; apoptosis was analyzed by flow cytometry. Results (1)The body weight was higher in HFS group than in other three groups, and progressively decreased in type 2 diabetes group. The glucose level was highest in diabetic group, and was similar between groups of HFS and NC. (2)The apoptosis showed tendency to ascend during course of disease in diabetes model group. (3)The expressions of Caspase-8 and PKC-β mRNA were significantly enhanced in diabetes model group than in normal control group, and had a tendency to ascend during the course of disease.(4)The myocardial cells of the diabetic rats were rarified and swelling, fibrosis was observed. (5)At the 16th week, the level of plasma glucose was correlated positively with the expressions of Caspase-8 and PKC-β mRNA. Conclusions The enhancement of expressions of Caspase-8 amd PKC-β may play iportat rols in the pathogenesis of diabetic cardiomyopathy,in which apoptosis of the cardiomyocytes increased.

Objective To study the development of cardiomyopathy complicated with type 2 diabetes mellitus in the rats. Methods The 120 health male Sprague-Dawley rats, weighing 180-220 g, were divided into 4 groups: (1)STZ-modeled diabetes, fed with high-carbohydrate plus high-fat diet (n=40);(2)fed with regular diet (n=30);(3)and (4)SD rats with citrate buffer instead of STZ injection, fed with high-carbohydrate and high fat diet (n= 25);and fed with regular diet (n= 25); At the 4th, 8 th, 12 th and 16 th week after the intra-peritoneal injection of STZ solution or citrate buffer solution, rats from each group were scarified and examined. Results There were no significant differences in body mass and blood glucose among those groups after one week of feeding (P＞0. 05).After 4 weeks of feeding before injection, the body mass, fasting insulin (FINS) and insulin sensitive index (ISI) were obviously increased in diabetes group and high-carbohydrate plus high-fat control group as compared with STZ control group and normal control group (P＜ 0. 05). There were no significant differences between diabetes group and high-carbohydrate plus high-fat control group,between STZ control group and normal control group (P＞0. 05). After injection, the blood glucose,body mass, ventricular mass, TG and TC were higher in diabetes group and high-carbohydrate plus high-lipid control group than in STZ control group and normal control group (P＜0.05). The above parameters were much higher in diabetes group than in high-carbohydrate plus high-lipid control group, but there was no difference between STZ control group and normal control group (P＜0. 05).Pathological examination showed that the weight of the heart was significantly increased, the myocardial cells were hypertrophied accompanying degenerative changes and apoptosis, the interstitial collagen fibers were hyperplasia in the diabetic rats. The ultrastructures also presented severe damage.These changes indicated that cardiomyopathy was induced in the diabetes rats. Although similar changes were found in the rats fed with high-carbohydrate plus high-fat diet, they were much less significant than those in the diabetic rats. Conclusions Cardiomyopathy developes frequently in the rats with type 2 diabetes mellitus induced by feeding high-carbohydrate plus high-lipid diet and single intra-peritonial injection of 30 mg/kg STZ solution.