G protein-coupled bile acid receptor 1(TGR5) is a specific membrane receptor of bile acids , playing an important role in the bile acid signaling network .Its activation has been proved to increase the glycemic control , regulate of blood lipid balance , enhance energy expenditure , exert anti-inflammatory actions and so on .It suggests that TGR5 may play an important role in metabolic diseases .

Aim To investigate if LPS increases the sterol regulatory element binding proteins ( SREBPs ) cleavage-activating protein ( SCAP )-SREBP2 expres-sion by activation of mTOR signal pathway in THP-1 macrophages , upgrading LDLr level , causing foam-cell formation .Methods THP-1 macrophages were incu-bated in serum free medium in the absence of 5 mg?L-1 LDL alone , or 5 mg? L-1 LDL plus 200 μg? L-1 LPS, or 5 mg? L-1 LDL plus 200 μg? L-1 LPS plus 10 μg? L-1 rapamycin .Morphological examination of macrophages was performed with Oil Red O staining . Expression changes of LDLr , SREBP2, SCAP, S6K1 and mTOR mRNA were detected by real time quantita-tive polymerase chain reaction ( PCR ) .Western blot was used to analyze protein expression changes of LD-Lr, S6K1 and mTOR.Translocation of SCAP-SREBP2 complex from the endoplasmic reticulum ( ER ) to the Golgi was determined by confocal microscopy .Results LPS enhanced transformation of THP-1 macrophages into foam cells by increased uptake of lipid as evi-denced by Oil Red O assay .LPS increased mRNA lev-els of LDLr, SREBP2, SCAP, S6K1 and mTOR ( P <0.05) .Rapamycin reduced the mRNA levels of LDLr , SREBP2,SCAP,S6K1 and mTOR induced by LPS ( P<0.05 ) .Western blot demonstrated that LPS also caused over-expression of protein of LDLr , S6K1 and mTOR(P<0.05).Rapamycin reduced the expression of protein of LDLr, S6K1 and mTOR induced by LPS ( P <0.05 ) .Confocal microscopy demonstrated LPS caused an escape of SCAP-SREBP2 complex from the ER to the Golgi .Rapamycin inhibited the translocation of SCAP-SREBP2 complex from the ER to the Golgi . Conclusions Inflammatory stress increases SCAP/SREBP2 expression by activation of mTOR signal path-way, resulting in an escape of SCAP-SREBP2 complex from the ER to the Golgi , furthermore elevating LDLr expression and causing foam-cell formation .Rapamy-cin reverses the activation of mTOR signal pathway and decreases lipid deposition in THP-1 macrophages in-duced by LPS .

Objective To discuss operative treatment of old fractures of pelvis. Methods Since February 2000, 14 cases with old fracture of pelvis have been treated in our hospital with operative scar or callus settlement, traction and reduction, and internal fixation. Results All patients were followed up from 6 months to 3 years and 6 months. According to such indexes as pelvic shape, length difference between lower limbs, gait, and radiogram, the scores were excellent in 8 cases, fine in 4 and poor in 2, with the excellent and good rate being 85.7%. Conclusion With reasonable design and appropriate method, operative treatment is fit for old fractures of pelvis because it can avoid severe disability and improve the quality of life of the patients.

Objective To study an improved isolated method of single human atrial myocytes.Methods Enzyme digestion method was used to isolate single myocytes from human atrial and whole-cell patch clamp technique was used to record small conductance calcium activated potassium current.Results This method obtained a large number of atrial myocytes.The total amount of atrial myocytes in SR group was 320±30 while AF group was 230±20 and the difference was statistically significant(P<0.01).In this study,a large number of simple and striated single atrial myocytes were obtained,and a typical small-conductance calcium-activated potassium channel current was recorded on the isolated atrial myocytes.Conclusion The established isolated method is simple,stable and effective.We can acquire a large amount of single atrial myocytes with good quality.

To investigate effects of tumor necrosis factor-alpha(TNF-alpha) and granulocyte-colony stimulation factor(G-CSF) on the transplantation rate of rabbit mesenchymal stem cells (MSCs) through intracoronary injection. Japanese white ears rabbits (2-3 months old) were used as myocardial injury models by intravenously injecting adriamycin, then they were divided into three groups randomly: (1) Blank group, (2) TNF-alpha group; (3) G-CSF group. There were 7 rabbits each group. Before transplantation, MSCs and rabbit models were neither intervened by cytokine in blank group; in TNF-alpha group, rabbits were injected TNF-alpha (5 microg/kg) through ear-edge vein one day before transplantation, MSCs were pretreated by TNF-alpha (10ng/ml)12 hours before transplantation. In G-CSF group, rabbits were injected G-CSF(10 microg/kg) intramuscular each day 3 days before transplantation. MSCs were pretreated by G-CSF(10 ng/ ml) 12 hours before transplantation. Separated by density gradient centrifugation and labeled by 4,6-biamidine-2-phenyliodole (DAPI) after cells expanded in vitro, MSCs were then transplanted through the root of aorta when the ascending aorta occluded above the sinus aortae. Myocardial pathological sections were made after 4 weeks and count transplanted cells under laser scanning confocal microscope and statiscally analyze. The amount of cells transplanted in rabbit myocardial were much more in TNF-alpha group G-CSF group than in blank group, there was statistically significant difference (P < 0.001). It sugested that TNF-alpha and G-CSF intervened the cultured MSCs, and animal model of myocardial injury could elevate the transplantation rate of intracoronary injection rabbit mesenchymal stem cells. The mechanism may have relation to that cytokine can enhance the attachment of MSCs to cardiac microvascular endothelium (CMVE).
Animals ; Cell Adhesion ; drug effects ; Coronary Vessels ; pathology ; Endothelial Cells ; pathology ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Myocardial Ischemia ; pathology ; therapy ; Rabbits ; Tumor Necrosis Factor-alpha ; pharmacology

Stem cells transplantation is a promising strategy for treating myocardial infarction and/or chronic heart failure; however, with respect to nonischemic heart failure, there are some limitations inherent in the current methods of transplantation. In this study, we investigated the feasibility of a novel method, i. e. transplantation through the root of aorta when the ascending aorta occluded above the sinus aortae. Japanese white ears rabbits were used as chronic heart failure models by intravenous injection of adriamycin. Autologous bone marrow mononuclear cells (MNC) were infused into the root of aorta when the ascending aorta was occluded by a couple of balloons above the sinus aortae. After 4 weeks, ejection fraction was significantly improved in MNC group. In conclusion, we have developed a unique method for efficient and safe cell transplantation based on infusion in aorta. This method, potentially suitable for nonischemic heart failure and could be used to achieve even and global supply of cells in heart.
Animals ; Aorta ; surgery ; Doxorubicin ; Feasibility Studies ; Heart Failure ; chemically induced ; surgery ; Rabbits ; Stem Cell Transplantation ; methods

To assess the changes of sarcolemma Na+/K+ ATPase (CMNKA) and sarcoplasmic reticulum membrane Ca2+ ATPase (SERCA) activities after stem cells transplantation in heart failure. Rabbit was used as heart failure model by intravenously injecting adriamycin. Autologous bone marrow mononuclear cells (BMCs), bone marrow mesenchymal stem cells (MSCs) or skeletal myoblasts (SMs) were introduced into coronary arteies through the root of aorta when two balloons occluding just above sinus of Valsalva. After 4 weeks, left ventricular ejection fraction (LVEF)was evaluated by echocardiography, and the activities of CMNKA and SERCA were measured by colorimeter. In BMCs (n=8)and MSCs (n=8) group, LVEF were significantly improved (P < 0.05). No significant improvement were seen in SMs group (n=6) compared to sham group (n=8). The CMNKA activity in all stem cells groups was significantly increased compared to sham group (P < 0.05). Meanwhile, in comparison with sham group, the incremental tendencies of SERCA activity were seen in stem cells groups. In conclusion, stem cells transplantation could increase the activities of CMNKA and SERCA in heart failure, a possible mechanism to improve heart function.
Animals ; Doxorubicin ; Female ; Heart Failure ; chemically induced ; enzymology ; therapy ; Male ; Myocardium ; enzymology ; Rabbits ; Random Allocation ; Sarcolemma ; enzymology ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Stem Cell Transplantation

To investigate the feasibility of introcoronary cell infusion into nonischemic heart failure (HF) heart and whether different types of stem cell transplantation would affect heart function to a similar degree. Japanese white ears rabbits were used as HF models by intravenous injection adriamycin. Autologous bone marrow mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts (SMs) or culture medium were infused into coronary arteries respectively by occluding the root of ascending aorta. The mortality during and 4 weeks after the procedure the mortality was 7.1% and 16.7% respectively. After 4 weeks, the ejection fraction (EF) in BMCs group had significant improvement (P < 0.05, n=8). No significant difference was seen in MSCs (n =8), SMs (n=6) and sham groups (n=8) compared with pretransplantation (P > 0.05). In sham group,the left ventricular endostolic diameter (LVED) had significant enlargement (P < 0.05), No significant difference was seen in MBCs, MSCs and SMs groups compared with pretransplantation (P > 0.05). Immunofluorescence revealed de novo expression of cardiac troponin I in BMCs and MSCs groups, cardiac troponin I was not detected in SMs group. In conclusions, intracoronary cell transplantation could provide effective cell delivery into dilated cardiomyopathy hearts and could be a useful strategy for treating CHF, BMCs cell transplantation may be the first choice in all the above cell types.
Animals ; Bone Marrow Transplantation ; Chronic Disease ; Coronary Vessels ; Heart Failure ; physiopathology ; surgery ; Infusions, Intra-Arterial ; Mesenchymal Stem Cell Transplantation ; Myoblasts, Skeletal ; transplantation ; Rabbits ; Random Allocation ; Stem Cell Transplantation ; methods ; Troponin ; metabolism ; Ventricular Function, Left ; physiology

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost