OBJECTIVETo investigate the mechanism of how curcumin improves pulmonary vascular remodeling associated with chronic pulmonary arterial hypertension.

METHODSThe model of chromic hypoxia hypercapniapulmoary remodeling was made. Twenty-four male rats were randomly divided into 4 groups (n = 6): group I (normoxia control group), group II (hypxia and hypercapnia model group), group II (disodium cromoglycate control group), group IV (curcumin treated group). The last 3 group rats were put in a hypoxia cabin where the concentrate of O2 was 8% - 11% and the concentrate of CO2 was 3% - 5%, for 8 h a day and lasting 4 w in total. Group III rats were intraperitoneally injected with disodium cromoglycate (20 mg/kg) and group IV rats were administrated with curcumin by gavage (150 mg/kg). The morphological changes of pulmonary vessel walls and the ultrastructure of mast cells were observed by the optics microscope and the transmission electron microscope. Mast cells and its degranulation state were measured by toluidine blue staining and immunohistochemistry. Data were expressed as means ± SD (standard deviation) and analyzed with SPSS17.0 software.

RESULTS(1) By optics microscopy observation, the value of WA/TA was significantly higher in II group than other groups (P < 0.05). (2) Electron microscope showed that the endothelial cells of pulmonary arterioles in III and IV group were near to I group and the proliferation of pulmonary arterial media smooth cell layer and collagen fibers in adventitia was much lighter than those in II group. The membrane of mast cells was more intact in I, III, IV group than II group. (3) The number of mast cells, the degranulation rate of master cells and the number of positive tryptase stained cells in II group were significantly more than those in other groups. (P < 0.05).

CONCLUSIONCurcumin may inhibit the remodeling of pulmonary vessel induced by chronic hypoxia hypercapnia by mast cell regulation.

Animals ; Cell Degranulation ; Curcumin ; pharmacology ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; Hypoxia ; physiopathology ; Lung ; pathology ; Male ; Mast Cells ; physiology ; ultrastructure ; Pulmonary Artery ; drug effects ; Rats ; Rats, Sprague-Dawley ; Vascular Remodeling ; drug effects

BACKGROUNDAcute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.

METHODSA randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).

RESULTSEtoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34).

CONCLUSIONSEtoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).

Adult ; Aged ; Arthritis, Gouty ; drug therapy ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Indomethacin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Pyridines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use

OBJECTIVETo investigate the expression of E2F1 gene in patients with acute leukemia(AL) and its clinical significance.

METHODSSeventy-two AL patients treated in March 2015 -March 2016 in our hospital were selected, and 24 healthy people were selected as controls. RT-PCR and Western blot were applied to determine the level of E2F1 gene transcription and expression, and the statistical analysis was performed to reveal the clinical value of E2F1 gene.

RESULTSThe relative expression levels of E2F1 gene and protein in bone marrow of AL patients was higher than that in control group (P<0.05). The levels of WBC, β-MG and LDH in the patients with high expression of E2F1 gene were higher than those in patients with low expression of E2F1 gene(P<0.05), but the E2F1 gene expression did not correlate with sex, fever, fatigue, bone marrow blast ratio, peripheral blood blasts ratio (P>0.05). The complete remission (CR) of patients with low expression of E2F1 was significantly higher than that of patients with high expression of E2F1(P<0.05). And the drug resistance in the patients with low expression of E2F1 gene was lower than that of patients with high expression of E2F1 gene (P<0.05). The expression level of E2F1 gene decreased significantly in patients with symptomatic remission after treatment (P<0.05). The expression levels of E2F1 gene in M1, M2 and M5 patients decreased significantly after treatment (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in the patients with low expression of E2F1 gene were higher than those in patients with high expression (P<0.05). Multivariate Cox regression analysis showed that the age and E2F1 gene were the independent influencing factors of OS (P<0.05); the sex and E2F1 gene were the dependent factors of DFS (P<0.05).

CONCLUSIONThe expression level of E2F1 gene in patients with AL has been found to be higher, the higher level of E2F1 gene closely relates with AL patients, E2F1 gene can be used as a biological target for the clinical treatment of AL.

Acute Disease ; Blood Cell Count ; Bone Marrow ; E2F1 Transcription Factor ; Humans ; Leukemia ; Prognosis ; Remission Induction

Objective To explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock. Methods A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group. Results A total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased (P < 0.05), with highest relative expression of BCL-2 in shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased (P < 0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion (P < 0.05). Conclusions HDACIs and autogenous transfusion can all protect the spleen injury because of the severe hemorrhagic shock. Its molecular mechanism may be related to the regulation on the expression of BCL-2/BAX and caspass3, which may affect the apoptosis process of cells.

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with lifestyle control on hepatic fat status, hepatic enzymology, glycolipid metabolism and anthropological parameters in patients with obese nonalcoholic fatty liver disease(NAFLD). METHODS: A total of 90 patients with obese NAFLD were randomized into an observation group (45 cases, 4 cases dropped off) and a control group (45 cases, 1 case dropped off). Lifestyle control was implemented in the control group. On the basis of the treatment in the control group, acupuncture was applied at Zhongwan (CV 12), Quchi (LI 11), Shuifen (CV 9), Huaroumen (ST 24), Daheng (SP 15), Guanyuan (CV 4), Qihai (CV 6), etc. EA was provided at Huaroumen (ST 24) and Daheng (SP 15) with dilatational wave, 2 Hz/100 Hz in frequency, 30 min each time, once every other day, 3 times a week. The treatment for 12 weeks was required in both of the two groups. Hepatic fat status [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)], hepatic enzymology [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)], glycolipid metabolism and insulin sensitivity [fasting plasma glucose (FPG), fasting serum lisulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)] and anthropological parameters [body weight (BW), body mass index (BMI), fat percentage (FP), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)] in the two groups were observed before and after treatment. RESULTS: ①Compared before treatment, hepatic CAP, LSM, serum ALT, AST and GGT after treatment were obviously reduced in the two groups (<0.05, <0.01). After treatment, CAP and ALT in the observation group were lower than the control group (<0.05). ②Compared before treatment, FINS, HOMA-IR, LDL-C, TC and TG after treatment were obviously reduced in the two groups (<0.05, <0.01),while the levels of HDL-C were increased (<0.05). Compared before treatment, FPG after treatment in the observation group was reduced (<0.05). Compared with the control group, FINS, HOMA-IR, TC and TG in the observation group were lower than those in the control group after treatment (<0.05). ③Compared before treatment, BW BMI, FP, WC, HC, WHR after treatment were obviously reduced in the two groups (<0.01). After treatment, WC and WHR in the observation group were lower than the control group (<0.05). CONCLUSION Electroacupuncture combined with lifestyle control can effectively treat obese nonalcoholic fatty liver disease, and present better therapeutic effect on hepatic fat status, glycolipid metabolism, insulin resistance, WC and WHR.