A series of novel tetrahydrocarboline derivatives was designed and synthesized in order to discover more potent peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual regulators. The structures of these compounds were confirmed by 1H NMR and HR-MS; their PPAR-regulating activities were evaluated in vitro. Compounds 6h, 6n, 6p and 6q exhibited more potent PPARalpha agonistic activities than the control drug WY14643, while compounds 60, 6g, 6i and 6q exhibited more potent PPARgamma agonistic activities than the control drug rosiglitazone. Compound 6q was discovered as a potent PPARalpha/gamma dual agonist and deserves further investigation.
Animals ; Carbolines ; chemical synthesis ; chemistry ; pharmacology ; Cells, Cultured ; Drug Design ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; PPAR alpha ; agonists ; PPAR gamma ; agonists ; Peroxisome Proliferator-Activated Receptors ; agonists ; Pyrimidines ; metabolism ; Structure-Activity Relationship ; Thiazolidinediones ; metabolism ; Transfection

Thiazolidinediones (TZDs) are currently the only recognized insulin sensitizers available for the clinical treatment of type 2 diabetes. Although their advantages are recognized, the profiles of numerous adverse effects hinder the continued use of these drugs. Peroxisome proliferator-activated receptor γ (PPARγ) is known as a receptor for TZDs, and its underlying mechanisms of pharmacological actions and adverse effects have been deeply explored. To maximally preserve the PPARγ-mediated insulin sensitizing effects and reduce the occurrence of related adverse effects, the concept of "selective PPARγ modulators (SPPARMs)" has been proposed and developed, guiding the development of new drugs. In this review, we summarize the recent research progress in the definition of SPPARMs, the candidate classification and the molecular underpinnings, as well as present the discovery of the YR series compounds as an example, and discuss the potential application prospects of SPPARMs.

ObjectiveTo summarize the early clinical experience of the extracorporeal membrane oxygenation (ECMO) for protecting the liver donation after cardiac death (DCD).Methods Review and analysis the clinical data of 17 cases of liver transplantation with the donors from Chinese citizen after cardiac death from July 2009 to May 2011 in our liver transplantation center,and comprehend the primary diseases and the relevant index of the donors,the flow-sheet of donation and obtain of the organs from the donation after cardiac death,and the apply methods of extracorporeal membrane oxygenation during those processes.ResultsAll 17 cases had been diagnosed as brain death before,and waited for cardiac death,so all were clearly the donation of brain death plus cardiac death(DBCD).During the processes waiting for cardiac death,extracorporeal membrane oxygenation were introducted in every case,and the using time were 51-380 (mean 187)min.The donation after brain death plus cardiac death (DBCD) were all harvested liver donors and were transplanted to 17 receivers respectively.In our center,there was no operational death in liver transplantation in this series.The post-operation liver function recovered satisfactory,without transplant liver non-function or recovering delay.One case died of the pulmonary infection one month later after operation,and the other 16 cases all survived and were followed up to now.The longest survival time was 29 months.ConclusionThe donation after brain death plus cardiac death (DBCD) was the special donation type for citizen in China.The extracorporeal membrane oxygenation (ECMO) could well control the warm ischemia for protecting the liver donor just without ethics dispute.So,the using of the extracorporeal membrane oxygenation (ECMO) for the liver donation after cardiac death(DCD)of citizen in our China have very important contribution.

Objective:To investigate the application value of lauromacrogol in the treatment of varicose veins of lower limb.Methods:The medical records of 75 patients (75 affected limbs) with varicosis of great saphenous vein of lower limbs confirmed between September 2013 and September 2015 were analyzed retrospectively.According to the treatment regimen,the patients were divided into two groups.Among them,33 cases (33 limbs) treated by ultrasound guided injection of foam sclerosing agent lauromacrogol were included in the lauromacrogol group while 42 cases (42 limbs) treated by high ligation of great saphenous vein combined with stripping were included in the operation group.The operation time,intraoperative blood loss,off-bed time,treatment costs and incidence of postoperative complications were recorded.Patients were followed up for 6 to 12 months after operation,and the recurrence rate was recorded.Results:The operation time,off-bed and length of hospital stay of the lauromacrogol group were shorter than those of the operation group;the intraoperative blood loss and hospitalization expenses were less than those of the operation group (P＜0.05);The incidence rates of subcutaneous hematoma and skin numbness in the lauromacrogol group were significantly lower than those in the operation group (P＜0.05);The 12-month recurrence rate in the lauromacrogol group (12.12％) was lower than that in the operation group (33.33％)(P＜0.05).Conclusion:Injection of foam sclerosing agent lauromacrogol is an alternative minimally invasive therapy for treating varicosis of great saphenous vein of lower limbs.

Objective To establish nucleic acid testing techniques for detecting Nipah virus (NiV) and Hendra virus (HeV), and to test the NiV and HeV in peripheral blood collected from domestic pigs, cows and goats in Chongqing. Methods Peripheral blood samples of 580 domestic pigs, 250 cows, 180 goats were collected from Chongqing since June 2007 to June 2008. The lymphocytes were separated by density gradient centrifugation and total RNA was extracted using Trizol method for detection of NiV and HeV with one-step real-time RT-PCR. Sequence identification and analysis were performed for positive PCR prod-ucts. Virus isolation and culture were adopted for positive samples, and epidemiologic reports were submit-ted. Results Nucleic acid detections searching for NiV and HeV were successfully performed in animal blood samples collected from Chongqing. "Takeoff points" were not found in fluorescence amplification curves of all samples. Curves kept the same slope, and assays were judged as negative. Conclusion Until now, Neither NiV or HeV infection has been found in domestic animals blood samples collected from Chongqing, which suggest a lower possibility of outbreaks of Nipah disease and Hendra disease in Chongqing in the near future.

Objective To investigate the epidemiology of BDV infection in Yili horses and Yili donkeys and to analyze phylogenetic source of BDV in Yili area, Xinjiang. Methods We established fluo- rescence quantitative nested RT-PCR to detect BDV p24 segment in peripheral blood mononuclear cells (PBMCs) of 518 Yili horses and 206 Yili donkeys in Yili area, Xinjiang. Positive products were validated by detecting BDV p40 segment and plasmid to preclude the contamination, and were sequenced to analyze the homology of gene sequence, amino acid sequence and phylogenetic tree. Results The positive rates of BDV infection in PBMCs of 518 Yili horses and 206 Yili donkeys were 0.97% and 1.94%, respectively. The results of BDV p40 segment verification were positive in all of the samples of BDV p24 positive. All the samples tested were not contaminated by plasmid. There was a homology of the gene sequence of positive PCR samples with strain He/80. And the gene sequence revealed more than 93% identical to H1766 and strain V. Conclusion Our study suggested BDV natural infection in Yili horses and Yili donkeys. The en- demic BDV had a high degree of identity to strain He/80.

OBJECTIVETo discuss the land surface temperature's effect on supervising the areas with snails, comparing the land surface temperature (LST) of the areas with snails with the LST of those without snails.

METHODSChoosing the lake areas of farmland in Jiangxi Province and the beach in the bank of Ganjiang, dividing into four areas according to snails. Picking up the normalized difference vegetation index (NDVI) and LST from the remote sensing data to find the difference between the areas with snails and the areas without snails, so as to illuminate the effects of the LST on distinguishing the areas with snails.

RESULTSThe NDVI of Dongfeng Wei (an area from farmland to lake) was 0 - 0.20, the NDVI of the areas with snails was 0.20 - 0.40. The NDVI of four areas is different (chi(2) = 104.69, P < 0.01). The LST of Dongfeng wei was 24 - 30 degrees C, Wuzhoutou without snails is 23 - 28 degrees C, Wuzhoutou with snails is 22 - 26 degrees C, Changjiangzhou was 20 - 24 degrees C. The LST of four areas is different (chi(2) = 115.23, P < 0.01). The analysis farther indicates the NDVI of areas without snails was lower than that of areas with snails, but the LST was higher.

CONCLUSIONThe NDVI and (or) the LST should be significantly different between the areas with snails and the areas without, it might be concluded that the LST should be a indication to some extent on judging whether some areas may be fit for snails.

Animals ; Environmental Monitoring ; Geographic Information Systems ; Snails ; physiology ; Spacecraft ; Temperature

OBJECTIVETo evaluate the clinical significance of MAIPA test in diagnosis of idiopathic thrombocytopenic purpura (ITP) and in the differential diagnosis of antoimmune thrombocytopenias from nonimmune thrombocytopenias.

METHODSA total of 321 thrombocytopenic patients (118 males, 203 females) from 14 centers were studied. A modified monoclonal antibody immobilization of platelet antigen (MAIPA) method was used to detect the platelet glycoprotein-specific autoantibodies (anti-GP IIb/IIIa, anti-GPIb/IX) to double-blindly evaluate its sensitivity and specificity for the diagnosis of ITP and to investigate the impact of the antibodies on platelet count.

RESULTSThe results showed that for the diagnosis of ITP, anti-GPIIb/IIIa, anti-GPIb/IX and both of them had the sensitivity of 39.75%, 32.64% and 55.23%; the specificity of 97.56%, 93.94% and 92.68%; the positive predictive value of 97.94%, 93.98% and 95.65%; the negative predictive value of 35.71%, 32.35% and 41.53%; and the total efficiency of 54.51%, 48.29% and 64.80%, respectively. The positivity of the autoantibodies in immune thrombocytopenias was incredibly higher than that in nonimmune thrombocytopenias. The platelet counts in the immune thrombocytopenias with autoantibody positivities were significantly lower than those without the autoantibodies. The platelet counts were negatively correlated with the concentration of the autoantibodies. The levels of anti-GPIIb/IIIa or anti-GPIb/IX or both of them dropped or disappeared in patients being responsive to steroid therapy.

CONCLUSIONMAIPA assay is proved to be of great value for the diagnosis of ITP and for differential diagnosis of immune thrombocytopenias from nonimmune thrombocytopenias.

Antibodies, Monoclonal ; immunology ; Antigens, Human Platelet ; immunology ; Autoantibodies ; immunology ; Blood Platelets ; Humans ; Prospective Studies ; Purpura, Thrombocytopenic, Idiopathic ; immunology

OBJECTIVETo assess the clinical value ofprocalcitonin in cirrhotic patients with severe infection by comparing the serum procalcitonin levels in those patients with and without liver cirrhosis when suffering from sepsis.

METHODSA total of 225 septic patients were included in the study,including 91 patients without hepatopathy, 80 patients with cirrhosis, and 54 patients with chronic liver disease. The serum procalcitonin level was measured in all patients and statistically assessed for correlation with relevant clinical biochemistry indicators. The t-test, ANOVA test, Mann-Whitney U test, chi-square test and Spearman's correlation analysis were used for statistical analyses.

RESULTSThe patients with cirrhosis showed significantly lower serum procalcitonin levels (0.84 (0.32-3.44) ng/ml) than the patients with no hepatopathy (2.17 (0.70-9.18) ng/ml) or the patients with chronic liver disease (2.12 (0.33-13.61) ng/ml) (both P less than 0.05); the patients in the no hepatopathy group and the chronic liver disease group showed statistically similar levels of serum procalcitonin (P=0.616). The patients with cirrhosis of Child-Pugh grade C showed significantly higher level of serum procalcitonin (1.25 (0.54-4.61) ng/ml) than those patients with Child-Pugh grade B (0.33 (0.14-1.31) ng/ml; P=0.026), suggesting that patients with Child-Pugh C stage cirrhosis may be more susceptible to gram-negative bacterial infection. In the cirrhosis group,serum procalcitonin level was positively correlated with white blood cell (WBC) count (r=0.312) and percentage of neutrophils (N%) (r=0.228) (both P less than 0.05). Correlation analysis of the no hepatopathy group and the chronic liver disease group showed no correlation between serum procalcitonin level and either WBC or N%.

CONCLUSIONUnder the sepsis condition, cirrhotic patients have lower serum procalcitonin level than patients without cirrhosis, and the serum procalcitonin level is positively correlated with WBC count and N%.

Calcitonin ; Calcitonin Gene-Related Peptide ; Humans ; Liver Cirrhosis ; Protein Precursors ; Sepsis

Objective To investigate the protective effect of polymyxin B (PMB) to the liver graft after liver transplantation and the underlying mechanism in rats.Methods Male SD rats were selected as the donors and recipients.Non-artery whole liver transplantation model was established in rats according to Kamada's two-cuff method.The rats were divided into two groups by the way of random number table method:control group (normal saline,0.5 ml) and PMB group (PMB,1 mg/ml,0.4 mg/kg+ normal saline 0.5 ml).The levels of portal vein plasma endtotoxin (EU/ml)were determined by endotoxin-analyzing machine of BET-24A. ALT,BUN,and TNF-α,IL-6 in serum were measured by using machine of Automatic Analyzer and ELISA,respectively.The CD14,TLR4,NFκB and AP-1 in the grafts were measured by RT-PCR and Western blotting,and pathological changes were observed. Results PMB decreased the levels of portal vein plasma endotoxin 1 h after reperfusion in PMB group as compared with control group (P＜0.05),and the levels of portal vein plasma endotoxin returned to the normal levels 6 h after reperfusion in both two groups (P＞0.05).After operation,the levels of ALT,TNFα and IL-6 in serum were significantly reduced (P＜0.05),the expression of CD14 and TLR4 mRNA in the grafts was significantly decreased (P＜0.05),the expression of Hsp60 protein and mRNA,and NF-κB and AP1 proteins in the grafts were reduced (P＜0.05),and the pathological damage to the grafts was significantly alleviated in PMB group as compared with control group.Conclusion PMB reduced the levels of portal vein plasma endotoxin after reperfusion in liver transplantation in rats.PMB improved liver function,reduced the injury of inflammatory response,decreased the levels of endotoxin signal pathway markers and alleviated the pathological damage to the grafts.