Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) catalyze the initial and rate limiting step in the catabolism of tryptophan, which is related to tumor immune tolerance and poor prognosis in patients. In this regard, two enzymes have become important therapeutic targets for tumor immunotherapy. So far, nine IDO1 inhibitors and three IDO1/TDO dual inhibitors have entered clinical trials. This review summarizes the research progress of IDO1 inhibitors, TDO inhibitors and IDO1/TDO dual inhibitors from the perspective of medicinal chemistry.

Investigation of the corporate governance at the pilot areas along with literature review of the outcomes of corporate governance reform;reasonable definition of the authority-responsibility relationship of the stakeholders and the impact on the corporate governance model;optimization of public hospital′s corporate governance to recommend an optimal design of such hospitals.Interests demands of stakeholders were considered as a key factor in the design of such governance;roles of the stakeholders in such governance were enhanced,to clarify the distribution of ownership,decision-making power and management rights,with widened supervision and narrowed management radius.

Objective To obtain a reliable estimate of the risk of H. pylori infection in causing pancreatic cancer ,by perform‐ing a M eta‐analysis of the existing observational studies evaluating the association .Methods Observational studies comparing the prevalence of H. pylori infection in patients with pancreatic cancer and healthy controls were identified through systematic search in the Medline ,EMBASE ,the Cochrane ,PubMed ,VIP database .H. pylori infection was confirmed by serological testing using an anti‐gen‐specific enzyme‐linked immunosorbent assay .Pooled adjusted odds ratios (AOR) and associated 95% confidence intervals (CI) were obtained by using a Dersimonian and Laird random‐effects model .Results Six studies involving a total of 2 335 patients met our eligibility criteria .A significant association between H. pylori seropositivity and development of pancreatic cancer (AOR=1 .38 , 95% CI:1 .08-1 .75 ;P=0 .009) was seen .No significant association had been seen on pooled analysis of the three studies assessing the relationship between CagA positivity and pancreatic cancer (AOR=1 .14 ,95% CI:0 .66-1 .97 ,P=0 .639) .Conclusion The da‐ta suggests an association between infection with H. pylori and the development of pancreatic cancer .Further research is needed to confirm our findings .

BACKGROUND: +Gz-induced acute dysencephalia and its protection is one of the significant topics in Aero-medical researches. Its pathological mechanism, however, is still unclear and protective measures should be developed further. OBJECTIVE: To observe the expression of inducible nitricoxide synthase (iNOS) in brain tissue after +Gz exposure and to analyze the protective effects of danshen and basic fibroblast growth factor (bFGF) on repeated +Gz exposure-induced brain injury. DESIGN: Randomized controlled animal study. SETTING: Researching Center of Molecular Biology, Air-force General Hospital of Chinese PLA.MATERIALS: The experiment was carried out at the Researching Center of Molecular Biology, Air-force General Hospital of Chinese PLA from April to August 2000. A total of 20 healthy SD rats of clean grade were divided into 5 groups according to randomly digital table, including control group, +Gz exposure group, bFGF group, danshen group and saline group with 4 in each group.METHODS: All rats were fixed on rotatory arm of centrifugal apparatus,and their heads were towards core of the apparatus. Except the rats in control group, the value of +Gz exposure was +14 Gz, and the growth rate was 1.5 G/s. The exposure at peak value lasted for 45 s. +Gz exposure was done for three times, and the interval was 30 minutes. Rats in the control group were also treated with the same +Gz exposing procedure, but the G value was +1 Gz. Rats in bFGF group and danshen group were intraperitoneally injected with 100 μg/kg of bFGF and/or 15 g/kg of danshen solution, respectively, at 30 minutes before centrifugation and immediateness after centrifugation; moreover, rats in saline group were injected with the same volume of saline. Six hours after exposure, rats were cut off their heads to obtain the brains which were maintained in liquid nitrogen for RNA extraction. The expression of iNOS mRNA in brain tissues of the rats in each group was detected with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and calculated on the basis of ratio between iNOS and glyceraldehyde-3-phosphate dehydrognase.MAIN OUTCOME MEASURES:Expressed level of iNOS mRNA in brain tissue of rats.RESULTS: Expression of iNOS mRNA in brain tissue was higher in repeated +Gz exposure group than that in control group (0.452 ±0.014,0.065±0.008, P ＜ 0.01); however, that was lower in bFGF group and dan-shen group than that in +Gz exposure group (0.196±0.010, 0.183±0.011,0.452±0.014, P ＜ 0.01).CONCLUSION: Repeated +Gz exposure can increase the expression of iNOS mRNA, this plays an important role in cerebral injury induced by repeated +Gz exposure. Moreover, bFGF and danshen have protective effects on cerebral injury induced by +Gz exposure.

AIM: To investigate the expression of MAT1 protein in pancreatic cancers and the relationship between MAT1 and clinicopathological features of pancreatic cancers. METHODS: 94 surgical specimens, including 70 pancreatic cancers, 10 pancreatic benign tumors, 14 chronic pancreatitis and 10 autopsy normal pancreas tissues, were analyzed immunohistochemically, and then MAT1 expression and clinicopathological features were compared. RESULTS: MAT1 was expressed mainly in the cancer cells,and also in the fibroblasts, where it was localized within the cytoplasm and nuclear envelope. MAT1 expression was found in 75.7% (53/70) of the cancers, but not detected or weakly expressed in control tissues. There was a significant difference in expression of MAT1 among the above four tissues (P

The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

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.

Objective To investigate the clinical characteristics and imaging manifestations of AIDS complicated with disseminated Penicillium marneffei (PM) infection. Methods A total of 12 patients with AIDS complicated with disseminated PM infection were collected and the symptoms, signs, laboratory examination results and image manifestations of these patients were analyzed retrospectively. Results (1) The diagnosis of PM infection in all the 12 cases were confirmed by peripheral blood culture.All the 12 cases (100％) had irregular fever (38-41 ℃) and enlarged lymph nodes, 8 cases (66％) had skin rashes; 8 cases (66％) had hepatomegaly; 9 cases (75％) had splenomegaly while 8 cases (66％) had anemia. (2) Imaging manifestation: Five cases manifested bilateral pulmonary disseminated miliary nodular shadows or lattice signs; 1 case showed enlarged hilar lymph node and 2 zases showed patchy shadow with pleuritis. One case presented sub-pleural curve line shadow at the posterior part of the right lower lung,and adhesion between the intestinal wall and intestinal mesentery in mass form in the abdomen by CT examination. Conclusion Patients suffering from AIDS (CD4T lymphocytes ＜50/μ L) with impaired immunity might be susceptible to complication of disseminated PM infection, which presents mainly damage of multiple organs and symptoms such as fever; enlargement of liver,spleen and lymph nodes, as well as specific skin maculopapular rashes. Imaging manifestations in the lungs were revealed as miliary nodular shadows and lattice-like shadows. Intensified abdominal CT might reveal presence of several enlarged postperitoneal lymph nodes and intestinal adhesion in shape of cakes.

Objective To determine the relationship between serum soluble Klotho (sKL) level and adverse outcome in maintenance hemodialysis (MHD) patients.Methods One hundred and twenty nine cases of MHD patients were collected prospectively.Serum sKL was detected by ELISA.Abdomen lateral plain was used as a criterion to determine the abdominal aortic calcification.The abdominal aortic calcification score (AAC) was calculated.Cox regression analysis was used to determine the risk factor of cardiovascular death (CVD) in MHD patients.Kaplan-Meier showed the relationship between sKL and CVD in MHD patients.Results There were 27 cases (20.9％) of allcause death and 19 cases (14.7％) of cardiovascular death.The median sKL was 612.6(379.2-816.6) nig/L,and log[iPTH] was an independent factor of sKL concentration.Low sKL had high AAC and CVD death rate.Kaplan-Meier method showed that the all-cause death rate was similar between two groups,and CVD death rate increased significantly in low sKL patients (P=0.036).Cox regression indicated that lower sKL level was associated with high CVD death rate [OR=0.352,95％CI(0.127-0.977),P=0.045].After adjustment for the general condition,biochemical indicators,the relationship still existed [OR=0.331,95％ CI (0.117-0.933),P=0.037].In no or mild vascular calcification patients (AAC ≤4),compared with high sKL patients,low sKL patients had no significant difference rate in all-cause mortality.The CVD mortality was significantly higher in high sKL (P=0.035) compared with low sKL.In severe calcification group (AAC ＞ 4),all-cause death and CVD death rates were similar between different sKL groups (P=0.991 and 0.522,respectively).Conclusions Lower sKL has the high CVD death rate and sKL level decreasing is an independent risk factor for CVD death in MHD patients.The lower sKL concentration in MHD patients with no or mild calcification may predict CVD mortality.This study suggests that sKL levels may be helpful in predicting the outcome of patients with MHD.