AngiotensinⅡ is a biologically activated peptide of the rennin-angiotensin system(RAS).Beside constracting vascular and regulating blood pressure,AngⅡplays an important role in the development of tumor,inflammation and angiogenesis.The expression and major intracellular signaling pathways of AngⅡ and AngⅡ receptors in tumor are reviewed.

Indoleamine 2,3-dioxygenase 1 (IDO1) is the rate-limiting enzyme which catalyses the metabolism of L-tryptophan(L-Trp) in the kynurenine pathway.It is overexpressed in many tumor cells and antigen presenting cells.This enzyme inhibits local immune response and supports tumor cells to evade immune surveillance by depleting L-Trp and producing kynurenine metabolites,thus,it is an important target for cancer immunotherapy.There are several IDO1 inhibitors with different scarfold under investigation,three of which have already entered clinical stage.The role of IDO1 in tumor immune tolerance and the research progress on IDO1 inhibitors in recent years are summarized in this paper.

Type 2 diabetes,a glucose and lipid metabolism disorder accompanied by chronic multiple organ damage,has become a huge threat to human health,α/β hydrolase domain-6 (ABHD6) regulates the insulin release negatively by hydrolyzing monoacylglycerol.Small molecule ABHD6 inhibitors have been proven to lower bloodglucose and regulates energy homeostasis,which is a potential candidate for the treatment of type 2 diabetes.This paper introduced the ABHD6 signaling pathway and its mechanism,then reviewed the progress of small molecule ABHD6 inhibitors with different structures in recent years,and analyzed the structure activity relationship.

OBJECTIVE：To synthesize Tacrine,a new drug for the treatment of Alzheimer′s disease.METHOD:With the 2-aminobenzoic acid as the starting material，Tacring was synthesized via condensation-cyclization,chlorization and amination.RESULTS:Each step was modified and improved.The overall yields was 40.7%.The melting point and IR、1HNMR of the product prepared were identical as that of the reportedone.CONCLUSION:The process can be easily controled and is suitable for a scale production.

Objective To investigate the influence of stigma on QOL of patients with mental disorders.Methods By using Link stigma series scale and schizophrenic quality of life scale,we assessed and analyzed 406 psychiatric patients′stigma and QOL, as well as the correlation and influence between them.Results The score of perceived devaluation-discrimination dimension of the stigma scale had positive correlation with total score of QOL,score of psycho-social dimension and score of motivation and energy dimension (P <0.05).The scores of challenge dimension and separation dimension in the stigma scale had positive correlation with motivation and energy dimension of the QOL scale (P <0.05).Regression analysis showed that stigma did not have influence on QOL of patients with mental disorders.Conclusion Stigma in psychiatric patients has no significant influence on QOL,but correla-tion relationship exists between them.The higher score of perceived devaluation-discrimination dimension,challenge dimension and separation dimension of stigma scale,the poor QOL the patient would have.

In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine ( TMP) /chalcone hybrids ( 2-26) were synthesized and evaluated based on the principle of bioisostere and hybrid-ization. They exerted inhibitory activity against adenosine diphosphate ( ADP )-induced and arachidonic acid ( AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC50 of 0. 14 mmol/L on ADP-induced platelet aggregation ( 9. 1 folds of TMP and 10. 5 folds of chalcone ) and 0. 09 mmol/L on AA-induced platelet aggregation ( 8. 8 folds of TMP and 10. 0 folds of chalcone) , which was superior to clinically used anti-platelet drug aspirin ( ASP, IC50 =0. 15 mmol/L) .

Objective:To study the effects of effective herbs in Yinchenhao Decoction(YD)on fatty deposition and TNF-?secretion of hepatic lipo-toxicity model in vitro.Methods:TG and TNF-?as the inspection target,apply the steatosis with TNF-?secretion lipo-toxicity model in vitro of HepG2 induced by long-chain FFA and uniform design U7(76)form for YD,which had 3 herbs,to compound 6 kinds of different prescriptions,in order to look for the effective herbs or optimized group in YD.Results:The Chinese medicine Yinchen and its optimized group-Yinchen and Zhizi combination can remarkably reduce the TG and TNF-?content.Conclusion:The Chinese medicine Yinchen and its optimized group-Yinchen and Zhizi combination were effective herbs in YD for inhibiting fatty deposition and TNF-?secretion of hepatic lipo-toxicity model in vitro.

Type 2 diabetes, an epidemic disorder characterized by high blood glucose level associated with microvascular complications, is one of the main causes of human suffer across the globe, with no effective medicine up to now. AMP-activated protein kinase(AMPK), a highly conserved serine/threonine protein kinase, is a key sensor and regulator of intracellular and whole-body energy metabolism. Small molecule AMPK direct activators have been proven to lower blood-glucose, which is a promising candidate for the treatment of type 2 diabetes. The progress on the research of small molecule AMPK direct activators in recent years is summarized in this paper.

With the rise of tumor immunotherapy, small molecule modulators targeting the immune system have become a research hotspot. As well-developed and mature targets, immunity protein kinases have attracted more and more attention. Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively and modulate the translation of mRNA. Herein we review the structural characteristics, mechanism, signaling transduction pathways and close relationship with tumors of MNKs.Meanwhile, the development process and clinical research progress of the MNKs inhibitors reported by different research institutions are introduced in detail.

Studies have found that a variety of tumors continue to activate PD-1(programmed cell death protein 1, PD-1)/PD-L1(programmed cell death-ligand 1)signaling pathway by up-regulating PD-L1 expression in tumor cells and microenvironment. The dysfunction of T cells leads to the occurrence of tumor immune escape. Several PD-1/PD-L1 monoclonal antibodies have been marketed to achieve significant clinical efficacy. However, because of the high production cost, the harsh conditions for storage and transportation, and the potential immunogenicity of monoclonal antibody, the seeking for PD-1/PD-L1 small molecule inhibitors has become a hot spot in the development of new drugs. In this paper, the biological mechanisms of PD-1/PD-L1 was introduced in detail. Based on the structural classification, the research progress of PD-1/PD-L1 small molecule inhibitors was reviewed, with a prospect of the development of small molecule inhibitors.