Protein-protein interactions (PPIs) are fundamental to many biological processes that play an important role in the occurrence and development of a variety of diseases. Targeting the interaction between tumour-related proteins with emerging small molecule drugs has become an attractive approach for treatment of human diseases, especially tumours. Encouragingly, selective PPI-based therapeutic agents have been rapidly advancing over the past decade, providing promising perspectives for novel therapies for patients with cancer. In this review we comprehensively clarify the discovery and development of small molecule modulators of PPIs from multiple aspects, focusing on PPIs in disease, drug design and discovery strategies, structure-activity relationships, inherent dilemmas, and future directions.

Humans ; HIV Infections ; HIV-1 ; Integrases ; China ; Drug Resistance, Viral ; Mutation

Humans ; Neutrophils ; Receptors, Cell Surface ; GPI-Linked Proteins ; HIV Infections ; Isoantigens

Objective To assess the value of endoscopic ultrasonography (EUS) and abdominal CT scan on preoperative T and N staging of advanced gastric cancer.Methods A total of 188 patients with advanced gastric cancer received EUS and CT scan to evaluate the T and N staging and lymphatic metastasis before surgical operation.The postoperative pathologic results acted as gold standard for comparison of the two methods.The results consistent with pathologic results were considered as correct otherwise were incorrect.The accuracy of EUS and CT and the each consistency of two methods with pathology were analyzed.Results For T staging, the accuracy of EUS and CT was 87.2%(164/188), 76.6%(144/188), respectively, and Kappa value of EUS and CT was 0.726 and 0.509, respectively.There was a statistical difference between the two methods(χ2=7.181,P=0.007).For lymph node metastasis, the accuracy of EUS and CT was 72.9%(137/188) and 79.8%(150/188), respectively, and Kappa value of EUS and CT was 0.397 and 0.487, respectively.No statistical difference was found between them(χ2=0.963,P=0.326).The consistency test between the two methods for T and N staging and lymph node metastasis revealed that the Kappa value was 0.507 and 0.649, respectively.The accuracy of EUS on T staging was 93.0%, 93.3%, 96.8% and 91.5% in cardiac cancer, gastric fundus cancer, gastric corpus cancer, and gastric antrum cancer, respectively.Corresponding Kappa value in the 4 different positions were 0.843,0.881,0.940 and 0.710, respectively according to consistency tests.The accuracy of gastric antrum cancer with pylorus invasion was 63.2% and the consistency test Kappa value was 0.340.Conclusion EUS is an accurate method for T staging and lymphatic metastasis of advanced gastric cancer, but there is a lower accuracy for T staging of gastric antrum cancer with pylorus invasion.

Objective To investigate the prevalence of chronic kidney disease (CKD) and its risk factors in Chinese elderly persons.Methods All of the people who underwent physical examination and treatment in the geriatric department of Beijing Hospital during January 2004 to January 2007 were included in the study.Age, body height, body mass index and blood pressure were recorded.Bloody urine was ascertained by phase-contrast microscope, and urine protein was measured by dipstick test.The hemoglobulin, serum eretinine, blood urea nitrogen, blood lipid and serum uric acid were measured by autobiochemical analyzer.HbsAg was checked by enzyme-linked immunosorbent assay (ELISA).Glomerular filtration rate (GFR) was estimated by Crockeroft-Gauh equation and abbreviated MDRD equation.Binary logistic regression analysis was used to test the risk factors for proteinuria and CKD.Results The prevalence of proteinuria was 4.9% in 1082 elderly persons.And 47.23% of the elderly suffered from decreased renal function.The morbidity of CKD was 48.43%.Binary logistic regression analysis showed that diabetes(OR= 2.257) and microscopic hematuria(OR=5.324) were the risk factors of proteinuria (both P<0.05).And the risk factors for CKD were hypertension(OR= 1.459), coronary arth'erosclerotic heart disease(OR=3.290), chronic obstructive lung diseases(OR=2.094), malignant tumor(OR=2.072), hyperuricemia(OR= 1.928),anemia(OR=8.122)and hematuria( OR= 1.604) (all P<0.05).Conclusions The morbidity of CKD in Chinese elderly persons was 48.43%.And the related risk factors were diabetes,hypertension, hyperuricemia, coronary artherosclerotic heart disease and chronic obstructive lung disease.