Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

Objective:To retrospectively analyze the clinical data of 73 children with non-Hodgkin′s lymphoma to determine its clinical features, pathological types and relationship with efficacy.Methods:In Shanghai Children′s Hospital from October 2014 to October 2018, 73 children with newly diagnosed non-Hodgkin′s lymphoma were enrolled for a retrospective study, with 52 males and 21 females, aged between 2 and 13 years old, so as to comprehensively assess cumulative organs, pathological diagnosis, stage of disease, surgery and efficacy.Results:Among the 73 children with non-Hodgkin′s lymphoma, 66 cases had a clear pathological diagnosis, including 38 cases of surgical pathology and 20 cases of biopsy pathology.All of them were confirmed by immunohistochemisty, and 8 cases were determined by flow cytometry.Meanwhile, 6 cases of the rest 7 cases obtained approximate pathological classification.Only 1 case was unknown.Among the 66 cases, Burkitt lymphoma was the most common in 31 cases, followed by 14 cases of T-lymphocyte type, 7 cases of enlarged lymphoma, 6 cases of B-lymphocyte type, 5 cases of diffuse large B lymphoma, 1 case of extranodal natural killer/T cell lymphoma-nasal type, 1 case of blastic plasmacytoid dendritic cell neoplasm, and 1 case of panniculitis-like T lymphoma.The initial site or cumulative organ involved multiple organs, with most common in neck(20 cases), abdominal cavity(15 cases), and mediastinum(6 cases). In view of outcomes and efficacy, the complete remission rates of stage Ⅱ, Ⅲ, and Ⅳ in clinical were 100.0%, 85.1%, and 72.2%, respectively.The event-free survival rates in stage Ⅲ and Ⅳ were lower than those in stage Ⅱ(80.9% vs. 66.7% vs. 100.0%). From the perspective of the main pathological types grouping, the results revealed that lymphoblastic lymphoma had a lower event-free survival rate than Burkitt′s lymphoma (73.7% vs.90.3%), while there was no statistical significance(all P>0.05). Conclusions:Non-Hodgkin′s lymphoma in children is more common in men, and less common in infants and young children.Pathological type is simpler than adults, Burkitt lymphoma is the most common type, and clinical stage and pathological type may be related to prognosis.

10.3969/j.issn.1007-3969.2013.05.004

Aged ; Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Drug Resistance, Neoplasm ; Exons ; Gastrectomy ; methods ; Gastrointestinal Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Gastrointestinal Stromal Tumors ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Imatinib Mesylate ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Piperazines ; therapeutic use ; Point Mutation ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; Pyrimidines ; therapeutic use

UNLABELLEDObjective: In order to assess the integrative cardiopulmonary function after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD), we used symptom limited maximum cardiopulmonary exercise testing (CPET).

METHODSAll 59 patients diagnosed stable CAD by coronary angiography and echocardiography from August to December of 2014 in our hospital, were divided two groups. PCI group, 31 patients received PCI and drugs. Control group, 28 patients received drugs therapy only. All patients performed CPET before and after the treatment.

RESULTSAll patients safely completed CPET without any complications. The control group, all functional parameters were unchanged (P > 0.05). PCI group, the anaerobic threshold, peak oxygen uptake and peak oxygen pulse increased significantly (P < 0.05) from baseline,but not for others (P > 0.05). For individual analysis, PCI group had higher rates of increase (≥ 10% of baseline) in both peak oxygen uptake and peak oxygen pulse than those of control group (P < 0.05).

CONCLUSIONCPET is an objective, quantitative, safe and effective method to evaluate the clinical therapeutic efficiency. PCI can improve the integrative cardiopulmonary function in CAD patients.

Anaerobic Threshold ; Coronary Angiography ; Coronary Artery Disease ; surgery ; Exercise Test ; Heart Rate ; Humans ; Oxygen ; Oxygen Consumption ; Percutaneous Coronary Intervention

OBJECTIVETo study on the reliability of the Akagi line as a reference axis to guide for rotational alignment of the proximal tibial component in total knee arthroplasty (TKA) the rotational alignment reference bony landmarks of the proximal tibial component on magnetic resonance image (MRI) were measured.

METHODSFrom January 2010 to December 2013, 80 normal knees of Chinese volunteers including 35 males and 45 females with an average age of (35.4±6.1) years were reviewed. The images of the knees were obtained by MRI. The surgical epicondylar axis (STEA) was identified in the femoral transverse sections and then was projected to the side of tibia, forming the SETA'. A line connecting the medial border of the patellar tendon and the middle of the posterior cruciate ligament insertion (Akagi line) and its vertical line (AK), as well as a line connecting the medial 1/3 of the patellar tendon and the middle of the posterior cruciate ligament insertion and its vertical line (AP), were identified in the tibial transverse sections. The angles were measured between the AK, AP and STEA'.

RESULTSThe angle between AK and STEA' was (0.59±2.07)°, and there was no significant difference between the two lines (t=-2.54, P=0.13). The mean angle between AP and STEA' was (3.21±2.04)°, and there was a significant difference between the two lines (t=14.05, P<0.05). There was a significant difference between the AK and AP (t=-11.68, P<0.05).

CONCLUSIONThe reliability of the Akagi line as a reference axis to guide for rotational alignment of the proximal tibial component in TKA is good.

Adolescent ; Adult ; Arthroplasty, Replacement, Knee ; methods ; Female ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Rotation ; Tibia ; surgery

Objective To study the effects of nitric oxide synthase(NOS) and nitric oxide(NO) in post-asphyxial renal injury in neonatal rats.Methods Forty-eight Wistar neonatal rats were randomly divided into 4 groups:controls,2 h,24 h and 48 h post-asphyxia groups (12 in each group).The rats were decapitated in different times(2 h,24 h and 48 h) after asphyxia for 30 minutes.The renals were dissected to determined the concentrations of NO and NOS.And the scores of renal tubules were measured under light microscope.Results Compared with control group,the levels of NO and NOS significantly increased at 2 h and 24 h after asphyxia.The scores of renal tubules were significant difference at 24 h and 48 h after asphyxia compared to controls.Conclusion These findings suggest NOS and NO may play an important role in the development of post-asphyxia renal injury.

Objective To detect the type of gene mutation of thalassemia in Kunming city.Methods Sixty-three cases highly suspec-tive of thalassemia were determined with the methods of ploymerase chain reaction(PCR) and reverse dot blot(RDB) for the type of gene mutation.Results According to gene analysis,35 cases were final diagnosed from 63 cases suspective of thalassemia.Among the total,4 cases were gene deficiency ?-thalassemia,and 30 cases were gene deficiency ?-thalassemia,and there was 1 case both ?-thalassemia and ?-thalassemia.There were 9 types of gene mutation with 15 gene combinations in 35 samples.The main type of ?-thalassemia was--SEA/??,there were 6 types with 11 gene combinations from the types of genes of ?-thalassemia,the highest incidence of gene mutation was 17 site,including 17 site homozygote,heterozygote and double heterozygote.Conclusions The thalassemia invasion of Yunnan has its characters,and it is valuable to launch further research.In the same patient,there are ?-thalassemia and ?-thalassemia,it signifies that those 2 types should be diagnosed in the same time,to prevent missed diagnosis.

Objective To investigate the effect of simulated microgravity on the proliferation and differentiation of the human megakaryocyte cells in vitro. Methods The fourth generation rotating cell culture system (RCCS-4) was used to generate the simulated microgravity environment. The cell viability was assessed by trypan blue staining method. The proliferation of cells was assessed by cell counting method and CCK8 method. The CD41+/CD61+ cells rate and the cells cycle were detected by flow cytometry. The expression levels of thrombopoietin receptor (c-mpl) and transcription factors were detected with RT-PCR. Results After 24, 48, 72 h, culture under simulated microgravity resulted in a significant decrease in the cell number , proliferative activity, cells in the G2/M phase and levels of c-mpl mRNA expression in comparison with that under the normal gravity (P < 0.05). After 48 h and 72 h culture, CD41+/CD61+ cells ratio decreased and RUNX-1 mRNA expression was down-regulated in cells of the group SMG compared with that of the group NG (P < 0.05). Conclusion Microgravity can inhibit the proliferation and differentiation of human megakaryocyte cells in vitro. The mechanism may be that TPO/c-mpl pathway was inhibited by down regulating the expression of c-mpl which transcriptional inhibition lead to.

Objective To understand the experience of women with heroin dependence in compulsory detoxification before the society-return.Methods A semi-structured interview was conducted with 15 women with heroin dependence in compulsory detoxification.Data were analyzed based on Colaizzi phenomenological research method.Results The feelings of women with heroin dependence in compulsory detoxification were classified into 3 themes,including negative self-concept,loneliness and helplessness,uncertainty about the future.Conclusions Nurses should pay attention to problems about women with heroin dependence in compulsory detoxification and provide effective measures to improve their physical and psychological health and help them to return to the society.