Alcohol Drinking ; adverse effects ; Cardiovascular Diseases ; etiology ; prevention & control ; Health Promotion ; Humans ; Risk Assessment

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 explore the antitumor mechanism of xianhe yanling recipe( XHYLR ). Methods The mechanism of action of 241 compounds contained in the Chinese medicine, XHYLR was studied by using computational pharmacological. Methods including molecular docking,biotechnology network,chemical space technology and the prediction of absorption,distribution,metabolism,excretion and toxicity( ADME/T). Results Most of the compounds in XHYLR had good drug-like properties. Distribution of 241 compounds in chemical space also revealed that these compounds showed similar anti-tumor activity. It suggested that the prescription of XHYLR was reasonable. The phenomena that one molecular interacted with multiple target proteins and several molecules interact with one target protein were observed in XHYLR. For example,the COX-2 interacted with 40 micromolecules,and catechin interacted with five targets including COX-2. Conclusion These results are helpful for understanding the complicated mechanism of anti-tumor activity of XHYLR.

Objective The study aimed to evaluate the application effect of clinical pathways in laparoscopic cholecystectomy patients by using the meta-analysis.Methods Published randomized controlled trials (RCT) about laparoscopic cholecystectomy patients were searched and screened in China National Knowledge Infrastructure (CNKI),China Scientific Journal Database by VIP,Wanfang Database under present standards.The quality of the included studies was evaluated by certain standards.The Review Manager 5.2 software was used for analysis.Results Totally 29 studies including 5 570 cases were eligible to the criteria (2 753 in the experimental group and 2 853 in the control group) altogether.The meta-analysis showed that the hospitalization time and hospitalization costs in the clinical nursing pathway group were significantly less than those of the control group (SMD=-1.69 and-3.75),the satisfaction degree and the mastering of health knowledge in the clinical nursing pathway group were significantly higher than those of the control group (RR=1.16 and 1.26),the differece had statistical significance.Conclusions Application effect of clinical nursing pathways is superior to the traditional nursing method in laparoscopic cholecystectomy patients.

Child ; Humans ; Practice Guidelines as Topic ; Sepsis ; therapy ; Shock, Septic ; therapy

Aged ; CD3 Complex ; metabolism ; Humans ; Immunohistochemistry ; Leukocyte Common Antigens ; metabolism ; Lymphoma, T-Cell, Peripheral ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Thyroid Neoplasms ; drug therapy ; metabolism ; pathology ; surgery

Objective To establish a sensitive,specific,simple and high-throughput method for detection of the epidermal growth factor receptor (EGFR) mutation in the plasma samples of patients with non-small cell lung cancer (NSCLS) by the use of mutant-enriched liquid chip (MEL) assay.Methods The specific probes for the EGFR exon19 E746-750 deletion,exon 21 L858R mutation and wild-type sequence were designed and coupled to the microspheres coding with different fluorescent dye.The probe coupling efficiency was verified by crossing hybridization test with biotin-labeled reverse sequence.A blood-based MEL approach which integrates a sensitive mutant-enriched PCR and quantitative high throughput liquid chip assay for assessment of EGFR mutations was developed.The sensitivity and specificity of MEL was further evaluated using the mixture with different copy numbers of mutant and wild-type plasmids as template.The mutations of exon 19 and 21 of EGFR gene in plasma samples from 201 patients with stage ⅢB or Ⅳ NSCLC who enrolled in the First Affiliated Hospital of Guangzhou Medical College from September 2008 to April 2010 were analyzed by both the MEL and the mutant-enriched PCR assay.The result comparison was made between direct sequencing and MEL in 50 cases whose EGFR gene type had been tested by MEL and mutantenriched PCR.The correlation of EGFR gene mutation and the response to the Geftinib treatment was analyzed in 16 patients with lung adenocarcinoma as well.Results The probes were successfully coupled to the microspheres encoding with different fluorescent dye,and could be specifically recognized by the corresponding target sequence.The MEL was capable of detecting as few as 10 copies of EGFR mutants (sensitivity was 0.1％).Among the enrolled 201 cases of advanced NSCLC,the detection rate of the EGFR exon19 E746-750 del and exon 21 L858R was 55.7％ (112/201) by MEL assay.Conpared with mutantenriched PCR[58.2％ (117/201)],the coincidence rate was 97.5％ (196/201).There was no statistically significant difference between the results of mutant-enriched PCR and MEL (x2 =3.20,P ＞ 0.05).The mutations detection rate was 22.0％ (11/50) by directing sequencing,which was significantly lower than by MEL[50.0％ (25/50),x2 =12.07,P ＜ 0.05].Among the 16 patients treated with Gefitinib,9 cases who had EGFR mutation showed a higher response rate(P =0.041)and prolonged progression-free survival (x2 =6.76,P =0.009) after the treatment compared to those 7 who without EGFR mutation.Conclusions A new method of MEL with accuracy,specificity,fast and high-throughput is established for the detection of EGFR 19 E746-750 deletion and exon 21 L858R mutations in plasma from advanced NSCLC patients.It has the ability to provide the most direct and valuable guidance for clinicians to make decision on EGFR tyrosine kinase inhibitors therapy in the advanced NSCLC paticnts.

Objective To compare the clinical effects of intramedullary nails and locking compression plate in the treatment of femur shaft fracture.Methods The clinical data and follow-up records of 43 patients with femur shaft fracture treated by intramedullary nails and locking compression plate were retrospectively reviewed.Including 31 males and 12 females with an average age of 40.07 years(25 to73).According to AO classification:5 cases were type A,24 cases were type B,14 cases were type C.26 patients in group A treated by intramedullary nails and 17 patients in group B treated by locking compression plate.Operation time,fracture union time,blood loss and complications were compared between the two groups.The Karlstrom and Olerud result were compared and analyzed.Results All patients were followed up at an average of 15 months(range 5-24) after surgery.According to Karlstrom and Olerud score system,the excellent and good rate of group A was 88.4％,higher than the group B 82.3％.But there was no significant difference between the two groups.In group A:the operation time (113.77 ±20.14)min,the blood loss in the operation (386.74 ± 65.16) ml,clinical bone healing (15.52 ± 1.77) weeks.All these outcomes were better than group B (P ＜ 0.01).One case in group A appeared screw loose,but X-ray showed the nail stable,the bone wasn't displacement.One case in group B appeared broken plate 1 month after operation,and received twice operation,the clinical outcome was good as well.Another 1 case with fracture delayed union in group B,after internal fixation removed,we check the X-ray showed bone union.Conclusion Two methods of treatment femur shaft fracture can all reach the above requirement.Fixation of intramedullary interlocking nail is the preferred surgery than locking compression plate.

0.05).3.Under light microscope, there was no change of the glomeruli detected in all of the LMWH-treated groups compared with the controls,while congestion and swel-ling in part glomeruli of group RSV were observed significantly. 4.Under electron microscope,glomerular structures of the LMWH-treated groups were almost normal compared with the control, while extensive foot process effacement was observed in group RSV under an electron microscope. 5.RSV RNA signal expressed weaker in the LMWH-treated groups than in group RSV.Conclusions Positive charged RSV destroys the glome-rular filtration barrier through its electrostatic interaction with the negative charged heparan sulfate(HS) of GBM. LMWH, as the analog of HS, charged with anion, competes with GBM HS to combine with RSV to keep the glomeruli from being infected and destroyed, and then reduce the proteinuria.

Objective To investigate the induction of tolerant dendritic cells(DOs)and its mechanism in mice.Methods The dendritic cell line derived from C57BL/6 mouse.DO2.4 cells were co-cultured with TGF-?_1(20 ng/ml)to induce the tolerant DCs(TGF?-DC)and stimulated wihh li- popolysaccharide(LPS)for 48 h to induce the mature DCs(LPS-DC).Special small interference RNA molecule(siRNA)of PIR-B was chemically synthesized and was transfected into TGF?-DC by lip2000 (si-DC).The expression of paired immunoglobin receptor A/B(PIR-A/B)in DC2.4 cells was mea- sured by semi-quantitative RT-PCR and flow cytometry(FCM).The allogeneic stimulating capacity of DCs was measured by mixed lymphocyte reaction(MLR)using ~3H-thymidine incorporation test with the Balb/c spleen cells as reaction cells.The concentration of IFN-?in supernatants of MLR from dis- tinct groups was tested by enzyme linked immunosorbent assay(ELISA).Results TGF-?_1 up-regula- ted the PIR-B mRNA expression and down-regulated the PIR-A mRNA expression(P