Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Intraoperative Complications ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Tracheotomy ; adverse effects ; methods ; Young Adult

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Recalls ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Structure-Activity Relationship

Objective To transfect PCDNA3.0-HIF1-? into the endothelial progenitor cells(EPCs),in order to provide the foundation for exploring myocardial vascular repairing capacity and angiogenesis of the EPCs transfected with HIF gene.Methods The EPCs were separated by the method of density gradient separation in the human bone marrow,and then the cells were inoculated in the fibronectin-packaged petri dishes complete medium with the concentration of 1?106?mL-1,and cultivated for 14 d. The expressions of the endothelial cell-specific components ecNOS and flk-1 were detected with RT-PCR; the cells were stained with acLDL-Dil and FITC-UEA-1; the PCDNA3.0-HIF1-? plasmid was transfected into the EPCs mediated by LipofectamineTM 2000,the transcription of HIF1-? was determined with RT-PCR; the expression of VEGF was detected with enzyme-linked immunosorbent assay (ELISA); the expression of HIF1-? was detected with Western blotting.Results After cultivated for 5 d,some round monocytes transformated into spindled inherent EPCs;7 d later,there were some cell colonies containing dozens of cells;10 d later,there were obvious cell clones; RT-PCR showed ecNOS band in 548 bp,flk-1 band in 819 bp; acLDL-Dil and FITC-UEA-1 double-staining was positive; RT-PCR showed specific band in 383 bp; ELISA showed the content of VEGF in the supernatant of EPCs transfected with HIF1-? was (20.53?2.33) ?g?L-1,and it was (3.96?1.67) ?g?L-1 in the EPCs transfected without HIF1-?,there was significant difference between two groups (P

AIM:To further elaborate the effect of glucocorticoid receptor(GR) decrease on level of inflammatory media in rats after critical scald.METHOD:The changes of phospholipase A 2(PLA 2) activity and concentrations of tumor necrosis factor alpha (TNF?) and malondialdehyde (MDA), the product of lipid peroxidation metabolism in plasma and tissue homogenate have been studied in scalded rats with or without GR blockade by RU38486.RESULTS:The PLA 2 activity and the concentrations of TNF? and MDA in plasma and homogenate of pulmonary and renal tissue in scalded rats were significantly higher than those in the controls( P

OBJECTIVETo evaluate the applicability of immune-related response criteria (irRC) in treating non-small cell lung cancer (NSCLC) by Chinese medicine (CM).

METHODSTotally 97 stage III a-IV NSCLC patients were predominantly treated with comprehensive CM. Curative effects were evaluated by three methods such as Response Evaluation Criteria in Solid Tumors (RECIST), Oncologic Curative Effect Evaluation Criteria of Chinese Medicine in Solid Tumor (draft, abbreviated as CM criteria), and irRC. The correspondency and consistency between irRC, RECIST and CM criteria were analyzed and compared. The objectivity of irRC in evaluating curative effect of Chinese medical treatment for NSCLC was assessed.

RESULTSThe correspondency rate of irRC to RECIST was 59. 79% with Kappa value of 0. 379 (U test, P <0. 01). The two criteria had certain correspondence, but with an unsatisfactory consistency. The correspondency rate of irRC to CM criteria rate was 83. 51% with Kappa value of 0.751 (U test, P <0. 01). The two criteria had good correspondence and consistency.

CONCLUSIONSCM criteria had good consistency with CM criteria in evaluating curative effect for Chinese medical treatment of advanced NSCLC. Its results could objectively reflect features and advantages of CM for treating advanced NSCLC.

Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; immunology ; Medicine, Chinese Traditional ; standards ; Treatment Outcome

Objective To compare the curative effect of high ligation+exfoliation and subfascial endoscopic perforator surgery(SEPS)for superficial varicose veins in calf+invagination spot-striping surgery in great venous varicosity.Methods Study group(42 patients)accepted SEPS+invagination spot-striping surgery and control group (42 patients)accepted traditional surgeries.Operation duration,bleeding volume in operation,the time of beginning movement away from bed after operation,hospitalization duration,the degree of pain,the scar,the recrudescence af- ter operation and the instance of the ulcer heals of two groups were compared.Results Operation duration,bleeding volume in operation,the time of begin movement away from bed after operation and hospitalization durations of study group were significantly lower than those of control group(P0.05).All of the patients in study group recovered without severe syndromes such as venous thrombosis,skin necrosis,lower limb functional disorder etc.They had no recrudesce after 4～16 months and were satisfied with the curative effect.Con- elusions The clinical curative effect of SEPS+invagination spot-striping surgery in great venous varicosity is superi- or to that of traditional operation and it has the advantages such as minor wound,few scars,light pains,short hospi- talization duration,without recrudescence,the ulcer heals quickly and so on.

BACKGROUND:Smooth muscle cells and transitional epithelial cells were traditionally used to construct tissue-engineered bladder and to perform double-sided implantation of scaffold.However,double-sided implantation is difficult to perform,because smooth muscle cells are difficult to isolate or culture in vitro and passage is limited.OBJECTIVE:To verify the feasibility of tissue-engineered bladder reconstruction with bone marrow mesenchymal stem cells(BMSCs)and bladder acellular matrix(BAM).DESIGN:A basic empirical study.SETTING:Linbaixin Medical Research Center,Second Affiliated Hospital,Sun Yat-sen University.MATERIALS:Experiments were performed at the Linbaixin Medical Research Center,Second Affiliated Hospital,Sun Yat-sen University from March 2006 to Mav 2007.The laboratory was the Opening Laboratory of Hospital Affiliated to Health Department of China.One-month old SD rats of either sex,weighting 80-100 g were provided by Animal Experimental Center of Sun Yat-sen University.Fresh porcine bladders were offered by Animal Experimental Center of Southern Medical University.METHODS:Whole bone marrow culture and successive adherence method was used to culture rat BMSCs in vitro.Flow cytometry was employed to detect surface antigen.Eradicator washing method was applied to prepare porcine BAM and measure its purity and characteristies.Third passage of BMSCs were inoculated in BAM and cultured in a medium containing vascular endothelial growth factor(VEGF165)(25 ng/L)in vive and in vitro to test compatibility.Cells cultured alone were considered to be controls for the in vivo trial,and materials non-implanted with cells were considered to be controls for in vitro trial.Suitable microenvironment was simulated to induce the differentiation of BMSCs.Four weeks and eight weeks later,compound materials were respectively removed to perform tissue section test.Simultaneously,immunohistochemistry keratin staining was conducted to examine regeneration of epithelial cells.MAIN OUTCOME MEASURE:Biocompatibility of BMSCs and BAM.RESULTS:①BMSCs were cultured by whole bone marrow method.Flow cytometry demonstrated that third passage of cells were positive for CD29(99.43%).②BAM had good biological characteristics.Homogen matrix and byssoid collagen appeared under a microscope.Compatibility trials showed good compatibility of BMSCs and BAM and well-growth cells.③Four weeks later,histological section test confirmed inflammatory cell infiltration,closely-arranged collagen and elastic fiber.Immunohistochemistry keratin staining showed lamellar and discontinuous simple epithelium.Eight weeks later,no inflammatory cell infiltration was found,and closely-arranged collagen and elastic fiber were detected.Immunohistochemistry keratin staining showed lamellar and continuous multiple epitheliums.CONCLUSIoN:With good compatibility,BMSCs and BAM appear to be an ideal material for bladder tissue engineering.

ObjectiveTo assess the safety and efficacy of retrograde ureteroscopy lithotomy (URSL)assisted antegrade percutaneous nephrolithotomy (PCNL) for complex upper ureteral calculi in semisupine-lithotomy position.MethodsFrom March 2007 to December 2010,a total of 95 patients with complex upper ureteral calculi underwent retrograde URSL assisted antegrade PCNL in semisupine-lithotomy position.Ureteral calculi size was 12 mm × 6 mm to 38 mm × 15 mm,24 cases combined with renal calculus.Firstly retrograde URSL was performed,once the stone fragments moved up to renal pelvis,a 16-22 F PCNL working channel was established under the ultrasound guidance through which lithotripsy was performed using an ureteroscope.Finally a 6-7 F double-J tube was indwelled.ResultsOperations were successfullycompleted in 93 patients.However,in it 2 patients were converted to open surgery because of significantureteral distortion due to previous open surgery.Operative time was(42.7 ± 14.9) min; estimated blood loss was(34.5 ± 26.1 ) ml.The ureteral calculi clearance rate was 100.0％,and renal calculus clearance rate inthose combined with renal calculus was 95.8％ (23/24).There were no major intraoperative and postoperative complications excepted early urinary leakage in 2 cases and fever ≥39℃ in 3 cases.ConclusionsRetrograde URSL assisted antegrade PCNL in semisupine-lithotomy position is safe and feasible for complex upperureteral calculi,especially non-opaque calculi,combined with renal calculus,easily ascending ureteral calculi and large calculi burden which has low calculi clearance rate after URSL.The outcomes are encouraging with fewer complications.It also avoids intraoperative change of patient's position.

AIM: To identify the non-steroid transcription factors upregulating the expression of L-plastin in hormone-independent prostate cancer, and partly elucidate the mechanism of hormone-refractory prostate cancer. METHODS: TF SEARCH software was used to analysis the possible binding sites of transcription factors in the 3’ end of L-plastin promoter that had been identified as important part of regulation response elements. Gel shift assay and supershift assay were used to confirm the transcription factors binding the speculated response elements. PCR site-mutagenesis technique was performed to delete the binding site of transcription factor and luciferase activity assay was carried out after deletion of the binding site. RESULTS: SP-1 respond element GGTGGGGCGGGGA located at -54- -41 of L-plastin promoter was identified with the TF SEARCH software. Gel shift assay and supershift assay confirmed that SP-1 was the transcription factor binding to GGTGGGGCGGGGA. Mutant deleted the SP-1 binding-site had low-luciferase activity than that of the naive. CONCLUSION: SP-1 plays an important role in the up-regulation of L-plastin expression in hormone-independent prostate cancer.

OBJECTIVETo provide a reference for the development and utilization of Dai medicine by investigate the present situation and existing problems of traditional Dai medicine.

METHODCombined with the previous relevant investigations and literature in the field, the key and the development direction of traditional Dai medicine were analyzed.

RESULTThe textual research, history, species, distribution, endangered resources, protection status etc. were elaborated and the key strategy of further investigation was expounded.

CONCLUSIONDai medicine resources should strengthen the basic research, such as the protection of traditional knowledge, the textual research, quality standard, chemical composition, biological activity, exploration of medicinal resources, especially monographic study on protection of major endangered medicinal resources should be intensified, which will be rise the level of development and utilization of Dai medicine resources.

China ; ethnology ; Conservation of Natural Resources ; history ; Drugs, Chinese Herbal ; history ; pharmacology ; History, 20th Century ; History, Ancient ; Medicine, Chinese Traditional ; history ; Plants, Medicinal ; growth & development