Objective To investigate the value of partial hepatectomy and vascular resection in the treatment of hilar cholangiocarcinoma. Methods Seventy four patients with hilar cholangiocarcinoma who underwent hepatectomy of Chinese People' s Liberation Army from January 2008 through December 2011 were analyzed retrospectively.Results Of the 74 patients,33 underwent radical resection and 19 palliative resection,22 received internal or external drainage.In the radical resection group,the median survival time was 27 months,and the overall survival rate at 1,2 and 3 years were 79％,64％ and 49％.In the palliative resection group,the median survival time was 14 months and the overall survival rate at 1,2 and 3 years were 56％,25％,and 19％.In the drainage group,the median survival time was 9 months and the overall survival rate at 1,2 and 3 years were 23％,15％,0.Conclusions Hepatectomy combined with hilar vascular resection helps increase survival rate of patients in radical excision of hilar cholangiocarcinoma and Surgical resection is the most elective method for treatment of hepatic hilar cholangiocarcinoma,and the radical resection might improve the prognosis of the patients with hilar cholangiocarcinoma.

To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of epirubicin hydrochloride (EPI) in rat plasma, daunorubicin hydrochloride was used as internal standard. The plasma samples were deproteinated with methanol, and separation was performed on a reversed-phase CAPCELL PAK C18 column (3.0 mm x 50 mm, 3 microm). The mobile phase contained methanol-0.1% formic acid (80:20). Detection was carried out by multiple reaction monitoring on a HP1200-6410 QQQ LC/MS system. Different preparations of EPI solution, EPI-LIP (EPI-liposome) and EPI-LTSL (EPI-thermosensitive liposome) was administered in rats by i.v with the same dosage (12 mg kg(-1)). The pharmacokinetic model and parameters were fitted and calculated by the DAS ver2.0 software. The calibration curve was linear in the range of 0.01-50 microg mL(-1). The limit of quantification was 0.01 microg mL(-1). RSDs of intra- and interbatch precisions were all less than 11.9%. The average extract recovery was 89.3% and 92.1%, respectively. The pharmacokinetics of EPI in rats with all preparations were fitted to three compartments, which all fast distributed and slowly eliminated. The t1/2 alpha, t1/2 beta, t1/2 gamma, AUC(0-infinity), and MRT(0-infinity) of EPI-LTSL group were 7.5, 1.3, 12.6, 12.9, 3.7 times those of EPI solution group; and 1.6, 1.4, 12.3, 2.9, 2.6 times those of EPI-LIP group. Moreover, the CL of the latter two groups was about 13.4 times of the former EPI-LTSL group. EPI-LTSL can significantly improve AUC and prolong the circulation time of EPI in rat plasma.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Drug Carriers ; Epirubicin ; administration & dosage ; blood ; pharmacokinetics ; Liposomes ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry

Liposomes and nanoparticles have been used as drug carriers to increase solubility, prolong drug duration in vivo, target drug delivery, reduce toxicity and combat multi-drug resistance. With major advances in the preparation techniques, preparation material, and surface modifiers in recent years, liposomes and nanoparticles delivery systems have achieved success in fields including cancer therapy, overcoming biological barriers, and biological drugs and vaccine carriage.
Drug Carriers ; Drug Delivery Systems ; methods ; Humans ; Liposomes ; Nanoparticles ; Vaccines ; administration & dosage ; chemistry

Objective To study the diagnosis and treatment of cytomegalovirus (CMV) infection after liver transplantation. Methods The clinical data of 111 patients who received liver transplantation from November 2000 to December 2007 in our hospital were analyzed retrospectively. The recipients were diagnosed as having CMV infection by the predisposing factors, clinical symptoms and detection of CMV-PP65 and CMV-IgM in peripheral blood specimens in combination with chest X-ray. The treatment of CMV infection was administration of Ganciclovir. Results Five recipients were diagnosed as having CMV infection, with the incidence of 4.5%. Two were diagnosed as having CMV pneumonitis, with the incidence of 1.8% (40% of the recipients having CMV infection). Two were both improved. Three were diagnosed as having CMV active infection. Two of them were cured and one was improved. Conclusion The detection of CMV-PP65 is necessary for early diagnosis and guiding treatment of CMV infection. Ganciclovir can exert significant therapeutic effects on CMV infection.

Objective To evaluate the two-stage repair in hypospadias cripples.Methods 35 patients with hypospadias cripples underwent two-stage repair.At the first stage,a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after the release of chordee.The second stage was performed 6 months after completion of the first stage.Tubularization of the replaced urethral plate was the preferred technique.Results There was no urethra stricture or “preplaced urethral plate ” atrophy.Fistula developed in 2 of 35 cases.Conclusion The twostaged technique was a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias.This technique could not only create a neourethra successfully,but also give the penis a near-normal shape and appearance.

Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.

AIMTo study the preparation conditions and its oral pharmacokinetic characteristics of cyclosporine A (CyA) pH sensitive nanoparticles.

METHODSThe CyA pH sensitive nanoparticles were prepared by the quasi-emulsion solvent diffusion technique (QESD). Male Sprague-Dawley (SD) rats weighing (250 +/- 20) g were selected and randomly divided into five groups. The bioavailability of CyA from nanoparticles and Neoral microemulsion were assessed at a dose of 15 mg x kg(-1) by gavage. The concentration of CyA in whole blood samples was detected by HPLC to evaluate the relative bioavailability of CyA pH sensitive nanoparticles.

RESULTSThe blood concentration profiles of CyA pH sensitive nanoparticles in rats fitted to two compartment models using 3P87 pharmacokinetic calculation program. Compared with the Neoral microemulsion, the relative bioavailability of CyA was 94.8%, 115.2%, 113.6% and 132.5% for CyA-E100, CyA-L100, CyA-L100-55 and CyA-S100 nanoparticles respectively.

CONCLUSIONCyA-S100 nanoparticles was shown to significantly improve the oral bioavailability of CyA compared with Neoral microemulsion (P < 0.05). While there were no significant differences between Neoral microemulsion and other CyA pH sensitive nanoparticles. With these results, the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed. Furthermore, this formulation approach can be used to improve the oral bioavailability of other poorly soluble and poorly absorbable drugs.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Hydrogen-Ion Concentration ; Male ; Nanostructures ; Random Allocation ; Rats ; Rats, Sprague-Dawley

AIMTo investigate the possibility of using stealth liposomes modified with arginine-glycine-aspartic acid (RGD) mimetic as the targeted carriers to achieve increased accumulation in tumor and enhanced intracellular delivery for the encapsulated anticancer drugs.

METHODSRGD mimetic (RGDm) as a ligand for integrins was synthesized and covalently conjugated to the active PEGylated phospholipids (DSPE-PEG-BTC) to form RGDm conjugate (DSPE-PEG-RGDm). Then RGDm-modified SL (RGDm-SL) containing DOX (RGDm-SL-DOX) and SL containing DOX (SL-DOX) were prepared by film dispersion followed by ammonium sulfate gradient method. The pH-sensitive probe, BCECF-AM, was used to study the binding of melanoma cells to DSPE-PEG-RGDm. Flow cytometry and confocal microscopy were performed to evaluate the cellular association or DOX uptake for RGDm-SL-DOX or SL-DOX in vitro.

RESULTSThe melanoma cells A375 and B16 showed enhanced binding to the immobilized DSPE-PEG-RGDm. The cells treated with RGDm-SL-DOX showed remarkable increase in cellular association or DOX uptake compared with SL-DOX.

CONCLUSIONThe RGDm-modified SL could be as the targeted carriers to facilitate the delivery of the encapsulated anti-cancer drugs into tumor cells by receptor-mediated way.

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; metabolism ; Cell Adhesion ; Cell Line, Tumor ; Cell Nucleus ; metabolism ; Doxorubicin ; administration & dosage ; metabolism ; Drug Carriers ; Drug Delivery Systems ; Humans ; Liposomes ; Melanoma, Experimental ; metabolism ; pathology ; Oligopeptides ; Phosphatidylethanolamines ; Polyethylene Glycols

OBJECTIVETo explore the correlation between Beijing genotype (Beijing family) strains of Mycobacterium tuberculosis (MTB) and drug resistance.

METHODSA computer retrieval of Medline, Embase, SCI, EBSCO, CNKI, Weipu and Wanfang databases from 1990 to 2010 was conducted. A total of 525 articles exploring the relationship of Beijing genotype of MTB and drug resistance were found through literature search. Following the inclusion and exclusion criteria, a Meta-subgroup analysis was conducted in Beijing genotype of MTB and drug resistance.

RESULTSA total of 38 articles were selected, including 22 articles on isoniazid resistance, 24 articles on rifampin resistance, 19 articles on ethambutol resistance, 18 articles on ethambutol resistance, 26 articles on multi-drug resistance (MDR). Meta-subgroup analysis showed that in China, there was an association between Beijing genotype and resistance to rifampin, ethambutol and MDR: rifampin (OR = 1.62, 95%CI: 1.13 - 2.31), ethambutol (OR = 1.67, 95%CI: 1.16 - 2.40), MDR (OR = 1.79, 95%CI: 1.20 - 2.68); in Russia, there was an association between Beijing genotype and resistance to isoniazid, rifampin, ethambutol and MDR: isoniazid (OR = 4.82, 95%CI: 3.19 - 7.29), rifampin (OR = 4.84, 95%CI: 3.84 - 6.10), ethambutol (OR = 3.32, 95%CI: 2.51 - 4.40), MDR (OR = 5.42, 95%CI: 3.36 - 8.74); in Vietnam, there was an association between Beijing genotype and resistance to isoniazid, rifampin, ethambutol and MDR: isoniazid (OR = 2.12, 95%CI: 1.55 - 2.91), rifampin (OR = 4.71, 95%CI: 3.01 - 7.36), ethambutol (OR = 3.78, 95%CI: 1.63 - 8.77), MDR (OR = 4.21, 95%CI: 1.58 - 11.18); in other countries, there was an association between Beijing genotype and resistance to isoniazid, rifampin, ethambutol and MDR: isoniazid (OR = 1.69, 95%CI: 1.19 - 2.42), rifampin (OR = 2.48, 95%CI: 1.92 - 3.19), ethambutol (OR = 3.04, 95%CI: 2.13 - 4.33), MDR (OR = 2.36, 95%CI: 1.52 - 3.68).

CONCLUSIONBeijing genotype of MTB was positively associated with three kinds of first-line anti-tuberculosis drugs (isoniazid, rifampin, ethambutol) and MDR, and the relationship intensity was different in different countries.

Antitubercular Agents ; pharmacology ; China ; DNA, Bacterial ; Drug Resistance, Multiple, Bacterial ; Genotype ; Humans ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Russia ; Tuberculosis, Multidrug-Resistant ; genetics ; microbiology ; Vietnam

AIMMultidrug resistance ( MDR) as a major obstacle to successful clinical cancer chemotherapy, searching a novel effective antiresistant drug would be necessary.

METHODSA novel doxorubicin anti-resistant stealth liposomes (DARSLs) was prepared by co-encapsulating doxorubicin (DOX) and verapamil (VER) into stealth liposomes with ammonium sulfate gradient remote loading approach. In vitro cytotoxity of various DOX formulations and in vivo toxicity of DARSLs were evaluated using DOX-resistant rat prostate cancer cell line (MLLB2), human uterus sarcoma cell line (MES-SA/DX5) and normal SD rats, separately.

RESULTSThe DARSLs liposome suspensions mainly consisted of homogeneous large unilamellar vesicles (LUV) with average particle size of (118.1 +/- 22.3) nm. Encapsulation efficiencies of DOX and VER in DARSLs were more than 90% and about 70%, respectively, when the ratio of DOX/VER/Lipid was 1: 0.11 :10 (w/w/w). In vitro cytotoxicity tests of the DARSLs using rat prostate cancer cell line (MLLB2) and human uterus sarcoma cell line (MES-SA/DX5) showed that 5 micromol x L(-1) VER significantly reversed DOX-resistance of these 2 cell lines and DARSLs was the most effective on inhibition of DOX-resistant cell growth. Besides, compared to FDFV, much slower DOX distribution (confocal microscopy) to nuclei and cytoplasm in MLLB2 cells for DARSLs suggested that it might possess distinct mechanism of cytotoxicity. Systemic and cardiac toxicity evaluations in normal SD rats suggested that liposomal encapsulation could significantly improve the severe cardiotoxicity arising from simultanous administration of DOX and VER.

CONCLUSIONDARSLs is a novel anticancer liposome formulation with lower cardiotoxicity, effective drug-resistance reversal and intravenous injection.

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; toxicity ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Doxorubicin ; administration & dosage ; pharmacology ; toxicity ; Drug Carriers ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Female ; Heart Rate ; drug effects ; Humans ; Liposomes ; Male ; Myocytes, Cardiac ; drug effects ; ultrastructure ; Prostatic Neoplasms ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoma ; pathology ; Uterine Neoplasms ; pathology