Objective · To identify broad-spectrum bacteriophages against extensively drug-resistant Klebsiella pneumonia and analyze their characteristics by biological and genomic methods. Methods · Multi-drug resistant Klebsiella pneumonia strains collected from a hospital were used as host bacteria to isolate and purify broad-spectrum phages in the wastewater at the same hospital area. The size and shape of phages were observed by transmission electron microscope. Titer, host range, pH stability and thermal stability were measured. Moreover, the DNA extracted from the phage SH-Kp152234 was sequenced and analyzed. Results · One strain of bacteriophage against Klebsiella pneumonia was isolated and named as SH-Kp152234. The electron microscope revealed it belongs to Podoviridae family. Moreover, genome of SH-Kp152234 showed to be a linear double-stranded DNA of 40578 bp with the GC content of 52.85%. It was predicted to have 49 open reading frames with related known functions.Conclusion · SH-Kp152234, with a broad host range and a short latent period, which could exert its activity in a wide range of temperature and pH, is a promising candidate to be exploited in the treatment of multiple drug-resistant Klebsiella pneumonia.

OBJECTIVETo evaluate the clinical effects of dynamic neutralization system (K-Rod) in treating multisegmental lumbar degenerative disease.

METHODSFrom October 2011 to October 2013, 20 patients with multisegmental lumbar degenerative disease were treated with dynamic neutralization system (K-Rod). There were 8 males and 12 females with an average age of 45.4 years old (ranged from 31 to 65) and an average course of 3.8 years (ranged from 9 months to 6.25 years). All patients had the history of low back and legs pain. Among them, 10 cases were far lateral lumbar disc herniation, 7 cases were lumbar spinal stenosis, 3 cases were lumbar spondylolisthesis (degree I in 2 cases and degree II in 1 case). Every patient had only one responsible segment which causing the symptom would have to be rigidly fixed during operations, and the adjacent intervertebral disc of the responsible segments at least 1 segment has already obvious degenerated. All patients underwent the operation to relieve compressed nerves and reconstruct spinal stability with K-Rod system (the responsible segments were fixed with interbody fusion, and the adjacent segments were fixed with dynamic stabilization). Visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA) and Oswestry Disability Index (ODI) were used to evaluate the clinical effects. Imaging data were used to analyze the range of motion (ROM), intervertebral disc height and intervertebral disc signal (according to modified Pfirrmann grading system) in degenerative adjacent segment.

RESULTSAll patients were followed up for more than 1 year, and preoperative symptoms obviously relieved. There were significant differences in VAS, JOA, ODI between preoperative and postoperative (postoperative at 1 week and 1 year) (P<0.05). Radiological examination showed that all responsible segments had already fused, and no looseness, displacement and breakage of internal fixations were found. Postoperative at 1 year, the ROM of adjacent segments were decreased (P<0.05). There was no significant difference in intervertebral disc height between preoperative and postoperative at 1 year (P>0.05). According to modified Pfirrmann grading system to classification for the 25 disks of adjacent segment, 8 disks (32%) got improvement, 15 disks (60%) got no change and 2 disks (8%) got aggravation at 1 year after operation.

CONCLUSIONDynamic neutralization system (K-Rod) combined with interbody fusion could obtain short-term clinical effects in the treatment of multisegmental lumbar degenerative disease.

Adult ; Aged ; Female ; Humans ; Intervertebral Disc Displacement ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Range of Motion, Articular ; Spinal Diseases ; surgery ; Spinal Fusion ; methods ; Spinal Stenosis ; surgery ; Spondylolisthesis ; surgery

BACKGROUNDBladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma (UTUC). This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy (NU) to prevent bladder recurrence after UTUC.

METHODSPatients with clinical diagnosis of UTUC were subjected to open trans-peritoneal NU and were randomly divided into two groups. One group received modified NU: clipping the distal ureter prior to NU; while the other group underwent traditional standard NU. Subsequent bladder recurrence was the primary endpoint.

RESULTSFrom January 2007 to December 2009, 85 eligible cases were enrolled in this study. Modified NU and standard NU were performed on 42 and 43 patients, respectively. Operation time ((215.73 ± 21.26) minutes vs. (220.19 ± 15.35) minutes), blood loss ((105.15 ± 11.32) ml vs. (110.12 ± 9.07) ml), transfusion event (11.20% vs. 9.78%), and the in-patient time (10.0 days vs 9.5 days) were not significant between the two groups. After a median follow-up of 28 months (5 - 60), six (14.3%) cases who received modified NU had bladder recurrence, which was significantly lower compared with 15 (34.9%) patients from the group that underwent standard NU (P = 0.026). In univariate and multivariate analysis, tumor grade (HR 4.33, 95%CI 2.66 - 6.30, P = 0.01) and operation type (HR 2.35, 95%CI 1.53 - 3.48, P = 0.041) were independent risk factors for subsequent bladder recurrence after UTUC.

CONCLUSIONSClipping the distal ureter at the beginning of NU significantly reduces bladder recurrence after UTUC. It is reasonable to conclude that clipping the distal portion of ureter trans-peritoneal is an effective surgical procedure for the treatment of UTUC.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Nephrectomy ; methods ; Ureter ; surgery ; Urinary Bladder Neoplasms ; surgery

Vincristine (VCR) is mainly used to treat acute lymphocytic leukemia, Hodgkin and non-Hodgkin lymphoma in clinic with definite therapeutic effect. But the obvious neurotoxicity and local stimulation of which limit its clinic use. In order to increase the lymph targeting to enhance the curative effect and to lower the adverse reaction of VCR, the VCR loaded transfersomes (VCR-T) were prepared with dry-film and ultrasonic dispersing methods, and the corresponding pharmaceutical properties, pharmacokinetical characteristics and the targeting ability were studied. The average particle size of VCR-T prepared was 63 nm with an entrapment ratio of 59%. The in vitro transdermal research with modified Franz cell showed that VCR-T permeated through the skin in accordance with polynomial equation, and with an accumulation permeation percentage of 67.4% up to 12 h. An HPLC method was utilized to determine the pharmacokinetics and tissue distribution of VCR. Compared with the iv injection of VCR solution, the retention time of VCR in blood was extended by 12 times with VCR-T, and the targeting index in rat lymph was increased by 2.75 times. As a result, transfersomes could penetrate the skin and enter into the systemic circulation carrying VCR with good lymph targeting ability, which makes it probably a new lymphtic targeting drug delivery system.
Administration, Cutaneous ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Drug Delivery Systems ; Liposomes ; chemistry ; Lymph Nodes ; metabolism ; Male ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; Spleen ; metabolism ; Surface-Active Agents ; chemistry ; Tissue Distribution ; Vincristine ; administration & dosage ; blood ; pharmacokinetics

Objective:To explore the association and gene-environment interaction between single nu-cleotide polymorphisms (SNPs)involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P)among Chinese population.Methods:A total of 806 NSCL/P trios were drawn by an international consortium,which conducted a genome-wide association study (GWAS)using a case-parent trio design to investigate genes affecting risks to NSCL/P.The transmission disequilibrium test (TDT)was used to explore the association between cell-cell adhesion genes,including CDH1,CT-NNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P.Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children.Four common maternal exposures including maternal smoking,environmental tobacco smoke,alcohol consumption and multivita-min supplementation during pregnancy were included in this study.Results:A total of 226 SNP markers were tested after quality control in this study.Although 23 SNPs in three genes (CTNNB1,CDH1, ACTN1)showed nominal significant association with NSCL/P in the TDT (P <0.05).There were no sig-nificant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P >0.000 2).Tests for gene-environment interaction yielded significant results be-tween rs7431 27 in ACTN1 and environmental tobacco smoke (P =0.000 1 )with an estimated OR (case |G and E)=2.00(95%CI:1 .23 -3.26)and OR (case |G no E)=0.59 (95%CI:0.38 -0.90).Among the lower P value results in gene-environment tests,there were no significant results be-tween rs1 475034,rs370535,rs227341 9 in ACTN1,rs1 06871 in CTNNB1 and environmental tobacco smoke interaction.There were also no significant results between rs7634000,rs2971 366,rs2634553, rs1 489032,rs762481 2 in PVRL3 and multivitamin supplementation during pregnancy in gene-environ-ment tests(P >0.000 2).Conclusion:There is no association between cell-cell adhesion genes,inclu-ding CDH1,CTNNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P when the genes are considered alone.But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.

Objective To evaluate the association of cervical cancer and the G/C single nucleotide polymorphism at codon 72 in p53 gene exon -4 in Chinese population.Methods Literatures were searched in CNKI,VIP,CBM, PubMed,EMBase,the Cochrane Library (Issue 1,2015),WanFang Data Database (1980—2015)with computer. Results Thirteen studies involving 1 780 cervical cancer patients and 1 5 17 healthy volunteers were included.According to the situation of the HPV infection in research object,thirteen studies were divided into two subgroups.The results of meta-analyses in the subgroup of non-HPV infection showed that the Chinese women having the genotype G/G presented no increased relative risk compared to that with the genotype C/C(OR=0.980,95%CI:0.558 -1.723).The allele G showed no increased relative risk compared to the allele C (OR=1.070,95%CI:0.789-1.449)The results of meta-analyses in the subgroup of HPV infection showed that the Chinese women having the genotype G/G presented no increased relative risk compared to that with the genotype C/C(OR=0.891,95%CI:0.213 -3.722).The allele G showed no increased relative risk compared to the allele C (OR =0.981,95%CI:0.493 -1.951 ).Conclusion This meta -analysis demonstrates that G/C single nucleotide polymorphism at codon 72 in p53 gene exon-4 were not associated with cervical cancer in Chinese women.

Objective To study the effect of tripterysium glycosides tablets on the pharmacokinetics of valsartan in rats combined with tripterysium glycosides tablets and valsartan. Methods 16 male Sprague-Dawley rats were randomly divided into two groups: the single administration group and the combined administration group. In the single administration group, the rats were given intragastric administration of valsartan (20 mg/kg) and the combined administered group was given intragastric administration of tripterysium glycosides tablets (10 mg/kg) and valsartan (20 mg/kg). Blood samples were taken at different time points and plasma concentrations of valsartan were determined by LC-MS. Pharma-cokinetic parameters were calculated. Results The maximum plasma concentration of valsartan was [(1. 57 ±0. 32) vs(1. 01±0. 28)μg/mL] and the plasma area under the curve was [(10. 01 ±0. 58) vs (6. 82±0. 77)mg·h/L], which were signifi- cantly increased in the combined administration group combined with the single administration group (P＜0. 05), indicating that valsartan metabolism was significantly inhibited. Conclusion Tripterysium glycosides tablets combined with valsartan has a significant effect on the pharmacokinetics of valsartan. This study plays a guiding role in the combined administration of valsartan and tripterygium glycosides tablets, which can avoid the occurrence of clinical adverse drug interactions.

This study was aimed to investigate the effect of homoharringtonine (HHT) on K562 cell proliferation, apoptosis and expression of BCL-2 and NF-κB proteins. The cells proliferation was assayed with MTT method, the cell apoptosis, cell cycle and BCL-2 expression were analyzed with flow cytometry, NF-κB protein expression was detected with Western blot. The results showed that HHT concentration-dependently inhibited proliferation of K562 cells, the IC50 at 48 h was 43.89 ng/ml. Treated with HHT 10 ng/ml for 48 h, K562 cell apoptosis significantly increased, cell cycle was blocked at G0/G1, the expression level of BCL-2 and NF-κB proteins was lower than that in control group (P < 0.05). It is concluded that HHT may inhibit the proliferation of K562 cells, and down-regulating expression levels of BCL-2 and NF-κB may be one of its anti-CML mechanisms.
Flow Cytometry ; Harringtonines ; pharmacology ; Humans ; K562 Cells ; NF-kappa B ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism

The study was aimed to investigate the synergistically effect of interferon-α (IFN-α) and homoharringtonine (HHT) on the proliferation, apoptosis, cell cycle of K562 cells and the expression of β-catenin. The proliferation, apoptosis, cell cycle and β-catenin mRNA expression of K562 cells treated with IFN-α and/or HHT were assayed with MTT, flow cytometry or RT-PCR respectively. The results showed that HHT alone, but not IFN-α alone, displayed a proliferation inhibition, apoptosis induction, G(0)/G(1) phase block and down-regulation of β-catenin expression in K562 cells with concentration- and time-dependent manners. The expression level of β-catenin mRNA after being treated with HHT was 0.5576 ± 0.0373, which were lower than that in control group (0.9369 ± 0.0142). The down-regulation of β-catenin expression in group of IFN-α combined with HHT was higher significantly than that in HHT group (0.3737 ± 0.0529 vs 0.5576 ± 0.0373, P < 0.05). Otherwise, HHT combined with IFN-α did not demonstrate obvious toxicologic effect on bone marrow mononuclear cells. It is concluded that IFN-α combined with HHT can enhance the cytotoxic effect of HHT on K562 cells, which may be associated with down-regulation of β-catenin expression.
Cell Proliferation ; drug effects ; Harringtonines ; pharmacology ; Humans ; Interferon-alpha ; pharmacology ; K562 Cells ; beta Catenin ; genetics ; metabolism

Objective To investigate the correlation between patients clinical characteristics and the number and subtype of circulating tumor cells (CTCs) from peripheral blood of perioperative hepatocellular carcinoma (HCC)patients by SE-iFISH.Methods 20 HCC patients undergoing radical resection were enrolled from June 2015 to June 2016.The SE-iFISH technique was used to separate and identify circulating tumor cells.The pathology and clinical data were used to evaluate patients survival in combination with CTCs characteristics.Results A total of 347 CTCs were detected,of which 114 were triploid,64 were tetraploid,and 165 were pentaploid.The number of preoperative CTCs and the number of preoperative triploids was significantly correlated with the presence of vascular tumor emboli (Z1 =-2.080,P =0.037,Z3 =-2.321,P =0.020) and TNM staging(Z2 =-2.148,P =0.032,Z4 =-2.526,P =0.012).Postoperative patients disease-free survival in high CTCs detection group was significantly shorter than that of CTCs low expression group (x2 1 =7.486,P =0.006,x22 =12.056,P =0.001).Conclusion Detection of the number and the specific subtypes of CTCs with SE-iFISH strategy in patients with HCC help predict treatment efficacy and prognosis.