Liposomes can be cleared by the reticuloendothelial system (RES) when it is in the blood circulation in the body. And they can accumulate in the organs rich in RES in the body by passive targeting. Targeting of the liposomes is an important factor for its use as a drug carrier, and particle size as well as surface charge are important for its in vivo targeting. In this paper, studies on the influences of particle size and surface charge of the liposomes on cell binding and phagocytosis mechanism were reviewed. A comprehensive review on passive targeting effect of the particle size and surface charge of liposomes on blood, liver, spleen as well as tumor tissue was made. At last, an outlook for future research directions was made.

Objective To evaluated the effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)on advanced non-small cell lung cancer (NSCLC)patients with different EGFR mutation status (exon 1 9 deletion and exon 21 mutation).Methods Seventy-two advanced NSCLC patients with EGFR mutation confirmed by histopathology were enrolled.All of the patients received first-line EGFR-TKI.The relationships between EGFR mutation status and objective response rate (ORR),disease control rate (DCR),progression free survival (PFS ) and overall survival (OS ) were analyzed.Results Of the 72 patients,37 patients expressed exon 1 9 deletion,35 patients expressed exon 21 mutation,and all of them could be evaluated.The ORR and DCR of patients with exon 1 9 deletion were higher than those of patients with exon 21 mutation (75.7%vs.51 .4%,χ2 =4.583,P=0.032;89.2%vs.68.6%,χ2 =4.636,P=0.031 ).The modified median PFS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (1 3.2 month vs.1 0.8 month,χ2 =4.700,P=0.030).The median OS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (30.2 month vs.25.6 month,χ2 =4.686,P=0.030).The side effects were similar between the two groups.The most common adverse reaction was rash,and the incidence had no significant difference between the two groups (48.7% vs.48.6%,χ2 =0.000,P=0.995 ).Conclusion EGFR mutation status is a predictor for PFS,OS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.NSCLC patients with EGFR exon 1 9 deletion are associated with longer survival time and better response rate compared with those with exon 21 mutation.

Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode's solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 μmol·L-1), but remained no change in the presence of Str (1 and 100 nmol·L-1). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol·L-1), but had no obvious effects on the action of Str (10 μmol·L-1). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 μmol·L-1) or the removal of Ca2+ from Tyrode's solution. In Na+, K+-free Tyrode's solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 μmol·L-1) was attenuated, while remained no change to Str (1 and 100 nmol·L-1). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+-free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+-ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.

Objective To explore the relationship between mutation status of epidermal growth factor receptor (EGFR) and efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced nonsmall ccll lung cancer (NSCLC).Methods The data of 72 outpatients and inpatients with stage Ⅲ b/ⅣNSCLC diagnosed by histopathology and harbored EGFR-activating mutations (exon 19 and exon 21) from January 2008 to December 2013 in Xuzhou Cancer Hospital were collected.All of them received first-line EGFR-TKI.The relationships between EGFR gene status and response rate or progression-free survival (PFS)were analyzed.Results Of the 72 patients with EGFR mutation,37 patients harbored exon 19 deletion,and 35 patients harbored exon 21 L858R point mutation.The efficacies of all patients were assessable.The objective response rate (ORR) was 63.9 ％ (46/72) and disease control rate (DCR) was 79.2 ％ (57/72) in all patients,including 2 cases of complete remission (CR),44 cases of partial remission (PR),1 1 cases stable disease (SD) and 15 cases of disease progression (PD).Patients with exon 19 deletion had a higher ORR [75.7 ％ (28/37) vs 51.4 ％ (18/35),P =0.032] and a higher DCR [89.2 ％ (33/37) vs 68.6 ％ (24/35),P =0.031]than patients with exon 21 L858R mutation.The PFS of patients with exon 19 deletion was significantly longer than that of patients with exon 21 L858R mutation (12.0 months vs 9.5 months,P =0.030).Cox multivariate analysis indicated that the gender,histological type,smoking history were the major influence factors of PFS.The differences of toxicity between the two groups were not significant.Conclusion EGFR-activating mutation is a predictor for PFS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.

Objective To explore the Kano model analysis in the application of midwife outpatient service quality management. Methods Kano questionnaire was consisted of 24 items, including five parts, environment facilities, service evaluation, service technology, the team service, delivery service′quality. Using the Kano model analysis, the impact factors of the midwife outpatient service quality in five different quality attributes were determined. It included property and had the opposite answer to the question, charisma, essential properties and one property. Results By identifing the quality index classification of the pregnant women with satisfactory service quality to midwife outpatient service, attributable to a property were 1,2,3,4,8,9,10,14,20,21;attributable to mandatory attributes were 13, belonging to the charm of the property had 5,6,7,11,12,15,16,17,18,19,22,23,24. Midwives outpatient had most of charisma attribute, 54.2%(13/24) of the total;The second was one attribute, 41.7% (10/24) of the total. The technology level of midwife was essential attribute. Conclusions Kano mode analysis technology will be introduced to the midwife outpatient service quality management to provide decision reference for improving the quality of the hospital management level, improve maternal satisfaction, improve the obstetric operation efficiency.

OBJECTIVETo investigate the effects of the resveratrol on proliferation and gap-junctional intercellular communication (GJIC) in human liver cancer cell line HepG2.

METHODSMTT assay was used to observe the effects of resveratrol on HepG2 cell growth, and the distribution of cell cycles was detected with flow cytometry (FCM). The effects of resveratrol on GJIC of HepG2 cells labeled with 5'-CFDA/AM was examined with fluorescence redistribution after photobleaching (FRAP) and confocal microscope.

RESULTSThe results of MTT assay indicated that the proliferation of HepG2 cells was significantly inhibited by resveratrol in a time- and dose-dependent manner. Resveratrol could arrest HepG2 cell growth in S phase, inhibit DNA synthesis and induce cell apoptosis. Furthermore, the levels of GJIC increased sharply after resveratrol treatment of the cells.

CONCLUSIONResveratrol is capable of inhibiting HepG2 cell proliferation, causing cell growth arrest at S phase and inducing cell apoptosis. Increased GJIC level contributes to the effect of resveratrol in HepG2 cell proliferation inhibition and its cancer chemopreventive activity.

Antineoplastic Agents, Phytogenic ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; physiopathology ; Cell Communication ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Gap Junctions ; drug effects ; Humans ; Liver Neoplasms ; pathology ; physiopathology ; S Phase ; drug effects ; Stilbenes ; pharmacology

OBJECTIVETo introduce a new method for detecting mitochondrial permeability transition pore (PTP) opening with flow cytometry using the resveratrol-inducing PTP opening model.

METHODSMitochondria were isolated from rat livers and selectively labeled with nonyl acridine orange. The mitochondrial membrane potential was detected using flow cytometry with TMRE (tetramethylrhodamine, ethyl ester) labeling. PTP opening induced by resveratrol was represented by the changes of mitochondrial side-scattering (SSC) detected by flow cytometry.

RESULTSFlow cytometry was capable of defining the purity of the mitochondria isolated. The fluorescence intensities and SSC of the mitochondria were decreased after resveratrol treatment, indicating that resveratrol could induce PTP opening. Ciclosporin A inhibited resveratrol-induced PTP opening.

CONCLUSIONFlow cytometric analysis allows accurate and convenient detection of mitochondrial membrane potential, mitochondrial swelling and PTP opening.

Animals ; Apoptosis ; Flow Cytometry ; Membrane Potential, Mitochondrial ; genetics ; Mitochondria, Liver ; metabolism ; Mitochondrial Membrane Transport Proteins ; metabolism ; Rats ; Rhodamines

Objective To investigate the capsular polysaccharide (CPS) serotypes and molecular characteristics of carbapenem resistant hypermucoviscous Klebsiella pneumoniae (CR-HMKP) and study the possible mechanism of carbapenem resistance. Methods A retrospective study was conducted on 18 nonduplicate CR-HMKP strains which were collected from the First Affiliated Hospital of Nanchang University from 2012 to 2016. The clinical data were retrieved from medical records. The capsular serotypes, resistance genes and virulence factors were detected by polymerase chain reaction and DNA sequencing. Antimicrobial susceptibility testing was determined on VITEK 2 compact system. The CR-HMKP strains were characterized molecularly by using PCR, multilocus sequence typing (MLST) and pulsed field gel electrophoresis (PFGE). Modified carbapenem inactivation method was used to screen carbapenemase-producing strains. Plasmid conjugation transfer experiments were carried out to study transmission of carbapenem resistance. Results Eighteen (2.7％) CR-HMKP isolates were identified, which belonged to 4 serotypes, including wzi128-K1 (n=1), wzi206-K57 (n=1), wzi2-K2 (n=2), and wzi64-K14.64 (n=14). PCR and sequencing analysis identified blaNDM-1 gene in 2 CR-HMKP strains, blaKPC-2 gene in 17 strains, qnrS1 gene in 18 strains, blaCTX-M-3 gene in 3 strains, blaCTX-M-14 gene in 18 strains, blaTEM-1 gene in 16 strains, blaSHV-12 gene in 17 strains, and rmtB in 5 strains. All the 18 CR-HMKP strains carried virulence-associated genes, including rmpA (88.9％, 16/18), magA (5.6％, 1/18), iroN (83.3％, 15/18), aerobactin (27.8％, 5/18), rmpA2 (66.7％, 12/18) and mrkD (100％, 18/18). Three sequence types (STs) were identified by MLST, including ST11 (15 strains), ST86 (2 strains), and ST412 (1 strain). PFGE resulted in three major PFGE clusters, of which cluster A corresponds to ST1 isolates, and cluster B corresponds to ST86 isolates, and cluster C corresponds to ST412 isolates. All the blaKPC-2- positive strains belonged to ST11. Plasmid conjugation was successful in 5 (27.8％) of the 18 CR-HMKP isolates. Conclusions wzi64-K14.64 is the predominant capsule serotype of the CR-HMKP strains in this hospital. KPC-2 gene conjugationmay contribute to the emergence of CR-HMKP isolates. In addition, CRHMKP strain may be the highly prevalent ST11, and highly virulent CPS serotypes harboring K1/K2.

Objective: To evaluate the efficacy and safety of apatinib combined with chemotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with negative driving genes. Methods: From January 2016 to March 2018, 62 advanced NSCLC patients with negative driving genes diagnosed at Xuzhou Cancer Hospital were randomly divided into study group (30 cases) and control group (32 cases), respectively. The patients in the study group were treated with standard first-line chemotherapy combined with apatinib, while those in control group were treated with chemotherapy alone. Results: The disease control rate (DCR) and objective remission rate (ORR) in the study group were 60.0% and 16.7%, respectively, higher than 46.9% and 9.3% in the control group, but without statistical difference (P>0.05). The median progression-free survival (PFS) of study group and control group were 6.4 months and 4.9 months, respectively (P=0.004), and the median overall survival (OS) were 11.3 months and 9.2 months, respectively (P=0.006). Multivariate survival analysis indicated that treatment regimen (P=0.001) was the independent prognostic factor of PFS, and PS score (P=0.002), clinical stage (P=0.02) and treatment regimen (P<0.001) were the independent prognostic factors of OS. After treatment, the incidence of hypertension and hand-foot syndrome in the study group were 46.7% and 53.3%, respectively, significantly higher than 3.3% and 0 in the control group, respectively (P<0.05). The incidence of grade 3-4 adverse drug reactions (ADRs) in the study group was 26.7% (8/30), mainly including hypertension, hand-foot syndrome and bone marrow suppression. The incidence of grade 3-4 ADRs in the control group was 15.6% (5/32), all of which were bone marrow suppression, without significant difference (P=0.286). There was no difference in serum levels of VEGF and CEA between the two groups before treatment. After treatment, the serum level of VEGF in the study group was (169.3±10.1) pg/ml, lower than (211.8±16.7) pg/ml of the control group (P<0.05). Conclusion Apatinib combined with first-line chemotherapy for advanced NSCLC patients with negative driving genes is safe and beneficial for survival. This therapeutic strategy can significantly prolong the PFS and OS, and further improvement and application can be considered as a choice in the clinical treatment.

OBJECTIVETo establish two double-antigen sandwich ELISA systems to detect anti-Afmp1cr and Afmp2cr antibodies of Aspergillus fumigatus.

METHODSRecombinant Afmp1cr and Afmp2cr proteins of A.fumigatus expressed in Pichia pastoris were obtained. Double-antigen sandwich ELISA systems for detecting specific anti-Afmp1cr and anti-Afmp2cr antibodies were developed after chessboard titrating to determine the appropriate concentrations of the recombinant proteins and HRP-labeled proteins. The sensitivity of the assay was evaluated using serum samples of rabbits immunized with Afmp1cr and Afmp2cr. The specificity of the assay was evaluated by detecting serum samples from healthy donors and patients with other pathogenic fungal and baterial infections. The performance of the two ELISA kits was furthered evaluated using serum samples from patients with suspected Aspergillus infection.

RESULTSThe established ELISA kits were capable of detecting anti-Afmp1cr and anti-Afmp2cr antibodies in immunized rabbit serum at the maximum dilutions of 800 and 3200, respectively. No cross-reactivity was observed in detecting serum from patients with other pathogenic fungal or bactetial infections. Both of the two kits yielded positive results in sera from two established Aspergillus-infected cases and a suspected case.

CONCLUSIONSTwo antibody-capture ELISA kits were developed for the laboratory diagnosis of A.fumigatus infection and can be potentially useful in the clinical diagnosis of Aspergillosis infections.

Animals ; Antibodies, Fungal ; isolation & purification ; Antigens, Fungal ; Aspergillosis ; diagnosis ; Aspergillus fumigatus ; Cross Reactions ; Enzyme-Linked Immunosorbent Assay ; Humans ; Pichia ; Rabbits ; Recombinant Proteins ; Sensitivity and Specificity