Cell-penetrating peptide (CPP) can be used in pharmaceutics as a highly efficient drug delivery transporter. In this study, four tumor cell lines (MCF-7, MDA-MB-231, C6, and B16F10) were used to observe the uptake of fluorescein isothiocyanate (FITC) labeled CPP and the effects of time and concentration of CPP on cell penetration was studied. The CPP exocytosis on C6 cell line was observed, and its exocytosis kinetics was described by zero order equation. In addition, low-temperature condition (4 degrees C) and endocytosis inhibitors were utilized to investigate the mechanism of CPP uptake by cells. Low-temperature condition did not show significantly inhibition on CPP uptake. Heparin, a membrane glycoprotein receptor inhibitor, showed strong inhibition effect (only 3%-10% of the control) on CPP uptake. Chlorpromazine, chloroquine and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) showed little effect on CPP uptake. This study indicated that CPP penetration had little selectivity on cell type, but the amount and rate of CPP penetration into cells were related to the type of cell lines. The adsorption of CPP on cell membrane induced by sulfate proteoglycan plays an important role on CPP penetration.

The paper is aimed to study the enzymatic hydrolysis of the activatable cell-penetrating peptide (ACPP) that was designed and synthesized. The ACPP was composed of three parts, polyanionic sequence peptide, peptide sequence that specifically cleaved by matrix metalloproteinase (MMP) and cell penetrating peptide (CPP). The ACPP was hydrolyzed by type IV collagenase (MMP-2/9) under the condition of 37 degrees C and was monitored by reversed-phase high performance liquid chromatography (RP-HPLC). The efflux of peak was collected and detected by matrix assisted laser desorption ionization orthogonal time of flight mass spectrometry (MALDIO-TOF-MS) to speculate the sequences of the peptide fragments. The results indicated that the ACPP could be cleaved by type IV collagenase at target site as predicted, released CPP. The half life of the cleavage was about 4 h. Meanwhile, the peptide fragments may be cleaved again at other sites by type IV collagenase.

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.

Cartilage antuumor component (CATC) was isolated from a 1 mol/L guanidine hydrochloride extract of bovine cartilage by acetone fractioned precipitation and superfiltration. Using human skin fibroblasts as a normal control, it was demonstrated that CATC inhibited the DNA synthesis of Hela, QGY7703 tumor cell lines and bovine artery endothelial cells, but accelerated the normal cells, when the concentration was below 1250 ?g/ml. At the concentration of 5 000 ?g/ml, CATC inhibited the two cell lines. With human tumor stem cell assay, CATC inhibited the stem cell growth of Hela and QGY7703 cell lines. These suggest that CATC has the effects of inhibiting angiogenesis and tumor cells.

Objective To study the organizational commitment and influencing factors of clinical nurses at tertiary hospital in Shenzhen. Methods 347 clinical nurses from a tertiary hospital were select-ed by stratified random sampling and investigated and analyzed for organizational commitment with ques-tionnaires. Results Total score for organizational commitment of clinical nurses was (60.45±9.99),in which, from the highest to the lowest, the scores for five aspects were normative commitment (14.49±2.97), affective commitment (13.50±3.57), ideal commitment (11.69±3.20), economic commitment (11.27±3.23), opportunity commitment (9.50±3.30),respectively, their influencing factors included age, nursing age, mari-tal status, professional tide. Conclusions The organizational commitment of clinical nurses is at higher-middle level, their influencing factors are multi-dimensional, demographic characteristics have different im-pact on five aspects of organizational commitment.

Objective To evaluate the influence of transcatheter arterial chemoembolization (TACE) with Alginate microsphere-Adriamycin on angiogenesis in VX2 liver tumor. Methods Thirty New Zealand rabbits were randomly divided into 5 groups (each n=6), and VX2 carcinoma was implanted in the left lobes of the livers. TACE was performed with Alginate microsphere (Group A), Alginate microsphere-Adriamycin (Group B), Lipiodol (Group C), Lipiodol-Adriamycin (Group D), and control group (Group E), respectively. Three weeks later, the animals were killed and the samples were evaluated with immunohistochemical reaction to examine the VEGF expression and MVD count. Results The positive rate of VEGF expression was 66.67%, 50.00%, 100%, 83.33% and 66.67% respectively in five groups (P>0.05). MVD count was 55.36±7.02, 41.27±8.45, 82.42±6.23, 67.81±11.42 and 62.46±7.54 respectively in five groups. MVD value of group C was higher than that of group A and group B (P<0.05); of group B was lower than that of group D (P<0.05). Spearman rank correlation analysis showed a correlation coefficient of 0.726 between VEGF and MVD (P<0.01). Conclusion TACE with Alginate microsphere-Adriamycin can reduce VEGF expression and MVD of VX2 liver tumor in rabbits, but the possibility of tumor blood vessels rapid occlusion and therefore resulting in tumor necrosis can not be ruled out.

Purpose To improve the early correct diagnosis and avoid misdiagnosis of cervical mucinous adenocarcinoma.Methods Twenty-one cases of cervical mucinous adenocarcinoma were reviewed and analyzed retrospectively.The expression of CEA and Ki-67 was detected in the tumor by immunohistochemical staining (LABC method).Results Of the twenty-one cases, three cases (14.3%) were missed out, in which one was missed out by TCT and the others by biopsy; four cases (19.0%) were diagnosed by biopsy as adenocarcinoma in situ with invasion not be excluded, and then further confirmed as invasive adenocarcinoma by LEEP; one case (4.8%) was diagnosed as cervicitis at first and was further detected as adenocarcinoma by LEEP; twelve cases (57.1%) were directly diagnosed as adenocarcinoma by biopsy; one case (4.8%) was diagnosed as adenocarcinoma with unknown origin, and then as cervical adenocarcinoma after hysterectomy. Immunohistochemically, ten cases were CEA positive (47.6%) and the expression of Ki-67 was increased (>20%).Conclusions Understanding of the cytologic and histologic features of adenocarcinoma in cervix might improve its early detection and correct diagnosis, so that timely treatment is guaranteed for patients.

Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.

Objective:To comprehensively evaluate the correlation between migraine and the risk of hemorrhagic stroke using Meta-analysis.Methods:The published observational studies on migraine and the risk of hemorrhagic stroke in PubMed, EMbase, Cochrane library, Chinese Biomedical Database, China Journal Full-text Database, Wanfang Database and VIP Database were retrieved by computers. The retrieval time limit was from the establishment of the databases to December 31, 2019. Two reviewers independently conducted the literature screening and data extraction, and evaluated the quality according to Newcastle Ottawa scale. Stata SE 12.1 software was used for Meta-analysis.Results:Six case-control studies and 7 cohort studies met the inclusion criteria, all of which were in English. The results of Meta-analysis showed that exposure to migraine increased the risk of hemorrhagic stroke (odds ratio [ OR] 1.47, 95% confidence interval [ CI] 1.23-1.76; P<0.001). Sensitivity analysis showed that the results were robust. Subgroup analysis showed that migraine with aura ( OR 1.38, 95% CI 1.05-1.81; P=0.019), migraine without aura ( OR 1.46, 95% CI 1.19-1.80; P<0.001), male ( OR 2.10, 95% CI 1.72-2.56; P<0.001) and female ( OR 1.53, 95% CI 1.22-1.92; P<0.001) migraine could increase the risk of hemorrhagic stroke. Conclusion:Regardless of the gender of patients and presence or absence of migraine aura, migraine can significantly increase the risk of hemorrhagic stroke.

Objective To retrospectively investigate and analyze the specially permitted aeromedical evaluation results of overage military flying personnel,in order to provide references for health management and related evaluation methods improvement.Methods The clinical data and evaluation results of overage flying personnel were collected from 2012 to 2023.Disease spectrum was analyzed,and qualified rates among different airplane types and aviation duties were compared.Results 79.57%of the 509 flying personnel were detected with diseases,and the top ten were hyperlipidemia,fatty liver,thyroid nodule,renal cyst,hepatic cyst,gallbladder polyps,hyperuricemia,carotid artery arteriosclerosis,hypertension and hepatic hemangioma.96.08%of the personnel were qualified to continue flying,1.96%were disqualified and 1.96%were temporarily disqualified.The qualified rates among different airplane types and aviation duties were not significantly different(P?>?0.05).Conclusion Overage military flying personnel could apply for specially permitted aeromedical evaluation to extend their flying lifespan.Attention should be paid to metabolic and cardiovascular diseases in aeromedical support and evaluation for these experienced flying personnel.