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.
Cell-Penetrating Peptides ; chemistry ; Drug Delivery Systems ; Enzymes ; chemistry ; Humans ; Neoplasms ; drug therapy

Background Subretinal transplantation of retinal pigment epithelium (RPE) cells for the treatment of age-related macular degeneration (AMD) have accelerated the drive to develop xeno-free cultivation system that support the rapid differentiation of human embryonic stem cells (hESCs) into ES-RPE cells.Objective This study was to report a modified xeno-free culture system and method for accelerating derivation of hESCs to differentiate into RPE cells.Methods This study was approved by Ethic Committee of Zhongshan Ophthalmic Center.HESC H1 line was cloned and cuhured in Vitronectin XFTM-coated 6-well dish with xenogenetic-free medium.Cells were cultured in 50 ng/ml noggin,10 ng/ml DKK-1 and 10 ng/ml insulin like growth factor-1 (IGF-1) medium for 2 days,and then the concentration of noggin was decreased to 10 ng/ml and 5 ng/ml basic fibroblast growth factor (bFGF) and cultured for the following 2 days.Sequentially,noggin and bFGF were removed and cultured for 2 days.Finally,1 μmol/L CHIR99021 was added in medium for 6 days.Morphological changes in the progress of ESCs differentiation into RPE were observed by Living Cell Imaging System.The expression of Mitf and RPE65,RPE cellsspecific markers,in the cells were detected by immunofluorescence technique,and the relative expression levels of RPE cells-specific marker mRNA were assayed using real time fluorescent quantitation PCR.Results Polygonalshape monolayer cells which contained pigments were initially observed at day 14 after cultured with the cobblestonelike arrangement.Mitf and RPE65 were strongly expressed in the hES-derived RPE cells 35 days after induced,showing red fluorescence,and the cells presented hexagonal shape at cultured day 60 with numerous pigment granules in cytoplasm.Compared with before differentiation,the expression levels of Mitf mRNA in hES-RPE cells increased by (3.43±2.77) folds and (8.91 ± 2.83) folds,and the expression levels of RPE65 mRNA increased by (14.60 ± 3.94) folds and (87.16 ±9.32) folds at day 7 and day 14 after differentiation,respectively (all at P＜0.05).Conclusions A defined xeno-free culture system is successfully established by adding niacinamide,DKK-l,noggin,IGF-1 and CHIR99021 in xeno-free medium,and this system can accelerate the derivation and differentiation of hESCs into RPE-like cells.

Calcinosis ; diagnostic imaging ; etiology ; Child ; Child, Preschool ; Female ; Globus Pallidus ; pathology ; Humans ; Male ; Osteogenesis Imperfecta ; complications ; genetics ; Skull ; diagnostic imaging ; Tomography, X-Ray Computed

Objective To evaluate the value of amplification and sequencing of 16S rRNA gene in the identification of clinical rare pathogenic bacteria,and guide the diagnosis and treatment for related clinical infection.Methods 12 bacterial isolates that were difficult,or unable to be identified with conventional laboratory methods,or with special phenotypes were collected. The 16S rRNA gene was amplified by polymerase chain reaction (PCR),then sequenced for identifying bacterial species through BLAST comparison,clinical characteristics of related infection were ana-lyzed.Results 12 clinical isolates were all positive for PCR amplification (about 1500 bp),species were all identi-fied (similarity≥99% ),the identified strains were Listeriamonocytogenes(n= 2),Brucellamelitensis(n= 2),Fu-sobacteriummortiferum(n= 1),Rothiaaeria(n= 1),Nocardiafarcinica(n= 1),Staphylococcussaccharolyticus (n= 1 ),Rhizobiumradiobacter(n= 1 ),Prevotellabivia(n= 1 ),Ralstoniamannitolilytica(n= 1 ),and Atopobium vaginae(n= 1 ). The sensitivity of 16S rRNA gene amplification was high,and the minimum detection limit of Escherichiacoli ATCC 25922 was 1.5×101 CFU/mL. Clinical data of 12 patients revealed that these strains can cause multi-sites and multi-types of infection,after patients received targeted antimicrobial therapy,11 improved, and 1 died.Conclusion Sequencing for 16S rRNA gene can rapidly and accurately identify rare,anaerobic,and difficult cultured bacteria,provide laboratory evidence for etiological diagnosis and treatment of different types of infection.

Objective To explore the effect of diabetic liaison nurses on controlling blood sugar levels in patients with hyperglycemia in department other than endocrinology. Methods Four hundred diabetic patients with high blood sugar were selected from January to December, 2014 in department other than endocrinology. They were divided randomly into 2 groups equally:the control group and the observation group. The control group received traditional nursing care, while blood sugar management was carried out by diabetic liaison nurse in the observation group. Result Pre-discharge sugar metabolism in the observation group was significantly better than that in the control group (P<0.05). Conclusion The diabetic liaison nurses in other departments than the endocrinology department can help control blood sugar levels in patients with hyperglycemiain.

Objective To investigate the effect of acupuncture at Zusanli, Sanyinjiao and Danzhong on mammary estrogen receptor (ER) and progesterone receptor (PR) expressions in rats with dimethylbenzanthracine (DMBA)-induced mammary cancer. Methods One hundred and twenty female SD rats aged 6-8 weeks were randomized into a model group of 60 rats and a blank group of 30 rats. The model group received an oral gavage of DMBA for model making. The blank group received an oral gavage of equal volume of sesame oil. At 15 weeks after model making, the model group of rats was randomized into treatment and control groups. The treatment group received acupuncture at Zusanli, Sanyinjiao and Danzhong, and the control and blank groups, only the same grasp and release. After the completion of acupuncture treatment (twenty-seventh week), abdominal venous blood was taken and serum tumor markers were determined by electrochemiluminescence immunoassay. Tumor masses were counted and their shapes were recorded. The mass was taken and its height, maximum diameter and vertical diameter were measured using a 1 mm precision vernier caliper. Pathological changes in tumor tissues, and ER and PR positive areas and mean optical densities were observed under an Olympus optical microscope.Results There were statistically significant post-treatment differences in the average number and volume of mammary tumors between the treatment group and the control or blank group (P<0.01,P<0.05) and between the control and blank groups (P<0.01). There were statistically significant post-treatment differences in the concentrations of various tumor markers (CA724, CA125, CA199, AEP, CA15-3, CEA and CA50) between the treatment or control group and the blank group (P<0.01,P<0.05) and between the control and blank groups (P<0.01). There was a statistically significant post-treatment difference in CA15-3 concentration between the treatment and control groups (P<0.01). There were statistically significant post-treatment differences in ER and PR positive areas and mean optical densities between the treatment group and the control or blank group (P<0.01) and between the control and blank groups (P<0.01).Conclusions Acupuncture can reduce the occurrence of rat DMBA-induced mammary tumor (including the number and volumes of the tumors). The mechanism of its action may be related to decreasing the concentrations of tumor markers CA724, CA125, CA199, CA15-3, AEP, CEA and CA50 and especially to decreasing CA15-3 concentration, and ER and PR positive areas and mean optical densities.

Objective To investigate the expression and clinical significance of β2 microglobin (β2-MG)protien and vascular endothelial growth factor (VEGF) protien in diffuse large B-cell lymphoma (DLBCL).Methods The expressions of VEGF protien and β2-MG protien were evaluated in 49 DLBCL patients which started the initial treatment by luminex suspension array.Results Among 49 DLBCL patients,expression of β2-MG protein was high in 37 cases and the expression of VEGF protein was high in 23 cases.The expression of VEGF protien and β2-MG protien were not related with gender,age,B symptoms,clinical stage and lactic acid (LDH).There was positive correlation between the high expression of β2-MG protien and chemotherapy (P =0.037).There was relevant trend between the higher expression of VEGF protien (P =0.067).Conclusion The expressions of VEGF protien and β2-MG protien are detected in DLBCL,both proteins may be the potencial markers of DLBCL and therapeutic targets for DLBCL.

Objective To explore exenatide in the treatment of metformin(MET)alone,sulfonylurea (SU)alone or MET + SU combination therapy with poor glycemic control in type 2 diabetic pa-tients and to find effective nursing measures.Methods 24 patients were randomly divided into the con-trol group and the exenatide group with 12 patients in each group.In the exenatide group,exenatide 5μg twice a day for 4weeks,then 10μg twice a day for 12 weeks.Changes of HbAlc,body weight,BMI,FBG,P2hBG,and rate of adverse reaction were compared between two groups.Results Glycosylated hemoglobin (HbAlc),body weight,BMI,FBG,P2hBG in the control group before and after treatment showed no significant difference,while the exenatide group showed better results compared with those before treatment and the control group.Nursing intervention played evident effect on reducing adverse effect such as nausea,vomiting,diarrhea,low blood sugar,headache.Conclusions For patients with type 2 diabetes,using MET,SU alone or MET + SU combination therapy showed poor results of blood sugar control,addition of exenatide therapy can effectively control blood sugar,nursing intervention can significantly alleviate the adverse effects of patients.

Objective To study the AmpC beta-lactarnase and its genotype mediated by plasmid in Escherichia coli.Methods AmpC beta-lactamase was detected based on that AmpC beta-laetamase can be inhibited by 3-aminophenylboronic acid(APB).MIC was ehecked by agar dilution method.Conjugation test was used to check the transfer of ampC gene.Gene chip and PCR were used to detect ampC gene.The amplified ampC gene were sequenced and analyzed by EMBOSS software.The molecular epidemiology of clinical isolates was investigated by Enterbacterial repetitive intergenic consensus(ERIC)typing method.Results In 74 strains of Escherichia coli insusceptible to cefoxtin,AmpC beta-lactamase was positive in 33 strains.8 strains possessed AmpC beta-lactamase of CIT group by gene chip and 8 transconjugants were obtained by conjugation test.CMY type ampC gene could be further amplified by specific CMY gene primers from both 8 clinical isolates of E.coli and plasmids extracted from 8 transconjugants.CMY-2 type ampC gene was found by sequencing(accession number DQ823449).The most transconjugants displayed similar MIC value(intermediate or resistant).ERIC genotyping showed 6 out of 8 isolates with CMY-2 ampC gene derived from different resource.Conclusion CMY-2 AmpC beta- lactamase mediated by plasmid could be detected in E.coli isolates from patients in the General Hospital of People Liberation Army,Beijing.The plasmid carried ampC gene could mediate multi-drug resistance.

OBJECTIVETo observe the effect of Liuweidihuang Pills in relieving cellphone electromagnetic radiation-induced histomorphological abnormality, oxidative injury, and cell apoptosis in the rat testis.

METHODSThirty adult male SD rats were equally randomized into a normal, a radiated, and a Liuweidihuang group, the animals in the latter two groups exposed to electromagnetic radiation of 900 MHz cellphone frequency 4 hours a day for 18 days. Meanwhile, the rats in the Liuweidihuang group were treated with the suspension of Liuweidihuang Pills at 1 ml/100 g body weight and the other rats intragastrically with the equal volume of purified water. Then all the rats were killed for observation of testicular histomorphology by routine HE staining, measurement of testicular malondialdehyde (MDA) and glutathione (GSH) levels by colorimetry, and determination of the expressions of bax and bcl-2 proteins in the testis tissue by immunohistochemistry.

RESULTSCompared with the normal controls, the radiated rats showed obviously loose structure, reduced layers of spermatocytes, and cavitation in the seminiferous tubules. Significant increases were observed in the MDA level (P < 0.01) and bax expression (P < 0.01) but decreases in the GSH level (P < 0.01) and bcl-2 expression (P < 0.01) in the testis issue of the radiated rats. In comparison with the radiated rats, those of the Liuweidihuang group exhibited nearly normal testicular structure, significantly lower MDA level (P < 0.05), bax expression (P < 0.01), and bcl-2 expression (P < 0.01).

CONCLUSIONLiuweidihuang Pills can improve cellphone electromagnetic radiation-induced histomorphological abnormality of the testis tissue and reduce its oxidative damage and cell apoptosis.

Animals ; Apoptosis ; drug effects ; radiation effects ; Body Weight ; drug effects ; radiation effects ; Cell Phone ; Drugs, Chinese Herbal ; pharmacology ; Electromagnetic Radiation ; Glutathione ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Radiation-Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules ; drug effects ; radiation effects ; Spermatocytes ; drug effects ; metabolism ; radiation effects ; Staining and Labeling ; Testis ; drug effects ; metabolism ; pathology ; radiation effects