Cyclic peptide drugs have gradually become an emerging research direction due to their some favorable properties such as high-efficiency binding affinity, high selectivity, lower toxicity, and stable metabolism. In recent years, the number of cyclic peptide drugs under clinical research has continued to increase. Unlike the previous cyclic peptide drugs, which were mostly derived from natural products and their derivatives, these cyclic peptide drugs are designed by genetically encoded display technologies which are based on rational design and in vitro evolution (such as BT1718, PTG-300, POL6326, etc). Among them, phage display technology has some advantages such as mature research system, low cost, and simpler operation that make it well recognized and praised by the majority of researchers in this field. Here, we reviewed the recent progress of applying phage display technology to explore diverse cyclic peptide libraries, which, we believe, will contribute more valuable candidate cyclic peptide drugs in clinical research.

Objective To explore the influence of electrical stimulation on prefrontal cortical neurons and synaptic ultramicrostructure of hypoxic-ischemic brain damage(HIBD)in neonatal rats.Methods The sixty 7-day-old newborn healthy SD rats were randomly divided into hypoxic-ischemic group(model group),electrical stimulation(intervention)group and sham operation group(control group),which 20 for each group.The models of perinatal HIBD rats were prepared by ligation of left common carotid artery with a temporary systemic hypoxia for 2 hours.Intervention group was subject to electric stimulation for 30 minutes,once everyday after surgery.Control group and model group were not subject to electric stimulation but caught to fix in corresponding period.Fastigial nucleus electric stimulations were performed for 3 d,14 d and 21 d.Five rats were killed in each group after the application of electron microscope to observe the brain cortex neurons and synaptic ultrastructure changes.Results In model group,the neuronal shrinkage,the amount of organelles dacrease,ob-vious edema of cytoplasm,obvious swellen mitochondria,and synapse quantity decrease,synaptic space fusion,obvious synaptic vesicle were observed.Intervention group different times,mitochondria hydrops gradually alleviated,synaptic space gradually cleared,synaptic vesicle increased,pathological changes obviously lessened compared to model group at the same time,and there was no apparent abnormality compared with control group on the 21st d.Conclusion Electric stimulation can promote the ultramicrostructures recovery of HIBD rats.

Objective To investigate the effects of electrical stimulation on vascular endothelial growth factor(VEGF) and its receptor expressions of neonatal rat brain with hypoxic-ischemic brain damage(HIBD).Methods Seventy-five 7-day-old newborn health SD rats were randomly divided into sham operation group(control group,n=25),hypoxia-ischemia group(model group,n=25) and the electrical sti-mulation group(intervention group,n=25).To bulid HIBD animal model of neonatal rats,the left common carotid artery was ligated and nitrogen-oxygen gas mixture was inhaled 2 hours.Fastigial nucleus stimulation was given 12 hours after the operation in intervention group,30 min?time-1,1 time?d-1,the time length was 1 d,3 d,7 d,14 d or 21 d,respectively.There was no electrical stimulation in model group and control group.The rats in these groups were captured at the corresponding time.Five rats in each group were killed at the corresponding pe-riods after electrical stimulation,the expression of VEGF and its receptor fam-like tyrosine kinase receptor(flt-1 / VEGFR1),fetal liver kinase receptor(flk-1/KDR/VEGFR2) in hippocampus were observed by immunohistochemistry.SPSS 15.0 software was used to analyze the data.Results The expression of VEGF,VEGFR1,VEGFR2 at every time point in electrical stimulation group were higher significantly than those in model group and control group(Pa0.05).Conclusion Electrical stimulation can promote the expression of VEGF and its receptors VEGFR1,VEGFR2.

Objective To investigate the effects of chrysin(ChR) on the induction of differentiation and apoptosis-promoting of HepG 2 human primary hepatocacinoma cells. Methods The HepG 2 cells were cultured in vitro, and then treated with ChR and all-trans retinotic Acid (RA), respectively, the alterations of nucleocytoplasm and tubulin arrangement after Gimsa staining and Coomassie brilliant blue staining were observed. The survival rate and the inhibitory rates of HepG 2 cells were determine by trypan blue counting method and MTT assay. The Alpha-fetoprotein(AFP) secretory amounts of the cells were detected by radioimmunoassay(RIA). The activities of alkaline phosphatase(ALP) andγ-glutamyltranspeptidase(γ-GT) were assayed by enzymatic reaction kit. The synthesis of tyrosine-α-ketoglutaric acid transaminase(TAT) in cells were investigated by Diamondstone spectrophotometry. Results After treatment with ChR or RA at 1.0~100μmol/L for 48 h, the proliferation of HepG 2 cells were inhibited significantly, compared with vehicle group (P<0.05 or P<0.01), the inhibitory potency of both ChR and RA on HepG 2 cells was equivalent and indicated in dose-dependent manner. After treatment with 10μmol/L ChR or RA for 48 h, HepG 2 cells disaggregated and grew to spindle-shape, their nuclei became smaller and the number of nucleolus were fewer. Furthermore, tubulin arrangement of cells tended to be more ordered and the tubulin synthesis increased significantly. At 24~96 hours treated with 10μmol/L ChR, the activities of TAT and ALP in cells were all increased distinctly (P<0.05, P<0.01), and the secretory amounts of AFP and the specific activities ofγ-GT were decreased significantly (P<0.05, P<0.01). Conclusion Chrysin can inhibit the proliferation of HepG 2 cells and induce them to differentiate to mature cells.

Objective To explore the effects and mechanisms of hepatitis B virus-X protein (HBx) on invasion and migration of hepatocellular carcinoma (HCC) cells.Methods The retrospective cohort study was conducted.The clinicopathological data of 30 patients with liver tumor (20 with HCC and 10 with benign tumor of liver) who were admitted to the Affiliated Hospital of Xuzhou Medical College between July 2014 and July 2015 were collected.HCC tissues of 20 patients with HCC (with history of HBV infection) were collected by surgical resection and peritumoral normal tissues (outside of tumor capsule) of 10 patients with benign tumor of liver (without history of HBV infection) were collected.The expressions of epidermal growth factor receptor 3 (ErbB3)in HCC tissues and peritumoral normal tissues were detected by immunohistochemistry (IHC).The relative expressions of ErbB3 and HBx in HCC tissues and peritumoral normal tissues were detected by Western blot,and relative expressions of ErbB3 in HepG2 of which green fluorescent protein (GFP) and GFP-HBx were respectively transfected were detected.The relative expressions of ErbB3 mRNA in HepG2 transfected by GFP and GFP-HBx were detected by real-time polymerase chain reaction (RT-PCR).The migration and invasion of HepG2 were respectively detected by Transwell assay with and without matrix.The measurement data with normal distribution were represented as $± s.The comparisons between groups were evaluated with the independent-sample t test.Correlation analysis was done by the Pearson test.Results (1) The expressions of ErbB3 were detected by IHC:relative value of mean optical density (MOD) of ErbB3 in HCC tissues of 20 patients with HCC and peritumoral normal tissues of 10 patients with benign tumor of liver were 2.54± 1.33 and O.99±0.29,respectively,with a statistically significant difference (t =6.542,P ＜ 0.05).(2) The relative expressions of ErbB3 and HBx were detected by Western blot:relative expressions of ErbB3 and HBx were respectively 0.79±0.13,1.10±0.28 in HCC tissues of 10 patients with HCC and 1.07±0.17,0 in peritumoral normal tissues of 10 patients with benign tumor of liver,with statistically significant differences (t =3.229,19.486,P＜0.05).The results of Pearson test showed that there was a positive correlation of expression between ErbB3 and HBx in HCC tissues (r=O.637,P＜ 0.05).(3) The relative expressions and transcriptional levels of ErbB3 were detected by Western blot and RT-PCR:relative expressions of ErbB3 in HepG2 of which GFP and GFP-HBx were respectively transfected were O.75±0.11 and 1.10±0.10,respectively,with a statistically significant difference (t=4.291,P＜0.05).The relative expressions of ErbB3 mRNA in HepG2 of which GFP and GFP-HBx were respectively transfected were O.38±0.03 and O.94±0.07,respectively,with a statistically significant difference (t=11.703,P＜O.05).(4) The effects of ErbB3 on migration and invasion of HepG2:numbers of transmenbrane cell in HepG2 of which His and His-ErbB3 were respectively transfected by Transwell assay with matrix were respectively 271± 18 and 463± 31,respectively,with a statistically significant difference (t =8.202,P＜0.05).Numbers of transmenbrane cell in HepG2 of which His and His-ErbB3 were respectively transfected by Transwell assay without matrix were respectively 315±38 and 549±34,respectively,with a statistically significant difference (t =8.310,P＜0.05).Conclusion HBx protein can promote the invasion and migration of hepatocellular carcinoma cells through up-regulating expressions of ErbB3 protein.

Objective To study whether the human bone marrow mesenchymal stem cells (HBMSCs) can repair damaged neural cells induced by okadaic acid (OA).Methods Neuroblastoma cell line SH-SY5Y cells were used to incubate with 20nmol/L okadaic acid for 24h,establishing Alzheimer's Disease cell model;Three groups were set up:normal group,okadaic acid-damaged (OA-damaged) group,hBMSCs-treatment group.The cells were injured for 24h with 20nmol/L OA in OA-damaged group,and treated with conditioned medium obtaining hBMSCs for 24h after 24h OA injury in the treatment group.Then CCK-8 was used for detecting cell vitality,immune fluorescence dyed microtubules and micro filaments for determining the dendritic cell length and fluorescence intensity,in addition,Western blotting for analyzing the protein level of phosphorylated tau and total tau proteins.Results Okadaic acid damaged SH-SY5Y cells,contributed to shrinkage,collapse,cavitation of the SH-SY5Y cell body,dendritic shortening and fracture,and irregular arrangement of microtubule microfilaments;while BMSCs conditioned medium made SHSYSY cell body become round and longer,dendrites restored,and microtubules and microfilaments arranged regularly,fluorescence intensity enhanced.Meanwhile,it also down-regulated the level of OA-induced tau phosphorylation.Conclusion hBMSCs have repair effects on the neural cell damage induced by okadaic acid.

0.05).PZs of clinical and environmental isolates were0.501?0.049and0.565?0.131,respectively(P

Aged ; Carcinoma, Small Cell ; genetics ; Case-Control Studies ; Cytochrome P-450 CYP2E1 ; genetics ; Female ; Humans ; Lung Neoplasms ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVETo review the transmission models of tuberculosis in heterogeneous population.

DATA SOURCESThe data used in this review were adopted mainly from the studies of models of tuberculosis reported from 1995 to 2006.

STUDY SELECTIONRelevant literature on transmission models of tuberculosis in heterogeneous populations are referenced.

RESULTSCasual/random factors and genetic factors are the main reasons for epidemics of tuberculosis in recent years. Mass public transport is playing the primary role in casually close contact which can facilitate the transmission of tuberculosis. Genetic susceptibility not only varies endemic prevalence levels, but also drastically alters the effects of treatment for tuberculosis patients. Detailed studies further exhibit that casual contact and genetic factor are responsible for over 30% - 40% of the total new cases in recent years. The prevalence of tuberculosis could double (from 33% to 60%) if a genetically susceptible phenotype is present in only 30% of the population. And some challenges have emerged along with these exciting results.

CONCLUSIONSCasual/random contact, public transport and genetic susceptibility are responsible for most new tuberculosis cases and a wide variation in endemic tuberculosis levels between regions. Hence, the transmission model of tuberculosis in a heterogeneous population can provide more clues to underlying mechanism of tuberculosis transmission than in a homogeneous population. However, many challenges remain for us in understanding transmission of disease.

Objective To investigate clinical manifestation of unspecified functional bowel disorder (UFBD), the features of coexistence with functional gastrointestinal disorder (FGID) and its relationship with psychological factors and sleep disturbance in the Chinese Army servicemen.Methodsc FGIDs were diagnosed based on the RomeⅢ Modular Questionnaire. The subjects were 189 servicemen with UFBD (UFBD group) and 372 without FGID (control group). All subjects completed symptom checklist 90 (SCL-90) and Pittsburgh Sleep Quality Index (PSQI) questionnaire.Results'Have to rush to the toilet when having a desire to defecate' was the most frequent symptom of UFBD (93.7%). More than one half of UFBD patients had the symptom 'a feeling of incomplete emptying as bowel movements' or 'straining during bowel movements'. Twenty-eight percent of UFBD subjects had combined FGID (namely cFGID). Among them, the most frequent was proctalgia fugax (7.9%), followed by cyclic vomiting syndrome (6.3%), functional fecal incontinence (6.3%), functional dyspepsia (4.8%) and belching (4.8%). The UFBD group scored significantly higher than the control group in the global severity index (GSI) and in all SCL-90 subscales (P<0.05). The scores of the four domains (sleep quality, sleep latency , sleep disturbance and daytime function disorder), total PSQI score and proportion of poor sleeping quality were significantly higher in the UFBD group than in the control group (P<0.05). The subjects scored significantly higher in combined FGID group than in UFBD group in GSI and in all of SCL-90 subscales, except for phobic anxiety subscales (P<0.05). However, there was no significant difference in each domain, total PSQI and proportion of poor sleeping quality between the cFGID group and UFBD group (P>0.05).ConclusionPathogenesis of UFBD may be closely correlated with psychiatric and psychological factors and sleep disturbance. cFGID are associated with an increased severity of psychopathological features.