Objective To explore the mediating role of self-esteem in optimism and suicidal risks,and the moderate effect of life events in optimism,suicidal risk and self-esteem.Methods 1 750 college students were surveyed with the life orientation test-revised (LOT-R),the suicidal behaviors questionnaire-revised (SBQ-R),rosenberg self-esteem scale(SES) and adolescent self-rating life events check list (ASLEC).Results The total scores of SBQ-R,LOT-R,SES and ASLEC of college students were (4.78±2.10),(23.17±3.22),(29.58±4.43)and (36.54±21.73).Optimism scores were negatively correlated with suicidal risk scores(r=-0.23,P＜0.01),optimism scores were positively correlated with self-esteem (r=0.50,P＜0.01).Scores of self-esteem scales were negatively correlated with suicidal risk scores(r=-0.35,P＜0.01).A structure equation model consists of optimism,self-esteem,suicidal risk and it had a better degree of fitting (the path form optimism to suicidal risk were r =-0.05,P＜0.05,RMSEA =0.05,GFI =0.90,NFI =0.92,CFI =0.93).The relationship between optimism and suicide risk were mediated by self-esteem(P＜0.01),which accounted for 76％of the total effects.The life events' moderating effects between self-esteem and suicide risk were significant(P＜0.01).Conclusion Self-esteem has a significant correlation with optimism and suicidal behaviors,self-esteem plays an intermediary role between optimism and suicidal behaviors,and life events play an regulation role between self-esteem and suicidal behaviors.

Objective To investigate the protective effect of agmatine (AGM) against peritoneal inflammatory response and neutrophil (PMN) infiltration induced by zymosan (ZYM) in mice. Methods Thirty-six adult male C57BL/6 mice were randomly divided into sham group, model group, and AGM treatment group. Peritonitis model was reproduced by intra-peritoneal injection of 1 mg/mL ZYM (0.5 mL), while equivalent phosphate buffer saline (PBS) was given to sham group. 200 mg/kg AGM was injected into peritoneal cavity after ZYM challenge in AGM treatment group. Six mice in each group were sacrificed at 2 hours and 6 hours, respectively, after reproduction of the model. Blood sample and peritoneal lavage fluid (PLF) were collected. The levels of keratinocyte-derived chemokine (KC), macrophage inflammatory protein 2 (MIP-2), tumor necrosis factor-α (TNF-α), interleukins-6 (IL-6) in serum and PLF were determined by enzyme linked immunosorbent assay (ELISA). The number of leukocytes and PMN in PLF were determined by hemocytometer and flow cytometry, respectively. Results Compared with sham group, all serum and PLF levels of KC, MIP-2, TNF-α and IL-6 were greatly elevated at 2 hours after ZYM injection in model group, while AGM treatment could dramatically reduce the levels of the above-mentioned cytokines in serum and PLF as compared with those of the model group [serum KC (ng/L): 990.7±137.9 vs. 2 053.2±262.7, MIP-2 (ng/L): 642.2±124.4 vs. 1 369.7±146.5, TNF-α (ng/L): 608.6±38.1 vs. 1 044.7±101.0, IL-6 (ng/L): 1 058.2±129.1 vs. 1 443.3±190.1; PLF KC (ng/L): 7 462.3±839.6 vs. 12 723.5±1 515.7, MIP-2 (ng/L): 1 570.8±193.4 vs. 3 471.4±384.7, TNF-α (ng/L): 1 115.8±156.7 vs. 1 499.2±231.2, IL-6 (ng/L): 2 646.5±223.2 vs. 3 126.7±291.4; all P < 0.05]. The expressions of KC, MIP-2 and TNF-α at 6 hours were significantly lower than those at 2 hours in model group and AGM treatment group, but IL-6 levels were further increased. The levels of KC and MIP-2 in serum and PLF at 6 hours were decreased to the levels of sham group. At 6 hours after the reproduction of the model, the number of total inflammatory cells and PMN of PLF in the model group was significantly higher than those of the sham group. In contrast, AGM notably lowered the number of inflammatory cells and PMN in peritoneal fluid after ZYM attack [total inflammatory cells (×109/L): 14.7±1.1 vs. 2.0±0.4, 10.1±1.2 vs. 14.7±1.1; PMN (×109/L): 11.37±1.22 vs. 0.18±0.05, 7.69±0.57 vs. 11.37±1.22, all P < 0.05]. Conclusion AGM can effectively alleviate acute peritoneal inflammatory injury induced by ZYM, mainly through reducing the secretion of inflammatory mediators and chemokines, and inhibiting the infiltration of leukocytes and neutrophils.

Objective:To purify a kind of deoxyribonuclease from earthworm Eisenia foetida (named earthworm DNase, EDNase) and study its characteristics. Methods: Acetone precipitation, ion-exchange chromatography, high performance liquid chromatography, SDS-PAGE, CapiUary electrophoresis isoelectric focusing and MALDI-TOP MS were used for the study. Results: This purified protocol improved 137-fold purification and 45.6 % recovery of enzyme activity. The molecular mass of EDNase was estimated to be 63 000. Mg2+ , Mn2+ and Ca2+ were strong inhibitors of EDNase, while Na+ slightly increasd the enzyme activity. The enzyme was completely stable in the pH range from 4. 4 to 5.2 and had a pH optimum of 4.8. The optimum temperature was 37℃ and the enzyme was stable up to 40 ℃. The pI of the enzyme was 6. 20. Km and Vmax for the enzyme were 1.52 g/L and 4. 89 mg/(mL ·min), respectively, with calf thymus DNA as substrate. The enzyme was able to degrade chromosemal DNA, linear λbacteriophage DNA as well as supereoiled plasmid DNA, but didn' t display any RNase activity. Conclusion: This kind of deoxyribonuclease possesses unique characteristics, which is different from the deoxyribonucleases which we have known before.

Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P<0.01).There was no significant difference in viral responses between patients previously treated with IFN plus RBV and those treated by IFN only (P>0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P<0.05), but no significant difference was observed in RVR (P>0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.

Objective To study the role and mechanisms of equilibrative nucleotide transporter 1(ENT1)on Alzheimer's disease(AD)by constructing ENT1 overexpression and knockdown plasmids.Methods Molecular cloning was used to construct the ENT1 overexpression(pAAV-ENT1-mCherry)and knockdown(pAAV-ENT1shRNA-ZsGreen)plasmids.The overexpression plasmids and the knockdown plasmids were transfected into N2A cells(mouse Neuro A2 cells)and N2A-APP cells(N2A cells stably expressing human APP695).The expression of ENT1 and inflammatory factors at mRNA and protein levels were detected by real-time qPCR and Western blotting,respectively,and the change in cell viability were measured with CCK-8 assay.Results Sequencing and real-time qPCR indicated that ENT1 overexpression and knockdown plasmids were successfully constructed.CCK-8 assay showed that ENT1 overexpression significantly reduced the cell survival rate within 24 h(P＜0.05),while its knockdown increased the cell survival rate(P＜0.01).Real-time qPCR displayed that overexpression of ENT1 enhanced the expression levels of inflammatory factors,such as IL-1β,TNF-α,C1q-a and C1q-b in N2A cells(P＜0.05),while ENT1 knockdown reversed the above changes in inflammatory factors in N2A-APP cells(P＜0.05).Conclusion Knockdown of ENT1 attenuates pathological changes in AD by reducing the inflammatory response.ENT1 may be a potential target in the pathological mechanism of AD.

Objective: To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph⁺ patients, MLL⁺ patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) . Conclusion Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

Chronic hepatitis B (CHB) poses a serious threat to the health of the Chinese people. Viral markers are of great significance during antiviral therapy and research and development of innovative drugs. However, traditional serovirological markers such as HBV DNA and hepatitis B surface antigen (HBsAg) have certain limitations in assessing the efficacy of antiviral treatment and accurately reflecting the transcriptional activity of covalently closed circular DNA (cccDNA). In recent years, the role of new viral markers such as HBV RNA, hepatitis B core-related antigen (HBcrAg) and quantitative anti-hepatitis B core protein (qAnti-HBc) have attracted more and more attention because of accurately reflecting the transcription activity of cccDNA, determining the therapeutic effect and predicting the risk of recurrence after drug discontinuation. This article briefly introduces the application of new and old markers in various stages of antiviral therapy in CHB patients, and combines the application of new viral markers in the evaluation of drug efficacy, and expounds its possible role in the research and development of new antiviral therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.