Objective To investigate the anti-hepatocarcinoma(anti-HCC) function of HLA-A2-restricted point-mutated Survivin peptide induced CTLs.Methods The HLA-A2-restricted Survivin nonapeptides were evaluated using bioinformatics software.The binding affinity of Survivin peptide to HLA-A2 molecular was determined with flow cytometry analysis.After peptide-induced CTLs were generated in vitro,flow cytometry and ELISA were performed to detect the levels of IFN-γ,which were secreted by reactive CTLs.Peptide-induced CTLs were co-cultured with hepatoma cell lines HepG2 and BEL-7402.The rates of tumor cells lysis were assayed using CytoTox 96(R) and the morphological changes of tumor cells were observed with inverted phase contrast microscope.Results Point-mutated Survivin nonapeptide Sur79M2 (KMSSGCAFL) was filtered out,which was shown higher scores compared with the wild-type peptide Sur79.Consistent with the results of software analysis,Sur79M2 showed higher binding ability in T2 binding assays.At the same time,Sur79M2-induced CTLs could release a large number of IFN-γ after incubated with target cells rather than Sur79.When co-cultured with HCC cell lines HepG2 and BEL-7402,Sur79M2-induced CTLs effectively lysis HepG2 on HLA-A2-restricted manner without killing effect on BEL-7402 that do not express HLA-A2 molecules.Conclusion Sur79M2 could elicited specific cytotoxic T lymphocytes in vitro,which were able to specifically kill HCC cell lines on HLA-A2-restricted manner.

OBJECTIVETo explore the stress related problems and risk factors among urban residents in the social transition period.

METHODSSamples including 3 666 subjects came from Hangzhou, Guangzhou, Chongqing and Taiyuan under multi-stage sampling procedure. Data were collected through a household interviewing survey. Stress was measured by the Chinese Perceived Stress Scales (CPSS). Distribution of health risk stress (HRS), high level stress were described along the demographic dimension. Multivariate logistic analysis was used to identify the predictors of HRS.

RESULTSCPSS was found to have good validity and reliability among this study sample. The mean score for the total sample was 24.22 +/- 5.81 and the overall prevalence of HRS was 44.54% (95% CI: 42.90 - 46.12). The difference between male (42.95%) and female (46.30%) was statistically significant (P < 0.05). The rate of HRS decreased with age, with the highest rate (59.29%) among those less than 21 years old. The rate of HRS also decreased as educational level increased and differed significantly by occupation. High school students, people who had never been employed and those who had lost their jobs had the highest rates of HRS. The rate of HRS was also related to marriage status, household's economic level, and the level of the social engagement of the subjects.

CONCLUSIONStress experienced by the urban residents became a serious health problem which requires special attention to be paid to certain subgroups in the population.

Adult ; Age Factors ; Aged ; China ; epidemiology ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Sex Factors ; Social Environment ; Stress, Psychological ; epidemiology ; Urban Health

OBJECTIVETo investigate the relationship between sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) of rabbit with chronic myocardial infarction (MI).

METHODSThirty rabbits were randomly assigned into two groups: MI group (n = 20): ligation of the anterior descending coronary; sham operation (SO) group (n = 10): without contrary ligation. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, during sympathetic nerve stimulation, TDR change (DeltaTDR) during sympathetic nerve stimulation and ventricular fibrillation threshold (VFT) were measured at the IBZ in MI group and corresponding zone in SO group. The distribution and densities of growth associated protein 43 (GAP43) and tyrosine hydroxylase (TH) positive nerves in ventricle were also detected with immunohistochemical techniques.

RESULTSEighteen rabbits in the MI group and 10 in the SO group survived to the end of the study. The densities of GAP43 and TH at the IBZ in the MI group were significantly higher than that at the corresponding zone in the SO group (both P < 0.05). The densities of GAP43 and TH in MI rabbits positively correlated with TDR at baseline, TDR or DeltaTDR during sympathetic nerve stimulation (all P < 0.01) and both showed a weak negative correlation with VFT (r =-0.44, P = 0.07; r = -0.41, P = 0.09, respectively).

CONCLUSIONSympathetic remodeling is correlated with electrical remodeling at the IBZ in rabbits with chronic MI.

Action Potentials ; Animals ; Humans ; Male ; Myocardial Infarction ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Sympathetic Nervous System ; physiopathology

OBJECTIVETo clone and express VP, gene from HBoV, and the expressed VP, protein was as the antigen in order to detect serum from children in Wenling area with lower respiratory tract infections.

METHODSThe VP, gene was recombined with the genome of Baculovirus, which infected the insect cell. The fusion protein with HA tag was applied to confirm the specificity of expressed protein. Furthermore, the recombinant protein was observed using electron microscopy. The 176 serum from children in Wenling area with lower respiratory tract infections was screened using Western blot.

RESULTSThe expressed VP2 protein was more than 60% in total proteins from insect cell, and MWt about 60 x 10(3). The virus-like particle (VLP) was observed using electron microscopy, and size about 20 nm. The 176 serum from children in wenling area with lower respiratory tract infections was screened using Western blot. The HBoV positive rate was 2.28% (4/176).

CONCLUSIONThe VP2 protein from human bocavirus was expressed in insect cell successfully. Through HA tag the VP2 protein was specific, and then the assay using SDS-PAGE with Western blot could detect and screen the antibody in serum from children with lower respiratory tract infections rapidly and accurately.

Animals ; Antibodies, Viral ; blood ; Bocavirus ; genetics ; immunology ; Capsid Proteins ; genetics ; immunology ; Child, Preschool ; Female ; Gene Expression ; Humans ; Infant ; Male ; Parvoviridae Infections ; blood ; diagnosis ; immunology ; virology ; Recombinant Proteins ; genetics ; immunology ; Spodoptera

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*

OBJECTIVE: To study the correlation between fractional exhaled nitric oxide (FeNO) and airway reversibility in children with IgE-mediated asthma. METHODS: A total of 86 children, aged 6-14 years, who were initially diagnosed with acute attack of asthma from September 2016 to August 2018 were enrolled as subjects. According to the results of serum specific IgE, they were divided into IgE mediated group with 61 children and non-IgE mediated group with 25 children. According to the results of allergen detection, the IgE mediated group was further divided into four groups with one, two, three, and four or more positive allergens. FeNO and the parameters of pulmonary ventilation function before and after dilation test were measured. Pearson correlation analysis was used to evaluate the correlation of FeNO with each parameter of pulmonary function. RESULTS: The IgE mediated group had significantly higher FeNO than the non-IgE mediated group (P<0.05). FeNO increased with the increase in the number of positive serum specific allergens (P<0.05). In the IgE mediated group, FeNO level was positively correlated with the change in forced expiratory volume in the first second (FEV1) and the improvement in percentage of predicted FEV1 after medication in bronchial dilation test (r=0.655 and 0.473 respectively, P<0.05). The FeNO level was not correlated with FEV1, percentage of predicted FEV1, peak expiratory flow (PEF), change in PEF after medication, percentage of predicted PEF (PEF%pred), and improvement in PEF%pred after medication (P>0.05). In the non-IgE mediated group, FeNO level was not correlated with the above indicators (P>0.05). CONCLUSIONS FeNO level is associated with the degree of allergies. For children with IgE-mediated asthma, FeNO is positively correlated with airway reversibility, which has a certain value in the diagnosis of asthma, disease evaluation, and understanding of airway reversibility. For children with non-IgE-mediated asthma, FeNO cannot be used to evaluate airway reversibility. These two types of asthma should be treated differently.
Adolescent ; Asthma ; Breath Tests ; Child ; Forced Expiratory Volume ; Humans ; Immunoglobulin E ; Nitric Oxide ; Respiratory Function Tests

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. Methods: Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. Results: From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. Conclusions This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.