Abstract
Background
Village clinic doctors (VCDs) are part of the health service force in rural China. VCDs’ job satisfaction (JS) is important to the stability of the three-tiered health service ...system. Since 2009, the Chinese government launched a new health care system reform (NHCSR) which affected VCDs significantly. This study aimed to analysing the effect of NHCSR on JS among VCDs.
Methods
All the data came from three surveys in Shandong Province conducted in 2012, 2015 and 2018. In 2012, an originally designed questionnaire was used to conduct a baseline survey of 405 VCDs from 27 townships in nine counties. In 2015 and 2018, 519 and 223 VCDs in the same counties were surveyed with the same questionnaire. Descriptive analysis and ANOVA were used to analyse the level and changes in VCDs’ JS.
Results
The mean scores of VCDs’ total JS were 2.664 ± 1.069, 3.121 ± 0.931 and 2.676 ± 1.044 in 2012, 2015 and 2018, respectively, with a significant difference (
F
= 28.732,
P
< 0.001). The mean scores of the medical practice environment and the job itself showed a continuous downward trend. The trends of the mean scores for job reward, internal work environment and organizational management were consistent with the trend for total JS.
Conclusion
The NHCSR had a partly negative impact on VCDs’ JS. Policy-makers should pay more attention to VCDs’ job reward and medical practice environment. With the implementation of new reform policies, VCDs’ JS should be the subject of more systematic and detailed research.
Objective This study is aimed to maximize the contrast of ultrasound imaging in limited nanometer size range, and enhance the accuracy of imaging by introducing specific targeting antibody. Methods A ...multiple scattering "FIG" nano contrast agent system was established by conventional nanobubble synthesis method. The structure of "FIG" nano contrast agent was composed of phospholipid as the bubble shell with self-decomposable nanoparticles loaded on the inner wall, and the specific antibody to glucose transporter 1 (GLUT-1) on the surface. Characterizations, in vitro and in vivo studies were employed to investigate the contrast and the accuracy of established nano bubble contrast agent. Results The in vitro imaging results revealed that with or without targeting ligand decoration, the "FIG" nano contrast agent system presented similar imaging enhancement, when compared with clinical used contrast imaging agent Sonovue. However, the imaging studies results in vivo showed that the "FIG" nano contrast agent syste
Highly sensitive staphylococcal enterotoxin B (SEB) assay is of great importance for the prevention of toxic diseases caused by SEB. In this study, we present a gold nanoparticle (AuNP)-linked ...immunosorbent assay (ALISA) for detecting SEB in a sandwich format using a pair of SEB specific monoclonal antibodies (mAbs) performed in microplates. First, the detection mAb was labeled with AuNPs of different particle sizes (15, 40 and 60 nm). Then the sandwich immunosorbent assay for SEB detection was performed routinely in a microplate except for using AuNPs-labeled detection mAb. Next, the AuNPs adsorbed on the microplate were dissolved with aqua regia and the content of gold atoms was determined by graphite furnace atomic absorption spectrometry (GFAAS). Finally, a standard curve was drawn of the gold atomic content against the corresponding SEB concentration. The detection time of ALISA was about 2.5 h. AuNPs at 60 nm showed the highest sensitivity with an actual measured limit of detection (LOD) of 0.125 pg/mL and a dynamic range of 0.125-32 pg/mL. AuNPs at 40 nm had an actual measured LOD of 0.5 pg/mL and a dynamic range of 0.5 to 128 pg/mL. AuNPs at 15 nm had an actual measured LOD of 5 pg/mL, with a dynamic range of 5-1280 pg/mL. With detection mAb labeled with AuNPs at 60 nm, ALISA's intra- and interassay coefficient variations (CV) at three concentrations (2, 8, and 20 pg/mL) were all lower than 12% and the average recovery level was ranged from 92.7% to 95.0%, indicating a high precision and accuracy of the ALISA method. Moreover, the ALISA method could be successfully applied to the detection of various food, environmental, and biological samples. Therefore, the successful establishment of the ALISA method for SEB detection might provide a powerful tool for food hygiene supervision, environmental management, and anti-terrorism procedures and this method might achieve detection and high-throughput analysis automatically in the near future, even though GFAAS testing remains costly at present.
Sonochemically prepared Pt, Au and Pd nanoparticles were successfully immobilized onto TiO2 with the assistance of prolonged sonication. Their photocatalytic activities were evaluated in H2 ...production from aqueous ethanol solutions. Beside the sonochemical method, the conventional impregnation method was also employed to prepare photocatalysts. The sonochemically prepared catalysts showed higher activities than did the conventional ones. Their photocatalytic activities depended on the work functions and the dimensions of supported noble metal nanoparticles. Smaller Pt nanoparticles effectively restricted recombination of electrons and holes and provided H2 at a higher rate.
Histone acetylation is one of the main mechanisms involved in regulation of gene expression. During carcinogenesis, tumor-suppressor genes can be silenced by aberrant histone deacetylation. This ...epigenetic modification has become an important target for tumor therapy. The histone deacetylation inhibitor, suberoylanilide hydroxamic acid (SAHA), can induce growth arrest in transformed cells. The aim of this study is to examine the effects of SAHA on gene expression and growth of glioblastoma multiforme (GBM) cells in vitro and in vivo.
The effect of SAHA on growth of GBM cell lines and explants was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Changes of the cell cycle and relative gene expression were detected by fluorescence-activated cell sorting, real-time reverse transcription-PCR, and Western blotting. After glioma cells were implanted in the brains of mice, the ability of SAHA to decrease tumor growth was studied.
Proliferation of GBM cell lines and explants were inhibited in vitro by SAHA (ED50, 2x10(-6) to 2x10(-5) mol/L, 5 days). SAHA exposure of human U87 and T98G glioma cell lines, DA66 and JM94 GBM explants, as well as a murine GL26 GBM cell line resulted in an increased accumulation of cells in G2-M of the cell cycle. Many proapoptotic, antiproliferative genes increased in their expression (DR5, TNFalpha, p21WAF1, p27KIP1), and many antiapoptotic, progrowth genes decreased in their levels (CDK2, CDK4, cyclin D1, cyclin D2) as measured by real-time reverse transcription-PCR and/or Western blot after these GBM cells were cultured with SAHA (2.5x10(-6) mol/L, 1 day). Chromatin immunoprecipitation assay found that acetylation of histone 3 on the p21(WAF1) promoter was markedly increased by SAHA. In vivo murine experiments suggested that SAHA (10 mg/kg, i.v., or 100 mg/kg, i.p.) could cross the blood-brain barrier as shown by prominent increased levels of acetyl-H3 and acetyl-H4 in the brain tissue. Furthermore, the drug significantly (P<0.05) inhibited the proliferation of the GL26 glioma cells growing in the brains of mice and increased their survival.
Taken together, SAHA can slow the growth of GBM in vitro and intracranially in vivo. SAHA may be a welcome addition for the treatment of this devastating disease.
Vaccination-route-dependent adjuvanticity was identified as being associated with the specific features of antigen-carrying nanoparticles (NPs) in the present work. Here, we demonstrated that the ...mechanical properties and the decomposability of NP adjuvants play key roles in determining the antigen accessibility and thus the overall vaccine efficacy in the immune system when different vaccination routes were employed. We showed that soft nano-vaccines were associated with more efficient antigen uptake when administering subcutaneous (S.C.) vaccination, while the slow decomposition of hard nano-vaccines promoted antigen uptake when intravenous (I.V.) vaccination was employed. In comparison to the clinically used aluminum (Alum) adjuvant, the NP adjuvants were found to stimulate both humoral and cellular immune responses efficiently, irrespective of the vaccination route. For vaccination via S.C. and I.V. alike, the NP-based vaccines show excellent protection for mice from
(
) infection, and their survival rates are 100% after lethal challenge, being much superior to the clinically used Alum adjuvant.
Nanoparticles have been identified in numerous studies as effective antigen delivery systems that enhance immune responses. However, it remains unclear whether this enhancement is a result of ...increased antigen uptake when carried by nanoparticles or the adjuvanticity of the nanoparticle carriers. Consequently, it is important to quantify antigen uptake by dendritic cells in a manner that is free from artifacts in order to analyze the immune response when antigens are carried by nanoparticles. In this study, we demonstrated several scenarios (antigens on nanoparticles or inside cells) that are likely to contribute to the generation of artifacts in conventional fluorescence-based quantification. Furthermore, we developed the necessary assay for accurate uptake quantification. PLGA NPs were selected as the model carrier system to deliver EsxB protein (a
antigen) in order to testify to the feasibility of the established method. The results showed that for the same antigen uptake amount, the antigen delivered by PLGA nanoparticles could elicit 3.6 times IL-2 secretion (representative of cellular immune response activation) and 1.5 times IL-12 secretion (representative of DC maturation level) compared with pure antigen feeding. The findings above give direct evidence of the extra adjuvanticity of PLGA nanoparticles, except for their delivery functions. The developed methodology allows for the evaluation of immune cell responses on an antigen uptake basis, thus providing a better understanding of the origin of the adjuvanticity of nanoparticle carriers. Ultimately, this research provides general guidelines for the formulation of nano-vaccines.
COVID-19 is caused by SARS-CoV-2 infection and was initially discovered in Wuhan. This outbreak quickly spread all over China and then to more than 20 other countries. SARS-CoV-2 fluorescent ...microsphere immunochromatographic test strips were prepared by the combination of time-resolved fluorescence immunoassay with a lateral flow assay. The analytical performance and clinical evaluation of this testing method was done and the clinical significance of the testing method was verified. The LLOD of SARS-CoV-2 antibody IgG and IgM was 0.121U/L and 0.366U/L. The specificity of IgM and IgG strips in healthy people and in patients with non-COVID-19 disease was 94%, 96.72% and 95.50%, 99.49%, respectively; and sensitivity of IgM and IgG strips for patients during treatment and follow-up was 63.02%, 37.61% and 87.28%, 90.17%, respectively. The SARS-CoV-2 antibody test strip can provide rapid, flexible and accurate testing, and is able to meet the clinical requirement for rapid on-site testing of virus. The ability to detect IgM and IgG provided a significant benefit for the detection and prediction of clinical course with COVID-19 patients.
Abstract The blood–brain tumor barrier (BTB) significantly limits delivery of therapeutic concentrations of chemotherapy to brain tumors. A novel approach to selectively increase drug delivery is ...pharmacologic modulation of signaling molecules that regulate BTB permeability, such as those in cGMP signaling. Here we show that oral administration of sildenafil (Viagra) and vardenafil (Levitra), inhibitors of cGMP-specific PDE5, selectively increased tumor capillary permeability in 9L gliosarcoma-bearing rats with no significant increase in normal brain capillaries. Tumor-bearing rats treated with the chemotherapy agent, adriamycin, in combination with vardenafil survived significantly longer than rats treated with adriamycin alone. The selective increase in tumor capillary permeability appears to be mediated by a selective increase in tumor cGMP levels and increased vesicular transport through tumor capillaries, and could be attenuated by iberiotoxin, a selective inhibitor for calcium-dependent potassium (KCa ) channels, that are effectors in cGMP signaling. The effect by sildenafil could be further increased by simultaneously using another BTB “opener”, bradykinin. Collectively, this data demonstrates that oral administration of PDE5 inhibitors selectively increases BTB permeability and enhances anti-tumor efficacy for a chemotherapeutic agent. These findings have significant implications for improving delivery of anti-tumor agents to brain tumors.
Neural progenitor-like cells have been isolated from bone marrow and the cells have the ability of tracking intracranial tumor. However, the capacity of the cells to deliver molecules for activating ...immune response against intracranial tumor and the identity of cellular and molecular factors that are involved in such immune responses have yet to be elucidated. Here, we isolated neural stem-like cells from the bone marrow of adult mice. The isolated cells were capable of producing progenies of three lineages, neurons, astrocytes, and oligodendrocytes, in vitro and tracking glioma in vivo. By genetically manipulating bone marrow-derived neural stem-like cells (BM-NSC) to express a recently discovered cytokine, interleukin (IL)-23, the cells showed protective effects in intracranial tumor-bearing C57BL/6 mice. Depletion of subpopulation lymphocytes showed that CD8(+) T cells were critical for the antitumor immunity of IL-23-expressing BM-NSCs and that CD4(+) T cells and natural killer (NK) cells participated in the activity. Furthermore, the IL-23-expressing BM-NSC-treated survivors were resistant to the same tumor rechallenge associated with enhanced IFN-gamma, but not IL-17, expression in the brain tissue. Taken together, these data suggest that IL-23-expressing BM-NSCs can effectively induce antitumor immunity against intracranial gliomas. CD8(+) T cells are critical for such antitumor activity; in addition, CD4(+) T cells and NK cells are also involved.
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