Constructing a Basefile for Simulating Kunming’s Medical Insurance Scheme of Urban Employees

Focusing on China’s medical insurance scheme which covers all employers and employees in urban areas, this research aims to assess the distributional impacts of medical insurance policies and to predict medical expenses by using microsimulation techniques. As an important part of the project, this article provides a brief overview of China’s medical insurance reform of urban employees and detail the techniques and processes to construct a basefile in 2005 for projecting the medical expenditures for urban employees over the period of 2006-2010. The main data used are administrative medical records of medical insurance participants provided by the Bureau of Labour and Social Security of Kunming, Yunnan Province. Along with the initial analysis for the raw datasets and age processing and adjustment for the individual records, monthly income information was imputed and personal savings accounts were established for each individual record. Important modelling parameters such as death rates and income adjustment factors were constructed. Furthermore, this article identifies medical insurance for government officials by using the combination of logarithm curve fitting and binary discriminant analysis. Based on this basefile, a static microsimulation model can be built to assess the implementation effects of the medical insurance policy and analyse the impact of the medical insurance scheme on urban employees.Urban medical insurance, China, microsimulation, basefile, Policy Research

Constructing an Urban Population Model for Medical Insurance Scheme Using Microsimulation Techniques

China launched a pilot project of medical insurance reform in 79 cities in 2007 to cover urban nonworking residents. An urban population model was created in this paper for China's medical insurance scheme using microsimulation model techniques. The model made it clear for the policy makers the population distributions of different groups of people, the potential urban residents entering the medical insurance scheme. The income trends of units of individuals and families were also obtained. These factors are essential in making the challenging policy decisions when considering to balance the long-term financial sustainability of the medical insurance scheme

Protective Effect of Tetramethylpyrazine on Myocardial Ischemia-Reperfusion Injury

Myocardial ischemia-reperfusion injury (MIRI) is a common pathological and physiological phenomenon. Tetramethylpyrazine is the extract of the traditional Chinese medicine Chuanxiong, which can exert protective effects on MIRI in multiple ways. This paper reviewed the current research progress and evidence about the cardiovascular effects of tetramethylpyrazine, which included protecting mitochondria and improving energy metabolism, scavenging oxygen free radicals (OFRs) to inhibit lipid peroxidation, attenuating calcium (Ca2+) overload and maintaining Ca2+ homeostasis in cells, inhibiting apoptosis and protecting myocardial cells, interfering with the inflammatory reaction and mitigating cell injury, interfering with cell signaling pathways, and improving function of endothelial cells and protecting myocardial cells. However, further rigorously designed randomized controlled trials are warranted

Safety Profile of Gutless Adenovirus Vectors Delivered into the Normal Brain Parenchyma: Implications for a Glioma Phase 1 Clinical Trial

Abstract Adenoviral vectors (Ads) have been evaluated in clinical trials for glioma. However, systemic immunity against the vectors can hamper therapeutic efficacy. We demonstrated that combined immunostimulation and cytotoxic gene therapy provides long-term survival in preclinical glioma models. Because helper-dependent high-capacity Ads (HC-Ads) elicit sustained transgene expression, in the presence of antiadenoviral immunity, we engineered HC-Ads encoding conditional cytotoxic herpes simplex type 1 thymidine kinase and immunostimulatory cytokine Fms-like tyrosine kinase ligand-3 under the control of the TetOn system. Escalating doses of combined HC-Ads (1?108, 1?109, and 1?1010 viral particles [VP]) were delivered into the rat brain. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points after vector delivery. Histopathological analysis did not reveal any evidence of toxicity or long-term inflammation at the lower doses tested. Vector genomes were restricted to the injection site. Serum chemistry did not uncover adverse systemic side effects at any of the doses tested. Taken together, our data indicate that doses of up to 1?109 VP of each HC-Ad can be safely administered into the normal brain. This comprehensive toxicity and biodistribution study will lay the foundations for implementation of a phase 1 clinical trial for GBM using HC-Ads.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98452/1/hgtb%2E2012%2E060.pd

Is Yangxue Qingnao Granule Combined with Antihypertensive Drugs, a New Integrative Medicine Therapy, More Effective Than Antihypertensive Therapy Alone in Treating Essential Hypertension?

Background. Yangxue Qingnao granule (YQG) combined with antihypertensive drugs, a new integrative medicine therapy, has been widely used for essential hypertension (EH) in China. This study aims to assess the current clinical evidence of YQG combined with antihypertensive drugs for EH. Methods. Randomized controlled trials(RCTs) published between 1996 and 2012 on YQG combined with antihypertensive drugs versus antihypertensive drugs in treating EH were retrieved from six major electronic databases, including The Cochrane Library, PubMed, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Data. Meta-analysis was performed on the overall effects on blood pressure. Results. Twelve randomized trials were included. Methodological quality of the trials was evaluated as generally low. Meta-analysis showed that YQG combined with antihypertensive drugs demonstrated potential effect for lowing either SBP (MD: −7.31 [−11.75, −2.87]; P=0.001) or DBP (MD: −5.21 [−8.19, −2.24]; P=0.0006) compared to antihypertensive drugs alone. Conclusions. It indicated that YQG combined with antihypertensive drugs is more effective than antihypertensive drugs alone in treating EH. However, more RCTs of larger scale, multicentre/country, longer follow-up periods, and higher quality are required to verify the efficacy of integrative medicine therapy over all antihypertensive therapies

Study of the Efficacy, Biodistribution, and Safety Profile of Therapeutic Gutless Adenovirus Vectors as a Prelude to a Phase I Clinical Trial for Glioblastoma

Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in humans. Systemic immunity against gene therapy vectors has been shown to hamper therapeutic efficacy; however, helper-dependent high-capacity adenovirus (HC-Ad) vectors elicit sustained transgene expression, even in the presence of systemic anti-adenoviral immunity. We engineered HC-Ads encoding the conditional cytotoxic herpes simplex type 1 thymidine kinase (TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Flt3L). Flt3L expression is under the control of the regulatable Tet-ON system. In anticipation of a phase I clinical trial for GBM, we assessed the therapeutic efficacy, biodistribution, and clinical and neurotoxicity with escalating doses of HC-Ad-TetOn-Flt3L + HC-Ad-TK in rats. Intratumoral administration of these therapeutic HC-Ads in rats bearing large intracranial GBMs led to long-term survival in ~70% of the animals and development of antiglioma immunological memory without signs of neuropathology or systemic toxicity. Systemic anti-adenoviral immunity did not affect therapeutic efficacy. These data support the idea that it would be useful to develop HC-Ad vectors further as a therapeutic gene-delivery platform to implement GBM phase I clinical trials

Release of HMGB1 in Response to Pro-Apoptotic Glioma Killing Strategies: Efficacy and Neurotoxicity

Purpose In preparation for a Phase I clinical trial utilizing a combined cytotoxic/immunotherapeutic strategy using adenoviruses expressing Flt3L (Ad-Flt3L) and thymidine kinase (Ad-TK) to treat glioblastoma (GBM), we tested the hypothesis that Ad-TK+GCV would be the optimal tumor killing agent in relation to efficacy and safety when compared to other pro-apoptotic approaches. Experimental Design and Results The efficacy and neurotoxicity of Ad-TK+GCV was compared with Ads encoding the pro-apoptotic cytokines (TNF-α, TRAIL, FasL), alone or in combination with Ad-Flt3L. In rats bearing small GBMs (day 4), only Ad-TK+GCV or Ad-FasL improved survival. In rats bearing large GBMs (day 9), the combination of Ad-Flt3L with Ad-FasL did not improve survival over FasL alone, while Ad-Flt3L combined with Ad-TK+GCV led to 70% long-term survival. Expression of FasL and TRAIL caused severe neuropathology, which was not encountered when we utilized Ad-TK+/−Ad-Flt3L. In vitro, all treatments elicited release HMGB1 from dying tumor cells. In vivo, the highest levels of circulating HMGB1 were observed after treatment with Ad-TK+GCV+Ad-Flt3L; HMGB1 was necessary for the therapeutic efficacy of AdTK+GCV+Ad-Flt3L, since its blockade with glycyrrhizin completely blocked tumor regression. We also demonstrated the killing efficacy of Ad-TK+GCV in human GBM cell lines and GBM primary cultures; which also elicited release of HMGB1. Conclusions Our results indicate that Ad-TK+GCV+Ad-Flt3L exhibits the highest efficacy and safety profile amongst the several pro-apoptotic approaches tested. The results reported further support the implementation of this combined approach in a Phase I clinical trial for GBM

T cell–derived inducible nitric oxide synthase switches off TH17 cell differentiation

RORγt is necessary for the generation of TH17 cells but the molecular mechanisms for the regulation of TH17 cells are still not fully understood. We show that activation of CD4+ T cells results in the expression of inducible nitric oxide synthase (iNOS). iNOS-deficient mice displayed enhanced TH17 cell differentiation but without major effects on either TH1 or TH2 cell lineages, whereas endothelial NOS (eNOS) or neuronal NOS (nNOS) mutant mice showed comparable TH17 cell differentiation compared with wild-type control mice. The addition of N6-(1-iminoethyl)-l-lysine dihydrochloride (L-NIL), the iNOS inhibitor, significantly enhanced TH17 cell differentiation, and S-nitroso-N-acetylpenicillamine (SNAP), the NO donor, dose-dependently reduced the percentage of IL-17–producing CD4+ T cells. NO mediates nitration of tyrosine residues in RORγt, leading to the suppression of RORγt-induced IL-17 promoter activation, indicating that NO regulates IL-17 expression at the transcriptional level. Finally, studies of an experimental model of colitis showed that iNOS deficiency results in more severe inflammation with an enhanced TH17 phenotype. These results suggest that NO derived from iNOS in activated T cells plays a negative role in the regulation of TH17 cell differentiation and highlight the importance of intrinsic programs for the control of TH17 immune responses

The influence of mass media on countryside leisure visit behaviour compared to the influence of childhood socialization: a structural model of relationships.

Those involved with the management of the countryside have an imperative to understand the drivers of behaviour towards it. This is particularly so, since the UK population is largely urban-based and yet still retains an attachment to green open spaces and engagement with the pastoral scene (DEFRA, 2009; Natural England, 2016). The media has been recognised as playing an important role in sustaining this attachment but its relative influence compared to the role of the family, other social groups and education is less well understood in this context. The aim of this research is to provide a measure of the influences that underpin this attachment, specifically to develop a better understanding of the role of mass media as a component of the socializing factors which influence attitudes towards leisure behaviour in the countryside. The measurement and exploration of these influences is based upon a pilot study, followed by a survey of 2775 respondents, in six urban centres in England during 2011 and 2012. The data was analysed in order to investigate the relative role of developmental and mass media influences on countryside leisure behaviour. The cognitive and emotional processes that catalyse these relationships were also evaluated. A structural model of relationships was then developed, which provided predictive measures of the formative influences upon countryside leisure behaviour. Three key findings emerged from the research. The first confirmed that interest in countryside leisure may be derived from early socialization influences but significantly there are sub-groups for whom this early experience is irrelevant. These sub-groups developed their interest in countryside in later adulthood, inspired by the cultural discourse of rural themes represented in the media. Secondly the research identified that the relative influence of early exposure to countryside interests from family and friends is weaker than the direct effect of media on current countryside visit behaviour. Thirdly the predictive relationship suggests that countryside knowledge, the normative and control influences of others and the media, work largely through emotional rather than cognitive processes in their effect upon countryside visit behaviour. A further outcome of the research identified a control influence upon attitudes and engagement with the countryside, driven by pragmatic considerations of countryside as a resource for housing and infrastructure needs. The significant findings from this research make a contribution to knowledge regarding the processes that influence countryside leisure attitudes and behaviour. Specifically, it confirms the importance of developing media strategy that reflects the emotional bond that people have with the countryside and targeting robust market segments, differentiated by media responsiveness and developmental influences. An effective media strategy is particularly important for those sections of the population, who have had little encouragement to engage with the countryside during childhood but are, in adulthood, responsive to its portrayal in the media