The HSP40 family chaperone isoform DNAJB6b prevents neuronal cells from tau aggregation.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder with clinical presentations of progressive cognitive and memory deterioration. The pathologic hallmarks of AD include tau neurofibrillary tangles and amyloid plaque depositions in the hippocampus and associated neocortex. The neuronal aggregated tau observed in AD cells suggests that the protein folding problem is a major cause of AD. J-domain-containing proteins (JDPs) are the largest family of cochaperones, which play a vital role in specifying and directing HSP70 chaperone functions. JDPs bind substrates and deliver them to HSP70. The association of JDP and HSP70 opens the substrate-binding domain of HSP70 to help the loading of the clients. However, in the initial HSP70 cycle, which JDP delivers tau to the HSP70 system in neuronal cells remains unclear. RESULTS: We screened the requirement of a diverse panel of JDPs for preventing tau aggregation in the human neuroblastoma cell line SH-SY5Y by a filter retardation method. Interestingly, knockdown of DNAJB6, one of the JDPs, displayed tau aggregation and overexpression of DNAJB6b, one of the isoforms generated from the DNAJB6 gene by alternative splicing, reduced tau aggregation. Further, the tau bimolecular fluorescence complementation assay confirmed the DNAJB6b-dependent tau clearance. The co-immunoprecipitation and the proximity ligation assay demonstrated the protein-protein interaction between tau and the chaperone-cochaperone complex. The J-domain of DNAJB6b was critical for preventing tau aggregation. Moreover, reduced DNAJB6 expression and increased tau aggregation were detected in an age-dependent manner in immunohistochemical analysis of the hippocampus tissues of a mouse model of tau pathology. CONCLUSIONS: In summary, downregulation of DNAJB6b increases the insoluble form of tau, while overexpression of DNAJB6b reduces tau aggregation. Moreover, DNAJB6b associates with tau. Therefore, this study reveals that DNAJB6b is a direct sensor for its client tau in the HSP70 folding system in neuronal cells, thus helping to prevent AD.

An analysis on rational use and affordability of medicine after the implementation of National Essential Medicines Policy and Zero Mark-up Policy in Hangzhou, China.

BACKGROUND: The National Essential Medicine Policy and the Zero Mark-up Policy was introduced to improve the rational use and affordability of medicine. This study analyzed the changes of medicine use at different Health Care Institutions in Hangzhou city after the implementation of National Essential Medicine Policy and the Zero Mark-up Policy. METHODS: Facility based survey was conducted in 17 Health Care Institutions and 16406 outpatient prescriptions in 2011 and 2013 were collected. Average number of medicines, average number of antibiotics and average expenditure per prescription were analyzed. Comparisons between 2011 and 2013, among different levels of Health Care Institutions and age groups were conducted. RESULTS: The average number of medicines per prescription, use of antibiotics, intramuscular (IM) injections and intravenous (IV) injections decreased while the use of hormones increased. No significant change of the average medicine expenditure per prescription was observed. Disparities among different levels of Health Care Institutions and different age groups existed. CONCLUSION: The problems of poly-pharmacy, overuse of antibiotics, intramuscular (IM) injections and intravenous (IV) injections and hormones still existed, however mitigated after the implementation of The National Essential Medicine Policy and the Zero Mark-up Policy.

Availability, use, and affordability of medicines in urban China under universal health coverage: an empirical study in Hangzhou and Baoji.

BACKGROUND: This study aimed to examine the availability, use, and affordability of medicines in urban China following the 2009 Health Care System Reform that included implementation of universal health coverage (UHC). METHODS: This longitudinal study was performed in Hangzhou (high income, eastern China) and Baoji (lower income, western China). Five yearly household surveys were conducted (one each year from 2009 to 2013) to evaluate the impact of UHC on medicines use and expenditure, and a health facility survey was conducted in 2013 to evaluate availability of medicines. A cohort of over 800 households in Hangzhou and Baoji was established in 2009, and 20 hospitals were included in the health facility survey. Medicines use was determined using data from health facility and household surveys. An average, two-week out-of-pocket medicines expenditure was calculated to assess the affordability of medicines. RESULTS: The number of medicines stocked in primary health facilities in Hangzhou decreased, while the number in Baoji increased. In Baoji, patients usually chose a pharmacy to buy medicines directly, despite the 48.2% increased availability of essential medicines in primary health care centers. The majority of survey respondents stated that their medicines need was basically met; however, medicines cost still accounted for a major part of their health expenditure. Medicines expenditure showed an increasing trend from 2009 to 2013. The average annual growth rate of household overall medical expenditure was significantly higher than that for household non-food consumption expenditure. CONCLUSIONS: Following China's Health Care System Reform and implementation of UHC, availability and use of medicines has improved in urban areas. However, the affordability of medicines is still a concern.

Application of Traditional Chinese Medicine in medical practice: a survey of community residents in Beijing, China.

OBJECTIVE: To investigate how community residents in Beijing understood and used Traditional Chinese Medicine (TCM) in their medical practice. METHODS: This was a cross-sectional study conducted on 3410 community residents from four large communities of Tongzhou district in Beijng, China. A validated, self-administered questionnaire comprised of three sections was used to gather the data. A systematic sampling procedure was applied to recruit the community residents. RESULTS: A total of 3410 participants completed the questionnaire survey. It showed that in highly educated residents, 33.4% (170) knew of the names of 3-10 Chinese herbals, 35.8% (182) knew of names of 3-10 traditional Chinese patent drug. Among all the respondent residents, 80.7% (2753) believed that TCM herbal therapy and TCM non-drug treatments were effective in disease treatment, health enhancement, 85.7% (2923) had taken traditional Chinese patent drug in their life, 56.8% (1937) of residents had used herbal decoction, 40.0% (1365) had received non-drug treatment of TCM, such as acupuncture, massage, cupping, auricular acupuncture. Among the elderly residents, 11.4% (98) often used Chinese patent drug and 9.8% (85) often used herbal decoction. In addition, 70.8% (2415) of residents were willing to accept knowledge and information on TCM for health enhancement and disease prevention, such as medicated diet, medicinal tea, Tai Chi and Qi Gong, although 82.8% (2825) of residents had never used them. CONCLUSION: Chinese patent drug and herbal decoction are widely used in the communities in Beijing, and there existed a possible close correlation between high educational level and better understanding of TCM. Age and occupation also correlated with the attitude to TCM therapies. The characteristics of the residents should be considered seriously in the course of promoting the understanding and application of TCM.

Economic Burden in Chinese Patients with Diabetes Mellitus Using Electronic Insurance Claims Data.

BACKGROUND: There is a paucity of studies that focus on the economic burden in daily care in China using electronic health data. The aim of this study is to describe the development of the economic burden of diabetic patients in a sample city in China from 2009 to 2011 using electronic data of patients' claims records. METHODS: This study is a retrospective, longitudinal study in an open cohort of Chinese patients with diabetes. The patient population consisted of people living in a provincial capital city in east China, covered by the provincial urban employee basic medical insurance (UEBMI). We included any patient who had at least one explicit diabetes diagnosis or received blood glucose lowering medication in at least one registered outpatient visit or hospitalization during a calendar year in the years 2009-2011. Cross-sectional descriptions of different types of costs, prevalence of diabetic complications and related diseases, medication use were performed for each year separately and differences between three years were compared using a chi-square test or the non-parametric Kruskal-Wallis H test. RESULTS: Our results showed an increasing trend in total medical cost (from 2,383 to 2,780 USD, p = 0.032) and diabetes related cost (from 1,655 to 1,857 USD) for those diabetic patients during the study period. The diabetes related economic burden was significantly related to the prevalence of complications and related diseases (p<0.001). The overall medication cost during diabetes related visits also increased (from 1,335 to 1,383 USD, p = 0.021). But the use pattern and cost of diabetes-related medication did not show significant changes during the study period. CONCLUSION: The economic burden of diabetes increased significantly in urban China. It is important to improve the prevention and treatment of diabetes to contribute to the sustainability of the Chinese health-care system.

Using primary care electronic health record data for comparative effectiveness research: experience of data quality assessment and preprocessing in The Netherlands.

AIM: Details of data quality and how quality issues were solved have not been reported in published comparative effectiveness studies using electronic health record data. METHODS: We developed a conceptual framework of data quality assessment and preprocessing and apply it to a study comparing angiotensin-converting enzyme inhibitors with angiotensin receptor blockerss on renal function decline in diabetes patients. RESULTS: The framework establishes a line of thought to identify and act on data issues. The core concept is to evaluate whether data are fit-for-use for research tasks. Possible quality problems are listed through specific signal detections, and verified whether they are true problems. Optimal solutions are selected for the identified problems. CONCLUSION: This framework can be used in observational studies to improve validity of results.

Comparing the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal function decline in diabetes.

AIM: To compare effectiveness of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) for protecting Type 2 diabetes mellitus (DM2) patients from renal function decline in a real-world setting. METHODS: Retrospective cohort study of new ACEi/ARB users in 2007-2012 in an unselected primary care DM2 population. Outcome is decline in renal function stage (combining estimated glomerular filtration rate and albuminuria). Patients were matched on a propensity score. Extended Cox models with time-varying covariates were used to estimate hazard ratios of outcome. RESULTS: The time to renal function decline for ARB users was slightly, but not significantly longer than for ACEi users (hazard ratio: 0.80; 95% CI: 0.58-1.10; p = 0.166). CONCLUSION: This study did not show significant differences between the classes in preventing renal function decline in DM2 patients in primary care.

Benefits of Chinese Medicine Among Patients with Diabetic Foot: An Expert Review from Clinical Studies.

BACKGROUND: Increasing attention is being given to the use of Chinese medicine (CM) for preventing and healing vascular complications of chronic ulcerative lesions of diabetic foot. OBJECTIVES: The purposes of this paper are to describe some benefits of CM for the treatment of diabetic foot and to provide some expert opinions based on some case studies and evidence from documented Chinese traditional medicine literature. METHODS: A critical review of the literature and a case report. RESULTS: Cumulative evidence in the literature indicate that CM preparations possess anti-inflammatory activities, antioxygenation, antibiosis, antibacterial, antiallergic and beneficial effect on the viability of fibroblasts. Case record suggested that after CM treatment the patient with Wagner Grade IV ulcers healed completely. CONCLUSION: It is becoming increasingly important for integrated CM and biomedicine therapy to treat diabetes-related vascular complications. The opportunities for effective CM interventions are significant, and more solid evidence is warranted to show the efficacy of CM in the treatment of diabetic foot ulcers in the near future.

Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy: a systematic review.

BACKGROUND: Structured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy. METHODS: A systematic literature search was performed in MEDLINE and EMBASE for the period from November 1, 1999 to Oct 31, 2011. Two reviewers independently assessed the quality of the articles included and extracted data. All cost-effectiveness results were converted to 2011 Euros. RESULTS: Up to October 2011, 434 articles were identified. After full-text checking and quality assessment, 30 articles were finally included in this review involving 39 study settings. All 6 ACEIs studies were literature-based evaluations which synthesized data from different sources. Other 33 studies were directed at ARBs and were designed based on specific trials. The Markov model was the most common decision analytic method used in the evaluations. From the cost-effectiveness results, 37 out of 39 studies indicated either ACEIs or ARBs were cost-saving comparing with placebo/conventional treatment, such as amlodipine. A lack of evidence was assessed for valid direct comparison of cost-effectiveness between ACEIs and ARBs. CONCLUSION: There is a lack of direct comparisons of ACEIs and ARBs in existing economic evaluations. Considering the current evidence, both ACEIs and ARBs are likely cost-saving comparing with conventional therapy, excluding such RAAS inhibitors.