The microtubule-associated protein 'tau' is primarily expressed within axons in the central nervous system where it stabilizes microtubules and aids in cargo transport. While basal phosphorylation of tau is normal, tau modifications, predominantly hyperphosphorylation, are critical in the pathogenesis of numerous neurodegenerative disorders known as the tauopathies. Over the years, tau has been shown to be a valuable and elusive target for the treatment of neurodegenerative diseases. Targeting tau via genetic, biological, and pharmacological approaches in vitro and in vivo may prevent degenerative pathologies. However, to date none of these approaches have been successful in human studies, albeit some promising studies are currently underway. This review aims to briefly discuss the biology and pathology of tau and summarize current treatment strategies in clinical trials.

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Background and objectives: According to Chinese White Paper on Osteoporosis Prevention (2009), an estimated number of 69 million Chinese people are experiencing osteoporosis caused by loss and deterioration of bone mineral density (BMD). Middle-aged women have a greater possibility in developing osteoporosis in comparison with men because of a decreased estrogen level and degeneration in physical fitness level. A Tai Chi-based intervention in the present study will be created based on four components consisting of fall-prevention/balance training, stretching/flexibility training, resistance training (Tai Chi push hand), and strength training. Design: A prospective three-arm parallel randomized controlled trial. Methods: This study will take place in ten community centers in southeast China, and postmenopausal women aged 50–65 years and without menses for 6–12 months will be recruited and randomly assigned into three groups with the allocation ratio of 1:1:1 (n = 50 for each group), including two experimental groups (a traditional Tai Chi group and a modified Tai Chi-based intervention group) and a control group. Participants in the control group will be asked to maintain their original lifestyle during the 12-month intervention period. Participants in the traditional Tai Chi and modified Tai Chi-based intervention groups will experience the traditional Yang-style Tai Chi and receive the modified Tai Chi-based intervention, respectively. The modified Tai Chi-based intervention contains four components: 1) eight Tai Chi based fall-prevention movements; 2) ten Qigong-based stretching/flexibility movements; 3) eight resistance training-based Tai Chi push hand movements; 4) eight Chen style-based Tai Chi movements. For both the experimental groups, study participants will experience four 60-minute Tai Chi training sessions weekly for 12 months. Outcome measures: BMD at multiple musculoskeletal regions is primary outcome measure. Secondary outcome measures include low limb muscle strength, physical function, and reaction time at both upper and low limbs, which will be measured at baseline and 12 months (at the end of the intervention). Discussion: Results of this study will provide preliminary evidence regarding the value of Tai Chi movement as an intervention for attenuating BMD loss in postmenopausal women. Ethics and dissemination: This study protocol was approved by the Institution Review Board of Shanghai Sports University (approval No. 11290502800) and will be performed in accordance with the principles of the Declaration of Helsinki. Patient recruitment started in August 2017. The analysis of primary outcome measures will be completed in October 2018. The estimated study completion date is June 2019. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR-IOR-15005887) on 27 January 2015.

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Background and objectives: Hypoxia is an important factor that affects bone formation and regulates bone growth. Therefore, many older adult patients living in high-altitude hypoxic areas exhibit osteoporosis. Oxidative stress-related hypoxia-inducible factors can induce abnormal expression of various factors including vascular endothelial growth factor (VEGF), insulin-like growth factor, and endothelin. However, it remains unclear whether these factors influence changes in bone metabolic markers. This study protocol aimed to investigate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude hypoxic area of China. Design: A prospective, single-center, non-randomized, controlled trial. Methods: One hundred and twenty older adult male patients with degenerative osteoporosis residing in the high-altitude area of China who receive treatment at the Affiliated Hospital of Qinghai University of China between January 2015 and February 2018 are being included in the osteoporosis group. One hundred and twenty healthy older adult males who concurrently received physical examination are being included in the control group. One day after admission, serum levels of hypoxia-inducible factor 1-alpha (HIF-1α), HIF-2α, VEGF, osteocalcin, and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured using an enzyme-linked immunosorbent assay. Bone mineral density in L1–4 segments, right femoral neck, and the greater trochanter of the femur was detected using dual-energy X-ray absorptiometry. Outcome measures: The primary outcome measure of this study is serum HIF-1α levels at 1 day after admission. Secondary outcome measures include serum levels of HIF-1α, HIF-2α, VEGF, osteocalcin, and TRACP 5b at 1 day after admission, as well as the correlation between serum levels of oxidative stress indicators (HIF-1α, HIF-2α, and VEGF) and bone metabolic markers (osteocalcin and TRACP 5b) at 1 day after admission. Discussion: Findings from this study aim to validate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude area of China. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval No. QHY1402G). The study was performed in accordance with the Declaration of Helsinki. Participants are informed of the study protocol and procedures, and sign an informed consent. Participant recruitment, blood sampling, and data collection began in January 2015 and will be ended in February 2018. Outcome measure analysis and trial completion will be in March 2018. Results will be disseminated through presentations at scientific meetings and/or by publication in peer-reviewed journals. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17012848).

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Background and objective: Previous studies have demonstrated that tissue Doppler echocardiography and two-dimensional speckle tracking echocardiography are minimally invasive imaging methods used to screen for coronary atherosclerotic heart disease. However, they are not highly sensitive and specific for patients with suspected heart disease presenting with normal ventricular wall motion or for patients with early coronary heart disease. The newly emerging three-dimensional longitudinal strain imaging technology can overcome these shortcomings and has become a relatively mature technique for quantitative assessment of myocardial function. The left ventricular global longitudinal peak strain (LVGLPS) measured by three-dimensional longitudinal strain imaging technology contributes to early diagnosis of high-risk coronary atherosclerotic heart disease. Design: Single-center, open-label, diagnostic trial. Methods: Three hundred older adult patients with suspected coronary atherosclerotic heart disease receiving treatment from January 2013 to December 2017 at the Department of Ultrasound Medicine, Taihe Hospital of China, are being included in this study. These patients will be divided into three groups: low-risk group (n = 100; ≥ 70* diameter stenosis in one or two branches of the right main coronary artery and the left circumflex artery), high-risk group (n = 100; ≥ 50* diameter stenosis in the left main coronary artery or ≥ 70* diameter stenosis in the left anterior descending branch), and control group (n = 100; < 50* diameter stenosis in the main coronary arteries and all branches). All patients will undergo conventional echocardiography followed by three-dimensional longitudinal strain imaging to measure the LVGLPS. The LVGLPS will be compared among the three groups. Outcome measures: The primary outcome measure is the sensitivity of the LVGLPS for prediction of coronary atherosclerotic heart disease. The secondary outcome measures are: (1) the specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and accuracy rate of the LVGLPS for prediction of coronary atherosclerotic heart disease; (2) change in the LVGLPS; (3) change in conventional echocardiography parameters; and (4) change in the receiver operating characteristic curve for prediction of high-risk coronary atherosclerotic heart disease using the LVGLPS. Discussion: The findings from this study will help to confirm that three-dimensional longitudinal strain imaging technology is highly sensitive and specific for patients with abnormal coronary arteries with suspected coronary heart disease but who present with normal ventricular wall motion. The change in the LVGLPS contributes to early diagnosis of high-risk coronary atherosclerotic heart disease in older adult patients. This helps clinicians to diagnose early coronary heart disease and take timely strategies to avoid serious cardiovascular events as much as possible. Ethics and dissemination: This study will be performed in accordance with the Declaration of Helsinki. All patients are informed of the study protocol and procedure and provide written informed consent. This trial was approved by Taihe Hospital (Affiliated Hospital of Hubei University of Medicine) (approval number: ethics No. 2013(03)) in January 2013. Participant recruitment and data collection began in January 2013 and will continue through December 2017. Outcome measure analysis will be performed and the trial will be completed in January 2018. Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. Trial registration: This trial was registered with the Chinese the Clinical Trial Registry (registration number: ChiCTR-DDD-17012839).

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