Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.OBJECTIVE To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis. DESIGN, SETTING, AND PARTICIPANTSMulticenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).INTERVENTIONS Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control. MAIN OUTCOMES AND MEASURESThe primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years. RESULTS Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, −5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, −5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, −0.2% [95% CI, −7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, −0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).CONCLUSIONS AND RELEVANCE Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The find...

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BackgroundCurrent studies of environmental health suggest a link between air pollution components, such as particulate matter (PM), and various diseases. However, the specific genes and regulatory mechanisms implicated in PM-induced diseases remain largely unknown. Epigenetic systems such as covalent modification of histones in chromatin may mediate environmental factors in gene regulation. Investigating the relationships between PM exposure and histone modification status may help understand the mechanisms underlying environment-associated health conditions.MethodsIn this study, we obtained genome-wide profiles of H3K27ac (histone 3 lysine 27 acetylation), known to be an active gene regulatory histone modification marker, in blood samples collected from four Chinese individuals exposed to high or low PM2.5 (particles with diameters up to 2.5 μm).ResultsThe genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) data indicated a comprehensive differential H3K27ac landscape across the individual genomes, which was associated with high PM2.5. Moreover, a substantial number of these PM2.5-associated differential H3K27ac markers were in genes involved in immune cell activation, potentially linking these epigenetic changes with air pollution-induced immune and inflammatory responses.ConclusionsOur study provides the first genome-wide characterization of H3K27ac profiles in individuals subjected to different exposure levels of PM2.5. Future systematic investigations of the relationships between air pollutants and histone modifications in large population samples are warranted to elucidate the contributions of histone modifications to environment-associated diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-015-0052-5) contains supplementary material, which is available to authorized users.

All biological bodies live in a thermal environment, including the human body, where skin is the interface with a protecting function. When the temperature is out of the normal physiological range, skin fails to protect, and the pain sensation is evoked. Furthermore, in medicine, with advances in laser, microwave and similar technologies, various thermal therapeutic methods have been widely used to cure disease/injury involving skin tissue. However, the corresponding problem of pain relief has limited further application and development of these thermal treatments. Skin thermal pain is induced through both direct (i.e. an increase/decrease in temperature) and indirect (e.g. thermomechanical and thermochemical) ways, and is governed by complicated thermomechanical-chemicalneurophysiological responses. However, a complete understanding of the underlying mechanisms is still far from clear. In this article, starting from an engineering perspective, we aim to recast the biological behaviour of skin in engineering system parlance. Then, by coupling the concepts of engineering with established methods in neuroscience, we attempt to establish multi-scale modelling of skin thermal pain through ion channel to pain sensation. The model takes into account skin morphological plausibility, the thermomechanical response of skin tissue and the biophysical and neurological mechanisms of pain sensation.

Background the course of depression is variable, but it is unknown how this variability over time affects long-term cognitive decline. Objective to examine the relationship of different trajectories of depressive symptoms on rates of subsequent cognitive decline in older adults. Design population-based cohort study. Setting communities in the USA and England. Subjects 17,556 older adults from the Health and Retirement Study and the English Longitudinal Study of Ageing. Methods depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, and trajectories were calculated using group-based trajectory modelling. Global cognitive function and three cognitive domains of memory, executive function and temporal orientation were assessed for up to 18 years. Results five trajectories of depressive symptoms were identified. Compared with the ‘non-depressed’ trajectory, the ‘worsening depressive symptoms’ trajectory (pooled β = −0.016 standard deviation (SD)/year, 95% confidence interval (CI): −0.021 to −0.010), ‘persistent depressive symptoms’ trajectory (pooled β = −0.016 SD/year, 95% CI: −0.024 to −0.008), and ‘mild depressive symptoms’ trajectory (pooled β = −0.008 SD/year, 95% CI: −0.014 to −0.003) were associated with faster rates of cognitive decline, while no such association was found for the ‘improving depressive symptoms’ trajectory (pooled β = 0.001 SD/year, 95% CI: −0.010 to 0.012). Conclusions subthreshold depressive symptoms are associated with an increased rate of cognitive decline, while individuals who show improving depressive symptoms do not exhibit accelerated cognitive decline. These findings raise the possibility that maintaining depressive symptoms as low as possible and ignoring the clinical threshold, might mitigate cognitive decline in older adults.

Coaxial electrospun fibrous membranes show favorable mechanical properties for use in guided bone regeneration (GBR). We used coaxial electrospinning technology to fabricate three-dimensional nanofiber membranes loaded with BMP-2 and IGF-1, and assessed the physicochemical and biological properties of these novel membranes in vitro. We fabricated four experimental groups of BMP-2/IGF-1/BSA-loaded membranes with different flow ratios (shell/core). Membrane characteristics were assessed by scanning and transmission electron microscopy, and laser confocal microscopy. Physicochemical and drug release properties were evaluated based on contact angle, mechanical property testing, X-ray diffraction analysis, and ELISA. The membranes were seeded with bone marrow-derived mesenchymal stem cells (BMMSCs) to estimate their biological properties based on cell viability and alkaline phosphatase (ALP) activity. The four membrane groups presented uniform diameters and core-shell structures. Acceleration of the shell solution flow rate increased the contact angle and mechanical properties of the fibrous membrane, while dual-factor addition did not impact fiber structure. Each drug-loaded membrane showed a gradually increasing release curve, with varying degrees of burst and sustained release. Compared to the other groups, the membranes with a core-shell flow ratio of 1:10 showed better drug-loading capacity and sustained release performance, higher biological properties and good barrier function. Optimal parameters were chosen based on the physical and chemical characteristics and biological properties of the membrane. Our results imply that the BMP-2/IGF-1/BSA-loaded coaxial electrospun fibrous membrane with optimum parameters is a suitable barrier membrane for GBR, and releases multiple factors promoting osteoconduction and osteoinduction.

Background: Unfavourable blood pressure (BP) level is an established risk factor for cardiovascular diseases (CVD), while the exact underlying reasons for unfavourable BP are poorly understood.  The INTERMAP China Prospective (ICP) Study is a prospective cohort to investigate the relationship of environmental and nutritional risk factors with key indicators of vascular function including BP, arterial stiffness, and carotid-intima media thickness. Methods: A total of 839 Chinese participants aged 40-59 years from three diverse regions of China were enrolled in INTERMAP in 1997/98; data collection included repeated BP measurements, 24-hour urine specimens, and 24-hour dietary recalls.  In 2015/16, 574 of these 839 persons were re-enrolled along with 208 new participants aged 40-59 years that were randomly selected from the same study villages.  Participant’s environmental and dietary exposures and health outcomes were assessed in this open cohort study, including BP, 24-hour dietary recalls, personal exposures to air pollution, grip strength, arterial stiffness, carotid-media thickness and plaques, cognitive function, and sleep patterns.  Serum and plasma specimens were collected with 24-hour urine specimens. Discussion:  Winter and summer assessments of a comprehensive set of vascular indicators and their environmental and nutritional risk factors were conducted with high precision.  We will leverage advances in exposome research to identify biomarkers of exposure to environmental and nutritional risk factors and improve our understanding of the mechanisms and pathways of their hazardous cardiovascular effects.  The ICP Study is observational by design, thus subject to several biases including selection bias (e.g., loss to follow-up), information bias (e.g., measurement error), and confounding that we sought to mitigate through our study design and measurements.  However, extensive efforts will apply to minimize those limitations (continuous observer training, repeated measurements of BP, standardized methods in data collection and measurements, and on-going quality control).

Background: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. Methods: A multicenter, patient- and outcome assessor–blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mmHg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mmHg reduction in SBP was also calculated. Results: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mmHg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was –5.0 (95% CI, –6.5 to –3.5) mmHg and –2.8 (95% CI, –3.7 to –1.9) mmHg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were –10.0 (95% CI, –12.1 to –7.9) mmHg and –3.8 (95% CI, –5.0 to –2.5) mmHg, respectively. The effect size did not differ among cuisines ( P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, –0.1 to 0.2; P =0.558). The incremental cost-effectiveness ratio per 1 mmHg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups ( P =0.259), and none of the adverse events was associated with the intervention. Conclusions: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures.