In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a left anterior cortical lesion followed by chronic mild stress (CMS) for three weeks. Through sucrose preference testing, PSD rats displayed depression-like behavior during the entire CMS period. In contrast, stroke rats displayed depression-like behavior in the first week post-stroke and recovered in the second week post-stroke. To investigate the PSD-induced protein expression changes, ipsilateral hippocampal protein expression in stroke, PSD, and control rats were comparatively analyzed. 46 differential proteins were identified, 22 of which were regulated in opposing directions by stroke and post-stroke stress. The majority of these 22 proteins were involved in neurogenesis, cytoskeletal remodeling, and energy metabolism. Additional proteins were functionally related to mitochondrial antioxidative stress systems. The differential proteins expressed in opposing directions by stroke and post-stroke stress may play a role in self-repair after adult brain lesions, suggesting that stroke induces self-repair mechanisms, while post-stoke stress mitigates them, in the rat hippocampus. Among these differential proteins dysregulated in opposing directions, three mitochondrial proteins involved in mitochondrial antioxidative stress - heat shock 70 kDa protein 9, peroxiredoxin-6, and prohibitin - were validated and may play an important role in stroke-injury self-repair and PSD-induced injury of hippocampal neurons. These findings offer new insight into deciphering the molecular mechanisms underpinning PSD's adverse effects on stroke recovery.
Background: Chinese Hypertension Intervention Efficacy (CHIEF) study is a large-scale randomised clinical trial across China, which compares the efficacy of two combination regimens in reducing cardiovascular events associated with hypertension. Methods: We reported the 48-week efficacy and tolerability of the two antihypertensive regimens in participants from Shandong Province, China. Eligible patients aged 50-79 years were randomised to receive amlodipine plus amiloride/hydrochlorothiazide (Group A) or amlodipine plus telmisartan (Group B). The doses of both regimens were titrated and other antihypertensive agents were added subsequently to achieve a blood pressure (BP) goal (<140/90 mmHg for general population, <130/80 mmHg for diabetics and <150/90 mmHg for elderly). Efficacy variables included the changes of BP, control rates (the proportion of patients achieving a BP goal), and response rates (the proportion of patients achieving a BP goal or a reduction of BP ≥20/10 mmHg). Safety was assessed by monitoring the incidence of adverse events (AEs). Results: Of the 349 patients enrolled, 314 were randomised and 291 completed the study (141 in Group A and 150 in Group B). At week 48, the BP was reduced by 28.77/15.55 mmHg in Group A and by 31.38/16.07 mmHg in Group B (p> 0.05 for comparisons between Group A and Group B). The control rates (71.79% vs. 77.22%; p = 0.270) and response rates (79.49% vs. 84.81%; p = 0.218) were also similar. For both regimens, the control rates in diabetic patients were relatively lower (31.91% and 32.50%), while those in elderly patients were pretty higher (90.74% and 97.62%). AEs were mild to moderate in severity (17.95% vs. 12.66%, p = 0.193). Conclusion: Both combination regimens, amlodipine plus amiloride/hydrochlorothiazide and amlodipine plus telmisartan, were effective and safe for the high-risk hypertensive patients.
Machining-induced surface integrity has an important effect on reliability and service life of the components used in the aerospace industry where titanium alloy Ti-6Al-4V is widely applied. Characterisation of machining-induced surface integrity and revealing its effect on fatigue life are conducive to structural fatigue life optimisation design. In the present study, surface topography, residual stress, microstructure and micro-hardness were first characterised in peripheral milling of titanium alloy Ti-6Al-4V. Then, low-cycle fatigue performances of machined specimens were investigated on the basis of the tension-tension tests. Finally, the effects of surface integrity factors (stress concentration factor, residual stress and micro-hardness) on fatigue performances were discussed. Results show that stress concentration can reduce the fatigue life while increasing the residual compressive stress, and micro-hardness is beneficial to prolonging the fatigue life, but when the surface material of the specimen is subjected to plastic deformation due to yield, the residual stress on the surface is relaxed, and the effect on the fatigue performance is disappeared. Under the condition of residual stress relaxation, the stress concentration factor is the main factor to determine the low-cycle fatigue life of titanium alloy Ti-6Al-4V. While for the specimens with no residual stress relaxation, micro-hardness was the key factor to affect the fatigue life, followed by residual stress and stress concentration factor, respectively.
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