Dosage exploration of combined B-vitamin supplementation in stroke prevention: a meta-analysis and systematic review.

BACKGROUND: The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention. OBJECTIVE: Our aim was to determine the optimal dosage range of a combination of folic acid, vitamin B12, and vitamin B6 supplementation in stroke prevention. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase database for randomized controlled trials published between January 1966 and April 2023, whose participants received B-vitamin supplementation and that reported the number of stroke cases. Relative risk (RR) was used to measure the effect of combined supplementation on risk of stroke using a fixed-effects model. Risk of bias was assessed with the Cochrane risk-of-bias algorithm. RESULTS: The search identified 14 randomized controlled trials of folic acid combined with vitamin B12 and vitamin B6 supplementation for stroke prevention that included 76,664 participants with 2720 stroke cases. In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively. Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas. In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16). CONCLUSIONS: Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification. Combined dosages not exceeding 0.8 mg/d for folic acid and 0.4 mg/d for vitamin B12 supplementation may be more effective for populations within these areas. This trial was registered at PROSPERO asCRD42022355077.

The influence of different shaped osteocyte lacunae on microcrack initiation and propagation.

BACKGROUND: The morphology of osteocyte lacunae varies in bones of different ages and bone pathologies. Osteocyte lacunae can cause stress concentration and initiate microcracks. However, the influence of changes in osteocyte lacunar shape on microcrack is unknown. Therefore, the aim of this study was to determine the effects of osteocyte lacunae with different shapes on microcrack initiation and propagation. METHODS: Osteon models containing osteocyte lacunae with different shapes were established. The progressive damage analysis method, based on computer simulations, was used to study the evolution of microdamage within the osteon, including the processes of intralaminar and interlaminar microdamage. FINDINGS: Models with larger DoE values can effectively delay or prevent the formation of linear microcracks, which ensures high fracture toughness of cortical bone. It is subjected to stronger mechanical stimulation, making it more sensitive to loads. Models with smaller DoE values increase the load threshold for microdamage generation and reduces its impact on bone mechanical performance, making it less susceptible to microdamage than models with larger DoE values. INTERPRETATION: These findings enhance the limited knowledge of the influence of the lacunar shape on microdamage and contribute to a better understanding of bone biomechanics.

Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults.

PURPOSE: We investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults. METHODS: This was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria. RESULTS: HR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, ß = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, ß = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, ß = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014). CONCLUSION: HR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

The fracture mechanical behavior simulation of calcium-deficient hydroxyapatite crystals by molecular dynamics and first-principles calculation.

Natural hydroxyapatite provides certain strength and stiffness to biological bones, and most of the studies on the strength of bone tissues have been carried out on hydroxyapatite (HAP). However, the Ca/P ratio of hydroxyapatite in bones is actually about 1.50, and the natural hydroxyapatite belongs to calcium-deficient hydroxyapatite (CDHA) with Ca vacancy defects. Therefore, this work focused on the effect of Ca vacancy defects on CDHA crystals through investigating the generation and expansion of microcracks under uniaxial tensile loading by combining molecular dynamics and first principles method. A series of crystal models with different Ca vacancy ratios are constructed and find that Ca vacancies degrade the mechanical properties of hydroxyapatite. Meanwhile the fracture behavior of crystals is detailed and find that the cracks arise at vacancies and extend along the direction of vacancies. Also, first-principles calculation is performed to reveal the mechanism of crack formation in MD simulations. It is found that the decrease of Ca-O bonding of CDHA causes the decrease of the stability of the crystal structure by analyzing the DOS of HAP and CDHA, and the cracks originate from Ca vacancies. This work performs more realistic simulations of CDHA with calcium vacancy defects in actual bone tissue and directly reveals the development and progression of bone fragility at the nanometer scale.

Single-cell analysis for BDNF and TrkB receptors in cardiac microvascular endothelial cells.

Recent studies revealed that BDNF-TrkB pathway plays an important role in cardiac microvascular endothelial cells (CMECs) mediated myocardial angiogenesis. Single-cell analysis is a powerful tool for studying gene expression in individuals since cellular heterogeneity and dynamic microenvironments which individual cell will experience. Little is currently known about the expression of BDNF and TrkB receptors at the single CMEC level. Our single-cell analysis of seven randomly selected CMECs for BDNF and TrkB receptors (FL, T1, T2) showed that under an in vitro culture environment, BDNF was expressed in two of the seven selected CMECs. None of the single CMEC expressed TrkB-FL. TrkB-T1 was expressed in all seven selected CMECs, while, TrkB-T2 was expressed in three of these. In addition, none of single CMEC was found to express both BDNF and three TrkB receptors or BDNF and TrkB-FL simultaneously. These results suggest that a stochastic or random expression pattern for BDNF and their receptors might be set in each of the CMEC to response requirement of the time and spatial change, regulation or pathophysiological change.