Efficacy and Safety of Direct Oral Anticoagulants (DOACs) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: a Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke. METHODS: Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims) as the randomization was broken. RESULTS: Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups. CONCLUSION: DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

Human expansion into Asian highlands in the 21st Century and its effects.

Most intensive human activities occur in lowlands. However, sporadic reports indicate that human activities are expanding in some Asian highlands. Here we investigate the expansions of human activities in highlands and their effects over Asia from 2000 to 2020 by combining earth observation data and socioeconomic data. We find that ∼23% of human activity expansions occur in Asian highlands and ∼76% of these expansions in highlands comes from ecological lands, reaching 95% in Southeast Asia. The expansions of human activities in highlands intensify habitat fragmentation and result in large ecological costs in low and lower-middle income countries, and they also support Asian developments. We estimate that cultivated land net growth in the Asian highlands contributed approximately 54% in preventing the net loss of the total cultivated land. Moreover, the growth of highland artificial surfaces may provide living and working spaces for ∼40 million people. Our findings suggest that highland developments hold dual effects and provide new insight for regional sustainable developments.

Spatiotemporal dynamics of forest ecosystem carbon budget in Guizhou: customisation and application of the CBM-CFS3 model for China.

BACKGROUND: Countries seeking to mitigate climate change through forests require suitable modelling approaches to predict carbon (C) budget dynamics in forests and their responses to disturbance and management. The Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3) is a feasible and comprehensive tool for simulating forest C stock dynamics across broad levels, but discrepancies remain to be addressed in China. Taking Guizhou as the case study, we customised the CBM-CFS3 model according to China's context, including the modification of aboveground biomass C stock algorithm, addition of C budget accounting for bamboo forests, economic forests, and shrub forests, improvement of non-forest land belowground slow dead organic matter (DOM) pool initialisation, and other model settings. RESULTS: The adequate linear relationship between the estimated and measured C densities (R2 = 0.967, P < 0.0001, slope = 0.904) in the model validation demonstrated the high accuracy and reliability of our customised model. We further simulated the spatiotemporal dynamics of forest C stocks and disturbance impacts in Guizhou for the period 1990-2016 using our customised model. Results shows that the total ecosystem C stock and C density, and C stocks in biomass, litter, dead wood, and soil in Guizhou increased continuously and significantly, while the soil C density decreased over the whole period, which could be attributed to deforestation history and climate change. The total ecosystem C stock increased from 1220 Tg C in 1990 to 1684 Tg C in 2016 at a rate of 18 Tg C yr-1, with significant enhancement in most areas, especially in the south and northwest. The total decrease in ecosystem C stock and C expenditure caused by disturbances reached 97.6 Tg C and 120.9 Tg C, respectively, but both represented significant decreasing trends owing to the decline of disturbed forest area during 1990-2016. Regeneration logging, deforestation for agriculture, and harvest logging caused the largest C stock decrease and C expenditure, while afforestation and natural expansion of forest contributed the largest increases in C stock. CONCLUSIONS: The forests in Guizhou were a net carbon sink under large-scale afforestation throughout the study period; Our customised CBM-CFS3 model can serve as a more effective and accurate method for estimating forest C stock and disturbance impacts in China and further enlightens model customisation to other areas.

Overexpression of sFlt-1 represses ox-LDL-induced injury of HUVECs by activating autophagy via PI3K/AKT/mTOR pathway.

Soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein, is involved in the pathogenesis of atherosclerosis (AS), and the underlying mechanism is still unclear. Here, we attempted to investigate the mechanism of action of sFlt-1 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL) to induce cell injury. ox-LDL treatment increased LC3-II/LC3-I ratio, Beclin-1 expression and GFP-LC3 puncta in HUVECs, suggesting that ox-LDL may induce autophagic flux impairment in HUVECs. ox-LDL-treated HUVECs displayed a decrease of sFlt-1 levels. Moreover, ox-LDL treatment reduced cell proliferation and elevated apoptosis in HUVECs, which was abrogated by sFlt-1 overexpression. Up-regulation of sFlt-1 repressed the activity of PI3K/AKT/mTOR signaling pathway and enhanced autophagy in HUVECs following ox-LDL treatment. Additionally, sFlt-1 overexpression-mediated increase of autophagy in ox-LDL-treated HUVECs was abolished by 3-methyladenine (autophagy inhibitor). 3-methyladenine abrogated the impact of sFlt-1 overexpression on proliferation and apoptosis in ox-LDL-treated HUVECs. This work confirmed that overexpression of sFlt-1 activated autophagy by repressing PI3K/Akt/mTOR signaling pathway, and thus alleviated ox-LDL-induced injury of HUVECs. Therefore, this study suggests that sFlt-1 may be a potential target for AS treatment.

Effect of Moxibustion on HIF-1α and VEGF Levels in Patients with Rheumatoid Arthritis.

Background: Moxibustion has a therapeutic effect of reducing swelling and relieving pain in patients with rheumatoid arthritis (RA) but its mechanism is uncertain. Objective: To evaluate the effect of moxibustion on serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with RA and to explore the possible mechanism of moxibustion. Methods: This study involved 46 RA patients who had fulfilled the inclusion criteria and were randomly assigned to a treatment group and a control group in an equal ratio. The control group was treated with methotrexate or leflunomide, while the treatment group received methotrexate or leflunomide and moxibustion at ST 36 (Zusanli), BL 23 (Shenshu), and Ashi points. Patients' clinical symptoms, RA-associated serum markers, and serum levels of TNF-α, IL-1ß, HIF-1α, and VEGF were compared in the two groups before and after intervention. Statistical analysis was performed using SPSS 21.0 statistical software. Results: 37 of 46 RA patients eventually completed the whole treatment course. Compared with the control group, the treatment group significantly improved the clinical symptoms (P < 0.05) but with no significant differences in RA-associated serum markers (P > 0.05). There were significant differences in TNF-α and IL-1ß among the groups after 8 weeks of treatment (P < 0.05). HIF-1α and VEGF were decreased in the treatment group after therapy (P < 0.05). VEGF was reduced in the control group (P < 0.05), while HIF-1α was not significantly improved (P > 0.05). The reductions of HIF-1α and VEGF in the treatment group were superior to the control group (P < 0.05). Conclusions: Moxibustion enhanced the anti-inflammatory and analgesic effects of conventional medicine and can enhance the effect of conventional medicine, downregulating HIF-1α/VEGF contents to inhibit angiogenesis.

Cardiovascular risk of sitagliptin in treating patients with type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (T2DM) have a very high risk of cardiovascular related events, and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs. Previous studies have shown that the dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP4i), such as sitagliptin, might reduce the incidence of major cardiovascular events (MACEs). However, the safety and efficacy of sitagliptin remains controversial, especially the safety for cardiovascular related events. Here, a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients. The literature research dating up to October 2018 was performed in the electronic database. The clinical trials about sitagliptin for T2DM patients were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria. The primary outcome was the MACE, and the secondary outcome was all-cause mortality. Finally, 32 clinical trials composed of 16082 T2DM patients were included in this meta-analysis. The results showed that: there was no significant difference between sitagliptin group and the control group on MACE (odds ratio (OR) = 0.85, 95% confidence intervals (CIs) = 0.63-1.15), myocardial infarction (MI) (OR = 0.66, 95% CI = 0.38-1.16), stroke (OR = 0.83, 95% CI = 0.44-1.54) and mortality (OR = 0.52, 95% CI = 0.26-1.07). These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM.

Structural Changes Induced by Acupuncture in the Recovering Brain after Ischemic Stroke.

The aim of this study was to observe the grey matter (GM) tissue changes of ischemic stroke patients, to explore the therapy responses and possible mechanism of acupuncture. 21 stroke patients were randomly assigned to receive either acupuncture plus conventional (Group A) or only conventional (Group B) treatments for 4 weeks. All patients in both groups accepted resting-state functional magnetic resonance (fMRI) scan before and after treatment, and the voxel-based morphometry (VBM) analysis was performed to detect the cerebral grey structure changes. The modified Barthel index (MBI) was used to evaluate the therapeutic effect. Compared with the patients in Group B, the patients in Group A exhibited a more significant enhancement of the changes degree of MBI from pre- to post-treatment intervention. VBM analyses found that after treatment the patients in Group A showed extensive changes in GMV. In Group A, the left frontal lobe, precentral gyrus, superior parietal gyrus, anterior cingulate cortex, and middle temporal gyrus significantly increased, and the right frontal gyrus, inferior parietal gyrus, and middle cingulate cortex decreased (P < 0.05, corrected). In addition, left anterior cingulate cortex and left middle temporal gyrus are positively related to the increase in MBI score (P < 0.05, corrected). In Group B, right precentral gyrus and right inferior frontal gyrus increased (P < 0.05, corrected). In conclusion, acupuncture can evoke pronounced structural reorganization in the frontal areas and the network of DMN areas, which may be the potential therapy target and the potential mechanism where acupuncture improved the motor and cognition recovery.

Strong enhancement of second-harmonic generation (SHG) response through multi-chiral centers and metal-coordination.

The hydrothermal reaction of CdCl2 with L (L =trans-2,3-dihydro-2-(4'-pyridyl)-3-(3"-cyanophenyl)benzo[e]indole) in the presence of NaN3 and water offers a novel route to [Cd(L-N3)2(H2O)2]n, a 1D infinite molecular box with approximate dimensions 10.37 x 6.64 è; 1 is shown to display a very strong SHG response that is 80 times that observed for urea.