A Systematic Review and Meta-Analysis of Efficacy and Safety of Cilostazol Prescription in Patients With Femoropopliteal Peripheral Artery Disease After Endovascular Therapy.

PURPOSE: The purpose of this study is to assess the efficacy and safety of cilostazol prescription in patients with femoropopliteal peripheral artery disease (PAD) after endovascular therapy (EVT). MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of all studies reporting the outcomes of cilostazol after femoropopliteal EVT of PAD up to September 2022. Clinical outcomes of interest included primary patency, in-stent restenosis (ISR), vessel re-occlusion, freedom from target lesion revascularization (TLR), repeat revascularization, all-cause mortality, amputation, major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs), and bleeding complication. RESULTS: A total of 4 randomized controlled trials (RCTs) and 8 observational studies containing a total of 4898 patients met the inclusion criteria and were included in this systematic review and meta-analysis. We found that the use of cilostazol was associated with higher primary patency after femoropopliteal artery EVT (odds ratio [OR]=1.67, 95% confidence interval [CI]=1.50-1.87, p<0.001, I2=33.2%), a lower risk of ISR (OR=0.43, 95% CI=0.29-0.63, p<0.001, I2=37.6%), repeat revascularization (OR=0.43, 95% CI=0.24-0.76, p<0.005, I2=27.4%), and vessel re-occlusion (OR=0.59, 95% CI=0.38-0.93, p<0.05, I2=0%). There was an increase in freedom from TLR rate (OR=2.19, 95% CI=1.58-3.05, p<0.001, I2=0%), as well as a reduction in the occurrence of MALEs (OR=0.50, 95% CI=0.29-0.85, p<0.05, I2=0%). However, there was no significant difference in amputation, MACEs, all-cause mortality, and major bleeding complications. Subgroup analysis showed that cilostazol treatment in patients with femoropopliteal drug-eluting stents (DES) implantation remained associated with higher primary patency and a lower risk of ISR. CONCLUSIONS: After EVT of femoropopliteal artery lesions, additional oral cilostazol enhances primary patency, reduces the occurrences of ISR and vessel re-occlusion, diminishes the risks associated with MALEs, lowers the need for repeat revascularization, and increases freedom from TLR rates. However, it does not impact amputation, MACEs, all-cause mortality, or major bleeding complications. These findings suggest cilostazol as a potentially safe and effective adjunct therapy in patients with femoropopliteal PAD after EVT. CLINICAL IMPACT: After undergoing endovascular therapy (EVT) for femoropopliteal artery lesions, the addition of cilostazol to antiplatelet therapy can significantly improve primary patency, reducing the incidence of in-stent restenosis, repeat revascularization, vessel re-occlusion, and major adverse limb events while increasing freedom from target lesion revascularization rate. The simultaneous use of drug-eluting stents in the femoropopliteal artery lesions, combined with cilostazol, potentially results in a synergistic anti-stenotic effect. This therapeutic approach does not appear to be associated with an increased risk of major bleeding events or all-cause mortality. These findings provide additional evidence supporting the treatment of anti-stenosis in patients with femoropopliteal artery lesions after EVT.

Silencing METTL3 Stabilizes Atherosclerotic Plaques by Regulating the Phenotypic Transformation of Vascular Smooth Muscle Cells via the miR-375-3p/PDK1 Axis.

PURPOSE: Atherosclerosis (AS) is a primary cause of cardiovascular diseases. This study investigated the mechanism of methyltransferase-like 3 (METTL3) in AS plaques via modulating the phenotypic transformation of vascular smooth muscle cells (VSMCs). METHODS: AS mouse models and MOVAS cell models were established through high-fat diet and the treatment of ox-LDL, respectively. METTL3 expression in AS models was detected via RT-qPCR and Western blot. The AS plaques, lipid deposition, and collagen fibers were examined via histological staining. The levels of Ly-6c, α-SMA, and OPN were examined via Western blot. The blood lipid indexes in mouse aortic tissues were determined using kits. The proliferation and migration of MOVAS cells were detected via CCK-8 and Transwell assays. The m6A modification level of mRNA was quantified. The binding relationship between pri-miR-375 and DGCR8, and the enrichment of m6A on pri-miR-375 were detected via RIP. The binding relationship between miR-375-3p and 3-phosphoinositide-dependent protein kinase-1 (PDK1) was verified via dual-luciferase assay. Joint experiments were designed to investigate the role of miR-375-3P/PDK1 in the phenotypic transformation of VSMCs. RESULTS: METTL3 was highly expressed in AS. Silencing METTL3 alleviated AS progression and stabilized AS plaques in mice, and limited the phenotypic transformation of VSMCs induced by ox-LDL. Silencing METTL3 inhibited m6A level and decreased the binding of DGCR8 to pri-miR-375 and further limited miR-375-3p expression. miR-375-3p targeted PDK1 transcription. miR-375-3p upregulation or PDK1 downregulation facilitated the phenotypic transformation of VSMCs. CONCLUSION: METTL3-mediated m6A modification promoted VSMC phenotype transformation and made AS plaques more vulnerable via the miR-375-3p/PDK1 axis.

Analysis of spatial differences in global regional human development index under planetary pressure and decomposition study of driving factors.

To urge nations worldwide to implement robust measures for enhancing human development and mitigating the pressures exerted on the planet by human activities in pursuit of sustainable development, this study encompasses 154 countries globally, using the seven major regions as focal points. Leveraging the Planetary Pressure Adjusted Human Development Index (PHDI) proposed by the United Nations Development Programme on December 15, 2020, as a metric for human development levels, this paper aims to standardize and internationally compare human development data from 1990 to 2021. Subsequently, employing the Theil index, the study assesses the global human development status across the seven regions to analyze spatial disparities in PHDI. Lastly, a comprehensive Generalized Diese Index Method (GDIM) is constructed to accurately reflect absolute and latent factors, dissecting the driving forces impacting global PHDI. The study explores critical pathways for high-quality human development within the harmonious coexistence between humanity and nature. It validates the robustness of GDIM results through a stepwise regression. Research findings indicate varying levels of PHDI development across regions, with a distinct spatial hierarchy evolving: higher human development levels in Europe and Eastern Europe, favorable levels in North and South America, similar levels in Oceania and Asia, and significant improvement potential in Africa. As globalization progresses, overall differences in PHDI gradually decrease; however, disparities persist between and within regions. Economic, technological, and per capita welfare effects consistently positively drive PHDI. In contrast, environmental pressure effects, social effects, per capita value-added effects, and output carbon intensity effects consistently exert hostile driving forces. Population size effects on PHDI show a fluctuating trend. Moreover, in terms of cumulative contribution values, the top three contributors to driving forces are economic, technological, and per capita welfare effects.

Associations of prenatal exposure to bisphenols with BMI growth trajectories in offspring within the first two years: evidence from a birth cohort study in China.

BACKGROUND: Prenatal bisphenol exposure has been reported to be associated with lower birth weight and obesity-related indicators in early childhood. These findings warrant an investigation of the relationship between prenatal bisphenol exposure and the dynamic growth of offspring. This study aimed to evaluate the relationship of maternal bisphenol concentration in urine with the body mass index (BMI) growth trajectory of children aged up to two years and to identify the critical exposure periods. METHODS: A total of 826 mother-offspring pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Maternal urine samples collected during the first, second, and third trimesters were analyzed for bisphenol A (BPA), bisphenol S, and bisphenol F (BPF) concentrations. Measurements of length and weight were taken at 0, 1, 3, 6, 8, 12, 18, and 24 months. Children's BMI was standardized using the World Health Organization reference, and group-based trajectory modeling was used to identify BMI growth trajectories. The associations between prenatal bisphenol exposure and BMI growth trajectory patterns were assessed using multinomial logistic regression models. RESULTS: The BMI growth trajectories of the 826 children were categorized into four patterns: low-stable (n = 134, 16.2%), low-increasing (n = 142, 17.2%), moderate-stable (n = 350, 42.4%), and moderate-increasing (n = 200, 24.2%). After adjusting for potential confounders, we observed that prenatal exposure to BPA during the second trimester [odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.09-4.43] and BPF during the third trimester (OR = 3.28, 95% CI = 1.55-6.95) at the highest quartile concentration were associated with an increased likelihood of the low-increasing BMI trajectory. Furthermore, in the subgroup analysis by infant sex, the positive association between the highest quartile of prenatal average urinary BPF concentration during the whole pregnancy and the low-increasing BMI trajectory was found only in girls (OR = 2.82, 95% CI = 1.04-7.68). CONCLUSION: Our study findings suggest that prenatal exposure to BPA and BPF (a commonly used substitute for BPA) is associated with BMI growth trajectories in offspring during the first two years, increasing the likelihood of the low-increasing pattern. Video Abstract (MP4 120033 kb).

The effect of China's carbon emission trading on eco-efficiency: an empirical study at the city level.

Carbon emission trading has been actively applied in many countries, and its operational effect has received widespread attention. However, previous studies mostly focused on single environmental effect, and the investigation of the comprehensive environmental effect needs to be further supplemented. Based on this, this paper explores the comprehensive environmental effect of carbon emission trading with eco-efficiency as the starting point. First, this paper measures eco-efficiency using the super-efficient minimum distance to strong efficient frontier (MinDS) model with undesirable outputs. Second, this paper uses the propensity score matching difference in difference (PSM-DID) model to quantify the effect of carbon emission trading on eco-efficiency. Finally, this paper examines the mediating mechanism of the effect of carbon emission trading on eco-efficiency based on the mediating effect model. The results show that carbon emission trading can improve the level of urban eco-efficiency. Energy savings and increased efficiency effectively mediate the promoting effect of carbon emission trading on eco-efficiency. The mediating push effect of R&D innovation and industrial structure restructuring has not yet appeared. This paper can not only provide policy basis for the improvement of carbon emission trading market but also provide reference for the construction of carbon emission trading market in developing countries.

Empirical analysis of energy consumption transfer in China's national economy from the perspective of production and demand.

Given the context of the global energy shortage and the deterioration of the ecological environment, this paper uses industrial linkage as a starting point to deeply explore the energy consumption of different sectors and its transfer characteristics. First, a dual evaluation of energy consumption in various sectors is conducted from the perspectives of production and demand to realize an integrated analysis from the energy consumption perspective. Second, based on industrial linkage, the economic input-output life cycle assessment (EIO-LCA) model is used to quantify the net transfer of energy consumption and identify the transfer of energy consumption pressure embodied in economic activities by various sectors. Finally, the energy consumption of various sectors is decomposed, and the transfer flow of energy consumption is measured to accurately quantify the degree of linkage in the energy consumption of sectors. The results show that the current direct energy consumption intensity of various sectors in China is continuously decreasing, but this decrease is insufficient to reverse the upward trend in energy consumption demand. From the perspective of production and demand, non-energy industrial sector is a key sector for reducing energy consumption, and the intersectoral linkage between the subsectors caused by product trade flows has a greater impact on the level of direct and embodied energy consumption. Direct and embodied energy consumption in the same sector can be ranked quite differently, and their levels may not be equal. Energy sector is the main net outflow sector of energy consumption, and the level of its direct energy consumption is much higher than that of its embodied energy consumption. It is worth noting that the scale of embodied energy consumption in construction industry is much higher than the scale of direct energy consumption. Construction is the sector with the greatest net inflow of energy consumed and is the main driver of the energy consumption transfer of energy sector and non-energy industrial sector.

Analysis of China's carbon emission driving factors based on the perspective of eight major economic regions.

Low-carbon transition has gradually become the focus of research on environmental issues. This paper takes China's eight major economic regions as the entry point. First, carbon emissions are measured according to United Nations' baseline methodologies. Second, the stochastic nonparametric data envelope analysis (StoNED) model is used to measure energy efficiency to improve the accuracy of the measurement. Finally, considering the temporal and spatial nonstationarity of carbon emission data, this paper constructs geographically and temporally weighted regression-stochastic impacts by regression on population, affluence, and technology (GTWR-STIRPAT) model, which can accurately analyze the impact of each driving factor of carbon emissions. This paper also explores efficient emission reduction paths in conjunction with the forcing mechanism. According to the study, China's carbon emissions show a decreasing trend from coastal areas to inland areas. In addition, there are significant problems with carbon emissions in China: some regions focus on improving energy efficiency but neglect increasing energy consumption; some regions focus on industrial development but neglect long-term emission reductions. Among the driving factors, energy efficiency, foreign trade, environmental regulations, and industrial structure have the effects of spatiotemporal heterogeneity, spatial heterogeneity, and time lag on carbon emissions, respectively. Graphical abstract.

Diversity of Crenarchaeota in terrestrial hot springs in Tengchong, China.

Diversity of Crenarchaeota was investigated in eight terrestrial hot springs (pH 2.8-7.7; temperature 44-96 degrees C) located in Tengchong, China, using 16S rRNA gene phylogenetic analysis. A total of 826 crenarchaeotal clones were sequenced and a total of 47 operational taxonomic units (OTUs) were identified. Most (93%) of the identified OTUs were closely related (89-99%) to those retrieved from hot springs and other thermal environments. Our data showed that temperature may predominate over pH in affecting crenarchaeotal diversity in Tengchong hot springs. Crenarchaeotal diversity in moderate-temperature (59-77 degrees C) hot springs was the highest, indicating that the moderately hot-temperature springs may provide optimal conditions for speciation of Crenarchaeota.

The neurokinin-1 receptor antagonist aprepitant ameliorates oxidized LDL-induced endothelial dysfunction via KLF2.

Atherosclerosis is the main cause of many cardiovascular diseases. Endothelial dysfunction is recognized as an early event in the development of atherosclerosis. Many drugs have been studied to mitigate hyperlipidemia-induced endothelial injury. Studies have demonstrated that neuropeptide substance P (SP) and its preferred receptor neurokinin receptor 1 (NK-1R) are involved in the pathological progression of cardiovascular disease. In this study, we show that aprepitant, a selective NK-1R antagonist, possesses beneficial effects that protect endothelial cells from oxidized low-density lipoprotein (ox-LDL)-induced inflammatory response and injury. Our data demonstrate that NK-1R is expressed in both aortic and vein-originated endothelial cells and that ox-LDL treatment induces NK-1R expression. Treatment with aprepitant suppresses induction of endothelial vascular adhesion molecule (VCAM-1 and E-selectin) and cytokine by ox-LDL. The presence of aprepitant mitigates adhesion of monocytes to endothelial cells and the reduction in eNOS/NO triggered by ox-LDL. Mechanistically, we demonstrate that aprepitant suppresses ERK5-KLF2 axis activation. Silencing of KLF2 abolishes the inhibitory role of aprepitant on ox-LDL-induced inflammatory response, suggesting that its action is dependent on KLF2. Collectively, our data support that aprepitant exerts an anti-inflammatory effect. Further research is required to investigate the therapeutic potential of aprepitant in vascular inflammation resulting from atherosclerosis.

[Detection of CDH1 gene methylation of suspension cells in abdominal lavage fluid from colorectal cancer patients and its clinical significance].

OBJECTIVE: To detect the CDH1 gene methylation of suspension cells in intraoperative abdominal lavage fluid from colorectal cancer patients, and to examine its association with clinicopathology and prognosis. METHODS: Real-time methylation-specific polymerase chain reaction (qMSP) was used to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands from intraoperative abdominal lavage fluid in 102 patients with colorectal cancer. The associations between methylation of CDH1 genes and clinicopathologic features and prognosis were investigated. RESULTS: Among the 102 colorectal cancer patients, aberrant methylation of CDH1 gene was detected in 47 patients. Significant associations were found between CDH1 methylation status and tumor size, growth pattern, differentiation, distant metastasis, and clinical staging (all P<0.05). The median progression-free survival was 25.98 months for CDH1 methylation group and 41.36 months for non-methylated group, and the difference was statistically significant (P<0.01). Cox model analysis revealed that CDH1 methylation status in intraoperative peritoneal lavage fluid was an independent factor associated with postoperative survival in colorectal cancer patients (50.23% vs. 86.51%, P=0.001). CONCLUSIONS: Colorectal cancer patients with aberrant methylation of 5'-CpG of CDH1 gene promoter of suspension cells in abdominal lavage have higher malignancy, more metastasis and worse prognosis.

Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis.

PURPOSE: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. METHODS: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which reported analysis of survival data about MCP-1 in solid tumors were included. Stata 11.0 was used for performing a meta-analysis on evaluating the relation between MCP-1 and clinical staging, overall survival (OS) and disease free survival (DFS). RESULTS: Eleven studies with a total of 1324 patients with solid tumors were included into our meta-analysis. The result showed that high concentration of MCP-1 was related to a worse OS (HR = 1.95, 95% CI 1.32-2.88). The subgroup analysis on different location of tumors showed that high concentration of MCP-1 meant bad prognosis in patients with digestive cancer (HR = 2.66, 95% CI 1.44-4.91) and urogenital cancer (HR = 2.23, 95% CI 1.61-3.10), even head and neck cancer (HR = 1.99, 95% CI 0.95-4.18) other than respiratory cancer (HR = 1.10, 95% CI 0.39-3.11). Another subgroup analysed on different sites of cancer and indicated a poor prognosis on adenocarcinoma (HR = 2.10, 95% CI 1.63-2.69). CONCLUSIONS: Our findings suggest that MCP-1 can be regarded as a poor prognostic maker for solid tumors and may represent important new therapeutic targets.

Fates of donor and recipient mitochondrial DNA during generation of interspecies SCNT-derived human ES-like cells.

To investigate nuclear donor and cytoplast recipient mitochondria fate and their effects on generation of interspecies somatic cell nuclear transfer (iSCNT)-derived human embryonic stem (ES)-like cells, iSCNT embryos were reconstructed between enucleated goat oocytes and human neural stem cells (hNSCs). A total of 10.74% cleaved embryos (13/121) developed to blastocyst stage. One typical primary ES-like (tpES-like) colony and two nontypical primary ES-like (non-tpES-like) colonies designated as non-tpES-like cell-1 and non-tpES-like cell-2, respectively, were obtained from the inner cell masses of iSCNT blastocysts. The tpES-like cells expressed ESC markers. Both human and goat mtDNA could be detected in the embryos at 2-8-, 16-32-cell, and blastocyst stages, and in tpES-like colony and two non-tpES-like colonies. Human mtDNA copies per cell from embryos at two- to eight-cell stage to the three colonies maintain almost its original level, whereas 2.88 x 10(5) goat mtDNA copies per oocyte decreased to 10.8 copies per tpES-like cell, 493 copies per non-tpES-like cell-1, and 77.6 copies per non-tpES-like cell-2, resulting in 43.75% (8.4/19.2), 1.24% (6.2/499), and 14.63% (13.3/90.9) mtDNA content in tpES-like cell, non-tpES-like cell-1, and non-tpES-like cell-2 was that of nuclear donor, respectively. Human-specific Tfam and Polg mRNA could be detected in cells of the three colonies. However, tpES-like colony failed to be passaged. The mRNA level of CoxIV encoded by nuclear donor in tpES-like cell was higher than that in non-tpES-like cell, but significantly lower than that of human ESC, suggesting proper nuclear-cytoplasmic communication would not be established in tpES-like cells. Thus, the data suggest that (1) goat oocytes could reprogram human neural stem cells (hNSCs) into embryonic state and further support the inner cell mass (ICM) of iSCNT blastocyst to form tpES-like colony; (2) nuclear donor mtDNA could be replicated and maintain its original level during the reduction of recipient mitochondrial DNA copies, (3) nuclear-cytoplasmic communication and recipient mtDNA copies might affect the derivation of iSCNT-derived ES-like cells.