Trends in statin use for the primary prevention of atherosclerotic cardiovascular disease among US adults by demographic characteristics, 1999-2020.

PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Statins, which are effective in preventing ASCVD, are underused, particularly for primary prevention. This study examined trends in statin use for primary ASCVD prevention from 1999 to 2020, focusing on demographic variations. METHODS: Utilizing data from the National Health and Nutrition Examination Survey, the present study includes individuals aged 18 years and older who had a greater than 10% risk of ASCVD over 10 years, and excluded patients with existing ASCVD. Subgroup analyses by demographic categories were performed. We calculated the changes in statin usage and used linear and quadratic tests to assess the linear and nonlinear trends in those changes. RESULTS: A total of 10,037 participants were included. Statin usage increased from 16.16% in 1999 to 36.24% in 2010, and 41.74% in 2020 (quadratic P-value < 0.001). In the 18-44 years age group, statin usage increased from 2.52% in 1999 to 8.14% in 2020 (linear P-value = 0.322), showing no significant linear trend. In the "never-married" group, statin usage increased from 19.16% in 1999 to 30.05% in 2020 (linear P-value = 0.256). CONCLUSION: Statin usage has shown a positive trend among populations requiring primary prevention for ASCVD. Currently, health policies are proving effective. However, the overall statin usage rate remains less than 50%. Additionally, young and never-married individuals should also receive special attention regarding statin usage as primary treatment for ASCVD.

The management of non-culprit vessel(s) in patients with unstable angina/non-ST elevation myocardial infarction and chronic kidney dysfunction.

BACKGROUND AND AIMS: The clinical effects of multivessel interventions in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non-culprit lession(s) among this cohort. METHODS: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48-month overall mortality between those undergoing multivessel PCI (MV-PCI) through a single-procedure or staged-procedure approach and culprit vessel-only PCI (CV-PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast-induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. RESULTS: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV-PCI had reduced all-cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48-0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 ) could not benefit from MV-PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (P interaction < 0.01; HR = 0.95, 95% CI = 0.65-1.45). Although the staged-procedure approach (N = 157) failed to bring additional survival benefits compared to single-procedure MV-PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV-PCI and CV-PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94-2.73). CONCLUSION: Among patients with UA/NSTEMI and non-diabetic CKD and an eGFR > 30 mL/min/1.73 m2 , MV-PCI was associated with a reduced risk of long-term death but did not increase the incidence of CIN during the management of MVD compared to CV-PCI. And staged procedures might be a preferable option over single-procedure MV-PCI.

Total Arterial Revascularization in Diabetic Patients Undergoing Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-Analysis.

Background: Total arterial revascularization (TAR) has gradually become accepted and recognized, but its effect and safety in diabetic patients are not clear. We performed a systematic review and meta-analysis to summarize the safety and efficacy of TAR and additionally evaluated the clinical outcomes of arterial revascularization using different arterial deployments in patients with diabetes. Methods: PubMed, Embase, and the Cochrane Library databases from inception to July 2022 for studies that studied the effect of arterial revascularization in diabetic patients undergoing isolated coronary artery bypass graft (CABG) were searched. The primary outcome was long-term ( ≥ 12 months of follow-up) death by any cause. The secondary efficacy endpoints were long-term ( ≥ 12 months) cardiovascular death, early sternal wound infection (SWI) and death ( ≤ 30 days or in hospital). Risk ratios (RRs), hazard ratios (HRs), and their corresponding 95% confidence intervals (CIs) were calculated to describe short-term results and long-term survival outcomes. Two different ways were used to analyze the effect of TAR and the impact of diabetes on the clinical outcomes of TAR. Results: Thirty-five studies were included in the study, covering 178,274 diabetic patients. Compared to conventional surgery with saphenous veins, TAR was not associated with increased early mortality (RR 0.77, 95% CI 0.48-1.23) and risk of SWI (RR 0.77, 95% CI 0.46-1.28). The overall Kaplan-Meier survival curves based on reconstructed patient data indicated a significant association between TAR and reduced late mortality (HR 0.52, 95% CI 0.48-0.67) and the curves based on the propensity-score matched (PSM) analyses suggested a similar result (HR 0.74, 95% CI 0.66-0.85). TAR could also effectively decrease the risk of cardiovascular death (HR 0.42, 95% CI 0.24-0.75). Through comparing the effect of TAR in patients with and without diabetes, we found that the presence of diabetes did not elevate the risk of early adverse events (death: RR 1.50, 95% CI 0.64-3.49; SWI: RR 2.52, 95% CI 0.91-7.00). Although diabetes increased long-term mortality (HR 1.06; 95% CI 1.35-2.03), the cardiovascular death rate was similar in patients with diabetes and patients without diabetes (HR 1.09; 95% CI 0.49-2.45). Regarding the selection of arterial conduits, grafting via the bilateral internal mammary artery (BIMA) decreased the risk of overall death (HR 0.67, 95% CI 0.52-0.85) and cardiovascular death (HR 0.55, 95% CI 0.35-0.87) without resulting in a significantly elevated rate of early death (RR 0.95, 95% CI 0.82-1.11). However, the evidence from PSM studies indicated no difference between the long-term mortality of the BIMA group and that of the single internal mammary arteries (SIMA) groups (HR 0.76, 95% CI 0.52-1.11), and the risk of SWI was significantly increased by BIMA in diabetes (RR 1.65, 95% CI 1.42-1.91). The sub-analysis indicated the consistent benefit of the radial artery (RA) application in diabetic patients (HR 0.71, 95% CI 0.63-0.79) compared to saphenous vein graft. In two propensity-score-matched studies, the evidence showed that the survival outcomes of the BIMA group were similar to that of the SIMA plus RA group but that grafting via the RA reduced the risk of sternal wound infection. Conclusions: Compared with conventional surgery using SVG, TAR was associated with an enhanced survival benefit in diabetes and this long-term gain did not increase the risk of early mortality or SWI. Given the increased infection risk and controversial long-term survival gains of grafting via the BIMA in diabetes, its wide use for grafting in this cohort should be seriously considered. Compared to using the right internal mammary artery (RIMA), RA might be a similarly effective but safer option for patients with diabetes.

Performance of the Risk Scores for Predicting In-Hospital Mortality in Patients with Acute Coronary Syndrome in a Chinese Cohort.

Background: The prognosis of patients with acute coronary syndrome (ACS) varies greatly, and risk assessment models can help clinicians to identify and manage high-risk patients. While the Global Registry of Acute Coronary Events (GRACE) model is widely used, the clinical pathways for acute coronary syndromes (CPACS), which was constructed based on the Chinese population, and acute coronary treatment and intervention outcomes network (ACTION) have not yet been validated in the Chinese population. Methods: Patients with ACS who underwent coronary angiography or percutaneous coronary intervention from 2011 to 2020, were retrospectively recruited and the appropriate corresponding clinical indicators was obtained. The primary endpoint was in-hospital mortality. The performance of the GRACE, GRACE 2.0, ACTION, thrombolysis in myocardial infarction (TIMI) and CPACS risk models was evaluated and compared. Results: A total of 19,237 patients with ACS were included. Overall, in-hospital mortality was 2.2%. ACTION showed the highest accuracy in predicting discriminated risk (c-index 0.945, 95% confidence interval [CI] 0.922-0.955), but the calibration was not satisfactory. GRACE and GRACE 2.0 did not significantly differ in discrimination (p = 0.1480). GRACE showed the most accurate calibration in all patients and in the subgroup analysis of all models. CPACS (c-index 0.841, 95% CI 0.821-0.861) and TIMI (c-index 0.811, 95% CI 0.787-0.835) did not outperform (c-index 0.926, 95% CI 0.911-0.940). Conclusions: In contemporary Chinese ACS patients, the ACTION risk model's calibration is not satisfactory, although outperformed the gold standard GRACE model in predicting hospital mortality. The CPACS model developed for Chinese patients did not show better predictive performance than the GRACE model.

Pentapeptide IIAEK ameliorates cholesterol metabolism via the suppression of intestinal cholesterol absorption in mice.

Dietary protein-derived peptides are effective in improving dyslipidemia and hypercholesterolemia. We previously identified a novel cholesterol-lowering pentapeptide IIAEK from milk beta-lactoglobulin. However, it remains unclear whether IIAEK affects the micellar solubility of cholesterol and the bile acid-binding ability to lower cholesterol. Moreover, there is no direct evidence that IIAEK inhibits intestinal cholesterol absorption and affects hepatic cholesterol and fecal steroid excretion in vivo. Herein, we showed that IIAEK did not affect the micellar solubility of cholesterol and the bile acid-binding ability. However, we found that IIAEK decreased serum and liver cholesterol levels and increased fecal steroid excretion in mice. Interestingly, IIAEK markedly suppressed the intestinal absorption of [3H]-cholesterol in mice. In conclusion, we found that IIAEK ameliorated cholesterol metabolism by suppressing intestinal cholesterol absorption without affecting in vitro micellar solubility of cholesterol and the bile acid-binding ability in mice.

Protamine-derived peptide RPR (Arg-Pro-Arg) ameliorates oleic acid-induced lipogenesis via the PepT1 pathway in HepG2 cells.

The protamine-derived peptide arginine-proline-arginine (RPR) can ameliorate lifestyle-related diseases such as obesity and hypercholesterolemia. Thus, we hypothesized that the hypolipidemic activity of RPR could attenuate events leading to non-alcoholic fatty liver disease. Addition of 2 m m oleic acid (OA) to the culture medium induced fatty liver conditions in HepG2 cells. The OA + RPR group showed significantly decreased cellular or medium triglyceride (TG) level compared with the OA group. Stearoyl-CoA desaturase-1 (SCD1) or sterol regulatory element-binding protein 1 (SREBP1) protein level was significantly lower in the OA + RPR group than in the OA group. In the R + P + R amino acid mixture-treated group, the TG level was not significantly different from that in the OA-treated group. The OA + RP- or OA + PR-treated groups showed significantly decreased cellular TG level compared with the OA group. Moreover, the effect of RPR disappeared when the peptide transporter 1 (PepT1) was knocked down with a siRNA. Collectively, our results demonstrated that RPR effectively ameliorated hepatic steatosis in HepG2 cells via the PepT1 pathway.

Eugeniin improves cholesterol metabolism in HepG2 cells and Caco-2 cells.

Considering the absence of prior studies on the cholesterol metabolism-improving effects of eugeniin, the present investigation aimed to explore the potential impact of eugeniin on cholesterol metabolism. This study sought to elucidate the molecular mechanisms involved in this process using HepG2 and Caco-2 cells treated with 5 µm eugeniin. The intracellular cholesterol levels in HepG2 and Caco-2 cells were significantly decreased in the 24-h eugeniin-treated group. The protein and messenger ribonucleic acid (mRNA) levels of the low-density lipoprotein receptor (LDLR) were increased, while 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase protein and mRNA levels were decreased in HepG2 cells 6 h of the eugeniin-treated group. Additionally, LDLR protein and mRNA levels were increased in HepG2 cells after 24 h of eugeniin treatment. In Caco-2, the protein and mRNA levels of ATP-binding cassette transporter 1 were increased after 24 h eugeniin treatment. This novel finding indicates that eugeniin improves cholesterol metabolism in human cell cultures.

The physiological blood concentration of phenylalanine-proline can ameliorate cholesterol metabolism in HepG2 cells.

We have previously reported that the dipeptide Phe-Pro affects lipid metabolism in vivo and in vitro, but very little is known regarding the mechanism of action of Phe-Pro after it is absorbed by the intestines via PepT1. In this study, we administered a single oral dose of Phe-Pro to rats and quantified its concentration in the portal plasma using LC-TOF/MS analysis. Additionally, the physiological blood concentration of Phe-Pro was added to the lipid accumulation model of HepG2 cells to decrease intracellular cholesterol and increase the expression of CYP7A1 and PPARα mRNA levels. Moreover, we analyzed the binding of PPARα and Phe-Pro using AlphaFold2. We found that Phe-Pro is a ligand for PPARα. To the best of our knowledge, this is the first study that shows Phe-Pro to be present in the portal plasma. We found for the first time that Phe-Pro ameliorated cholesterol metabolism in HepG2 cells.

Sex Differences in the Relationship Between Self-Reporting of Snoring and Cardiovascular Risk:An Analysis of NHANES.

Background: Identifying risk factors for cardiovascular disease (CVD) is critical for effective prevention and management. While classic CVD risk factors have been extensively studied, there is a scarcity of research on the association between snoring and CVD risk, particularly in the context of sex differences. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. Participants were initially categorized based on the severity of snoring or the presence of snoring.Within the snoring group, they were further classified by sex. Analysis was carried out using multivariate logistic regression. Results: Our study included 12,681 participants aged 18 years or older. When compared to the non-snoring group, individuals in the moderate snoring group had a higher odds ratio (OR) of 1.418 (95% CI 1.083 to 1.857, p = 0.011), while those in the severe snoring group had a higher OR of 1.882 (95% CI 1.468 to 2.409, p < 0.001). In the snoring group, individuals were further categorized by gender: 4527 males and 4131 females. Importantly, male patients showed a higher OR for atrial fibrillation (4.945, 95% CI 1.187 to 20.598, p = 0.028) compared to females. Additionally, male patients had a higher OR for coronary heart disease (2.002, 95% CI 1.152 to 3.479, p = 0.014) compared to females. Conclusion: Sex plays a significant role in the relationship between snoring and CVD risk. Males with snoring have a higher risk of developing CVD compared to females. In particular, male snorers are nearly five times more likely to develop atrial fibrillation and about twice as likely to experience coronary artery disease in comparison to female snorers. It is recommended that healthcare providers and public health officials prioritize cardiovascular risk assessments for male individuals who exhibit symptoms of snoring.

Heterogeneous body compositions and all-cause mortality in acute coronary syndrome patients: a ten-year retrospective cohort study.

BACKGROUND: The association of different body components, including lean mass and body fat, with the risk of death in acute coronary syndrome (ACS) patients are unclear. METHODS: We enrolled adults diagnosed with ACS at our center between January 2011 and December 2012 and obtained follow-up outcomes via telephone questionnaires. We used restricted cubic splines (RCS) with the Cox proportional hazards model to analyze the associations between body mass index (BMI), predicted lean mass index (LMI), predicted body fat percentage (BF), and the value of LMI/BF with 10-year mortality. We also examined the secondary outcome of death during hospitalization. RESULTS: During the maximum 10-year follow-up of 1398 patients, 331 deaths (23.6%) occurred, and a U-shaped relationship was found between BMI and death risk (P nonlinearity = 0.03). After adjusting for age and history of diabetes, the overweight group (24 ≤ BMI < 28 kg/m2) had the lowest mortality (HR = 0.53, 95% CI: 0.29-0.99). Predicted LMI and LMI/BF had an inverse linear relationship with a 10-year death risk (P nonlinearity = 0.24 and P nonlinearity = 0.38, respectively), while an increase in BF was associated with increased mortality (P nonlinearity = 0.64). During hospitalization, 31 deaths (2.2%) were recorded, and the associations of the indicators with in-hospital mortality were consistent with the long-term outcome analyses. CONCLUSION: Our study provides new insight into the "obesity paradox" in ACS patients, highlighting the importance of considering body composition heterogeneity. Predicted LMI and BF may serve as useful tools for assessing nutritional status and predicting the prognosis of ACS, based on their linear associations with all-cause mortality.

Mapping Theme Trends and Research Frontiers in Dexmedetomidine Over Past Decade: A Bibliometric Analysis.

Background: Dexmedetomidine, an α2-adrenergic receptor (α2-AR) agonist, is extensively used in clinical and animal studies owing to its sedative, analgesic, and anxiolytic effects. The diverse range of research domains associated with dexmedetomidine poses challenges in defining pivotal research directions. Therefore, this study aimed to conduct a qualitative and quantitative bibliometric study in the field of dexmedetomidine over the past decade to establish current research trends and emerging frontiers. Methods: Relevant publications in the field of dexmedetomidine between 2014 and 2023 were extracted from the Web of Science Core Collection database. The bibliometric analysis, incorporating statistical and visual analyses, was conducted using CiteSpace (6.1.R6) and R (4.3.1). Results: The present study encompassed a total of 5,482 publications, exhibiting a consistent upward trend over the past decade. The United States and its institutions had the highest centrality. Ji, Fuhai, and Ebert, Thomas J. were identified as the most productive author and the most cited author, respectively. As anticipated, the most cited journal was Anesthesiology. Moreover, cluster analysis of cited references and co-occurrence of keywords revealed that recent studies were primarily focused on sedation, delirium, and opioid-free anesthesia. Finally, a timeline view of keywords clusters and keywords burst demonstrated that primary research frontiers were stress response, neuroinflammation, delirium, opioid-free anesthesia, peripheral nerve block, and complications. Conclusion: Current research trends and directions are focused on sedation, delirium, and opioid-free anesthesia, as evidenced by our results. The frontier of future research is anticipated to encompass basic investigations into dexmedetomidine, including stress response and neuroinflammation, as well as clinical studies focusing on delirium, opioid-free anesthesia, peripheral nerve block, and associated complications.

Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Allopurinol for Secondary Prevention in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effects of allopurinol in patients with cardiovascular disease are not well defined; therefore, the latest evidence is summarized in this study. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) of allopurinol in patients with cardiovascular disease published up to 11 February 2023. The primary outcome was cardiovascular death. RESULTS: We combined the results of 21 RCTs that included 22,806 patients. Compared to placebo/usual care, allopurinol treatment was not associated with a significant reduction in cardiovascular death (RR 0.60; 95% CI 0.33-1.11) or all-cause death (RR 0.90; 95% CI 0.72-1.12). However, evidence from earlier trials and studies with small sample sizes indicated that allopurinol might confer a protective effect in decreasing cardiovascular death (RR 0.34; 95% CI 0.15-0.76) across patients undergoing coronary artery bypass grafting (CABG) or having acute coronary syndrome (ACS). In comparisons between allopurinol and febuxostat, we observed no difference in cardiovascular death (RR 0.92; 95% CI 0.69-1.24) or all-cause death (RR 1.02; 95% CI 0.75-1.38). CONCLUSION: Allopurinol could not reduce cardiovascular (CV) death or major adverse CV outcomes significantly in patients with existing cardiovascular diseases. Given the limitations of the original studies, the potential advantages of allopurinol observed in patients undergoing CABG or presenting with ACS necessitate further confirmation through subsequent RCTs. In the comparisons between allopurinol and febuxostat, our analysis failed to uncover any marked superiority of allopurinol in reducing the risk of adverse cardiovascular incidents.

Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.

Cognitive disorders are mental health disorders that can affect cognitive ability. Surgery and anesthesia have been proposed to increase the incidence of cognitive dysfunction, including declines in memory, learning, attention and executive function. Tau protein is a microtubule-associated protein located in the axons of neurons and is important for microtubule assembly and stability; its biological function is mainly regulated by phosphorylation. Phosphorylated tau protein has been associated with cognitive dysfunction mediated by disrupting the stability of the microtubule structure. There is an increasing consensus that anesthetic drugs can cause cognitive impairment. Herein, we reviewed the latest literature and compared the relationship between tau protein and cognitive impairment caused by different anesthetics. Our results substantiated that tau protein phosphorylation is essential in cognitive dysfunction caused by anesthetic drugs, and the possible mechanism can be summarized as "anesthetic drugs-kinase/phosphatase-p-Tau-cognitive impairment".

CuO decorated vacancy-rich CeO2 nanopencils for highly efficient catalytic NO reduction by CO at low temperature.

With the rapid development of transportation and vehicles, the elimination of NOx and CO has highly attracted public attention. In this work, vacancy-rich CeO2 nanopencil supported CuO catalysts (CuO/CeO2-NPC) were successfully prepared for NO reduction by CO. Importantly, CeO2 with nanopencil-like shape (CeO2-NPC) have been synthesis by solvothermal method for the first time. The physicochemical properties of all samples were studied in detail by combining the means of X-ray diffraction (XRD), Raman spectroscopy, electron paramagnetic resonance (EPR), X-ray photoelectron spectroscopy (XPS), H2-temperature-programmed reduction (H2-TPR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), N2 physisorption (Brunauer-Emmett-Teller), and NO and CO temperature-programmed desorption (NO-TPD and CO-TPD) techniques. Compared with CeO2 nanorods and nanoparticles supported CuO catalysts (CuO/CeO2-NR and CuO/CeO2-NP), the CuO/CeO2-NPC catalysts showed the highest catalytic activity, affording more than 90% NO conversion at 69 °C as well as excellent H2O tolerance at 150 °C, which is superior to catalysts previously reported. Characterization results indicated that the synergistic effect between the well-dispersed CuO and the CeO2 nanopencil support enables a favorable electron transfer between these components and enhances the density of surface oxygen vacancies and Cu+ species, which consequently accelerating the redox cycle. The results indicated that the morphology control of CeO2 support could be an efficient way to evidently enhance the catalytic performance for NO + CO reaction.

Rose polyphenols exert antiobesity effect in high-fat-induced obese mice by regulating lipogenic gene expression.

Obesity presents a major risk factor in the development of cardiovascular diseases. Recent reports indicate that many kinds of polyphenols have the potential to prevent metabolic diseases. We hypothesized that rose polyphenols (ROSE) have the effect of improvement in lipid metabolism. In this study, we investigated whether rose polyphenols affected lipid metabolism and exerted antiobesity. To clarify the mechanism, C57BL/6J mice were fed a high-fat diet containing 0.25% ROSE for 35 days. Compared with the control group, body weight gain and adipose tissue weight in the 0.25% ROSE group were significantly decreased. Serum cholesterol and hepatic triglyceride concentrations significantly decreased, whereas fecal triglyceride was significantly increased in the 0.25% ROSE group. Liver stearoyl-CoA desaturase 1 (Scd1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and acyl-CoA:cholesterol acyltransferase 1 (Acat1) mRNA as well as protein stearoyl-CoA desaturase 1 concentrations were significantly lower in the 0.25% ROSE group than that in the control group. The mRNA and the protein concentrations of adipose triglyceride lipase, hormone-sensitive lipase, and peroxisomal acylcoenzyme A oxidase 1 in white adipose tissue were significantly higher in the 0.25% ROSE group than that in the control group. The components in rose polyphenols were quantified by liquid chromatography-tandem mass spectrometry, and we consider that ellagic acid plays an important role in an antiobesity effect because the ellagic acid content is the highest among polyphenols in rose polyphenols. In summary, rose polyphenols exhibit antiobesity effects by influencing lipid metabolism-related genes and proteins to promote lipolysis and suppress lipid synthesis.

Antidyslipidemia Pharmacotherapy in Chronic Kidney Disease: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND AND AIMS: The benefits and safety of antidyslipidemia pharmacotherapy in patients with chronic kidney disease were not well defined so the latest evidence was summarized by this work. METHODS: This systematic review and Bayesian network meta-analysis (NMA) included searches of PubMed, Embase, and Cochrane Library from inception to 28 February 2022, for randomized controlled trials of any antilipidaemic medications administered to adults with chronic kidney disease [CKD: defined as estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 not undergoing transplantation], using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool to assess the certainty of the evidence. RESULTS: 55 trials and 30 works of them were included in our systematic review and NMA, respectively. In comparisons with no antidyslipidemia therapy or placebo, proprotein convertase subtilisin/Kexin type 9 inhibitors plus statin (PS) was the most effective drug regimen for reducing all-cause mortality (OR 0.62, 95% CI [0.40, 0.93]; GRADE: moderate), followed by moderate-high intensity statin (HS, OR 0.76, 95% CI [0.60, 0.93]; I2 = 66.9%; GRADE: moderate). PS, HS, low-moderate statin (LS), ezetimibe plus statin (ES), and fibrates (F) significantly decreased the composite cardiovascular events. The subgroup analysis revealed the null effect of statins on death (OR 0.92, 95% CI [0.81, 1.04]) and composite cardiovascular events (OR 0.94, 95% CI [0.82, 1.07]) in dialysis patients. CONCLUSION: In nondialysis CKD patients, statin-based therapies could significantly and safely reduce all-cause death and major composite cardiovascular events despite the presence of arteriosclerotic cardiovascular disease and LDL-c levels. Aggressive medication regimens, PS and HS, appeared to be more effective, especially in patients with established CAD.

METTL3 suppresses neuropathic pain via modulating N6-methyladenosine-dependent primary miR-150 processing.

Methyltransferase-like 3 (METTL3)-modulated N6-methyladenosine (m6A) was recently identified as an important epigenetic regulation type during RNA processing and contributes to multiple pathological processes. Neuropathic pain (NP) is induced by a lesion of the somatosensory nervous system, and the detailed pathways by which METTL3/m6A regulated to modulate gene dysregulation and enable NP have remained unclear. Therefore, this study investigated the function of METTL3-mediated m6A methylation on miRNA maturation, and investigated how this regulation contributes to NP progression. A rat model characterized with typical NP was established by a spared nerve-injury (SNI) method. By analyzing the expression levels of METTL3 and m6A methylation, we found that METTL3, along with m6A methylation, was dramatically downregulated in NP rats in contrast to the sham ones. Functionally, enhanced METTL3 promoted the m6A methylation in total RNAs and inhibited NP progression, whereas silencing METTL3 suppressed m6A methylation and increased NP severity. Mechanistically, METTL3 accelerated miR-150 maturation via mediating m6A methylation of primiR-150 at locus 498, cooperating with the "m6A reader" YTHDF2. Meanwhile, miR-150 could directly target brain-derived neurotrophic factor (BDNF) mRNA, and the METTL3/miR-150/BDNF regulatory pathway was finally established. Clinically, we proved that serum METTL3 mRNA was also downregulated in Shingles patients with NP, suggesting its diagnostic potential. In conclusion, we demonstrated an essential function of METTL3-regulated N6-methyladenosine during NP progression via modulating primiR-150 maturation. Serum METTL3 could effectively differentiate NP patients from healthy people, and is useful for dynamic monitoring of diseases after treatment. Therefore, the METTL3/miR-150/BDNF pathway may be a promising therapeutic target for NP patients.

Endoscopic transcortical expanded transforaminal transvenous transchoroidal approach to third ventricle lesion resection using an endoport.

OBJECTIVE: To investigate the clinical experience and application value of endoscopic resection of lesions in and around the third ventricle using a transcortical expanded transforaminal transvenous transchoroidal approach with an endoport. METHODS: Clinical data and follow-up results of seven patients who underwent the removal of lesions in the third ventricle and its adjacent area with an endoport-guided endoscopic system from January 2018 to December 2020 in the Department of Neurosurgery, Zhongshan Hospital Affiliated to Fudan University, were analyzed retrospectively. Two other patients from the Affiliated Pediatric Hospital of Fudan University and the Affiliated Hospital of Guizhou Medical University, respectively, were included in the analysis. RESULTS: A total of nine cases of third ventricle tumors were included in the study, including six women and three men, with an average age of 37.8 years (4-84 years old) and a follow-up time of 6-44 months. These nine tumor cases included two pilocytic astrocytomas, one diffuse midline glioma (H3 K27-altered), two craniopharyngiomas, two choroid plexus (CP) papillomas, one germinoma, and one pineal parenchymal tumor of intermediate differentiation. Total resection was completed in eight cases, with one near-total resection. There were no complications related to the surgical approach, such as epilepsy, aphasia, or hemiplegia. CONCLUSIONS: The endoscope transcortical expanded transforaminal transvenous transchoroidal approach using an endoport can safely and effectively remove third ventricle lesions. This approach can reach a wide area, from the anterior to the posterior third ventricle.

Revascularization vs. Conservative Medical Treatment in Patients With Chronic Kidney Disease and Coronary Artery Disease: A Meta-Analysis.

BACKGROUND: As a strong risk factor for coronary artery disease (CAD), chronic kidney disease (CKD) indicates higher mortality in patients with CAD. However, the optimal treatment for the patients with two coexisting diseases is still not well defined. METHODS: To conduct a meta-analysis, PubMed, Embase, and the Cochrane database were searched for studies comparing medical treatment (MT) and revascularization [percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] in adults with CAD and CKD. Long-term all-cause mortality was evaluated, and subgroup analyses were performed. RESULTS: A total of 13 trials met our selection criteria. Long-term (with at least a 1-year follow-up) mortality was significantly lower in the revascularization arm [relative risk (RR) = 0.66; 95% CI = 0.60-0.72] by either PCI (RR = 0.61; 95% CI = 0.55-0.68) or CABG (RR = 0.62; 95% CI = 0.46-0.84). The results were consistent in dialysis patients (RR = 0.68; 95% CI = 0.59-0.79), patients with stable CAD (RR = 0.75; 95% CI = 0.61-0.92), patients with acute coronary syndrome (RR = 0.62; 95% CI = 0.58-0.66), and geriatric patients (RR = 0.57; 95% CI = 0.54-0.61). CONCLUSION: In patients with CKD and CAD, revascularization is more effective in reducing mortality than MT alone. This observed benefit is consistent in patients with stable CAD and elderly patients. However, future randomized controlled trials (RCTs) are required to confirm these findings.