Attenuating lipid metabolism in atherosclerosis: The potential role of Anti-oxidative effects on low-density lipoprotein of herbal medicines

Atherosclerosis (AS) is a multifactorial chronic disease with great harm to the health of human being, which is a basic pathogenesis of many cardiovascular diseases and ultimately threatens human life. Abnormal blood lipid level is one of the most common diagnostic indicators of AS in clinic, and lipid metabolism disorder is often observed in patients with AS. Cholesterol is an important lipid in the human body, which is of great significance for maintaining normal life activities. Generally, cholesterol is transported to peripheral tissues by low-density lipoprotein (LDL), and then transported to the liver by high-density lipoprotein (HDL) via its cholesterol reverse transport function, and finally discharged. Under oxidative stress condition, LDL is commonly oxidized to the form ox-LDL, which is ingested by macrophages in large quantities and further forms foam cells, disrupting the normal metabolic process of cholesterol. Importantly, the foam cells are involved in forming atherosclerotic plaques, whose rupture may lead to ischemic heart disease or stroke. Furthermore, ox-LDL could also promote the development of AS by damaging vascular endothelium, promoting the migration and proliferation of smooth muscle cells, and activating platelets. Therefore, inhibiting LDL oxidation may be an effective way to improve lipid metabolism and prevent AS. In recent years, increasing studies have shown that herbal medicines have great potentiality in inhibiting LDL oxidation and reducing ox-LDL induced foam cell formation. Accordingly, this paper summarized current research on the inhibitory effects of herbal medicines against LDL oxidation and foam cell formation, and made a brief description of the role of cholesterol and LDL in lipid metabolism disorder and AS pathogenesis. Importantly, it is suggested that herbal medicines could inhibit LDL oxidation and regulate cholesterol homeostasis via downregulation of CD36 and SR-A, whereas upregulation of ABCA1 and ABCG1

Spatial Evolution, Driving Mechanism, and Patch Prediction of Grain-Producing Cultivated Land in China

China has implemented strict policies for protecting cultivated land, and the Chinese government has focused on the non-grain production (NGP) of cultivated land. This study aimed to analyze the spatial evolution law of grain-producing cultivated land (GPCL) in China between 2000 and 2018, explore the mechanism of GPCL, and simulate the spatial characteristics of GPCL in 2036. We used the Geographic Information System (GIS) and a patch-generating land-use simulation model, a new model that proposes a land expansion analysis strategy by improving previous rule-mining methods. China’s grain production rate (GPrate) shows a gradual upward trend between 2000 (36.98%) and 2018 (47.18%). The mutual conversion of GPCL and non-grain-producing cultivated land (NGPCL) are the primary transfer types. The evolution of GPCL is driven by climatic, economic, and social factors, of which population density is the most important factor. GPCL expansion patches are distributed in densely populated, economically developed, and warm and humid plain areas. Further, the simulation results showed that the GPrate in 2036 is estimated to be 41.39%, with GPCL transfer-in significantly exceeding the amount transferred out. Our results further cultivated land evolution-associated research and provide a basis for formulating scientific land-use policies for cultivated land protection for other countries

Evaluation and Hydrological Application of CMADS Reanalysis Precipitation Data against Four Satellite Precipitation Products in the Upper Huaihe River Basin, China

Satellite- and reanalysis-based precipitation products are important data source for precipitation, particularly in areas with a sparse gauge network. Here, five open-access precipitation products, including the newly released China Meteorological Assimilation Driving Datasets for the Soil and Water Assessment Tool (SWAT) model (CMADS) reanalysis dataset and four widely used bias-adjusted satellite precipitation products [SPPs; i.e., Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis 3B42 Version 7 (TMPA 3B42V7), Climate Prediction Center (CPC) morphing technique satellite-gauge blended product (CMORPH-BLD), Climate Hazards Group Infrared Precipitation with Station Data (CHIRPS), and Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Climate Data Record (PERSIANN-CDR)], were assessed. These products were first compared with the gauge observed data collected for the upper Huaihe River basin, and then were used as forcing data for streamflow simulation by the Xin’anjiang (XAJ) hydrological model under two scenarios with different calibration procedures. The performance of CMADS precipitation product for the Chinese mainland was also assessed. The results show that: (1) for the statistical assessment, CMADS and CMORPH-BLD perform the best, followed by TMPA 3B42V7, CHIRPS, and PERSIANN-CDR, among which the correlation coefficient (CC) and root-mean-square error (RMSE) values of CMADS are optimal, although it exhibits certain significant negative relative bias (BIAS; −22.72%); (2) CMORPH-BLD performs the best in capturing and detecting rainfall events, while CMADS tends to underestimate heavy and torrential precipitation; (3) for streamflow simulation, the performance of using CMADS as input is very good, with the highest Nash-Sutcliffe efficiency (NSE) values (0.85 and 0.75 for calibration period and validation period, respectively); and (4) CMADS exhibits high accuracy in eastern China while with significant negative BIAS, and the performance declines from southeast to northwest. The statistical and hydrological evaluations show that CMADS and CMORPH-BLD have high potential for observing precipitation. As high negative BIAS values showed up in CMADS evaluation, further study on the error sources from original data and calibration algorithms is necessary. This study can serve as a reference for selecting precipitation products in data-scarce regions with similar climates and topography in the Global Precipitation Measurement (GPM) era

Simeprevir restores the anti-Staphylococcus activity of polymyxins

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) infection poses a severe threat to global public health due to its high mortality. Currently, polymyxins are mainly used for the treatment of Gram-negative bacterial-related infection, while exhibiting limited antibacterial activities against Staphylococcus aureus (S. aureus). However, the combination of antibiotics with antibiotic adjuvants is a feasible strategy for the hard-treated infection and toxicity reducing. We will investigate the antibacterial activity of simeprevir (SIM), which treated for genotype 1 and 4 chronic hepatitis C, combined with polymyxins against MRSA through high-throughput screening technology. In our study, the synergistic antibacterial effect of SIM and polymyxins against S. aureus in vitro was found by checkerboard assay and time-growth curve. The cytotoxicity of SIM combined with polymyxin B sulfate [PB(S)] or polymyxin E (PE) in vitro was evaluated using CCK-8, human RBC hemolysis and scratch assays. In addition, we investigated the eradication of biofilm formation of S. aureus by biofilm inhibition assay and the killing of persister cells. Moreover, we evaluated the therapeutic effect and in vivo toxicity of the combination against MRSA in murine subcutaneous abscess model. Furthermore, it was preliminarily found that SIM significantly enhanced the destruction of MRSA membrane by SYTOX Green and DISC3(5) probes. In summary, these results reveal that the therapy of SIM combined with polymyxins (especially PE) is promising for the treatment of MRSA infection

Prevalence and associated factors of frailty in patients with chronic kidney disease:a cross-sectional analysis of PEAKING study

Aim: Frailty is common and is reported to be associated with adverse outcomes in patients with chronic diseases in Western countries. However, the prevalence of frailty remains unclear in individuals with chronic kidney disease (CKD) in China. We examined the prevalence of frailty and factors associated with frailty in patients with CKD.Methods: This was a cross-sectional analysis of 177 adult patients (mean age 54 ± 15 years, 52% men) with CKD from the open cohort entitled Physical Evaluation and Adverse outcomes for patients with chronic Kidney disease IN Guangdong (PEAKING). Frailty at baseline were assessed by FRAIL scale which included five items: fatigue, resistance, ambulation, illnesses, and loss of weight. Potential risk factors of frailty including age, sex, body mass index, and daily step counts recorded by ActiGraph GT3X + accelerometer were analyzed by multivariate logistic regression analysis.Results: The prevalence of prefrailty and frailty was 50.0% and 11.9% in patients with stages 4-5 CKD, 29.6% and 9.3% in stage 3, and 32.1% and 0 in stages 1-2. In the multivariate logistic regression analysis, an increase of 100 steps per day (OR = 0.95, 95% CI 0.91-0.99, P = 0.01) and an increase of 5 units eGFR (OR = 0.82, 95% CI 0.68-0.99, P = 0.045) were inversely associated with being frail; higher BMI was associated with a higher likelihood of being frail (OR = 1.52, 95% CI 1.11-2.06, P = 0.008) and prefrail (OR = 1.25, 95% CI 1.10-1.42, P = 0.001).Conclusion: Frailty and prefrailty were common in patients with advanced CKD. A lower number of steps per day, lower eGFR, and a higher BMI were associated with frailty in this population

#1088 Interaction of general obesity and abdominal obesity with frailty in patients with chronic kidney disease: a nationally representative analysis

Background and AimsGeneral and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results. We explored the relationship between general and abdominal obesity and frailty in CKD patients.MethodThis cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES 2003-2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as body mass index (BMI) above 30 kg/m2, and abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The association of general and abdominal obesity with frailty were analyzed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined.Results5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 mL/min/1.73 m2. The prevalence of frailty was 40.7%. The prevalence of general obesity and abdominal obesity was 43.3% and 71.5%, respectively. Neither general nor abdominal obesity alone was associated with frailty. There was interaction between general and abdominal obesity with frailty (Table 1). Compared to individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty [odds ratio (OR): 1.53, 95% confidence interval (CI): 1.20-1.95]. General obesity was associated with being frail when CKD patients had abdominal obesity (OR: 1.59, 95% CI: 1.08-2.36) (Fig. 1).ConclusionThere may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects

#1060 Prevalence and adverse outcomes of hypokalemia and the role of potassium supplementation in patients receiving peritoneal dialysis

Background and AimsHypokalemia is common and potentially life-threatening in patients undergoing peritoneal dialysis (PD). The reported prevalence of hypokalemia in PD patients varies significantly across studies, with ongoing debate about its association to adverse outcomes and the effects of potassium supplementation.MethodWe searched MEDLINE, Embase, Web of Science and references from eligible studies from database inception through September 2023 without language restriction for randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional studies on the prevalence and adverse outcomes (all-cause mortality, cardiovascular mortality, infection-related mortality, and PD-associated peritonitis) of hypokalemia or the role of potassium supplementation in patients receiving PD. Random effects meta-analysis is conducted to pool Hazard ratio (HR) and 95% confidence interval (CI) for the outcomes of interest. The certainty of findings was rated according to GRADE criteria.ResultsOut of 3 298 reports identified, 23 studies involving 59 433 participants met inclusion criteria. The prevalence of hypokalemia across all definitions was 37.9% (95% CI: 27.2-52.7%), 19.0% (95% CI: 13.0-27.6%) (Fig. 1), and 4.4% (95% CI: 1.9-10.2%) for patients with potassium level below 4.0, 3.5 and 3.0 mmol/L. Hypokalemia was associated with increased risk of all-cause mortality (HR: 1.49; 95% CI: 1.18-1.89) (Fig. 2), cardiovascular mortality (HR: 1.50; 95% CI: 1.19-1.88), and PD-associated peritonitis (HR: 1.53; 95% CI: 1.23-1.88). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for subgroup and sensitivity analyses were consistent with the primary finding. Only two studies examined the impact of correcting hypokalemia with potassium supplementation in PD patients, and the results are inconclusive.ConclusionHypokalemia is common and portends poorer survival and higher risk of peritonitis among PD patients. Further research into the optimal prevention and treatment strategies for hypokalemia is warranted to improve outcomes