<b><i>Background:</i></b> Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. <b><i>Methods:</i></b> A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. <b><i>Results:</i></b> The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8–61.0) μM. During a median follow-up of 63.7 months (IQR, 43.9–87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01–1.48; <i>p</i> = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07–1.76; <i>p</i> = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02–1.94; <i>p</i> = 0.038) in men but not in women. <b><i>Conclusions:</i></b> Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.
Aerobic exercise, which has been shown to have beneficial effects on plasma lipids, has been recommended as an effective measure to improve the prognosis of individuals with coronary heart disease (CHD). Apolipoprotein C3 (apoC3) is associated with hypertriglyceridemia and is therefore closely related to CHD.We measured apoC3 concentration change in patients with CHD before and after long-term aerobic exercise.Thirty-eight patients with coronary heart disease were randomly assigned to a non-exercise group (19 patients) or exercise group (19 patients). Both groups received essential drugs for CHD. The non-exercise group was kept sedentary while the exercise group performed moderate-intensive aerobic exercise for 8 weeks. Lipid levels and apoC3 levels were measured on the first day and 8 weeks later.Exercise for 8 weeks led to a significant decrease in concentration of triglyceride and apoC3 compared with the baseline. Triglyceride concentration changes were positively associated with apoC3 level changes.Aerobic exercise can improve the lipid profile. It is effective in decreasing triglycerides by targeting apoC3 levels in patients with coronary heart disease.
Objective
To study the effect of Jade-Screen Powder (JSP) on regulating expression of 5 microRNAs associated with helper T cells in asthmatic mouse model.
Methods
Forty Balb/c mice were randomly divided into 4 groups, 10 mice for each group, namely normal control, asthma model, JSP treatment and Dexamethasone treatment.The mouse models of allergic inflammation on both upper and lower airways were established by ovalbumin sensitization and challenge.Interleukin(IL)-13 and IL-17 expressions were detected from lung homogenates by ELISA.Hematoxylin and eosin staining was also performed to observe the pathological changes in the lung tissue.The expressions of miR-146a, miR-146b, miR-210, miR-126 and miR-21a were detected by quantitative real time PCR from splenocytes.
Results
The lower levels of IL-13 [(6.382±1.690) μg/L] and IL-17 [(24.212±1.250) μg/L] were found in JSP treatment group compared with those in the asthma model group [(20.154±7.960) μg/L; (50.312±5.770) μg/L, rseparately], there was significant difference in IL-13 between JSP group and the asthma model group, as well as IL-17 (t=3.785, P=0.005; t=9.891, P=0.000). Same findings were found in Dexamethasone treated group as well [IL-13: (9.366±3.460) μg/L, IL-17: (29.132±4.960) μg/L; t=2.779, P=0.024; t=6.225, P=0.000]. However, upregulation of miR-210 was observed in JSP treatment group (2.052±0.871) compared with that in the asthma model group (4.034±1.379) (3.95 folds, t=2.718, P=0.026). Meantime, the expression of miR-126 in JSP group (4.920±0.924) and Dexamethasone group (3.862±1.510) increased compared with asthma model group (6.024±0.447) (2.15 folds, t=2.405, P=0.043, and 4.48 folds, t=-3.069, P=0.015).
Conclusions
Th2 and Th17 T cells participate in the pathogenesis of asthma and the asthmatic process can be inhibited by JSP.JSP may affect the helper T cells by regulating miR-210 and miR-126.
Key words:
Asthma; Interleukin-13; Interleukin-17; MicroRNA; Jade-Screen Powder
The IMbrave150 Phase III trial demonstrated superiority of atezolizumab and bevacizumab (Atezo/Bev) over sorafenib for unresectable hepatocellular carcinoma (HCC). The present study aims to evaluate the feasibility ofTARE in combination with Atezo/Bev for treatment of intermediate and advanced staged HCC. Retrospective review at a single institution was performed between May 2021 and December 2022. Patients who received TARE using yttrium-90 (Y90) with concomitant or sequential Atezo/Bev systemic treatment were included. The following outcomes were retrieved: overall survival (OS), radiologic tumor response, progression-free survival, technical adverse events related to TARE, and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0. Ten consecutive patients with intermediate (n = 4) and advanced stage HCC (n = 6) were treated with TARE and sequential/concomitant Atezo/Bev. Tumor control was achieved in all TARE-treated target lesions (100%). Overall disease progression occurred in 4 patients with PFS of 78.8% and 66.7% at 6- and 12- months, respectively. Two patients died at follow-up, with 6-month and 12-month OS rates of 90.0% and 77.1%, respectively. Three (75%) patients with intermediate stage disease were downstaged into Milan criteria. One patient developed grade 3 transaminitis and hypoglobulinemia, while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis. This study demonstrates initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC. Further prospective studies with larger sample size are warranted.
Abstract Low-density lipoprotein cholesterol (LDL-C) lowering is the main goal of atherosclerotic cardiovascular disease prevention, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is now a validated therapeutic strategy that lowers serum LDL-C and reduces coronary events. Ironically, the most widely used medicine to lower cholesterol, statins, has been shown to increase circulating PCSK9 levels, which limits their efficacy. Here, we show that geranylgeranyl isoprenoids and hepatic Rap1a regulate both basal and statin induced expression of PCSK9 and contribute to LDL-C homeostasis. Rap1a prenylation and activity is inhibited upon statin treatment, and statin mediated PCSK9 induction is dependent on geranylgeranyl synthesis and hepatic Rap1a. Accordingly, treatment of mice with a small molecule activator of Rap1a lowered PCSK9 protein and plasma cholesterol and inhibited statin mediated PCSK9 induction in hepatocytes. The mechanism involves inhibition of the downstream RhoA-ROCK pathway and regulation of PCSK9 at the post transcriptional level. These data further identify Rap1a as a novel regulator of PCSK9 protein and show that blocking Rap1a prenylation through lowering geranylgeranyl levels contributes to statin-mediated induction of PCSK9.
e16182 Background: Intrahepatic cholangiocarcinoma (iCCA) is a primary hepatic malignancy arising from peripheral intrahepatic bile ducts with poor survival and increasing incidence. Treatment regimen has changed in the last two decades, whereas new molecular targeted therapies have emerged. The present study aims to characterize changes in treatment outcomes of iCCA using a national representative database. Methods: Data were retrieved from the Surveillance, Epidemiology and End Results (SEER) 18 Research Plus Database. Overall survival (OS) was analyzed based on age, gender, race, histological grade, stage, and treatment. Predictors of OS were evaluated by Cox regression models. Statistical analysis was performed with Stata 15.1 (STATA Corp., College Station, TX, USA). Results: The overall observed OS from 2000 to 2018 at 12, 36, and 60 months were 42.6%, 16.4%, and 10.2%, respectively. The median survival time (MST) increased from 6 to 11 months from 2000-2004 time period to 2015-2018 (p < 0.0001). Such an improved trend was observed in all stage groups (p < 0.0001). Among patients diagnosed after 2015, the 12, 24, and 36 month OS were 45.9%, 26.4% and 17.4 %, respectively; the MST were 25, 13, and 6 months for patients with localized (12-month OS: 72.7%; 36-month OS: 37.5% ), regional (12-month OS: 51.4%; 36-month OS: 18.9%), and distant diseases(12-month OS: 28.2%; 36-month OS: 4.5%), respectively (p < 0.0001). On multivariable analysis, older age, female, grade, stage, whether surgery, chemotherapy or radiotherapy was performed were statistically significant predictors of OS (p < 0.001). Conclusions: Survival outcomes of iCCA improved in the last twenty years in all cancer stages. Age, gender, grade, stage, and whether interventions were performed were prognostic factors.
Objective To explore the effects of nerve growth factor(NGF)on IL-1β AND IL-4 in bronchoalveolar lavage fluid(BALF)in guinea pig models of asthma.Methods Thirty guinea pigs were randomly allocated to three groups:normal group;asthma group;anti-NGF group.The asthmatic models were established by injection and inhalation of OVA,the anti-NGF models by injection of anti-NGF antibody peritoneally three hours before inhalation OVA,and the animals in the control group were given PBS by both injection and inhalation.At 24 hour after the last OVA challenge,BALF was collected.Inflammatory cells in BALF were counted;the levels of IL-1β and IL-4 were measured by enzyme-linked immunosorbent assay(ELISA).Results Compared with the control group and asthma group,the total numbers of inflammatory cells,the counts of eosinophils,macrophage and lymphocyte of BALF in anti-NGF group showed significant differences(P0.05).The levels of IL-1β and IL-4 of BALF in asthma group were significantly different from those in the control and anti-NGF groups(P0.05).Conclusion NGF can regulate the levels of IL-1β and IL-4 of BALF in asthma models of guinea pig,NGF may contribute to immune inflammation in asthma.
Dyslipidemia is the risk of cardiovascular disease, and their relationship is clear. Lowering serum cholesterol can reduce the risk of coronary heart disease. At present, the main treatment is taking medicine, however, drug treatment has its limitations. Exercise not only has a positive effect on individuals with dyslipidemia, but can also help improve lipids profile. This review is intending to provide information on the effects of exercise training on both tranditional lipids, for example, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and new lipids and lipoproteins such as non-high-density lipoprotein cholesterol, and postprandial lipoprotein. The mechanisms of aerobic exercise on lipids and lipoproteins are also briefly described.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
