Brain Structural Bases of Tendency to Forgive: evidence from a young adults sample using voxel-based morphometry

Abstract Tendency to forgive refers to one’s global dispositional level of forgiveness across situations and relationships. Brain imaging studies examined activation patterns underlying forgiving response, yet focal differences in brain structures related to tendency to forgive have never been investigated. In this study, voxel-based morphometry was used to investigate relations between gray matter/white matter volume (GMV/WMV) and individual differences in tendency to forgive in a large young sample. Participants were 199 young students (60 men) who completed the tendency to forgive scale (TTF) and underwent an anatomical magnetic resonance imaging scan. Results showed that higher TTF scores were associated with larger GMV in the regions of dorsolateral prefrontal cortex, and smaller GMV in the regions of the right insular cortex and inferior frontal gyrus (IFG). Moreover, higher TTF scores were also related to smaller WMV in the regions of the left IFG. Together, these findings suggest structural variations for individual differences in the tendency to forgive, distributed across different brain regions associated with empathic response and cognitive control

Development of an Ultra-High Performance Liquid Chromatography Method for Simultaneous Determination of Six Active Compounds in Fructus aurantii and Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Rats Administered with Different Doses

A rapid, accurate, and sensitive ultra-high performance liquid chromatography (UHPLC) method was established for simultaneously detecting naringin, hesperidin, neohesperidin, meranzin hydrate, naringenin, and hesperetin in Fructus aurantii (FA) decoction. Analysis was performed on Waters BEH (R) C18 (50 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.2 mL/min by using (A) acetonitrile and (B) 0.5% acetic acid-water as the mobile phase. The method was well validated on linearity, precision, recoveries, and stability. Then, we used the same UHPLC conditions for quantitative analysis of meranzin hydrate, naringenin, and hesperetin in rat plasma. The method proved to be linear within the concentration ranges of 3.3–3300 ng/mL for meranzin hydrate, 6.95–3555 ng/mL for naringenin, and 1.8–236 ng/mL for hesperetin. The RSD of precision ranged from 1.22% to 9.08%, and the average extraction recovery ranged from 96.49 ± 1.42% to 102.01 ± 3.16%. Besides, we performed a comparative pharmacokinetic study after oral administration of FA decoction at a low dose of 15 g/kg and high dose of 30 g/kg body weight for seven days to rats. The AUC(0–t) and Cmax of meranzin hydrate, naringenin, and hesperetin were multiplied significantly with the increase of FA dosage, and the t1/2 of meranzin hydrate was faster than naringenin and hesperetin in the two groups

An exploratory clinical trial of apatinib combined with intensity‐modulated radiation therapy for patients with unresectable hepatocellular carcinoma

Abstract Purpose To evaluate the clinical efficacy and safety of apatinib combined with intensity‐modulated radiation therapy (IMRT) in patients with unresectable hepatocellular carcinoma (uHCC). Materials and methods Open‐label, single‐arm, exploratory clinical trial of apatinib combined with IMRT for uHCC patients. Patients aged 18–75 years with adequate hematological, liver, and renal functions and Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were enrolled in this study from March 2017 to September 2020. Patients were received IMRT (biological effective dose: 46–60 Gy) and continuous apatinib (250–500 mg/day) oral administration until HCC progression or unacceptable toxic effects. The endpoints included progression‐free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety. The trial registration number is ChiCTR‐OPC‐17011890. Results A total of 33 patients have taken part in the study. The median age was 58 years old (range 32–77), 27 (81.9%) patients were ECOG PS 0–1, and 28 (84.9%) patients were male. In addition, 25 (75.7%) patients suffered from hepatitis B, 32 cases (97.0%) were in Barcelona Clinic Liver Cancer (BCLC) Stages B–C, and eight (24.2%) had portal vein involvement. Moreover, 12 (36.4%) and 21 (63.6%) patients received apatinib as first‐line and second or later‐line therapy, respectively. The average follow‐up was 11.4 months, the median PFS was 7.8 months (95% confidence interval: 3.9–11.7). The OS rates at 6 and 12 months were 96.7% and 66.2%. The ORR and DCR were 15.1% and 81.8%, respectively. Hepatic toxicity was the most common treatment‐related adverse events in Grades 3–4 (12.1%). No radiation‐induced liver disease and Grade 5 toxicity were recorded. Conclusion Apatinib combined with IMRT is a safe and effective method to improve PFS and DCR and has good anti‐tumor activity in patients with uHCC

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

#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

Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer.

Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation between the GFRA1 expression, methylation, and prognosis of patients. Our results show DNA hypomethylation-mediated upregulation of GFRA1 in invasive CRC, and it was found to be correlated with poor prognosis of CRC patients. Furthermore, GFRA1 methylation-modified sequences were found to have potential as methylation diagnostic markers of highly metastatic CRC. The targeted demethylation of GFRA1 by dCas9-TET1CD and gRNA promoted CRC metastasis in vivo and in vitro. Mechanistically, demethylation of GFRA1 induces epithelial-mesenchymal transition (EMT) by promoting AKT phosphorylation and increasing c-Jun expression in CRC cells. Collectively, our findings indicate that GFRA1 hypomethylation can promote CRC invasion via inducing EMT, and thus, GFRA1 methylation can be used as a biomarker for the early diagnosis of highly metastasis CRC