Background: The ipsilateral renal parenchymal volume (RPV) experiences a sharp decrease shortly after partial nephrectomy (PN), mainly due to surgical remove or devascularization of kidney tissue. However, the subsequent change of RPV and its association with glomerular filtration rate (GFR) fast decline remains unknown. Our objective was to investigate the change of ipsilateral RPV and renal function status from new baseline (1–12 months after PN) to latest follow-up (≥1 year) after PN, and to explore factors associated with ipsilateral RPV decrease rate and correlation between RPV decrease and GFR fast decline. Materials and methods: A retrospective review of 367 patients with PN was conducted. Three-dimensional reconstruction of computed tomography (CT)/MRI images was performed for RPV calculation. Spectrum score was used to assess the degree of acute kidney injury (AKI) in the operated kidney after PN. GFR decline greater than 3 ml/min/1.73 m 2 /year was defined as GFR fast decline. One hundred fourteen patients underwent abdominal surgery was used as control. Predictive factors for subsequent decrease of RPV rate and GFR fast decline were evaluated by linear and logistic regression, respectively. Results: With a median interval time of 21.1 (interquartile range:13.8–35.5) months, median ipsilateral RPV significantly decreased from 118.7 (interquartile range:100.7–137.1) ml at new baseline to 111.8 (IQR: 92.3–131.3) ml at latest follow-up. The interval time [β: 1.36(0.71–2.01), P <0.001] and spectrum score [β: 5.83 (2.92–8.74), P <0.001] were identified as independent predictors of ipsilateral RPV decrease rate. GFR fast decline was observed in 101 (27.5%) patients. Annual ipsilateral RPV decrease rate [odds ratio:1.67 (1.05–2.67), P =0.03] and overweight [odds ratio:1.63 (1.02–2.60), P =0.04] were independent predictors of GFR fast decline. Conclusions: Ipsilateral RPV experienced a moderate but significant decrease during follow-up after PN, especially in those with severer acute kidney injury. The presence of GFR fast decline was found to be associated with reduction of ipsilateral RPV, particularly in overweight individuals.
Abstract Background Nearly 90% locoregionally advanced nasopharyngeal carcinoma (LANPC) responds to induction chemotherapy (IC) with significant tumor volume shrinkage. Radiotherapy always follows IC, and reduced volume has been proposed. However, the efficacy and safety of reduced‐volume radiotherapy is uncertain. Methods In this multi‐center, noninferiority, randomized, controlled trial, patients with LANPC who completed IC were randomly assigned (1:1) to receive reduced‐volume radiotherapy based on post‐IC tumor volume (Post‐IC group) or conventional volume radiotherapy based on pre‐IC tumor volume (Pre‐IC group). The primary endpoint was locoregional relapse‐free survival, with a noninferiority margin of 8%. Secondary endpoints comprised adverse events, and quality of life (QoL). Results Between August 7, 2020, and May 27, 2022, 445 patients were randomly assigned to Post‐IC ( n = 225) or Pre‐IC ( n = 220) groups. The average volume receiving radical dose was 66.6 cm 3 in Post‐IC group versus 80.9 cm 3 . After a median follow‐up of 40.4 months, the 3‐year locoregional relapse‐free survival was 91.5% in the Post‐IC group versus 91.2%, with a difference of 0.3% (95% confidence interval −4.9% to 5.5%). The incidence of grade 3‐4 radiation‐related toxicity was lower in the Post‐IC group including: acute mucositis (19.8% vs 34.1%), late otitis media (9.5% vs 20.9%) and late dry month (3.6% vs 9.5%). The Post‐IC group had better QoL for global health status, physical functioning, emotional functioning, dry mouth and sticky saliva. Conclusions In this trial, reduced‐volume radiotherapy was noninferior to conventional volume radiotherapy in locoregional relapse‐free survival, and was associated with lower toxicities and improved QoL. (ClinicalTrials.gov identifier NCT04384627).
Gaming disorder, including internet gaming disorder (IGD), was recently defined by the World Health Organization as a mental disease in the 11th Revision of the International Classification of Diseases (ICD-11). Thus, reducing IGD is warranted. Maladaptive cognitions related to internet gaming (MCIG) have been associated with IGD, while impulsivity, self-control, parental influences, and peer influences are key risk factors of IGD. Previous literature suggests that MCIG is associated with the aforementioned 4 risk factors and IGD, and may thus mediate between these risk factors and IGD. These potential mediations, if significant, imply that modification of MCIG may possibly alleviate these risk factors' harmful impacts on increasing IGD. These mediation hypotheses were tested in this study for the first time.This study tested the mediation effects of MCIG between intrapersonal factors (impulsivity and self-control) and IGD, and between interpersonal factors (parental influences and peer influences) and IGD among adolescents in China.An anonymous, cross-sectional, and self-administered survey was conducted among secondary school students in classroom settings in Guangzhou and Chengdu, China. All grade 7 to 9 students (7 to 9 years of formal education) of 7 secondary schools were invited to join the study, and 3087 completed the survey. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) checklist was used to assess IGD. MCIG was assessed by using the Chinese version of the Revised Internet Gaming Cognition Scale. Impulsivity, self-control, and parental or peer influences were measured by using the motor subscale of the Barratt Impulsiveness Scale, the Brief Self-Control Scale, and the modified interpersonal influence scale, respectively. Structural equation modeling was conducted to examine the mediation effects of MCIG between these risk factors and IGD.The prevalence of IGD was 13.57% (418/3081) and 17.67% (366/2071) among all participants and adolescent internet gamers, respectively. The 3 types of MCIG (perceived rewards of internet gaming, perceived urges for playing internet games, and perceived unwillingness to stop playing without completion of gaming tasks) were positively associated with IGD. Impulsivity, self-control, parental influences, and peer influences were all significantly associated with the 3 types of MCIG and IGD. The 3 types of MCIG partially mediated the associations between the studied factors and IGD (effect size of 30.0% to 37.8%).Impulsivity, self-control, and interpersonal influences had both direct and indirect effects via MCIG on IGD. Modifications of the 3 types of MCIG can potentially reduce the harmful impacts of impulsivity and interpersonal influences on IGD and enhance the protective effect of self-control against IGD. Future longitudinal studies are warranted.
AbstractThe objective of this study was to elucidate the structural features of the stereoisomers of Val-Val and Val-Val-Val that afford optimal binding affinity for the apical oligopeptide transporter in human intestinal Caco-2 cells. Three-dimensional conformations of cephalexin and Val stereoisomers were optimized using Chem-X molecular modeling software. Molecular features associated with the optimized conformations of the Val stereoisomers were analyzed to identify potential relationships with their binding affinities for the apical oligopeptide transporter. For Val-Val stereoisomers, the distance between the N-terminal amino group and the C-terminal carboxyl group, d(N1-C7), was found to have a linear relationship with their binding affinities at the 95% confidence level. For Val-Val-Val stereoisomers, three molecular features were found to have linear relationships with their binding affinities at the 95% confidence level. These features included: a) the distance between the N-terminal amino group and the C-terminal carboxyl group, d(N1-C11); b) the distance between the N-terminal amino group and the second peptide bond, d(N1-N9); and c) the molecular dipole moment. Principal component analysis on all molecular features of Val-Val-Val stereoisomers identified three components that accounted for 90% of the variance. A linear model built with these three components by multiple linear regression adequately described the binding affinities (r2 = 0.90). Results from the current study suggest that the distance between the N-terminal amino group and the C-terminal carboxyl group is important for interaction with the apical oligopeptide transporter in Caco-2 cells. In addition, the binding affinities of the Val-Val-Val stereoisomers appear to be influenced by additional factors, including the position of the second peptide bond and the molecular dipole moment.Key Words: Caco-2molecular modelingoligopeptide transporterstructure-transport
Sodium taurocholate cotransporting polypeptide (NTCP), which is highly expressed in the sinusoidal membrane of hepatocytes, maintains bile acid homeostasis and participates in the hepatic disposition of a variety of endogenous substances as well as xenobiotics. Manifested by the involvement of organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) in the hepatic uptake of statin drugs, sinusoidal membrane transporters play an important role in the pharmacokinetics and pharmacodynamics of these agents. It has been speculated that NTCP may function as an alternative pathway for statin hepatic uptake, complementary to OATP1B1 and OATP1B3. In the current study, we produced stable NTCP-expressing human embryonic kidney 293 (HEK293) cells and developed a fluorescence-based assay using flow cytometry for measuring NTCP transport with chenodeoxycholyl-(Nε-7-nitrobenz-2-oxa-1,3-diazole)-lysine (CDCA-NBD) as the substrate. NTCP-mediated CDCA-NBD transport was time-dependent and exhibited typical Michaelis–Menten kinetics, with a K m of 6.12 µM. Compounds known to interact with NTCP, including chenodeoxycholic acid and taurocholic acid, displayed concentration-dependent inhibition of NTCP-mediated CDCA-NBD transport. We report here a systematic evaluation of the interaction between statins and the NTCP transporter. Utilizing this system, several statins were either found to inhibit NTCP-dependent transport or act as substrates. We find a good correlation between the reported lipophilicity of statins and their ability to inhibit NTCP. The objective was to develop a higher-throughput system to evaluate potential inhibitors such as the statins. The in vitro assays using CDCA-NBD as fluorescent substrate are convenient, rapid, and have utility in screening drug candidates for potential drug–NTCP interactions.
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