NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt/β-catenin pathway in HK-2 cells

BackgroundNuclear receptor binding protein 1 (NRBP1) and ATP-binding cassette subfamily G member 2 (ABCG2) was the gout risk gene and high-capacity urate exporter respectively. However, the relationship between NRBP1 and ABCG2 and the underlying molecular mechanism contributing to these associations are unknown.MethodsFirstly, the efficiency of the overexpression and knockdown of NRBP1 was confirmed by western blot. Next, the effect of NRBP1 overexpression and knockdown on the expression of ABCG2, organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) was detected by qRT-PCR and western blot. At the same time, the cellular location of ABCG2 and its expression after NRBP1 overexpression and knockdown was tested by immunofluorescence (IF) staining. Then, the mechanism of NRBP1 modulates ABCG2 expression was evaluated by western blot with or without the β-catenin inhibitor (21H7).ResultsThe lentivirus system was used to generate stable NRBP1 overexpression, while the plasmids carrying a NRBP1 siRNA was generated to knockdown NRBP1 expression in HK-2 cells. Meanwhile, the overexpression of NRBP1 significantly decreased the mRNAs and proteins expression of GLUT9 and URAT1, while the knockdown of NRBP1 increased the mRNAs and proteins expression of ABCG2 significantly. In addition, the NRBP1 modulates the expression of ABCG2 was by ctivating the Wnt/β-catenin pathway in HK-2 cells according to the IF and western blot results.ConclusionTaken together, our study demonstrated that NRBP1 inhibition played an essential role in attenuating hyperuricemia and gout by upregulation of ABCG2 via Wnt/β-catenin signaling pathway in HK-2 cells.     

儿童吉兰-巴雷综合征交感皮肤反应的特点分析北大核心CSCD

目的探讨交感皮肤反应(sympathetic skin response,SSR)对儿童吉兰-巴雷综合征(Guillain-Barrésyndrome,GBS)早期诊断及预后评估的价值。方法回顾性收集2018年10月-2022年11月收治的25例GBS患儿的临床资料,选取同期诊断为抽动障碍的30例患儿作为对照组,比较两组患儿间SSR的特点,并分析SSR与自主神经功能障碍(autonomic dysfunction,AD)、疾病严重程度及预后的关系。结果GBS组患儿急性期SSR异常率高于对照组(P<0.001)。联合SSR和神经传导早期(发病2周内)诊断GBS的灵敏度、特异度和准确度分别为84%、100%和93%。SSR异常患儿AD比例及疾病高峰时Hughes评分与SSR正常患儿比较差异均无统计学意义(P>0.05)。短期(发病1个月)预后不良患儿SSR测定全部(7/7)异常。结论SSR可以用于早期辅助诊断儿童GBS和监测疾病治疗情况。     

Plan quality score to evaluate the dwell time deviation restricted inverse planning by simulated annealing and graphically optimized treatment plans for template based interstitial brachytherapy

PurposeTo evaluate the impact of dwell time deviation constraint (DTDC) on the quality of IPSA-optimized treatment plans in comparison with graphical plans using plan quality scores (PQS).Material and methodsSeventy optimized plans (graphical & IPSA with different DTDC values) of ten cervical cancer patients were generated. Various DVH parameters like D₉₀, V₁₀₀, V₁₅₀, V₂₀₀, V₃₀₀ were compared to evaluate the impact of DTDC on target coverage and high dose regions inside target for different plans. Similarly, for the OAR dose, values of D_2cc were compared. Various planning parameters like CI, COIN, DHI, DNR, ODI, EI and gain factor (GF) for different OARs were calculated. Based on these indices a plan quality score (PQS) was formulated and calculated. PQS values were used to see the impact of DTDC on plan quality of IPSA in comparison with dosimetric quality of graphical plan.ResultsWe have found that target coverage is similar for IPSA and graphically optimized treatment plans. However, dose homogeneity was improved in IPSA compared to graphical optimization whereas conformality was better in graphically optimized plans. OAR dose was less in IPSA plans. High-dose regions inside the target were also reduced in IPSA comparatively. However, IPSA plans optimized with various values of DTDC did not necessarily reduce high-dose regions beyond 0.6. Plan quality scores (PQS) were 6.31, 6.31, 6.34, and 6.17 for the graphically optimized plan, IPSA with DTDC values of 0.0, 0.4, and 1.0 respectively.ConclusionWe found that IPSA is dosimetrically advantageous over graphical optimization. IPSA with a DTDC value of 0.4 improved overall plan quality. However, DTDC value beyond 0.6 produces dosimetrically sub-optimal plans hence the use of DTDC should be very selective and limited.     

Asistencia ventricular de larga duración en España (2007-2020). I informe del registro REGALAD

Introduction and objectivesThis report presents the clinical characteristics, outcomes and complications of all consecutive patients implanted with a long-term mechanical circulatory support device in Spain between 2007 and 2020.MethodsAnalysis of the Spanish Registry of durable ventricular assist devices (REGALAD) including data form Spanish centers with a mechanical circulatory support program.ResultsDuring the study period, 263 ventricular assist devices were implanted in 22 hospitals. The implanted device was an isolated continuous-flow left ventricular assist device in 182 patients (69%), a pulsatile-flow device (58 isolated left ventricular and 21 biventricular) in 79 (30%), and a total artificial heart in 2 patients (1%). The strategy of the implant was as bridge to heart transplant in 78 patients (30%), bridge to candidacy in 110 (42%), bridge to recovery in 3 (1%) and destination therapy in 72 patients (27%). Overall survival at 6, 12 and 24 months was 79%, 74% and 69%, respectively, and was better in continuous-flow left ventricular assist devices (84%, 80%, and 75%). The main adverse events related to this therapy were infections (37% of patients), bleeding (35%), neurological (29%), and device malfunction (17%).ConclusionsDurable ventricular assist devices have emerged in Spain in the last few years as a useful therapy for patients with advanced heart failure. As in other international registries, the current trend is to use continuous-flow intracorporeal left ventricular devices, which are associated with better results. Adverse events continue to be frequent and severe.Full English text available from:www.revespcardiol.org/en