Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma:a randomized comparative study

Background:Both portal vein embolization(PVE)and associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant(FLR).Methods:This study was a single-center,prospective randomized comparative study.Patients with the diagnosis of hepatitis B related hepatocellular carcinoma(HCC)were randomly assigned in a 1:1 ratio to the 2 groups.The primary endpoints were tumor resection and three-year overall survival(OS)rates.Results:Between November 2014 to June 2016,76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups(n=38)and TACE+PVE groups(n=38).Thirty-seven patients(97.4%)in the ALPPS group compared with 25 patients(65.8%)in the TACE+PVE group were able to undergo staged hepatectomy(risk ratio 1.48,95%CI:1.17-1.87,P<0.001).The three-year OS rate of the ALPPS group(65.8%)(95%CI:50.7-80.9)was significantly better than the TACE+PVE group(42.1%)(95%CI:26.4-57.8)(HR 0.50,95%CI:0.26-0.98,two-sided P=0.036).However,no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found(HR 0.80,95%CI:0.35-1.83,two-sided P=0.595).Major postoperative complications rates after the stage-2 hepatectomy were 54.1%in the ALPPS group and 20.0%in the TACE+PVE group(risk ratio 2.70,95%CI:1.17-6.25,P=0.007).Conclusions:ALPPS resulted in significantly better intermediate-term OS outcomes,at the expenses of a significantly higher perioperative morbidity rate compared with TACE+PVE in patients who had initially unresectable HBV-related HCC.

One-versus two-stage partial hepatectomy for large resectable solitary hepatocellular carcinomas determined preoperatively to have a narrow resection margin:a propensity score matching analysis

Background:For patients with a large but resectable solitary hepatocellular carcinoma(HCC)of>5 cm in diameter,it is often difficult to achieve a sufficient resection margin.There is still no study on whether a two-stage hepatectomy to increase a narrow resection margin would be beneficial.Methods:From August 2014 to February 2017,patients with a large but resectable solitary HCC of>5 cm and a preoperative estimated resection margin of<1.0 cm were retrospectively studied.They were divided into one-and two-stage resection groups.A retrospective analysis was performed,followed by propensity score matching(PSM)analysis.Disease recurrence,survival,intraoperative and postoperative data were compared.Results:Before PSM,the 1-,2-,3-and 4-year recurrence-free survival rates for the one-and two-stage groups were 44.3%,31.7%,24.3%,19.2%versus 60.6%,45.4%,43.5%,32.3%,respectively(P=0.007).The corresponding OS rates were 61.0%,45.2%,43.8%,38.4%versus 69.6%,62.5%,60.7%,57.3%,respectively(P=0.029).After PSM,the 1-,2-,3-and 4-year recurrence-free survival rates for the one-and two-stage groups were 44.0%,31.5%,27.3%,21.0%versus 60.6%,45.4%,43.5%,32.3%,respectively(P=0.013).The corresponding OS rates were 62.5%,41.1%,41.1%,37.5%versus 69.6%,62.5%,60.7%,57.3%,respectively(P=0.038).Differences in the resection margins between the one-and two-stage groups before[0.3(0-0.5)versus 1.2(0.8-2.2)cm]and after[0.2(0-0.5)versus 1.2(0.8-2.2)cm]PSM were also significant.Conclusions:Two-stage hepatectomy allowed a wider resection margin for patients with a resectable but solitary HCC of>5 cm,and resulted in significantly better long-term survival outcomes after partial hepatectomy.

慢病管理是多发性骨髓瘤治疗的新模式

多发性骨髓瘤是发病率第二的血液系统恶性肿瘤,其特征是浆细胞的恶性克隆扩增。随着新药和新疗法的不断问世,多发性骨髓瘤患者治疗方式发生改变,生存期也越来越长,慢病管理模式将成为多发性骨髓瘤治疗的新模式。本文将就慢病管理的概念、慢病管理在多发性骨髓瘤中的必要性、应用情况、价值和获益进行论述。