Sepsis during short bowel syndrome hospitalizations:Identifying trends,disparities,and clinical outcomes in the United States

BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Pre-hospital assessment with ultrasound in emergencies: implementation in the field

BACKGROUND: Point-of-care ultrasound(US) is a proven diagnostic imaging tool in the emergency department(ED). Modern US devices are now more compact, affordable and portable, which has led to increased usage in austere environments. However, studies supporting the use of US in the prehospital setting are limited. The primary outcome of this pilot study was to determine if paramedics could perform cardiac ultrasound in the fi eld and obtain images that were adequate for interpretation. A secondary outcome was whether paramedics could correctly identify cardiac activity or the lack thereof in cardiac arrest patients.METHODS: We performed a prospective educational study using a convenience sample of professional paramedics without ultrasound experience. Eligible paramedics participated in a 3-hour session on point-of-care US. The paramedics then used US during emergency calls and saved the scans for possible cardiac complaints including: chest pain, dyspnea, loss of consciousness, trauma, or cardiac arrest.RESULTS: Four paramedics from two distinct fire stations enrolled a total of 19 unique patients, of whom 17 were deemed adequate for clinical decision making(89%, 95%CI 67%–99%). Paramedics accurately recorded 17 cases of cardiac activity(100%, 95%CI 84%–100%) and 2 cases of cardiac standstill(100%, 95%CI 22%–100%).CONCLUSION: Our pilot study suggests that with minimal training, paramedics can use US to obtain cardiac images that are adequate for interpretation and diagnose cardiac standstill. Further large-scale clinical trials are needed to determine if prehospital US can be used to guide care for patients with cardiac complaints.

Association of non-alcoholic fatty liver disease with gallstone disease in the United States hospitalized patient population

BACKGROUND Gallstones and cholecystectomy have been proposed as risk factors for nonalcoholic fatty liver disease(NAFLD).The reason for this may be that both gallstones,as well as NAFLD share several risk factors with regards to their development.Currently,there is a lack of sufficient evidence showing an association between these clinical conditions.AIM To determine whether there is a meaningful association between gallstones and cholecystectomy with NAFLD.METHODS We queried the National Inpatient Sample database from the years 2016 and 2017 using International Classification of Diseases,10th revision,Clinical Modification diagnosis codes to identify hospitalizations with a diagnosis of gallstone disease(GSD)(includes calculus of gallbladder without cholecystitis without obstruction and acquired absence of gallbladder)as well as NAFLD(includes simple fatty liver and non-alcoholic steatohepatitis).Odds ratios(ORs)measuring the association between GSD(includes gallstones and cholecystectomy)and NAFLD were calculated using logistic regression after adjusting for confounding variables.RESULTS Out of 14294784 hospitalizations in 2016-2017,159259 were found to have NAFLD.The prevalence of NAFLD was 3.3%in patients with GSD and 1%in those without.NAFLD was prevalent in 64.3%of women with GSD as compared to 35.7%of men with GSD.After controlling for various confounders associated with NAFLD and GSD,multivariate-adjusted analysis showed that there was an association between NAFLD with gallstones[OR=6.32;95%confidence interval(CI):6.15-6.48]as well as cholecystectomy(OR=1.97;95%CI:1.93-2.01).The association between NAFLD and gallstones was stronger in men(OR=6.67;95%CI:6.42-6.93)than women(OR=6.05;95%CI:5.83-6.27).The association between NAFLD and cholecystectomy was stronger in women(OR=2.01;95%CI:1.96-2.06)than men(OR=1.85;95%CI:1.79-1.92).P value was less than 0.001 for all comparisons.CONCLUSION NAFLD is more prevalent in women with GSD than men.The association between NAFLD and cholecystectomy/gallstones indicates that they may be risk factors for NAFLD.

Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration

Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.

Impact of index admission cholecystectomy vs interval cholecystectomy on readmission rate in acute cholangitis: National Readmission Database survey

BACKGROUND Elective cholecystectomy(CCY)is recommended for patients with gallstone-related acute cholangitis(AC)following endoscopic decompression to prevent recurrent biliary events.However,the optimal timing and implications of CCY remain unclear.AIM To examine the impact of same-admission CCY compared to interval CCY on patients with gallstone-related AC using the National Readmission Database(NRD).METHODS We queried the NRD to identify all gallstone-related AC hospitalizations in adult patients with and without the same admission CCY between 2016 and 2020.Our primary outcome was all-cause 30-d readmission rates,and secondary outcomes included in-hospital mortality,length of stay(LOS),and hospitalization cost.RESULTS Among the 124964 gallstone-related AC hospitalizations,only 14.67%underwent the same admission CCY.The all-cause 30-d readmissions in the same admission CCY group were almost half that of the non-CCY group(5.56%vs 11.50%).Patients in the same admission CCY group had a longer mean LOS and higher hospitalization costs attrib-utable to surgery.Although the most common reason for readmission was sepsis in both groups,the second most common reason was AC in the interval CCY group.CONCLUSION Our study suggests that patients with gallstone-related AC who do not undergo the same admission CCY have twice the risk of readmission compared to those who undergo CCY during the same admission.These readmis-sions can potentially be prevented by performing same-admission CCY in appropriate patients,which may reduce subsequent hospitalization costs secondary to readmissions.

Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease:A systematic review and meta-analysis

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma(HCC).Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics.However,it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD.AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD.METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD.The difference in HCC risk between statin users and non-users was calculated among MASLD patients.We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction.RESULTS A total of four studies consisting of 291684 patients were included.MASLD patients on statin therapy had a 60%lower pooled risk of developing HCC compared to the non-statin group[relative risk(RR)=0.40,95%CI:0.31-0.53,I2=16.5%].Patients taking lipophilic statins had a reduced risk of HCC(RR=0.42,95%CI:0.28-0.64),whereas those on hydrophilic statins had not shown the risk reduction(RR=0.57,95%CI:0.27-1.20).The higher(>600)cumulative defined daily doses(cDDD)had a 70%reduced risk of HCC(RR=0.30,95%CI:0.21-0.43).There was a 29%(RR=0.71,95%CI:0.55-0.91)and 43%(RR=0.57,95%CI:0.40-0.82)decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD,respectively.CONCLUSION Statin use lowers the risk of HCC in patients with MASLD.The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.

二甲双胍对炎症状态下人视网膜血管内皮细胞生物学行为的保护作用及其机制

背景研究表明炎性过程参与糖尿病视网膜病变（DR）的发生和发展，而炎症作用的靶细胞为视网膜血管内皮细胞（RVECs）。二甲双胍是临床上常用的降血糖药物，近年来表明其可发挥保护心血管、预防肿瘤和保护血－脑屏障等多重生物学效应，但其对炎症状态诱导的人视网膜血管系统异常是否具有防护作用尚不清楚。目的观察二甲双胍对肿瘤坏死因子-α（TNF-α）刺激下人视网膜血管内皮细胞（RVECs）增生、移行以及分泌单核细胞趋化蛋白-1（MCP-1）和白细胞介素-8（IL-8）的影响，探讨二甲双胍对炎症环境中人RVECs生物学行为的保护作用。方法对原代RVECs进行培养和传代并分为正常对照组、5 mmol/L二甲双胍组、TNF-α（2.5 ng/ml）组、TNF-α＋不同浓度（5、10、20、40 mmol/L）二甲双胍组，分别按照分组方法在培养液中添加相应药物处理24 h。分别于处理前及处理后24 h采用Image-Pro Plus Software 7.0软件计数各组细胞数目；采用MTS法检测各组RVECs的吸光度（A490）值以评价细胞的代谢活力；采用Transwell小室法检测各组迁移细胞数；采用ELISA法检测各组细胞上清液中MCP-1和IL-8质量浓度，并对各组间检测结果进行比较。结果正常对照组、5 mmol/L二甲双胍组、TNF-α组、TNF-α＋5 mmol/L二甲双胍组、TNF-α＋10 mmol/L二甲双胍组、TNF-α＋20 mmol/L二甲双胍组和TNF-α＋40 mmol/L二甲双胍组细胞数目总体比较差异有统计学意义（F＝189.31，P〈0.01）；各组细胞代谢活力（A490值）分别为0.32±0.02、0.32±0.03、0.97±0.02、0.90±0.05、0.76±0.15、0.74±0.05和0.41±0.03；各组细胞移行数目分别为（1 214±49）、（1 200±45）、（1 648±43）、（1 309±48）、（1 279±73）、（961±60）和（942±106）/视野；各组细胞上清液中MCP-1质量浓度分别为（0.385±0.050）、（0.362±0.060）、（2.285±0.200）、（1.131±0.180）、（0.622±0.120）、（0.537±0.090）和（0.492±0.130）μg/ml，IL-8质量浓度分别为（0.385±0.080）、（0.390±0.120）、（1.123±0.130）、（0.899±0.180）、（0.680±0.060）、（0.417±0.090）和（0.335±0.100）μg/ml，组间A490值、移行细胞数、MCP-1质量浓度和IL-8质量浓度的总体比较差异均有统计学意义差异（F＝73.31、103.89、150.92、268.32，均P〈0.01），TNF-α组细胞数目、A490值、移行细胞数、MCP-1质量浓度和IL-8质量浓度均明显高于正常对照组，TNF-α＋10 mmol/L二甲双胍组、TNF-α＋20 mmol/L二甲双胍组、TNF-α＋40 mmol/L二甲双胍组细胞数目、A490值、移行细胞数、MCP-1质量浓度和IL-8质量浓度均明显低于TNF-α组，差异均有统计学意义（均P〈0.05）。结论二甲双胍对TNF-α诱导的人RVECs增生、移行及分泌MCP-1、IL-8的能力均有抑制作用，从而可能对炎症环境中的RVECs发挥保护作用。

正常和去势大鼠胫骨皮质机械性显微损伤的比较研究

目的观察骨质疏松病理状态对机械性显微损伤产生和修复的影响。方法SD大鼠去势和假手术后3个月在右胫骨钻孔造成机械性损伤,分别在钻孔后1、2、4周后取材,进行标本碱性品红染色,制作50μm厚切片在光镜和荧光显微镜下观察,并利用BIOQUANT图像分析软件对显微损伤进行定量分析。结果镜下观察发现损伤呈现片状的弥散性损伤和线性裂纹。对线性裂纹的统计学分析发现,裂纹的数量密度和长度密度在去卵巢组明显地高于假手术组（P〈0.01）。对弥散性损伤的统计学分析发现：去卵巢组的损伤骨表面的比率明显高于假手术组（P〈0.05）;损伤面积比在两组之间的差异没有统计学上的差异（均为P〉0.05）。随着时间的延长,弥散性损伤和线性裂纹都有逐渐减少的倾向,其中损伤面积比在各组的不同时间点之间存在着统计学上的差异（P〈0.01）。结论在雌激素缺乏导致的骨质疏松骨上,植入物可产生更多的显微损伤。随着时间的延长,这些显微损伤可逐渐修复。

大鼠皮质骨上机械性显微损伤的修复机制研究

目的研究大鼠皮质骨上植入物造成的机械性显微损伤的修复机制。方法 30只SD大鼠随机分为两组,一组行卵巢切除术,另一组行假手术。3个月后在右侧胫骨行钻孔术,分别于钻孔后1、2、4周后处死,处死前注射四环素和钙黄绿素进行标记。将含有钻孔的骨段(1 cm)应用大块碱性品红染色,甲基丙烯酸甲酯包埋后切成约50μm厚的切片。应用Bioquant图象分析系统对切片进行骨形态计量学分析。结果去卵巢大鼠和假手术大鼠都出现了与显微损伤有关的骨吸收腔,其中去卵巢组的孔隙率和骨吸收腔明显高于假手术组(P<0.05);随着术后时间的延长,吸收腔的数目逐渐增加,各时间点之间的差异有明显的统计学意义(P<0.05)。结论去卵巢大鼠的孔隙率和骨吸收腔数明显高于假手术大鼠,反映了在雌激素缺乏和较多裂纹形成两种因素刺激下,去卵巢大鼠皮质骨内的重建更为活跃,这会降低骨的强度从而增加骨折的危险性。

TAP系统分离纯化MT1-MMP-hTAP融合基因蛋白复合物及表达效应评估

目的 应用TAP系统分离纯化的MT1 MMP hTAP蛋白复合物的表达效应。方法 应用TAP系统分子生物学特性采用IgG和钙调蛋白亲和胶粒二次亲和层析法分离纯化MT1 MMP hTAP蛋白复合物。PAP免疫染色及Westernblot法检测蛋白表达效应。结果 PAP免疫染色显示MT1 MMP hTAP融合基因在鸡成纤维细胞内有效表达 ,融合蛋白染色呈深蓝色 ,Westernblot法检测经TAP系统分离纯化后MT1 MMP hTAP蛋白复合物分子稳定表达在相应 68× 10 3 位置。结论 TAP系统分离纯化MT1 MMP hTAP蛋白复合物及其在动物细胞的构建成功并有效表达为在人类肿瘤细胞建立TAP纯化蛋白质体系和寻找MT1 MMP

普萘洛尔(心得安)对灰鼠噪声性聋的影响

目的 研究噪声和 β受体阻滞剂普萘洛尔 (心得安 )对灰鼠耳蜗复合动作电位和耳蜗血流的影响。方法 使用 1/ 2倍频程窄带 ,噪声其中心频率 15 0 0Hz ,强度 115dBSPL ,持续刺激 90分钟。观察不同浓度普萘洛尔对灰鼠耳蜗复合动作电位和耳蜗血流的影响。结果 在噪声刺激期腹膜内注射不同浓度普萘洛尔 ,对耳蜗血流和噪声暂时性阈移无影响。结论 耳蜗微循环中可能无 β受体 。

Axonal remodeling of the corticospinal tract during neurological recovery after stroke

Stroke remains the leading cause of long-term disability.Hemiparesis is one of the most common post-stroke motor deficits and is largely attributed to loss or disruption of the motor signals from the affected motor cortex.As the only direct descending motor pathway,the corticospinal tract(CST)is the primary pathway to innervate spinal motor neurons,and thus,forms the neuroanatomical basis to control the peripheral muscles for voluntary movements.Here,we review evidence from both experimental animals and stroke patients,regarding CST axonal damage,functional contribution of CST axonal integrity and remodeling to neurological recovery,and therapeutic approaches aimed to enhance CST axonal remodeling after stroke.The new insights gleaned from preclinical and clinical studies may encourage the development of more rational therapeutics with a strategy targeted to promote axonal rewiring for corticospinal innervation,which will significantly impact the current clinical needs of subacute and chronic stroke treatment.

Remodeling dendritic spines for treatment of traumatic brain injury

Traumatic brain injury is an important global public health problem.Traumatic brain injury not only causes neural cell death,but also induces dendritic spine degeneration.Spared neurons from cell death in the injured brain may exhibit dendrite damage,dendritic spine degeneration,mature spine loss,synapse loss,and impairment of activity.Dendritic degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain injury.Normal function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target cells.During synaptic plasticity,the numbers and shapes of dendritic spines undergo dynamic reorganization.Enlargement of spine heads and the formation and stabilization of new spines are associated with long-term potentiation,while spine shrinkage and retraction are associated with long-term depression.Consolidation of memory is associated with remodeling and growth of preexisting synapses and the formation of new synapses.To date,there is no effective treatment to prevent dendritic degeneration and synapse loss.This review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain injury.The mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive,possibly including blocking activation of Cofilin induced by beta amyloid,Ras activation,and inhibition of GSK-3 signaling pathway.Further understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.

Thrombocytopenia after liver transplantation:should we care?

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation(LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes.

Short and long term outcomes of 200 patients supported by continuous-flow left ventricular assist devices

AIM: To study the institutional experience over 8 years with 200 continuous-flow(CF)- left ventricular assist devices(LVAD).METHODS: We evaluated our institution's LVAD database and analyzed all patients who received a CF LVAD as a bridge to transplant(BTT) or destination therapy from March 2006 until June 2014. We identified 200 patients, of which 179 were implanted with a Heart Mate II device(Thoratec Corp., Pleasanton, CA) and 21 received a Heartware HVAD(Heart Ware Inc., Framingham, MA).RESULTS: The mean age of our LVAD recipients was 59.3 years(range 17-81), 76%(152/200) were males, and 49% were implanted for the indication of BTT. The survival rate for our LVAD patients at 30 d, 6 mo, 12 mo, 2 years, 3 years, and 4 years was 94%, 86%, 78%, 71%, 62% and 45% respectively. The mean duration of LVAD support was 581 d(range 2-2595 d). Gastrointestinal bleeding(was the most common adverse event(43/200, 21%), followed by right ventricular failure(38/200, 19%), stroke(31/200, 15%), re exploration for bleeding(31/200, 15%),ventilator dependent respiratory failure(19/200, 9%) and pneumonia(15/200, 7%). Our driveline infection rate was 7%. Pump thrombosis occurred in 6% of patients. Device exchanged was needed in 6% of patients. On multivariate analysis, preoperative liver dysfunction, ventilator dependent respiratory failure, tracheostomy and right ventricular failure requiring right ventricular assist device support were significant predictors of post LVAD survival.CONCLUSION: Short and long term survival for patients on LVAD support are excellent, although outcomes still remain inferior compared to heart transplantation. The incidence of driveline infections, pump thrombosis and pump exchange have declined significantly in recent years.

Down-Regulation of Neurocan Expression in Reactive Astrocytes Promotes Axonal Regeneration and Facilitates the Neurorestorative Effects of Bone Marrow Stromal Cells in the Ischemic Rat Brain

脑卒中后缺血组织边界形成胶质疤痕,抑制轴突再生。神经蛋白聚糖是一种轴突延长抑制分子,在卒中后胶质疤痕中表达上调。骨髓基质干细胞(BMSCs)可降低胶质疤痕壁的厚度,加速缺血周边区的轴突重塑。为了进一步明确BMSCs在轴突再生中的作用及机制,本文重点研究脑缺血组织中BMSCs对神经蛋白聚糖表达的作用。31只成年雄性Wistar大鼠大脑中动脉阻塞(MCAo)2 h,24 h后从中选择16只给予尾静脉注射3×106鼠BMSCs(BMSCs组),15只注射磷酸盐缓冲生理盐水(对照组)。缺血后8 d处死实验大鼠,免疫染色表明反应性星形胶质细胞是神经蛋白聚糖的原始来源,且BMSCs组缺血半暗带脑组织的神经聚糖表达明显低于对照组,生长相关蛋白43表达高于对照组,这在蛋白印迹分析中得到确认。为了进一步检测BMSCs在星形胶质细胞神经蛋白聚糖表达中的作用,用激光捕获显微切割法从缺血周边区收集单纯的反应性星形胶质细胞。BMSCs组的神经蛋白聚糖基因表达明显下调(n=4/组)。原代培养的星形胶质细胞也表现出相同改变,糖氧剥离的星形胶质细胞再给氧时与BMSCs共培养会抑制神经蛋白聚糖基因的表达上调(n=3/组)。本研究表明BMSCs通过下调梗死周边星形胶质细胞中神经蛋白聚糖的表达来促进轴突再生。

Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo

Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.

Cold water swimming pretreatment reduces cognitive deficits in a rat model of traumatic brain injury

A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats（cold water swimming for 3 minutes at 4℃） spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34~＋ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.

Emerging potential of exosomes for treatment of traumatic brain injury

Traumatic brain injury（TBI） is one of the major causes of death and disability worldwide.No effective treatment has been identified from clinical trials.Compelling evidence exists that treatment with mesenchymal stem cells（MSCs） exerts a substantial therapeutic effect after experimental brain injury.In addition to their soluble factors,therapeutic effects of MSCs may be attributed to their generation and release of exosomes.Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types.Exosomes play a pivotal role in intercellular communication.Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI.Therapeutic effects of exosomes derive from the exosome content,especially micro RNAs（mi RNAs）.mi RNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes.Compared with their parent cells,exosomes are more stable and can cross the blood-brain barrier.They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells.Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery,potentially for a variety of neural injuries and neurodegenerative diseases.This review discusses the most recent knowledge of exosome therapies for TBI,their associated challenges and opportunities.