心室肌脂肪:一个意想不到的远期生存生物标志物?

正目的非增强CT常常观察到心肌脂肪,但对其认识不足,本文旨在探究心肌内脂肪与全因死亡率的关系,无论是否有心肌梗死病史。方法本回顾性队列研究收集了不     

Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury

Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10⁶ hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10⁶ cells/kg),medium(1×10⁶ cells/kg)and high(4×10⁶ cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10⁶ hUC-MSCs/kg is an alternative approach for treating subacute SCI.     

美国≥65岁女性的数字二维乳腺摄影与断层成像对比

正摘要虽然乳腺癌的发病率和死亡率随着年龄的增长而增加,但有关老年妇女筛查乳腺X线检查的益处和风险,以及老年妇女二维数字乳腺X线摄影(DM)和数字乳腺断层成     

Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.     

Significant impact of cryopreserved amniotic membrane on acute ocular Stevens-Johnson syndrome and toxic epidermal necrolysis

The ocular surface is covered by an epithelium encompassing an area including the cornea,the limbus and the conjunctiva bordered by the upper and lower lids.The healthy state of the ocular surface epithelium depends on a stable and protective preocular tear film when the eye is open.A stable preocular tear film is governed by sound ocular surface defense that involves effective neuroanatomic integration of compositional and hydrodynamic factors by two neural reflexes (1).     

Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel protein.Its expression is restricted to prostate epithelial cells.The exact function is unknown.This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells.ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative vs.strong ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa.ANO7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa.     

Glial regenerative response in the imaginal discs of Drosophila melanogaster

<正>Glial cells play a key role during nervous system development and actively participate in all the cellular processes involved in maintaining its structural robustness and functional plasticity.In response to neuronal damage,glial cells proliferate,migrate to the injured region and change their morphology,function,and behavior     

Tandem pore TWIK-related potassium channels and neuroprotection

TWIK-related potassium channels(TREK) belong to a subfamily of the two-pore domain potassium channels family with three members, TREK1, TREK2 and TWIK-related arachidonic acid-activated potassium channels. The two-pore domain potassium channels is the last big family of channels being discovered, therefore it is not surprising that most of the information we know about TREK channels predominantly comes from the study of heterologously expressed channels. Notwithstanding, in this review we pay special attention to the limited amount of information available on native TREK-like channels and real neurons in relation to neuroprotection. Mainly we focus on the role of free fatty acids, lysophospholipids and other neuroprotective agents like riluzole in the modulation of TREK channels, emphasizing on how important this modulation may be for the development of new therapies against neuropathic pain, depression, schizophrenia, epilepsy, ischemia and cardiac complications.     

多参数MR成像全肿瘤直方图分析三阴性乳腺癌与其他亚型的鉴别

正摘要目的利用多参数MR成像图谱和全肿瘤直方图分析三阴性(TN)乳腺癌与其他分子亚型鉴别的影像学生物标志。方法本回顾性研究包括134例浸润性导管癌病人。从     

慢性血栓栓塞性肺动脉高压病人在球囊血管成形术前后的肺灌注血容量CT、肺灌注SPECT、肺血管造影的临床及预测价值比较

正摘要目的使用双能量CT计算肺灌注血容量(PBV)诊断肺血栓栓塞已被广泛接受。本研究评价慢性血栓栓塞性肺高压(CTEPH)病人在球囊肺血管成形术(BPA)前、后的肺