Establishment of a rhesus monkey model of middle cerebral artery ischemia and reperfusion using a microcatheter embolization method

Nonhuman primates are closest to humans in terms of lineage, and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans. Therefore, nonhuman primates could be utilized to simulate the process of ischemic stroke in the human. Few studies, however, have reported the use of endovascular technology to establish a rhesus monkey stroke model. In the present study, seven adult, male, rhesus monkeys were selected and, following anesthesia, a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow, thereby resulting in middle cerebral artery occlusion. After 2 hours, the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion. Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery. Magnetic resonance imaging revealed the existence of ischemic brain lesions, and neurological examination showed sustained functional deficits following surgery. The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non-craniotomy invasion and reproducibility. The scope and degree of ischemic damage using this model was controllable. Therefore, this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.

LIC color texture enhancement algorithm for ocean vector field data based on HSV color mapping and cumulative distribution function

Texture-based visualization method is a common method in the visualization of vector field data.Aiming at adding color mapping to the texture of ocean vector field and solving the ambiguity of vector direction in texture image,a new color texture enhancement algorithm based on the Line Integral Convolution(LIC)for the vector field data is proposed,which combines the HSV color mapping and cumulative distribution function calculation of vector field data.This algorithm can be summarized as follows:firstly,the vector field data is convoluted twice by line integration to get the gray texture image.Secondly,the method of mapping vector data to each component of the HSV color space is established.And then,the vector field data is mapped into HSV color space and converted from HSV to RGB values to get the color image.Thirdly,the cumulative distribution function of the RGB color components of the gray texture image and the color image is constructed to enhance the gray texture and RGB color values.Finally,both the gray texture image and the color image are fused to get the color texture.The experimental results show that the proposed LIC color texture enhancement algorithm is capable of generating a better display of vector field data.Furthermore,the ambiguity of vector direction in the texture images is solved and the direction information of the vector field is expressed more accurately.

The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains unclear.This is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)GGOs.The primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and non-responders.Finally,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs occurred.The total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time.Correspondingly,the mIHC analysis showed more CD8^(+)T cells infiltrated in responders.Besides,responders’cytokine concentrations of EGF and CTLA-4 increased during treatment.The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders.Collectively,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns.Such effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

浙江田螺山遗址剖面记录的水文环境变化

浙江余姚田螺山遗址是新石器时代河姆渡文化的一处保存良好的代表性遗址,为研究宁绍平原地区古环境变化及其对文化聚落的影响提供了良好的材料.本研究在田螺山遗址T005探方的西壁获取了厚达263 cm的连续地层剖面,对样品进行了系统的岩性地层描述、加速器质谱(AMS)^(14)C测年、高分辨率XRF(X射线荧光光谱分析)元素扫描、硅藻和粒度的综合分析.研究结果表明,该剖面反映的环境演变过程可以分为3个阶段:(1)河姆渡第一、二期文化时期(265～211 cm,约7.0～6.5 cal ka BP),该层堆积混杂,砂含量较高,含石块及陶片,受人类活动影响明显,具有海相性指示意义的Ca元素强度相对较低,优势硅藻种为淡水需氧气生种,指示了淡水的沼泽环境,受海水影响较小;(2)文化层之上为黏土质粉砂与白灰色砂互层的平行层理,与下覆文化层为不整合接触,沉积厚度达183 cm(211～28 cm),年代约4.2～4.0 cal ka BP, Ca元素强度较高,硅藻组合中优势种为咸水和半咸水种,推测该时期可能为风暴潮引起的洪水的快速沉积;(3)第三阶段(28～0 cm)为混杂堆积,含较多铁锰氧化物斑点, Ca元素强度低,硅藻主要属种为淡水附生种,可能为现代水稻田环境.本研究主要揭示了田螺山遗址7.0～6.5 cal ka BP的水文环境背景以及4.2 cal ka BP左右的事件沉积,对深入了解田螺山遗址先民生活的环境背景及区域极端事件具有重要意义.

Stenting for symptomatic intracranial arterial stenosis in China:1-year outcome of a multicentre registry study

background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.

Targeting of VPS 18 by the lysosomotropic agent RDN reverses TFE3-mediated drug resistance

Dear Editor,Multidrug resistance(MDR)is still a major challenge for successful cancer treatments.Numerous mechanisms that confer therapy-induced drug resistance have been extensively investigated to explore how to combat the MDR.In this regard,lysosomal sequestration has demonstrated to be a mechanism contributing to drug resistance via an/,off-target,/effect in which hydrophobic and weakly basic chemotherapeutic agents are trapped in lysosomes,sequestering them from their targets.