Formononetin Enhances Autophagy Flux in The Penumbra of Cerebral Ischemia and Improves Nerve Damage

Objective Formononetin(FOR),a traditional Chinese medicine,has been widely used for nerve protection and nerve function rehabilitation after cerebral stroke.However,the role of FOR in autophagic lysosome function in cerebral ischemiareperfusion damage has not been investigated.This study aimed to explore whether the therapeutic benefits of FOR were influenced by the regulation of autophagy flux.Methods Male Sprague-Dawley rats were separated into sham,model,and MCAO+FOR(30 mg/kg)groups after undergoing middle cerebral artery occlusion(MCAO)and ischemia-reperfusion(I/R).Then,the brain tissues in the ischemic penumbra were obtained to detect the proteins in autophagic/lysosomal pathway with antibodies of Beclin-1,LC3,SQSTM1/P62,Ubiquitin,LAMP-2,Cathepsin B(CTSB)and Cathepsin D(CTSD)by Western blot and immunofluorescence,respectively.Meanwhile,the therapeutic effectiveness was evaluated by measuring infarct volume,neurological impairments,and neuronal necrosis.Results The findings of this study demonstrate that FOR treatment exhibits a dual effect by enhancing the autophagic activities of Beclin-1 and LC3 in neurons,while simultaneously improving the autophagic clearance function,as evidenced by reinforced lysosomal activities of LAMP-2,CTSB,and CTSD,as well as reduced autophagic accumulation of Ubiquitin and P62 in the MCAO+FOR group compared to the MCAO group.Additionally,7 d of FOR treatment dramatically reduced neurological deficits,infarct volume,and neuronal death caused by cerebral ischemia.Conclusion These findings suggest that the neuroprotective mechanism of FOR therapy in accelerating recovery from ischemic stroke may involve the increase of autophagy flux in the penumbra.

Artificial intelligence software for assessing brain ischemic penumbra/core infarction on computed tomography perfusion:A real-world accuracy study

BACKGROUND With the increasingly extensive application of artificial intelligence(AI)in medical systems,the accuracy of AI in medical diagnosis in the real world deserves attention and objective evaluation.AIM To investigate the accuracy of AI diagnostic software(Shukun)in assessing ischemic penumbra/core infarction in acute ischemic stroke patients due to large vessel occlusion.METHODS From November 2021 to March 2022,consecutive acute stroke patients with large vessel occlusion who underwent mechanical thrombectomy(MT)post-Shukun AI penumbra assessment were included.Computed tomography angiography(CTA)and perfusion exams were analyzed by AI,reviewed by senior neurointerventional experts.In the case of divergences among the three experts,discussions were held to reach a final conclusion.When the results of AI were inconsistent with the neurointerventional experts’diagnosis,the diagnosis by AI was considered inaccurate.RESULTS A total of 22 patients were included in the study.The vascular recanalization rate was 90.9%,and 63.6%of patients had modified Rankin scale scores of 0-2 at the 3-month follow-up.The computed tomography(CT)perfusion diagnosis by Shukun(AI)was confirmed to be invalid in 3 patients(inaccuracy rate:13.6%).CONCLUSION AI(Shukun)has limits in assessing ischemic penumbra.Integrating clinical and imaging data(CT,CTA,and even magnetic resonance imaging)is crucial for MT decision-making.

Penumbra血管抽吸装置治疗急性缺血性脑卒中的术中护理

目的探讨Penumbra血管抽吸装置治疗急性缺血性脑卒中的术中护理要点。方法 15例急性缺血性脑卒中患者采用Penumbra血管抽吸装置治疗,总结其术中护理经验。结果 15例患者中12例术中血流开通,3例因颅内血管迂曲或严重狭窄,配合使用Solitaire支架取栓,术中血流再通。术中护士、麻醉医师与手术医师配合良好,生命体征监护操作及记录良好,无手术器械递送错误,影像资料记录完整。结论 Penumbra血管抽吸装置治疗急性缺血性脑卒中手术需要护士充分的术前准备和熟练的术中护理配合,护士掌握术中观察要点对顺利完成急诊取栓手术起重要作用。

Penumbra取栓系统在急性脑梗死中的应用

目的探讨Penumbra取栓系统在急性脑梗死中治疗的可行性和安全性。方法通过对9例急性脑梗死患者实施Penumbra取栓系统治疗,其中大脑前动脉A1段栓塞6例、大脑中动脉M1段栓塞1例、颈内动脉C1段狭窄1例、颈内动脉主干栓塞1例;起病距介入治疗时间3 h内5例,3～6 h 2例,〉24 h 2例。结果 7例6 h以内急性脑梗死患者主要栓塞血管得到100%开通,2例发病后超过24 h的患者临床表现得到明显好转（其中颈内动脉C1段狭窄1例、颈内动脉主干栓塞l例）。结论 Penumbra取栓系统治疗6 h以内急性脑梗死,能尽快使闭塞的血管开通,是一种有效且安全的介入治疗术式。

比较Penumbra系统取栓与SolitaireAB支架取栓治疗大脑中动脉血栓的疗效

目的比较Penumbra系统取栓及SolitaireAB支架取栓术治疗大脑中动脉血栓的疗效。方法选取2012年1—8月北京武警总医院神经血管外科20例急性大脑中动脉血栓形成患者,将患者随机分A组(采用Penumbra系统取栓治疗)和B组(采用SolitaireAB支架取栓治疗)。比较两组患者术前及术后1周的美国国立卫生研究院卒中量表(NIHSS)评分以及随访30d、90d患者残疾评分表(mRs)评分情况。结果两组患者术后NIHSS评分均有下降,A组患者术后1周的NIHSS评分低于B组,差异有统计学意义(P<0.05)。A组患者出院90d的mRs评分低于B组,差异有统计学意义(P<0.05)。结论 Penumbra系统取栓较SolitaireAB支架取栓术获得再通率更高、术后生存质量更好,故值得推广。

Penumbra血栓抽吸系统在急性脑梗死治疗中的有关技术

静脉内重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator,r-tPA）,至今仍是唯一获美国FDA批准的治疗急性缺血性脑卒中的方法。但由于症状出现后治疗黄金时间窗的限制,仅有一小部分（1.8%-4.3%）缺血性脑卒中患者得到静脉内r-tPA治疗。此外,大血管闭塞时静脉内r-tPA治疗效果有限。最近,动脉内机械取栓装置的应用,

Penumbra系统取栓辅助动脉溶栓治疗急性大脑中动脉闭塞的疗效观察

目的评价Penumbra系统取栓辅助动脉溶栓治疗急性大脑中动脉闭塞的可行性、安全性及疗效。方法 5例急性大脑中动脉闭塞患者接受Penumbra系统取栓辅助动脉溶栓治疗。结果 5例患者中5例获得完全再通,均获得良好疗效。未见颅内出血并发症。结论 Penumbra系统取栓辅助动脉溶栓治疗急性大脑中动脉闭塞安全、可行、有效的方法。

规范化护理对急性脑梗死患者Penumbra取栓术后NIHSS及mRS评分的影响

选择2018年1月至2020年1月就诊于中国医科大学附属盛京医院神经外科的40例急性脑梗死患者,均采用Penumbra颅内血栓抽吸系统完成急诊取栓治疗。将患者分为观察组(采用规范化护理)和对照组(采用常规护理),每组20例。采用美国国立卫生研究院卒中量表(NIHSS)和改良Rankin量表(mRS)评价患者的神经功能受损情况。结果发现,Penumbra抽吸导管取栓术治疗后实施卒中规范化护理有助于改善急性脑梗死患者神经功能恢复效果,具有临床应用和推广价值。

Penumbra系统取栓与动脉溶栓治疗大脑中动脉早期血栓形成的疗效观察

目的探讨Penumbra系统取栓治疗与动脉溶栓治疗大脑中动脉血栓形成的早期效果。方法选取25例大脑中动脉血栓者,根据不同的治疗方式分为2组。A组行动脉溶栓治疗,B组行Penumbra系统取栓治疗。观察2组的治疗效果。结果 A组成功7例,成功率58%;B组成功13例,成功率100%。2组治疗效果比较差异有统计学意义(P<0.05)。结论 Penumbra系统取栓较机械取栓中其他设备取栓更安全,血管再通率更高,更有利于挽救缺血的脑组织,值得推广。

Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury

Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated,mitochondrial,and endoplasmic reticulum stress pathways.Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury,and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra.Here,we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12,caspase-3 and the endoplasmic reticulum stress marker 78 k Da glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours.Furthermore,numbers of terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury.These findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra,and may play an important role in the pathophysiology of secondary brain injury.

Penumbra系统取栓治疗大脑中动脉早期血栓形成的疗效

目的探讨24 h内Penumbra系统取栓治疗大脑中动脉早期血栓形成的疗效及安全性。方法选择大脑中动脉早期血栓形成的患者38例随机分为治疗组(n=20)和对照组(n=18)。治疗组于发病24 h内经Penumbra系统取栓治疗,对照组实施常规抗血小板凝集治疗。比较2组患者治疗前后美国国立卫生院神经功能缺损(NHISS)评分、Barthel指数(BI)与改良Rankin量表(mRS)评分情况,并记录患者死亡、继发出血等不良事件发生情况。结果治疗组患者治疗后24 h、7 d、30 d的NHISS评分低于对照组,且BI评分高于对照组(P<0.05或P<0.01)。治疗后90 d时,治疗组BI评分及mRS评分较对照组显著改善(P<0.05)。2组死亡率差异无统计学意义(P>0.05)。结论 Penumbra系统取栓安全有效,有利于挽救缺血的脑组织。

中医情志护理结合循证护理在急性脑梗死Penumbra取栓术后的应用价值

目的探讨中医情志护理结合循证护理在急性脑梗死Penumbra取栓术后的应用价值。方法选取河南省直第三人民医院2019年5月至2020年12月收治的92例急性脑梗死患者进行分析,所有患者均接受Penumbra取栓术治疗。将患者应用随机数表法分为A、B、C组,A组30例,B组30例,C组32例。A组患者接受循证护理,B组患者接受中医情志护理,C组患者接受中医情志联合循证护理。应用神经功能缺损量表(NIHSS)来评价患者的神经功能,应用抑郁自评量表(SDS)与焦虑自评量表(SAS)来评价患者心理状态,应用生活质量问卷(WHOQOL-100)评价患者生活质量。结果护理后3组患者NIHSS评分均明显降低,且C组低于B组和A组(P<0.05);护理后3组患者SAS、SDS评分降低,C组低于B组和A组(P<0.05);护理后3组患者相关生活质量评分均升高,C组高于B组和A组(P<0.05)。结论对脑梗死患者应用中医情志护理结合循证护理能够提升患者神经功能,改善不良情绪,进而提升患者治疗后的生活质量。

Quantifying lateral penumbra advantages of collimated spot-scanning beam for intensity-modulated proton therapy

Intensity-modulated proton therapy(IMPT)is becoming essential for proton therapy and is under rapid development.However,for IMPT,the lateral penumbra of the spot-scanning proton beam is still an urgent issue to be solved.Patient-specific block collimators(PSBCs),which can block unnecessary doses,play a crucial role in passive scattering delivery technology but are rarely used in spot scanning.One objective of this study is to investigate the lateral penumbra variations of intensity-modulated spot scanning with and without a PSBC.For fields with varying degrees of sharpness and at varying depths in a water phantom,the lateral penumbral widths were calculated using a Monte Carlo-based dose engine from RayStation 6.The results suggest that the lateral penumbral widths can be reduced by more than 30%for uniform target volumes,regardless of whether a range-shifter is used,and that the maximum dose beyond the field edges can be reduced significantly.The results of patient cases show that the doses in organs-at-risk near the edge of the target volume decrease if a PSBC is implemented.This study demonstrates that intensity-modulated spot scanning with a PSBC can effectively reduce the lateral penumbra and block unnecessary doses and is therefore promising for clinical applications in spot-scanning proton therapy.

Ischemic penumbra in retina endures： vascular neuropathology is reconciled

A physiological state of＂normoxia＂obtains when tissue oxygen tension（pO_2）is sufficient to drive mitochondrial respiration throughout a volume of cells.Between 30-40%of the available oxygen is normally extracted from hemoglobin as it passes through neural tissue.

Leakage-Penumbra effect in intensity modulated radiation therapy step-and-shoot dose delivery

AIM: To study the leakage-penumbra(LP) effect with a proposed correction method for the step-and-shoot intensity modulated radiation therapy(IMRT).METHODS: Leakage-penumbra dose profiles from 10 randomly selected prostate IMRT plans were studied. The IMRT plans were delivered by a Varian 21 EX linear accelerator equipped with a 120-leaf multileaf collimator(MLC). For each treatment plan created by the Pinnacle3 treatment planning system,a 3-dimensional LP dose distribution generated by 5 coplanar photon beams,starting from 0o with equal separation of 72 o,was investigated. For each photon beam used in the stepand-shoot IMRT plans,the first beam segment was set to have the largest area in the MLC leaf-sequencing,and was equal to the planning target volume(PTV). The overshoot effect(OSE) and the segment positional errors were measured using a solid water phantom with Kodak(TL and X-OMAT V) radiographic films. Film dosimetric analysis and calibration were carried out using a film scanner(Vidar VXR-16). The LP dose profiles were determined by eliminating the OSE and segment positional errors with specific individual irradiations. RESULTS: A non-uniformly distributed leaf LP dose ranging from 3% to 5% of the beam dose was measured in clinical IMRT beams. An overdose at the gap between neighboring segments,represented as dose peaks of up to 10% of the total BP,was measured. The LP effect increased the dose to the PTV and surrounding critical tissues. In addition,the effectdepends on the number of beams and segments for each beam. Segment positional error was less than the maximum tolerance of 1 mm under a dose rate of 600 monitor units per minute in the treatment plans. The OSE varying with the dose rate was observed in all photon beams,and the effect increased from 1 to 1.3 Gy per treatment of the rectal intersection. As the dosimetric impacts from the LP effect and OSE may increase the rectal post-radiation effects,a correction of LP was proposed and demonstrated for the central beam profile for one of the planned beams. CONCLUSION: We concluded that the measured dosimetric impact of the LP dose inaccuracy from photon beam segment in step-and-shoot IMRT can be corrected.

R-L Method and BLS-GSM Denoising for Penumbra Image Reconstruction

When neutron yield is very low, reconstruction of coding penumbra image is rather difficult. In this paper, low-yield （109） 14 MeV neutron penumbra imaging was simulated by Monte Carlo method. The Richardson Lucy （R-L） iteration method was proposed to incorporated with Bayesian least square-Gaussian scale mixture model （BLS-GSM） wavelet denoising for the simulated image. Optimal number of R-L iterations was gotten by a large number of tests. The results show that compared with Wiener method and median filter denoising, this method is better in restraining background noise, the correlation coefficient Rsr between the reconstructed and the real images is larger, and the reconstruction result is better.

Learning and memory changes in rats following exogenous human hepatocyte growth factor gene injection into cerebral ischemic penumbra

Human hepatocyte growth factor can be used to treat cerebral infarction, administered by lateral ventricular, cerebellomedullary cistern or subarachnoid injections. However, the target gene ex-pression product is scarcely found in the ischemic penumbra, but extensively distributes in other regions, increasing the risks of gene therapy. The present study directly transfected hepatocyte growth factor gene into the ischemic penumbra of rats with transient middle cerebral artery occlusion. Immunohistochemical analysis revealed that infarct volume was significantly decreased, hepatocyte growth factor protein expression level and vessel quantity in the ischemic penumbra were significantly increased, and learning and memory were significantly improved.

Penumbral Dose Characteristics of Physical and Virtual Wedge Profiles

Purpose: Both physical and virtual wedges are used in radiotherapy to get uniform and desired dose distribution in clinical setting. All linear accelerators of different venders have computer controlled dynamic wedges called virtual wedge filters. Penumbra is one of the important photon beam characteristics needed to be understood in radiation therapy at the time of commissioning of Treatment Planning system (TPS) as well as applying various treatment planning algorithms in clinical applications. In this study we measured the dose profiles of open field, physical wedges (PW) and virtual wedges (VW) for energies (6 MV & 15 MV), various field sizes (10 × 10, 15 × 15 & 20 × 20 cm2), depths (dmax, 10 cm, 20 cm) and wedge angles (15°, 30°, 45° and 60°). From beam profile we calculated the penumbral width for open and wedged fields. The study was carried out on Siemens ONCOR IMRT Plus linear accelerator. The obtained penumbral width of PW and VW of all wedge angles was subtracted from the penumbral width of open field. The deviations in penumbral width were compared and statistically analyzed as a function of energy, depth, field size and wedge angles. Material and Method: The penumbral width was measured using IBA CC13 ion chamber in IBA Blue phantom (a 3D water phantom). The source to surface distance (SSD) during our study was kept 100cm and measurement was taken for 10 × 10, 15 × 15, 20 × 20 cm2 field sizes and for 15°, 30°, 45°, 60° wedges. These measurements were taken for both 6 MV and 15 MV photon energies. Virtual wedge profiles were acquired using LDA-99 linear detector array (IBA, Germany). The deviations in penumbral width for both PW and VW were calculated by subtracting the penumbral width from open field penumbral width in gun direction (in-plane) and deviation in VW penumbral width, and were obtained by subtracting the open field penumbral width in left-right direction (cross-plane) direction. The measured deviations were plotted for both PW and VW. Statistics on the measured deviations was performed by using SPSS Version 15. Results & Conclusion: The results of one way ANOVA (Analysis of Variance) show that the deviations are significant with energy and the deviations are higher in lower energy than higher energy. The deviations increase as depth increases, the deviations are also significant with depth. The deviations increase with field sizes;the deviations as a function of field size are highly significant. The deviations are higher in PW than VW but the deviations with wedge type are in-significant. As wedge angle increases, deviations also increase and the effect of wedge angle is highly significant on deviations.

Penumbra lunar eclipse observations reveal anomalous thermal performance of Lunakhod 2 reflectors

As the signal reflected by the corner-cube reflector arrays is very weak and easily submerged during the full moon,we analyze the influence of the thermal effect of corner-cube reflector arrays on the intensity of lunar laser ranging echo.Laser ranging measurements during the penumbra lunar eclipse verify suspected thermal deformation in the Lunakhod 2 reflectors.Signal levels vary over two orders of magnitude as the penumbra eclipse progresses.This can be explained by the change in the dihedral angle of the corner-cube reflectors caused by the temperature.The results show that when the dihedral angle errors reach 1,the energy is reduced by 100 times compared with the ideal corner-cube reflector.In the experiment,our findings suggest that when the corner-cube reflector arrays enter the penumbra of the earth,the effective echo signal level which reaches 0.18 photons/s far exceeds the historical level of the full moon.However,11 minutes after the penumbra lunar eclipse,the effective echo rate of Lunakhod 2 will drop two orders of magnitude.The mechanism can explain the acute signal deficit observed at full moon.

Effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia

Objective:To observe the effect of Xingnaojing injection on penumbra transformation in rats with acute cerebral ischemia.Methods:The rat model of middle cerebral artery occlusion(Middle cerebral artery occlusion,MCAO)was established by suture occlusion.Except the sham operation group,the other groups were randomly divided into model group and Xingnaojing group.The rats in Xingnaojing group were intraperitoneally injected with Xingnaojing injectionaccording to 0.18ml/100g,and the sham operation group and model group were given the same amount of normal saline respectively.24 hours after the establishment of the model,the morphological changes of neurons in the penumbra of the rats were observed by Nissl staining,the ultrastructural changes of neurovascular unit(Neurovascular unit,NVU)were observed by transmission electron microscope(Transmission electron microscope,TEM),and the apoptosis of the ischemic penumbra was detected by in situ apoptosis(TdT-mediated Dutp Nick-End Labeling,TUNEL).Magnetic resonance imaging was used to observe the ischemic evolution of the penumbra of the same rat at 4.5 h and 24 h,respectively.Results:Compared with the sham operation group,the number of neurons in the model group was significantly reduced,the structure of Nissl corpuscles was destroyed,the outline was blurred or disappeared,the pathological morphology of NVU ultrastructure was obviously damaged under transmission electron microscope,a large number of apoptotic cells could be seen in the model group by TUNEL staining(P<0.01),and magnetic resonance imaging showed that there was a large area infarction in the brain tissue of the model group.Compared with the model group,the pathomorphology of neurons and NVU ultrastructure in Xingnaojing group was significantly improved,the number of apoptotic cells was significantly decreased(P<0.01),and the loss rate of penumbra was significantly lower in Xingnaojing group(P<0.05).Conclusion:Xingnaojing injection can improve the state of neurons in ischemic penumbra,reduce the injury of glial cells and microvessels,inhibit apoptosis,promote the transformation of penumbra in rats with acute cerebral ischemia,and save part of penumbra to some extent.it has a certain protective effect on the brain tissue of penumbra in the acute stage of cerebral ischemia.