Treatment of radiation-induced brain injury with bisdemethoxycurcumin

Radiation therapy is considered the most effective non-surgical treatment for brain tumors.However,there are no available treatments for radiation-induced brain injury.Bisdemethoxycurcumin(BDMC)is a demethoxy derivative of curcumin that has anti-proliferative,anti-inflammatory,and anti-oxidant properties.To determine whether BDMC has the potential to treat radiation-induced brain injury,in this study,we established a rat model of radiation-induced brain injury by administe ring a single 30-Gy vertical dose of irradiation to the whole brain,followed by intraperitoneal injection of 500μL of a 100 mg/kg BDMC solution every day for 5 successive weeks.Our res ults showed that BDMC increased the body weight of rats with radiation-induced brain injury,improved lea rning and memory,attenuated brain edema,inhibited astrocyte activation,and reduced oxidative stress.These findings suggest that BDMC protects against radiationinduced brain injury.

Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis:Useless or useful?-A literature review

Radiotherapy(RT)is the backbone of multimodality treatment of more than half of cancer cases.Despite new modern RT techniques,late complications may occur such as radiation proctitis(RP).The natural history of RP is unpredictable.Minor symptoms may resolve spontaneously or require conservative treatment.On the other hand,for similar and uncomplicated clinical contexts,symptoms may persist and can even be refractory to the progressive increase in treatment measures.Over the last decades,an enormous therapeutic armamentarium has been considered in RP,including hyperbaric oxygen therapy(HBOT).Currently,the evidence regarding the impact of HBOT on RP and its benefits is conflicting.Additional prospective and randomised studies are necessary to validate HBOT’s effectiveness in the‘real world’clinical practice.This article reviewed the relevant literature on pathophysiology,clinical presentation,different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

Mesenchymal stem cell therapy for acute radiation syndrome: Innovative medical approaches in military medicine

After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.

Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy:A review of recent advances

Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor recurrence.To overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic agents.This review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer treatment.Firstly,we introduce the classification and properties of hydrogels.Next,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and brachytherapy.We also discuss hydrogels used in combination therapy involving RT and immunotherapy.Lastly,we highlight the challenges that hydrogels face in RT.By surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.

Advances in extracellular vesicle-based combination therapies for spinal cord injury

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

Local low-dose X-ray radiation promotes homing of mesenchymal stem cells to the injured mouse spinal cord

BACKGROUND： Bone marrow-derived mesenchymal stem cells （BMSCs） are a potentially useful source for cell replacement therapy following spinal cord injury. However, the homing characteristics of BMSCs in vivo remain unclear. Low-dose radiation has been shown to promote homing of BMSCs to exposed sites. OBJECTIVE： To investigate the effects of low-dose local radiation to non-injured areas on the ability of human BMSCs to home to the injured mouse spinal cord, as well as recovery of spinal cord injury. DESIGN, TIME AND SE＇I-FING： A randomized, controlled, animal experiment was performed at the Central Laboratory, Second Affiliated Hospital of Soochow University between October 2007 and October 2008. MATERIALS： BMSCs were isolated from four adult, human donors. METHODS： Fifty adult, female, Balb/c mice were subjected to adjusted weight-drop impact resulting in complete paraplegia. Three days later, mice were randomly assigned to a radiation ＋ transplantation group （n = 23） and a transplantation group （n = 20）. In total, 2 x 106 carboxyfluorescein diacetate succinimidyl ester-labeled BMSCs were injected into each mouse via the caudal vein. Mice in the radiation ＋ transplantation group received 2.5 Gy local X-ray irradiation 2 hours before BMSCs injection. MAIN OUTCOME MEASURES： The homing of BMSCs to injured cord and irradiated skin after transplantation was observed by fluorescence microscope; the structure recovery of injured cord was assessed by magnetic resonance imaging. RESULTS： Compared with the transplantation group, at 24 hours after transplantation, the number of BMSCs was significantly increased in the injured area and the exposed site （P 〈 0.05）, and inflammation and edema were significantly alleviated in the injured cord in the radiation ＋ transplantation group. CONCLUSION： Local low-dose radiation has the potential to promote homing of BMSCs and recovery of spinal cord injury, although the radiated region was not injured area.

Study on Oxygen Supply and Protection of Bone Marrow in Acute Radiation injured Mice

After irradiated by & Gy 60Co γ-ray, mice were intraperitoneally injected immediately with 0.2 ml 100 % compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72±1. 05kpa. During irradiation, the level of PbO2 decreased to 10. 78±1. 17 kpa (P＜0. 001). And 3 days after irradiation, PbO2 decreased to 9. 75±0. 52 kpa, suggesting that the commonly used 'blood-activating and stasis-eliminating' Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenviroment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.

Study on the Protective Effects of Compound Blood-activating Soup on Bone Marrow Hematopoietic Cells in Acute Radiation Injured Mice

After irradiation with 8 Gy 60Coγ-ray,mice were immediaterly given intraperitoneal injection of 200 mg 100 % compound blood-activating soup twice a day. On the 3rd and 7th day, the P53 gene expression of bone marrow hematopoietic cells in Chinese drug group was found to be higher than that in normal group, and it was also significantly higher than that in control group. The expression level of GADD153 gene which was not expressed in normal group was much lower in Chinese drug group than that in control group. On the 7th day after irradiation, the P53 and GADD153 gene expression levels of splenic mononuclear cells were consistent with those of bone marrow hematopoietic cells both in Chinese drug group and control group. On the 3rd and 7th day, the bone marrow hematopoietic tissue volume in Chinese drug group was higher than that in control group, with no difference found between the two groups. While on the 14th day, the difference became significant (P＜0. 01). The results showed that commonly used blood-activating and stasis-eliminating drugs may strengthen .the viability of hematopoietic cells and promote the rehabilitation of hematopoiesis by inducing wt-P53 expression to block the bone marrow hematopoietic cells in G1 phase, during which DNA could be repaired.

Potential for a pluripotent adult stem cell treatment for acute radiation sickness

Accidental radiation exposure and the threat of deliberate radiation exposure have been in the news and are a public health concern. Experience with acute radiation sickness has been gathered from atomic blast survivors of Hiroshima and Nagasaki and from civilian nuclear accidents as well as experience gained during the development of radiation therapy for cancer. This paper reviews the medical treatment reports relevant to acute radiation sickness among the survivors of atomic weapons at Hiroshima and Nagasaki, among the victims of Chernobyl, and the two cases described so far from the Fukushima Dai-Ichi disaster. The data supporting the use of hematopoietic stem cell transplantation and the new efforts to expand stem cell populations ex vivo for infusion to treat bone marrow failure are reviewed. Hematopoietic stem cells derived from bone marrow or blood have a broad ability to repair and replace radiation induced damaged blood and immune cell production and may promote blood vessel formation and tissue repair. Additionally, a constituent of bone marrow-derived, adult pluripotent stem cells, very small embryonic like stem cells, are highly resistant to ioniz-ing radiation and appear capable of regenerating radiation damaged tissue including skin, gut and lung.

护肝片预防性治疗抗结核药物性肝损伤的Meta分析

目的:评价预防性使用护肝片对anti-TB DILI的有效性和安全性,明确护肝片对anti-TB DILI的预防作用。方法:对6个主要的中文和英文数据库进行了检索,从数据库建立之日起至2021年12月,不限制语言和发表偏倚。两名作者根据纳入和排除标准独立选择合格的研究,然后提取数据并进行Meta分析。结果:本研究共纳入18项研究的4270例患者,Meta分析结果显示预防性使用护肝片与anti-TB DILI发生率降低相关[RR=0.29,95%CI(0.24,0.36),P<0.05],敏感性分析提示结果稳健。预防性服用护肝片在4周内[RR=0.27,95%CI(0.16,0.48),P<0.001]和4周后[RR=0.34,95%CI(0.17,0.66),P=0.001]均可显著降低anti-TB DILI的发生率,且异质性较低。在乙型肝炎表面抗原阳性(HBsAg+)患者中的anti-TB DILI发生率也显著降低[R=0.25,95%CI(0.15,0.39),P<0.001]。结论:在抗结核治疗的患者中预防性使用护肝片可降低anti-TB DILI发生,尤其在HBsAg+的患者中有更多获益。由于纳入研究的方法学质量不高,尚需要更多高质量的研究来进一步验证其有效性和安全性。

鼻咽癌放射治疗患者放射性脑损伤的危险因素分析及风险预测模型构建

目的探讨影响鼻咽癌放射治疗患者发生放射性脑损伤的危险因素,并构建风险预测模型。方法回顾性选取郑州大学第五附属医院2021年1月至2022年1月放射治疗后发生放射性脑损伤的40例鼻咽癌患者作为发生组,另选取同期接受放射治疗后未发生放射性脑损伤的61例鼻咽癌患者作为未发生组。收集两组患者的一般资料及临床指标,采用logistic回归性分析检验影响鼻咽癌放射治疗患者并发放射性脑损伤的危险因素,同时依据回归分析结果构建风险预测模型,绘制受试者工作特征(ROC)曲线检验风险预测模型对鼻咽癌放射治疗患者放射性脑损伤发生的预测价值。结果两组患者双侧颞叶最高照射剂量、血清胶质纤维酸性蛋白(GFAP)、血清环氧化酶-2(COX-2)及血浆纤维蛋白原(Fib)差异有统计学意义(P<0.05)。logistic回归性分析显示,高水平双侧颞叶最高照射剂量、血清GFAP、血清COX-2及血浆Fib是影响鼻咽癌放射治疗患者放射性脑损伤发生的危险因素(P<0.05)。构建风险预测模型,ROC内部验证显示曲线下面积(AUC)为0.911,AUC的95%CI为0.851~0.972,特异度0.967,敏感度0.775,约登指数0.742,(P<0.001)。结论双侧颞叶最高照射剂量、血清GFAP、血清COX-2及血浆Fib是影响鼻咽癌放射治疗患者放射性脑损伤发生的危险因素。

中医非药物疗法治疗骨伤术后疼痛临床观察

目的探讨分析中医非药物疗法治疗骨伤术后疼痛的临床效果。方法选择遂川县中医院于2020年1月—2022年1月收治的60例骨伤术后疼痛患者,采取随机数字表法分组,奇数患者纳入观察组(30例),实施中医非药物疗法,偶数患者纳入对照组(30例),实施常规治疗。对比两组临床疗效、焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分、视觉模拟量表(VAS)评分、生活质量评分以及关节活动度(ROM)等情况。结果观察组临床总有效率为93.33%(28/30),高于对照组的70.00%(21/30)(P<0.05)。治疗后,观察组SAS、SDS、VAS和生活质量评分以及ROM均优于对照组,差异均有统计学意义(P<0.05)。结论应用中医非药物疗法治疗骨伤,可有效缓解患者疼痛以及因疾病产生的焦虑、抑郁等不良情绪,其关节活动度改善明显,生活质量切实提升,值得临床大力推广、应用。

Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

抗肿瘤药物对慢性放射性肠损伤影响的病理学研究

目的从病理学角度探讨抗肿瘤药物对宫颈癌慢性放射性肠损伤组织的影响。方法回顾性分析2016年8月至2023年4月期间安徽医科大学第一附属医院宫颈癌慢性放射性肠损伤患者的临床病理资料。根据RTOG/EORTC评分标准对49例患者的放射性肠损伤临床症状进行评分和严重程度分级。根据药物治疗方案分为抗血管生成药物治疗组和无抗血管生成药物治疗组,紫杉类药物化疗组和无紫杉类药物化疗组。采用病理学半定量评分系统评估患者的慢性放射性肠损伤程度,分别比较对应亚组间微血管计数、狭窄血管计数、狭窄血管比例、病理总分、溃疡、炎症、水肿、坏死和纤维化指标的差异。并使用Cox分析慢性放射性肠损伤患者发生严重并发症的独立危险因素。结果抗血管生成药物治疗组的狭窄血管计数、狭窄血管比例、溃疡和炎症程度均高于无抗血管生成药物治疗组,差异有统计学意义(P均<0.05);而抗血管生成药物治疗组的微血管计数和纤维化程度均低于无抗血管生成药物治疗组,差异有统计学意义(P均<0.05)。紫杉类药物化疗组与无紫杉类药物化疗组间的病理学指标比较,差异无统计学意义(P均>0.05)。Cox多因素分析显示,抗血管生成药物不是慢性放射性肠损伤患者发生严重并发症的独立危险因素(P>0.05)。结论抗血管生成药物加重了宫颈癌慢性放射性肠损伤组织的血管狭窄、溃疡和炎症,但减轻了纤维化。紫杉类药物对宫颈癌慢性放射性肠损伤组织无明显影响。

纳米制剂用于放射性肠损伤防护的研究进展

[背景]辐射引起的急、慢性肠道损伤是腹部/盆腔实体肿瘤放疗常见的并发症,发病机制主要与肠上皮细胞、血管内皮细胞、微生物屏障和免疫屏障的损伤以及肠壁组织纤维化有关.目前,氨磷汀被认为是预防放射性肠损伤的有效药物,然而半衰期短、副作用大等缺点限制了其临床应用,因此,开发低毒、高效的放射性肠损伤防护药物具有十分重要的意义.[进展]药物防护是放射性肠损伤的研究重点,但合成小分子化合物、天然植物化合物仍存在溶解性差、生物利用度低等缺点.随着载体材料和制剂技术的快速发展,纳米制剂在减轻药物毒副作用、延长药物半衰期和提高药物生物利用度上发挥了重要作用,一些具有本征放射性的纳米材料和药物递送载体在减轻放射引起的肠损伤方面显现出巨大潜力,成为具有广泛应用前景的替代策略.[展望]本文从放射性肠损伤的发病机制出发,综述化学药物和纳米制剂在放射性肠损伤中的应用和研究进展,以期为开发新型的放射性肠损伤防护制剂提供思路.从材料选择上需考虑生物安全性良好的天然材料,从保护效果和病人用药依从性上可优先考虑口服药物递送策略.

药物联合应用对中草药相关肝损伤的影响

随着中医药在全球范围内的广泛使用和临床中药物联用情况的增多,中草药相关肝损伤(HILI)和药物安全性事件频发,这给中药新药研发和中医产业发展带来了重大挑战。目前,在系统归纳总结药物联用对HILI的影响,梳理其临床特征、发生过程和互作机制,尤其是研究中西药联用后的药效动力学和药代毒理学过程等方面,仍然存在较大不足。亟需进一步构建系统整合的研究体系,特别是在靶标分子、细胞间交流、组织间串扰和体内毒性评价等方面,开展更加精准、特异和早期的研究。通过临床与基础并行的病证基础研究,提出符合中医药理论和应用规律的HILI防控策略,将为提升病证场景下的中西药物联用水平提供基础支撑和可信证据。

细胞角蛋白检测对儿童ALL药物性肝损伤预测价值

目的探究血清细胞角蛋白18-M30(CK18-M30)和18-M65(CK18-M65)对儿童急性淋巴细胞白血病(ALL)治疗后发生药物性肝损伤(DILI)的预测价值。方法2019年3月—2022年2月,新乡医学院第一附属医院收治ALL病儿66例,依据DILI分为观察组49例(发生)和对照组17例(未发生),观察组依据DILI病情分为轻度、中度和重度亚组。收集病儿相关临床资料,检测血清CK18-M30和CK18-M65活力。分析发生DILI的影响因素及血清CK18-M30和CK18-M65表达对并发DILI的预测价值。结果观察组血清CK18-M30和CK18-M65活力高于对照组(t=14.230、12.735,P<0.05)。DILI病情越严重,血清CK18-M30和CK18-M65活力越高(F=20.122、5.551,P<0.05)。ALL疾病危险程度、感染、输血、血清CK18-M30和CK18-M65活力等均为ALL病儿发生DILI的危险因素(OR=1.869~2.866,95%CI=(1.205~1.799)~(2.773~4.257),P<0.05),保肝药应用则为发生DILI的保护因素(OR=0.522,95%CI=0.395~0.670,P<0.05)。血清CK18-M30和CK18-M65预测ALL病儿发生DILI的受试者工作特征曲线下面积(AUC)分别为0.739和0.699,两者联合预测效能更高。结论ALL病儿血清CK18-M30和CK18-M65活力可作为发生DILI的预测指标。

养阴清肺汤治疗肺癌放疗并发放射性肺损伤患者的疗效及对其转化生长因子-β1和白细胞介素-6水平的影响

目的探讨养阴清肺汤治疗肺癌放疗并发放射性肺损伤患者的疗效及对其转化生长因子-β1(Transforming growth factor-β1,TGF-β1)、白细胞介素-6(Interleukin-6,IL-6)水平的影响。方法选取2022年1月—2023年1月期间上海中医药大学附属龙华医院收治的肺癌放疗并发放射性肺损伤患者70例,按随机数字表法分为对照组和观察组,每组各35例。对照组给予醋酸泼尼松片等常规西医治疗,观察组在对照组基础上联合养阴清肺汤治疗。治疗2周后,观察比较两组患者临床疗效、不良反应情况,治疗前后中医证候积分、肺功能指标[最大呼气流速峰值(Peak expiratory flow,PEF)、用力肺活量(Forced vital capacity,FVC)、第1秒用力呼吸容积(Forced expiratory volume in one second,FEV1)、FEV1/FVC]、KPS评分、生活质量评分(QLQ-C30)、TGF-β1、IL-6水平。结果治疗后两组患者咳嗽少痰、咯血量多、胸痛、潮热盗汗、口渴口干、气急心烦评分均较治疗前明显降低,差异有统计学意义(P<0.05);且观察组中医证候积分明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者PEF、FVC、FEV1、FEV1/FVC水平均较治疗前升高,差异有统计学意义(P<0.05);且观察组肺功能指标均明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者KPS、QLQ-C30评分均较治疗前升高,差异有统计学意义(P<0.05);且观察组KPS、QLQ-C30评分均明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者TGF-β1、IL-6水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组TGF-β1、IL-6水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后观察组临床总有效率94.29%(33/35)明显高于对照组74.29%(26/35),差异有统计学意义(P<0.05)。治疗期间,两组患者均未见与用药相关的不良反应发生。结论养阴清肺汤联合醋酸泼尼松片等西医常规治疗肺癌放疗并发放射性肺损伤疗效确切,能够进一步缓解患者临床症状,降低TGF-β1、IL-6水平,保护肺功能,改善患者生活质量。

药物治疗在肝切除术中预防缺血再灌注损伤的研究进展

肝切除术中常采用肝门阻断和控制中心静脉压的方法减少出血,保证手术视野清晰,从而使手术顺利进行,但在肝门阻断和开放过程中会导致肝脏缺血再灌注损伤(hepatic ischemia-reperfusion injury,HIRI)、胃肠道淤血、肠源性细菌移位等问题。因此,围术期采取各种措施减轻因肝门阻断引起的HIRI进而提高手术的安全性成为肝切除术的研究热点。缺血预处理、亚低温处理、药物治疗、抗凋亡基因治疗等方法应运而生,其中药物治疗具有可操作性强、相对安全、临床上易操作等优势,因而受到广泛关注。本文对有助于改善HIRI的部分代表药物及作用机制进行总结,为HIRI的临床诊治提供参考。

失血性休克后肾脏保护的研究进展

失血性抗休克是一种由于创伤等原因引起的临床常见的急危重症。尤其是肾脏在缺血缺氧后引起的局部组织灌注不足和细胞缺氧,极易导致急性肾损伤。临床上在不断探寻患者失血性休克后更安全、实用和有效的复苏方法,如从晶胶液体到高渗液体、从常压复苏到低压复苏、从纠正血压到恢复组织细胞的氧供、从维持血流动力学稳定到抑制细胞凋亡、从血管活性药到中药再到酶抑制剂的应用等等,以达到更好地保护肾脏的目的。本文就近年来关于失血性休克患者肾脏的保护研究进展进行综述。