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.

TLD calibration and absorbed dose measurement in a radiation-induced liver injury model under a linear accelerator

The application of a thermoluminescent detector(TLD) for dose detection at the liver irradiation site in mice under linear accelerator precision radiotherapy and the use of a single high dose to irradiate the mouse liver to construct a biological model of a radiation-induced liver injury(RILD) in mice were to determine the feasibility of constructing a precision radiotherapy model in small animals under a linear accelerator. A 360° arc volumetric rotational intensity-modulated radiotherapy(VMAT) plan with a prescribed dose of 2 Gy was developed for the planned target volume(PTV) at the location of the TLD within solid water to compare the difference between the measured dose of TLD and the assessed parameters in the TPS system. The TLD was implanted in the livers of mice, and VMAT was planned based on TLD to compare the measured and prescribed doses. C57BL/6 J mice were randomly divided into control and 25-Gy radiation groups and were examined daily for changes in body weight. They were euthanized at 3 and 10 weeks after radiation, and the levels of liver serum enzymes such as alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) were measured to observe any pathological histological changes in the irradiated areas of the mouse liver. The measured values of solid underwater TLD were within ± 3% of the Dmean value of the evaluation parameter in the TPS system. The mice in the 25-Gy radiation group demonstrated pathological signs of radiation-induced liver injury at the site of liver irradiation. The deviation in the measured and prescribed doses of TLD in the mouse liver ranged from-1.5 to 6%;construction of an accurate model of RILD using the VMAT technique under a linear accelerator is feasible.

Follow-up strategy for early detection of delayed pseudoaneurysms in patients with blunt traumatic spleen injury: A single-center retrospective study

BACKGROUND The spleen is the most commonly injured solid organ in blunt abdominal trauma,and splenic pseudoaneurysm rupture is associated with a high risk of mortality.Nonoperative management has become the standard treatment for hemodynam-ically stable patients with splenic injuries.On the other hand,delayed splenic pseudoaneurysms can develop in any patient,and at present,there are no known risk factors that may reliably predict their occurrence.Furthermore,there is a lack of consensus regarding the most appropriate strategies for monitoring and mana-ging splenic injuries,especially lower-grade(I-III).AIM To determine the predictors of pseudo-aneurysm formation following splenic injury and develop follow-up strategies for early detection of pseudoaneurysms.METHODS We retrospectively analyzed patients who visited the Level I Trauma Center bet-ween January 2013 and December 2022 and were diagnosed with spleen injuries after blunt abdominal trauma.RESULTS Using the American Association for the Surgery of Trauma spleen injury scale,the splenic injuries were categorized into the following order based on severity:Grade I(n=57,17.6%),grade II(n=114,35.3%),grade III(n=89,27.6%),grade IV(n=50,15.5%),and grade V(n=13,4.0%).Of a total of 323 patients,35 underwent splenectomy and 126 underwent angioembolization.19 underwent delayed angioembolization,and 5 under-went both initial and delayed angioem-bolization.In 14 patients who had undergone delayed angioembolization,no extravasation or pseudoaneurysm was observed on the initial computed tomography scan.There are no particular patient-related risk factors for the formation of a delayed splenic pseudoaneurysm,which can occur even in a grade I spleen injury or even 21 days after the injury.The mean detection time for a delayed pseudoaneurysm was 6.26±5.4(1-21,median:6,inter-quartile range:2-9)days.CONCLUSION We recommend regular follow-up computed tomography scans,including an arterial and portal venous phase,at least 1 week and 1 month after injury in any grade of blunt traumatic spleen injury for the timely detection of delayed pseudoaneurysms.

Rabbit model of radiation-induced lung injury

Objective:To explore the feasibility of establishing an animal model of chronic radiationinduced lung injury.Methods:Twenty-eight New Zealand white rabbits were randomly divided into 3 groups(the right lung irradiation group,the whole lung irradiation group and the control group).Animal model of radiation-induced lung injury was established b) highdoes radiotherapy in the irradiation groups,then all rabbits underwent CT and pathological examinations at 1.2.4.8.12.16 weeks,respectively after radiation.Results:Within 4 weeks of irradiation,some rabbits in the right lung irradiation group and whole lung irradiation group died. CT and pathological examinations all showed acute radiation pneumonitis.At 8-12 weeks after irradiation,CT scanning showed ground glass samples signs,patchy shadows and fibrotic stripes. Pathological examination showed the fibrosis pulmonary alveolar wall thickened obviously. Conclusions:The clinical animal model of chronic radiation-induced lung injury which corresponds to practical conditions in clinic can be successfully established.

Correlation between miR-564, TGF-β1, and radiation-induced lung injury

Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury.

Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

BACKGROUND： Previous studies have shown that transplantation of vascular endothelial growth factor （VEGF）-modified neural stem cells （NSC） provides better outcomes, compared with neural stem cells, in the treatment of brain damage. OBJECTIVE： To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury, and to determine neuron-specific enolase （NSE） expression in the brain. DESIGN, TIME, AND SETTING： The randomized, controlled study was performed at the Linbaixin Experimental Center, Second Affiliated Hospital, Sun Yat-sen University, China from November 2007 to October 2008. MATERIALS： VEGF-modified C17.2 NSCs were supplied by Harvard Medical School, USA. Streptavidin-biotin-peroxidase-complex kit （Boster, China） and 5, 6-carboxyfluorescein diacetate succinimidyl ester （Fluka, USA） were used in this study. METHODS： A total of 84 Sprague Dawley rats were randomly assigned to a blank control group （n = 20）, model group （n = 20）, NSC group （n = 20）, and a VEGF-modified NSC group （n = 24）. Rat models of radiation-induced brain injury were established in the model, NSC, and VEGF-modified NSC groups. At 1 week following model induction, 10 pL （5 ×10^4 cells/μL） VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups. A total of 10μL saline was injected into rats from the blank control and model groups. MAIN OUTCOME MEASURES： NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation. RESULTS： NSE expression was significantly decreased in the brains of radiation-induced brain injury rats （P 〈 0.05）. The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups, compared with the model group （P 〈 0.05）. NSE expression significantly increased in the VEGF-modified NSC group, compared with the NSC group, at 6 weeks following transplantation （P 〈 0.05）. CONCLUSION： VEGF-modified NSC transplantation increased NSE expression in rats with radiation-induced brain injury, and the outcomes were superior to NSC transplantation.

Radiation-induced brain injury after a conventional dose of intensity-modulated radiotherapy for nasopharyngeal carcinoma:a case report and literature review

A 61-year-old female nasopharyngeal carcinoma patient was admitted to the hospital with sudden cognitive dysfunction one month after Volumetric Intensity Modulated Arc Therapy(VMAT)conventional dose radiotherapy,and the initial diagnosis was radiation-induced brain injury(RBI).After comprehensive treatment with steroid hormones,the patient’s condition rapidly improved.Typically,in nasopharyngeal carcinoma patients treated with VMAT,the incidence of RBI is extremely low when the temporal lobe dose is less than 65 Gy or 1%of the volume is less than 65 Gy.When this limit is exceeded,RBI may occur in varying degrees.However,in this case,even though the temporal lobe dose was under the prescribed limit,the patient still experienced RBI.The rare observations in this case can be used as a reference,and clinicians should seriously consider the possibility of RBI in similar cases.

Time-dependent Changes in CT of Radiation-induced Liver Injury:A Preliminary Study in Gastric Cancer Patients

In this study, the time-dependent changes on dynamic computed tomograph (CT) of radiation-induced liver injury in gastric cancer patients was examined.The CT images of 52 gastric cancer patients who had received chemoradiotherapies were reviewed on the PACS system.Dynamic CT scan was performed in all the subjects.Our results showed that 18 patients were found to have radiation-induced liver injury.The CT findings of radiation-induced liver injury in gastric cancer patients tend to show up one month after radiation treatment.The damaged area was of low density on all three phases, and then it was enhanced on portal vein phase or delay phase.The focal radiation reaction of liver without basic disease vanished 9-11 months later after treatment.We are led to conclude that dynamic CT is of help in the diagnosis of CRT-induced liver injury, and it may be the method of choice for following up the whole course of the CRT-induced liver injury, i.e., form hepatic damage to healing.The classification of CT findings we recommend can avoid the influence of technological factors, and thereby serve as a better guide for treatment of CRT-induced liver injury.

Prevention and treatment of radiation-induced lung injury by hydroxypiperquin phosphate: a clinical and experimental study

Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs.

Tacrolimus may play a role in dermatitis and radiation-induced skin injury through cellular senescence

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects,resulting in radiation-induced skin injury(RSI).Premature cellular senescence,caused by oxidative stress and/or DNA damage from chemical or physical agents,leads to the decrease of cellular proliferation and physiological function.Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury.Atopic dermatitis and RSI have similar inflammatory symptoms.The treatment of tacrolimus(TAC)in atopic dermatitis may be associated with premature cellular senescence.TAC can prevent the onset of cellular senes-cence by inactivating the p38 mitogen-activated protein kinase(p38 MAPK).The activation of p38 MAPK can induce the senescence-associated secretory phenotype(SASP)by enhancing the transcriptional activity of nuclear factor kappa-B(NF-κB),which ultimately leads to premature cellular senescence.FK506 binding protein 51(FKBP51)exhibits resistance to ionizing radiation,but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study.This review discusses the mechanism of cellular senes-cence in RSI and the role of TAC in both dermatitis and RSI.

硒代蛋氨酸对黄曲霉毒素B_(1)致兔脾脏损伤的保护作用

【目的】旨在探究硒代蛋氨酸(selenomethionine,SeMet)对黄曲霉毒素B_(1)(aflatoxin B_(1),AFB_(1))致家兔脾脏损伤的保护作用。【方法】选取50只35日龄家兔,随机分为5组,每组10只,分别为对照组(基础饲粮)、模型组(0.3 mg/kg BW AFB_(1)+基础饲粮)、Se-1组(0.2 mg/kg SeMet+0.3 mg/kg BW AFB_(1)+基础饲粮)、Se-2组(0.4 mg/kg SeMet+0.3 mg/kg BW AFB_(1)+基础饲粮)、Se-3组(0.6 mg/kg SeMet+0.3 mg/kg BW AFB_(1)+基础饲粮),试验期共21 d。试验结束后取脾脏,通过HE染色观察脾脏组织形态学变化、免疫组化染色观察PCNA蛋白表达量和TUNEL染色观察细胞凋亡率,并检测脾脏组织中氧化应激水平和炎性因子的含量。【结果】与对照组相比,模型组家兔脾脏可见红髓与白髓排列紊乱,淋巴细胞数量明显减少,PCNA蛋白的表达降低并出现大量凋亡细胞。与模型组相比,饲料中添加SeMet可明显改善家兔AFB_(1)中毒引起的脾脏病理损伤;同时提高了脾脏组织中总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性(P<0.01),降低了丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和IL-1β含量(P<0.01),有效缓解了AFB_(1)中毒引起的氧化应激和炎症反应。【结论】饲料中添加SeMet可以通过提高抗氧化酶的活性,降低炎性因子的表达,有效改善AFB_(1)引起的家兔脾脏损伤。其中以0.2 mg/kg SeMet的缓解效果最佳。

国医大师韩明向基于“内伤脾胃,百病由生”理论论治慢性咳嗽

基于“内伤脾胃,百病由生”理论论述国医大师韩明向治疗慢性咳嗽的临床经验。韩明向教授认为,慢性咳嗽的病因较为复杂,内伤脾胃与慢性咳嗽的发病有着密切的联系,“肺脾亏虚是内因,痰、瘀贯穿始终”为主要矛盾,肺脾失调为慢性咳嗽的重要因素。因此,韩明向教授在慢性咳嗽治疗上不局限于肺,运用“培土生金”这一核心治法,肺脾同治,灵活用药,多脏腑施治,疗效可观,结合验案进一步佐证。

基于“双枢同调”论柴平汤在内伤杂病中的应用

“百病生于气”,气机的升降出入不畅往往是内伤杂病产生的关键,其中脾胃为三焦升降之枢纽,少阳为内外阴阳出入之枢纽,基于肝脾二者在生克五行和中土五行中存在相生相克的复杂关系,应用“双枢同调”的治疗原则,以柴平汤加减治疗内伤杂病,疏肝健脾,调畅人体气机,恢复人体阴平阳秘,对于临床上多种内伤杂病的治疗具有较好疗效。

健脾清化方改善局灶节段性肾小球硬化的效应机制研究

目的:探讨健脾清化方对局灶节段性肾小球硬化(FSGS)小鼠及阿霉素诱导足细胞损伤的保护作用,并观察其对炎症反应、氧化应激及细胞凋亡的影响。方法:(1)体内实验:实验组balb/c小鼠,采用单次尾静脉注射阿霉素(10.5 mg/kg)的方法建立FSGS动物模型,造模后连续灌胃给药6周。测定24 h尿蛋白(定量)、血肌酐,及肾组织内超氧化物歧酶、丙二醛、过氧化氢酶的水平。并采用H&E、Masson、PAS染色,观察肾组织病理损伤程度。透射电镜观察肾脏超微结构。免疫荧光nephrine/p-JAK2双染观察足细胞上p-JAK2的表达。免疫印迹法检测(western blotting,WB)肾组织中p-JAK2/JAK2、p-STAT3/STAT3、TGF-β1蛋白表达水平。(2)体外实验:实验1:采用CCK-8法检测阿霉素及健脾清化方对细胞活力的影响,并筛选出造模和健脾清化方干预浓度。DCFH-DA荧光探针检测各组足细胞ROS的含量。流式细胞术测定足细胞凋亡情况。WB检测p-JAK2/JAK2、p-STAT3/STAT3、TGF-β1的蛋白表达水平以及RT-qPCR检测STAT3下游凋亡因子BAX、BAD、Caspase3、p21、Blc-2、和炎症因子IL-6、IL-1β、TNF-α的mRNA表达情况。实验2:WB检测JAK2激动剂C-A1对p-JAK2/JAK2,p-STAT3/STAT3蛋白表达的影响。结果:(1)体内实验:与对照组相比,模型组小鼠肾小球硬化,足细胞足突广泛融合,肾组织p-JAK2荧光表达明显增加。24 h尿蛋白定量、血肌酐、MDA升高,SOD、CAT降低(P<0.05)。p-JAK2/JAK2、p-STAT3/STAT3、TGF-β1表达升高。与模型组相比健脾清化方干预后足细胞损伤缓解,肾组织P-JAK2荧光表达降低,24 h尿蛋白定量、血肌酐、MDA降低,SOD、CAT升高。p-JAK2/JAK2、p-STAT3/STAT3、TGF-β1表达降低(P<0.05)。(2)体外实验:实验1:CCK-8法确定阿霉素造模浓度为0.4μg/mL,健脾清化方干预低中高浓度分别为1 mg/mL,2 mg/mL,4 mg/mL。与对照组比较,模型组凋亡细胞数量、ROS含量增多,p-JAK2/JAK2、p-STAT3/STAT3、TGF-β1蛋白表达升高(P<0.05),BAX、BAD、Caspase3、p21、IL-6、TNF-α、IL-1β的mRNA表达降低,Blc-2 mRNA表达升高(P<0.05),与模型组比较,健脾清化方干预后,凋亡细胞数量、ROS含量减少,JAK2/STAT3、TGF-β1蛋白表达降低,BAX、BAD、Caspase3、p21、IL-6、TNF-α、IL-1β的mRNA表达升高,Blc-2的mRNA表达降低,且成量效关系(P<0.05)。实验2:与对照组相比,C-A1组p-JAK2/JAK2蛋白表达升高(P<0.05),与ADR+H组相比,ADR+H+C-A1组p-STAT3/STAT3蛋白表达升高(P<0.05)。结论:健脾清化方可通过抑制JAK2/STAT3信号通路,调节炎症反应、细胞凋亡、氧化应激从而延缓FSGS足细胞损伤的进展。

高原腹部创伤对猪免疫器官的影响

为探究高原腹部创伤对免疫器官的影响,该研究选取33只长白仔猪,随机分为平原腹部创伤组(LN组)和高原腹部创伤组(HC组),每组按0、8、24 h时间点采集脾脏、胸腺、肠系膜淋巴结组织样品,并制作脾脏和胸腺组织切片,HE染后观察组织结构变化。结果表明,腹部创伤后猪免疫器官脾脏、胸腺和肠系膜淋巴结有间质毛细血管扩张充血、淋巴细胞数量减少等病理变化。

基于“脾胃内伤,百病由生”调节肠道菌群改善支气管扩张反复发作的思路探讨

支气管扩张症,从中医角度来说可归类于“咳嗽”“肺痈”“血证”等范畴,临床表现为咳嗽、咳大量脓痰及反复咯血,分为急性加重期和稳定期。笔者通过探讨“脾胃内伤,百病由生”的理论内涵,探究肠道菌群与支气管扩张反复发作的联系,得出支气管扩张的根本病机是脾胃亏虚、元气不足,病位在肺,与脾胃密切相关,为达治病求本之效,治法上以补脾益胃为主、升阳泻火为辅,同时佐以祛湿之品,以期为临床治疗支气管扩张拓宽新的思路。

基于万全“亦有诸般不可攻”理论探讨小儿功能性便秘的辨治策略

功能性便秘是小儿时期常见胃肠道疾患,全球小儿功能性便秘患病率为0.5%~32.2%,严重影响患儿生活质量。万全为我国古代著名儿科医家,其创新性地提出小儿“脾常不足”等五脏有余不足思想,临证注重调理脾胃,对现代小儿疾病的诊疗具有重要指导作用。万全在《育婴家秘·卷之四·大小便病》中提出了小儿便秘的治疗总原则:“大便鞕结须宜下,亦有诸般不可攻。”基于万全“脾常不足”“大便鞕结须宜下,亦有诸般不可攻”的小儿便秘辨治理论,结合近现代研究,认为小儿功能性便秘病因多归于燥热内结、乳食积滞、脾虚不运、气机郁滞和血虚肠燥,病机关键为脾虚食伤。据此提出小儿功能性便秘临证治疗应明辨虚实,将运脾助通贯穿于治疗始终,分别从急下、消导、缓下、顺气、辛润等方面探讨小儿功能性便秘的辨治策略,以期为小儿功能性便秘的临床诊疗及调护提供参考。

Proteomic analysis of acute radiation-induced rectal injury in rats

Objective:To comprehensively elucidate overall protein alterations associated with acute radiation-induced rectal injury in rats.Methods:A rat model of acute radiation-induced rectal injury was established by irradiating rectal segments with a single dose of 17.5 Gy X-rays.These segments were then collected at 7 d and 10 d post-irradiation.Tandem mass tag-based quantitative proteomic analysis was then performed.Results:65,526 peptides were identified,corresponding to 8,088 proteins.Hematoxylin-eosin staining revealed characteristic epithelial cell degeneration and necrosis,intestinal gland atrophy and dilatation,and interstitial inflammatory cell infiltration.Inflammation was more pronounced in the 10 d irradiation group than in the 7 d irradiation group.Overall,127 up-and 108 downregulated proteins were identified at 7 d post-irradiation,and 122 up-and 44 downregulated proteins were identified at 10 d post-irradiation.Notably,17 up-and 6 downregulated proteins were consistently co-expressed at both time points.The expression of three of these proteins was validated via real-time quantitative PCR:polypeptide YY(Pyy),thymidylate synthase(Tyms),and tetraspanin(CD9).Tyms transcript levels were significantly higher in irradiated rectal tissues(P<0.05).Pyy transcript levels were significantly higher at both time points(P<0.05).Finally,CD9 mRNA expression was significantly lower in both the 7 d and 10 d irradiation groups(P<0.05).Conclusions:The potential targets were found to prevent and treat acute radiation-induced rectal injury in clinical practice.

Evaluating a novel protective agent against radiation-induced acute intestinal injury

Objective:To develop and synthesize a novel derivative of ethyl pyruvate,named TZC02,and investigate its radioprotective effects against ionizing radiation(IR)-induced intestinal injury in mice.Methods:Male C57BL/6J mice weighing(20±2)g in the survival experiment were randomly divided into five groups(n=10 in each):control group,IR group,IR+TZC02(50 mg/kg)group,IR+TZC02(100 mg/kg)group,and IR+TZC02(200 mg/kg)group.Mice's survival rates were monitored for 7 d.In other experiments,the male mice were randomly divided into three groups(n=5 per group):control group,IR group,and IR+TZC02(100 mg/kg)group.TZC02 was intragastrically administered 1 h before 12 Gy abdominalγ-ray irradiation(ABI)and 24 h,48 h after irradiation,respectively.Three days after IR exposure,small intestinal tissues were collected and the number of small intestinal crypts was determined using hematoxylin&eosin(H&E)staining.Immunohistochemical analysis was used to assess the regenerative capacity of the small intestine(SI)and radiation-induced damage,stemness markers or DNA repair surrogates,including Ki67,lysozyme,and villus.The expressions of histone H2AX phosphorylation(γH2AX)and caspase-3 were evaluated through immunofluorescence analyses.Additionally,in vitro cultured small intestinal organoids were employed to investigate the effects of TZC02 on SI regeneration after irradiation.Results:The administration of TZC02 significantly improved the 7 d-survival rate of mice exposed to 12 Gy ABI(P<0.05).Compared to the IR group,TZC02 treatment attenuated the decrease of SI Ki67-positive cells[(59.60±6.33)vs.(37.70±7.82),t=11.89,P<0.0001]and Paneth cells[(9.90±1.37)vs.(5.50±1.71),t=6.02,P<0.001]in five crypts,and reduced structural damage to the SI[villus height,(349.49±60.17)μm vs.(294.72±40.09)μm;t=3.39;P<0.05].TZC02 also significantly decreased the crypt apoptosis detected by caspase-3[(10.75±1.26)vs.(29.83±2.56),t=13.39,P<0.0001]and DNA damage detected by gH2AX[(10.40±1.14)vs.(29.60±2.70),t=10.13,P<0.0001].The organoid survival 7 d post-irradiation further confirmed the protective effects of TZC02(area of organoids,(0.119±0.081)mm^(2)vs.(0.080±0.037)mm^(2);t=2.30;P<0.05).Conclusions:This study demonstrate that TZC02 can offer effective protection against IR-induced intestinal injury,suggesting its potential as a promising protective compound for patients treated with radiotherapy.

柳氮磺胺吡啶联合脆弱拟杆菌治疗对溃疡性结肠炎小鼠脾脏中Treg比例的影响

目的:探究柳氮磺胺吡啶联合脆弱拟杆菌治疗对溃疡性结肠炎小鼠脾脏中Treg比例的影响。方法:研究时间为2020年1月1日至2022年12月31日,选取32只BALB/c小鼠作为本研究的实验对象,按照不同处理方法分为对照组、模型组、单纯治疗组、联合组(柳氮磺胺吡啶联合脆弱拟杆菌),各8只。对照组不做处理,模型组、单纯治疗组、联合组均使用葡萄糖硫酸钠盐制作慢性溃疡性结肠炎小鼠。模型组实施建模,单纯治疗组在模型组的基础上每天给予柳氮磺胺吡啶治疗,联合组在建模的基础上每天同时给予柳氮磺胺吡啶、脆弱拟杆菌治疗。治疗7周后处死小鼠,取出小鼠的结肠组织进行检测,并对比4组疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)、结肠组织A20蛋白表达量及脾脏组织Treg比例。结果:与对照组相比,模型组DAI评分、CMDI评分均升高,且A20蛋白相对表达量与Treg比例均降低;与模型组对比,单纯治疗组DAI评分、CMDI评分均降低,且A20蛋白相对表达量与Treg比例均升高;与单纯治疗组对比,联合组DAI、CMDI评分显著降低,且A20蛋白相对表达量与Treg比例均升高。结论:在溃疡性结肠炎小鼠的研究中发现,使用柳氮磺胺吡啶、脆弱拟杆菌治疗具有较高的效果,可以有效改善小鼠的脾脏组织中Treg比例。