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 irradiat...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.展开更多
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 derivati...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.展开更多
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 li...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.展开更多
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 irradiatio...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.展开更多
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-...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.展开更多
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 treatme...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.展开更多
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 t...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.展开更多
BACKGROUND The incidence of rectal cancer is increasing worldwide,and surgery remains the primary treatment modality.With the advent of total mesorectal excision(TME)technique,the probability of tumor recurrence post-...BACKGROUND The incidence of rectal cancer is increasing worldwide,and surgery remains the primary treatment modality.With the advent of total mesorectal excision(TME)technique,the probability of tumor recurrence post-surgery has significantly decreased.Surgeons'focus has gradually shifted towards minimizing the impact of surgery on urinary and sexual functions.Among these concerns,the optimal dissection of the rectal lateral ligaments and preservation of the pelvic floor neuro-vascular bundle have become critical.To explore the optimal surgical technique for TME and establish a standardized surgical protocol to minimize the impact on urinary and sexual functions,we propose the eight-zone dissection strategy for pelvic floor anatomy.AIM To compare the differences in surgical specimen integrity and postoperative quality of life satisfaction between the traditional pelvic floor dissection strategy and the innovative eight-zone dissection strategy.METHODS We analyzed the perioperative data of patients who underwent laparoscopic radical resection of rectal cancer at Qilu Hospital of Shandong University between January 1,2021 and December 1,2023.This study included a total of 218 patients undergoing laparoscopic radical surgery for rectal cancer,among whom 109 patients underwent traditional pelvic floor dissection strategy,and 109 patients received the eight-zone dissection strategy.RESULTS There were no significant differences in general characteristics between the two groups.Patients in the eight-zone dissection group had higher postoperative specimen integrity(88.1%vs 78.0%,P=0.047).At the 3-month followup,patients in the eight-zone surgery group had better scores in urinary issues(6.8±3.3 vs 5.3±2.5,P=0.045)and male sexual desire(2.2±0.6 vs 2.5±0.5,P=0.047)compared to the traditional surgery strategy group.CONCLUSION This study demonstrates that the eight-zone dissection strategy for laparoscopic lateral ligament dissection of rectal cancer is safe and effective.Compared with the traditional pelvic floor dissection strategy,this approach can reduce the risk of nerve injury and minimize the impact on urinary and sexual functions.Therefore,we recommend the clinical application of this strategy to better serve patients with rectal cancer.展开更多
BACKGROUND Benign rectal strictures can be categorized as primary(disease-related)and secondary(surgical anastomosis-related).Secondary strictures arise from surgical complications,whereas primary strictures have dive...BACKGROUND Benign rectal strictures can be categorized as primary(disease-related)and secondary(surgical anastomosis-related).Secondary strictures arise from surgical complications,whereas primary strictures have diverse etiologies,including various inflammatory conditions.Benign strictures are usually managed by surgery and endoscopy.We present an unusual etiology of benign rectal stricture caused by the repeated insertion of foreign objects into the rectum for sexual purposes,resulting in rectal injury and subsequent chronic inflammation.CASE SUMMARY A 53-year-old man presented to the outpatient clinic of the Colorectal Surgery Department with symptoms of chronic constipation and bloody stools.The patient previously experienced rectal injury due to foreign object insertion for sexual purposes.Colonoscopy revealed benign circumferential narrowing of the rectum.He underwent treatment by endoscopic argon plasma coagulation and balloon dilation and follow-up as an outpatient for 4 months.A colonoscopy at the end of the follow-up period revealed no evidence of rectal stricture relapse.CONCLUSION A history of rectal injury,followed by chronic inflammation,should be considered in patients with benign rectal strictures.Management with endoscopic argon plasma coagulation and balloon dilation can prevent the need for surgical resection of benign rectal strictures.展开更多
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 chemo...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.展开更多
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 ...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.展开更多
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 fro...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.展开更多
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 m...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.展开更多
Background:Few studies on anastomotic condition after rectal-cancer resection and its effect on anastomotic leakage(AL)are available up to now.This study aimed to investigate potential radiation-induced injury left on...Background:Few studies on anastomotic condition after rectal-cancer resection and its effect on anastomotic leakage(AL)are available up to now.This study aimed to investigate potential radiation-induced injury left on surgical margins of anterior resection after neoadjuvant chemoradiotherapy(nCRT)and its association with AL.Methods:We retrospectively identified 161 consecutive patients who underwent anterior resection with nCRT,neoadjuvant chemotherapy without radiation(nCT)or no neoadjuvant therapy between 2014 and 2015.Tissue samples of resection margins were assessed using a specific histopathological score and microvessel density in submucosa.Propensity score matching was used to balance the baseline characteristics.Association between AL and histopathological features was analysed.Results:AL occurred in 13 of 54 patients undergoing nCRT,5 of 48 patients undergoing nCT and 7 of 59 patients without neoadjuvant therapy.Comparisons after matching showed median(range)histopathological scores as follows:3(0–8)vs 0(0–3)vs 0(0–2)for the proximal margin(P<0.001);4(2–9)vs 0(0–4)vs 0(0–3)for the distal margin(P<0.001).Correspondingly,mean(SD)microvessel densities were as follows:21.7(7.9)vs 27.2(8.6)vs 27.3(9.4)for the proximal margin(P=0.003);18.1(9.3)vs 25.2(12.9)vs 24.9(7.4)for the distal margin(P<0.001).Among patients undergoing nCRT,AL was associated with increased histopathological score(P=0.003)and decreased microvessel density(P=0.004)on the proximal margin.Conclusions:Surgical margins of rectal-cancer resection are exposed to certain radiation-induced injury after nCRT.AL is associated with aggravated radiation damage on the proximal margin.展开更多
We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver...We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury,and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa,from the rectum to the anus,and this is the first description of a case that developed a severe liver disorder after this treatment; hence,an analysis of future cases as they accumulate is desirable.展开更多
Dear Editor,Rhabdomyolysis(RM)is a pathophysiological process in which creatine kinase and myoglobin from skeletal muscle cells are released into circulation,leading to lethal acute kidney injury(AKI),hypovolemic shoc...Dear Editor,Rhabdomyolysis(RM)is a pathophysiological process in which creatine kinase and myoglobin from skeletal muscle cells are released into circulation,leading to lethal acute kidney injury(AKI),hypovolemic shock,electrolyte disturbances and disseminated intravascular coagulation.Although injuries were the first reported and best-known reason for RM,infection currently contributes to approximately 5%of RM[1,2].展开更多
Objective: The aim of our study was to examine whether irradiation combined with pemetrexed can exacerbate pulmonary injury. Methods: Two groups of male Wister Rats were subjected to bilateral apex of lungs irradiatio...Objective: The aim of our study was to examine whether irradiation combined with pemetrexed can exacerbate pulmonary injury. Methods: Two groups of male Wister Rats were subjected to bilateral apex of lungs irradiation(a single dose of 12 Gy), with or without pemetrexed(20 mg/kg) by intraperitoneal injection at the same time; a third group of weightand age- matched animals were treated with pemetrexed alone, as the same dose scheme, time and root of injection. The fourth group served as control. The whole lung mounts were dissected to histological evaluation, while serum cytokine transforming growth factor-β1(TGF-β1) analysis were compared at 1, 7, 21, 35, 49 days post-irradiation after irradiation. Results: Histological examination showed a thickening of alveolar septal, accumulation of inflammatory cells. The irradiation treatment group and the radiation-chemo treatment group showed a statistically significant higher level of TGF-β1(P < 0.05) than other two groups, but there were no differences between these two irradiation groups. Conclusion: These results demonstrated that pemetrexed can not aggravate pulmonary injury and it could be safely used in concurrent or sequential radio-chemotherapy in lung adenocarcinoma.展开更多
基金supported by the Wuxi Taihu Talent Plan for excellent medical expert teams(No.2021-9)the Key Research&Development Program of Jiangsu Province(no.BE2020637)+1 种基金the Military Logistics Research Program(No.BKJ18J003)the Young Talent Program of China National Nuclear Corporation and the Program for Innovative Research of Xuzhou Medical University(No.XYFC2020002),China.
文摘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.
基金supported by the National Natural Science Foundation of China,No.82002400(to GJZ)Scientific Research Project of Hu nan Health Committee,No.20201911and No.20200469(both to ZJX)+2 种基金Scientific Research Project of Hunan Health Committee,No.20211411761(to HMW)the Natural Science Foundation of Hunan Province,No.2020JJ5512(to GJZ)a grant from Clinical Medical Technology Innovation Guidance Project in Hunan Province,No.2020SK51822(to ZJX)。
文摘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.
基金supported by the Natural Science Foundation of Anhui Province (No.2208085MA13)Wu Je Ping Medical Foundation (No.320.6750.2020-10-40)the Key Research and Development Program of Anhui Province (No.202004J07020052)。
文摘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.
文摘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.
基金Supported by grants from the Fundamental Research for South-Central University for Nationalities(No.PJS140011604)Chen Xiaoping Foundation Development of Science and Technology of Hubei(No.CXPJJH11800004-015)
文摘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.
基金Supported by:the National Natural Science Foundation of China,No.30870750the Doctor Priming Program of Natural Foundation of Guangdong Province,No. 8451008901000672+1 种基金the Medical Scientific Research Foundation Program of Guangdong Province,No. B2008044the Youth Teacher Foundation Program of Sun Yat-sen University, No,3177915
文摘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.
基金Supported by grants from the Sichuan Medical Research Youth Innovation Project(No.Q18031)the 2018 City School Strategic Cooperation Research Project(No.18SXHZ0542)。
文摘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.
文摘BACKGROUND The incidence of rectal cancer is increasing worldwide,and surgery remains the primary treatment modality.With the advent of total mesorectal excision(TME)technique,the probability of tumor recurrence post-surgery has significantly decreased.Surgeons'focus has gradually shifted towards minimizing the impact of surgery on urinary and sexual functions.Among these concerns,the optimal dissection of the rectal lateral ligaments and preservation of the pelvic floor neuro-vascular bundle have become critical.To explore the optimal surgical technique for TME and establish a standardized surgical protocol to minimize the impact on urinary and sexual functions,we propose the eight-zone dissection strategy for pelvic floor anatomy.AIM To compare the differences in surgical specimen integrity and postoperative quality of life satisfaction between the traditional pelvic floor dissection strategy and the innovative eight-zone dissection strategy.METHODS We analyzed the perioperative data of patients who underwent laparoscopic radical resection of rectal cancer at Qilu Hospital of Shandong University between January 1,2021 and December 1,2023.This study included a total of 218 patients undergoing laparoscopic radical surgery for rectal cancer,among whom 109 patients underwent traditional pelvic floor dissection strategy,and 109 patients received the eight-zone dissection strategy.RESULTS There were no significant differences in general characteristics between the two groups.Patients in the eight-zone dissection group had higher postoperative specimen integrity(88.1%vs 78.0%,P=0.047).At the 3-month followup,patients in the eight-zone surgery group had better scores in urinary issues(6.8±3.3 vs 5.3±2.5,P=0.045)and male sexual desire(2.2±0.6 vs 2.5±0.5,P=0.047)compared to the traditional surgery strategy group.CONCLUSION This study demonstrates that the eight-zone dissection strategy for laparoscopic lateral ligament dissection of rectal cancer is safe and effective.Compared with the traditional pelvic floor dissection strategy,this approach can reduce the risk of nerve injury and minimize the impact on urinary and sexual functions.Therefore,we recommend the clinical application of this strategy to better serve patients with rectal cancer.
文摘BACKGROUND Benign rectal strictures can be categorized as primary(disease-related)and secondary(surgical anastomosis-related).Secondary strictures arise from surgical complications,whereas primary strictures have diverse etiologies,including various inflammatory conditions.Benign strictures are usually managed by surgery and endoscopy.We present an unusual etiology of benign rectal stricture caused by the repeated insertion of foreign objects into the rectum for sexual purposes,resulting in rectal injury and subsequent chronic inflammation.CASE SUMMARY A 53-year-old man presented to the outpatient clinic of the Colorectal Surgery Department with symptoms of chronic constipation and bloody stools.The patient previously experienced rectal injury due to foreign object insertion for sexual purposes.Colonoscopy revealed benign circumferential narrowing of the rectum.He underwent treatment by endoscopic argon plasma coagulation and balloon dilation and follow-up as an outpatient for 4 months.A colonoscopy at the end of the follow-up period revealed no evidence of rectal stricture relapse.CONCLUSION A history of rectal injury,followed by chronic inflammation,should be considered in patients with benign rectal strictures.Management with endoscopic argon plasma coagulation and balloon dilation can prevent the need for surgical resection of benign rectal strictures.
文摘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.
文摘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.
基金supported by the Beijing Municipal Natural Science Foundation(7202139 and 7162137),China.
文摘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.
基金funded by the National Nature Science Foundation of China(81972975)the CAMS Medicine and Health Technology Innovation Project(2021-I2M-1-060,2021-RC310-010)+1 种基金the Major Program of Applied Basic Research Projects of Tianjin(22JCZDJC00430)the Natural Science Foundation of Tianjin City(20JCYBJC00250),China.
文摘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.
基金This work was supported by Sun Yat-sen University Clinical Research 5010 Program(grant numbers 2017008)National Natural Science Foundation of China(grant numbers 81573078).
文摘Background:Few studies on anastomotic condition after rectal-cancer resection and its effect on anastomotic leakage(AL)are available up to now.This study aimed to investigate potential radiation-induced injury left on surgical margins of anterior resection after neoadjuvant chemoradiotherapy(nCRT)and its association with AL.Methods:We retrospectively identified 161 consecutive patients who underwent anterior resection with nCRT,neoadjuvant chemotherapy without radiation(nCT)or no neoadjuvant therapy between 2014 and 2015.Tissue samples of resection margins were assessed using a specific histopathological score and microvessel density in submucosa.Propensity score matching was used to balance the baseline characteristics.Association between AL and histopathological features was analysed.Results:AL occurred in 13 of 54 patients undergoing nCRT,5 of 48 patients undergoing nCT and 7 of 59 patients without neoadjuvant therapy.Comparisons after matching showed median(range)histopathological scores as follows:3(0–8)vs 0(0–3)vs 0(0–2)for the proximal margin(P<0.001);4(2–9)vs 0(0–4)vs 0(0–3)for the distal margin(P<0.001).Correspondingly,mean(SD)microvessel densities were as follows:21.7(7.9)vs 27.2(8.6)vs 27.3(9.4)for the proximal margin(P=0.003);18.1(9.3)vs 25.2(12.9)vs 24.9(7.4)for the distal margin(P<0.001).Among patients undergoing nCRT,AL was associated with increased histopathological score(P=0.003)and decreased microvessel density(P=0.004)on the proximal margin.Conclusions:Surgical margins of rectal-cancer resection are exposed to certain radiation-induced injury after nCRT.AL is associated with aggravated radiation damage on the proximal margin.
文摘We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury,and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa,from the rectum to the anus,and this is the first description of a case that developed a severe liver disorder after this treatment; hence,an analysis of future cases as they accumulate is desirable.
基金This study is supported by the Science and Technology Planning Project of Guangdong Province,China(No.2016A020215235).
文摘Dear Editor,Rhabdomyolysis(RM)is a pathophysiological process in which creatine kinase and myoglobin from skeletal muscle cells are released into circulation,leading to lethal acute kidney injury(AKI),hypovolemic shock,electrolyte disturbances and disseminated intravascular coagulation.Although injuries were the first reported and best-known reason for RM,infection currently contributes to approximately 5%of RM[1,2].
文摘Objective: The aim of our study was to examine whether irradiation combined with pemetrexed can exacerbate pulmonary injury. Methods: Two groups of male Wister Rats were subjected to bilateral apex of lungs irradiation(a single dose of 12 Gy), with or without pemetrexed(20 mg/kg) by intraperitoneal injection at the same time; a third group of weightand age- matched animals were treated with pemetrexed alone, as the same dose scheme, time and root of injection. The fourth group served as control. The whole lung mounts were dissected to histological evaluation, while serum cytokine transforming growth factor-β1(TGF-β1) analysis were compared at 1, 7, 21, 35, 49 days post-irradiation after irradiation. Results: Histological examination showed a thickening of alveolar septal, accumulation of inflammatory cells. The irradiation treatment group and the radiation-chemo treatment group showed a statistically significant higher level of TGF-β1(P < 0.05) than other two groups, but there were no differences between these two irradiation groups. Conclusion: These results demonstrated that pemetrexed can not aggravate pulmonary injury and it could be safely used in concurrent or sequential radio-chemotherapy in lung adenocarcinoma.