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Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Neural Regeneration Research 2024年第7期19卷 1608-1617页

作者： Yanan Dou Xiaowei Fei Xin He Yu Huan Jialiang Wei Xiuquan Wu Weihao Lyu Zhou Fei Xia Li Fei Fei Department of Neurosurgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual *** is repo rted to play a protective role in neuroinflammation in the ***,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain *** our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion *** in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller *** found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion ***,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte *** opposite results we re observed with Homerla ove ***,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion *** together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

关键词： caspase-8 Homer1a interleukin-18 interleukin-1β intraocular pressure ischemia/reperfusion injury JSH-23 Müller cells NLRP3 nuclear factor-kB p65 retina

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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang Department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion *** mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion ***,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic *** explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,*** bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting *** between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in *** data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory ***

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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Clinicopathological analysis of small intestinal metastasis from extra-abdominal/extra-pelvic malignancy

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4138-4145页

作者： Zhi Zhang Jing Liu Peng-Fei Yu Hai-Rui Yang Jin-Yang Li Zhi-Wei Dong Wei Shi Guo-Li Gu Department of general Surgery Anhui Medical University First Affiliated HospitalHefei 230002Anhui ProvinceChina Department of general Surgery Air Force Clinical CollegeChina Medical UniversityBeijing 100142China Department of general Surgery Air Force Medical CenterAir Force Clinical College of China Medical UniversityBeijing 100142China Department of general Surgery Air Force Medical CenterChinese People’s Liberation ArmyFifth Clinical(Air Force Clinical College)of China Medical UniversityBeijing 100142China Department of general Surgery Beijing Changping HospitalBeijing 102200China Department of general Surgery Air Force Medical CenterBeijing 100142China

BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely ***,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its ***,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and *** To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small *** The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the air force Medical Center,Chinese People’s Liberation *** descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and *** Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular *** median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 *** small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstr

关键词： Small intestinal Metastases Clinicopathological features Prognostic analysis Malignancy

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Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis

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Neural Regeneration Research 2024年第3期19卷 642-649页

作者： Xiuling Tang Tao Yan Saiying Wang Qingqing Liu Qi Yang Yongqiang Zhang Yujiao Li Yumei Wu Shuibing Liu Yulong Ma Le Yang Precision Pharmacy&Drug Development Center Department of PharmacyTangdu HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Clinical Pharmacy Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina Department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The First Medical Center of Chinese PLA General HospitalBeijingChina Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreAir Force Medical UniversityXi’anShaanxi ProvinceChina

β-Sitosterol is a type of phytosterol that occurs naturally in *** studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic *** we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced *** investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic *** addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its *** conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.

关键词： apoptosis blood-brain barrier β-sitosterol cerebral ischemia/reperfusion injury cholesterol overload cholesterol transport endoplasmic reticulum stress ischemic stroke molecular docking NPC1L1

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Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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Zoological Research 2024年第3期45卷 663-678页

作者： Li-Rong Liang Bing Liu Shu-Hui Cao You-Yi Zhao Tian Zeng Mei-Ting Zhai Ze Fan Dan-Yi He San-Xin Ma Xiao-Tong Shi Yao Zhang Hui Zhang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of AnesthesiologySchool of StomatologyAir Force Medical UniversityXi’anShaanxi 710032China Department of Anesthesiology 986th Air Force HospitalAir Force Medical UniversityXi’anShaanxi 710032China

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive ***,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive ***,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly *** this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal *** neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral *** indicated that ADNP was significantly down-regulated following developmental exposure to *** adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine ***,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane ***-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by *** analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic *** of Wnt signaling was restored in the davunetide-treated ***,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general *** study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity

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BTF3L4 Overexpression Mediates APAP-induced Liver Injury in Mouse and Cellular Models

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Journal of Clinical and Translational Hepatology 2024年第3期12卷 245-256页

作者： Junchao Lin Aqiang Fan Zhujin Yifu Qibing Xie Liu Hong Wei Zhou State Key Laboratory of Cancer Biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi’anShaanxiChina Department of Digestive Surgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxiChina

Background and Aims:Acetaminophen(APAP)-induced liver injury(AILI)has an increasing incidence ***,the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently *** study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in ***:We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4(BTF3L4)was the only outlier transcription factor overexpressed in the AILI model in ***3L4 overexpression increased the degree of liver injury in the AILI ***:BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial *** BTF3L4 expression increases the degree of apoptosis,reactive oxygen species generation,and oxidative stress,which induces cell death and liver *** damage of mitochondrial function by BTF3L4 triggers a cascade of events,including reactive oxygen species accumulation and oxidative *** to the available AILI data,BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of ***:Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.

关键词： BTF3L4 APAP-induced liver injury Apoptosis Mitochondrial morphology Inflammation

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Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation

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Journal of Geriatric Cardiology 2024年第2期21卷 200-210页

作者： Qing YAN Jia-Qi LIANG Yi-De YUAN Yuan LI Jia-Li FAN Wen-Huan WU Pan XU Jia-Hong XUE Department of Cardiovascular Medicine the Second Affiliated Hospital of Xi’an Jiaotong UniversityShaanxiChina Department of Cardiovascular Medicine Zichang People’s HospitalShaanxiChina Department of Ultrasound Xijing HospitalAir Force Military Medical UniversityShaanxiChina

BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin *** study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the Second Affiliated hospital of Xi'an Jiaotong University were included in this *** participants were grouped based on cumulative TyG index values tertiles within 3 months after *** regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF *** predictive value of all risk factors was assessed by receiver operating curve *** There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values *** adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index *** restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index *** considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after *** longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

关键词： atrial fibrillation index

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Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang Department of general Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina Department of general Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of general Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina Department of general Surgery Tianjin Medical University General HospitalTianjinChina Department of Anorectal Tianjin People's HospitalTianjinChina Department of Radiology Beijing Friendship hospital Capital Medical UniversityBeijingChina Department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Thoracic Surgery/Institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

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In vivo imaging of the neuronal response to spinal cord injury:a narrative review

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Neural Regeneration Research 2024年第4期19卷 811-817页

作者： Junhao Deng Chang Sun Ying Zheng Jianpeng Gao Xiang Cui Yu Wang Licheng Zhang Peifu Tang Department of Orthopedics The Fourth Medical Center of Chinese PLA General Hospital National Clinical Research Center for Orthopedics Sports Medicine and Rehabilitation School of Life Sciences Tsinghua University Department of Orthopedics Air Force Medical CenterPLA Medical School of Chinese PLA Institute of Orthopedics The First Medical CenterChinese PLA General Hospital Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are *** in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and *** review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to *** then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience ***,we identify the challenges and possible solutions for spinal cord neuron imaging.

关键词： anterior horn neurons calcium imaging central nervous system dorsal horn neurons dorsal root ganglion in vivo imaging neuronal response spinal cord injury spinal cord two-photon microscopy

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Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

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International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu Xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi Department of Radiation Oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China Department of Oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China Department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China School of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration ***,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet *** system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： X-ray excited photodynamic therapy singlet oxygen low dose X-Ray irradiation efficient antitumor therapy anti-tumor immunity

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