1.Experience in Treating Children Chronic Cough based on the Theory of Healthy Qi Deficiency and Pathogenic Qi Retention
Shuzi ZHANG ; Yiwen YU ; Qiongqiong XING ; Hang SU ; Zichao DING ; Zhenhua YUAN ; Ying DING ; Suping YU ; Xianqing REN
Journal of Traditional Chinese Medicine 2024;65(24):2589-2592
		                        		
		                        			
		                        			The main pathogenesis of chronic cough in children is the disorder of ascending and descending of qi movement caused by healthy qi deficiency and pathogenic qi retention. The deficiency of lung, spleen, and kidney is the root of the disease, and the retention of phlegm-fluid, food accumulation, and fire from constraint is the branch pathogenesis of the disease. In the treatment, we should reinforce and tonify healthy qi, dispel pathogen and regulate qi, with Yupingfeng Powder (玉屏风散) as the basic prescription. For lung qi deficiency syndrome, modified Yupingfeng Powder could be used for supplementing lung to consolidate the exterior; for lung and spleen qi deficiency syndrome, modified Yupingfeng Powder plus Shenling Baizhu Powder (参苓白术散) could be used for supplementing lung and fortifying the spleen, treating with both supplementation and transformation; for lung kidney qi deficiency syndrome, modified Yupingfeng Powder combined with Suzi Jiangqi Decoction (苏子降气汤) could be used for supplementing lung and replenishing kidneys, absorbing qi to the root. All the above prescriptions could combine the method of dispelling phlegm, promoting digestion and guiding out food stagnation, soothing the liver and draining fire to remove the solid pathogens, in order to treat the root and branch simultaneously, and the cough will stop if the ascending and descending of qi movement recover as usual. 
		                        		
		                        		
		                        		
		                        	
2.Knockdown of chemokine receptor 3 inhibits hepatoblastoma cell proliferation and migration by weakening Wnt/β-catenin signaling pathway
Dao-Kui DING ; Yu-Hang YUAN ; Yan-An LI ; Xi-Chun CUI ; He-Ying YANG ; Jia DU ; Yang-Guang SU
Chinese Pharmacological Bulletin 2024;40(12):2347-2354
		                        		
		                        			
		                        			Aim To investigate the role and mecha-nism of CXC chemokine receptor 3(CXCR3)in hepa-toblastoma(HB).Methods The expression of CX-CR3 was detected by immunohistochemical and West-ern blot in 16 cases of HB tissue and adjacent normal liver tissue.The HB cells(Huh-6 and HepT1)were transfected with Con-shRNA,CXCR3-shRNA1,and CXCR3-shRNA2,respectively,and then divided into the Con-shRNA group,CXCR3-shRNA1 group,and CXCR3-shRNA2 group.Cell proliferation was detected by CCK-8 assay and EdU staining.Cell migration and invasion were detected by scratch and Transwell as-says.The expressions of β-catenin,c-Myc,cyclin D1,MMP-7 and MMP-9 were detected by Western blot.The tumor formation and tumor volume in each group were assessed using nude mouse xenograft tumor model,while the expressions of MMP-9 and Ki67 in tumor tissue were examined by immunohistochemistry.Results The expression of CXCR3 was up-regulated in HB tissue(P<0.01).Compared to the Con-shR-NA group,the viability,proliferation,migration and invasion of Huh-6 and HepT1 cells in the CXCR3-shR-NA1 and CXCR3-shRNA2 groups were reduced(P<0.01),the expressions of the Wnt/β-catenin signaling pathway related proteins were attenuated(P<0.01),the tumor grew slowly and the volume was significantly reduced(P<0.01),and the expressions of MMP-9 and Ki67 in tumor tissue decreased(P<0.01).Con-clusions Downregulation of CXCR3 hinders the pro-liferation and migration of HB cells,potentially as-cribed to the attenuation of Wnt/β-catenin signaling regulation.
		                        		
		                        		
		                        		
		                        	
3. The hippocampal proteomics mechanism of thalidomide in Alzheimer's disease model mice induced by Aβ
Su-Hui WU ; Han ZHANG ; Yu-Hang ZHANG ; Ting-Yuan NIU ; Han-Bing LI ; Jian-Feng GAO ; Gen-Lin LI
Chinese Pharmacological Bulletin 2023;39(2):315-325
		                        		
		                        			
		                        			 Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer's disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism. Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups. The drugs were administered by gavage every day for 21 days. After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins. Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05). Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complex ,Ⅱ, and of the brain tissues of AD mice(P<0.05). A total of 4 378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05). Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer's disease. Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ 
		                        		
		                        		
		                        		
		                        	
4.Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023)
Yuan XIONG ; Bobin MI ; Chenchen YAN ; Hui LI ; Wu ZHOU ; Yun SUN ; Tian XIA ; Faqi CAO ; Zhiyong HOU ; Tengbo YU ; Aixi YU ; Meng ZHAO ; Zhao XIE ; Jinmin ZHAO ; Xinbao WU ; Xieyuan JIANG ; Bin YU ; Dianying ZHANG ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Qikai HUA ; Mengfei LIU ; Yiqiang HU ; Peng CHENG ; Hang XUE ; Li LU ; Xiangyu CHU ; Liangcong HU ; Lang CHEN ; Kangkang ZHA ; Chuanlu LIN ; Chengyan YU ; Ranyang TAO ; Ze LIN ; Xudong XIE ; Yanjiu HAN ; Xiaodong GUO ; Zhewei YE ; Qisheng ZHOU ; Yong LIU ; Junwen WANG ; Ping XIA ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Dongliang WANG ; Fengfei LIN ; Jiangdong NI ; Aiguo WANG ; Dehao FU ; Shiwu DONG ; Lin CHEN ; Xinzhong XU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Yingze ZHANG ; Xiaobing FU ; Guohui LIU
Chinese Journal of Trauma 2023;39(6):481-493
		                        		
		                        			
		                        			Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.
		                        		
		                        		
		                        		
		                        	
5.Expert consensus on diagnosis, prevention and treatment of perioperative lower extremity vein thrombosis in orthopedic trauma patients (2022 edition)
Wu ZHOU ; Faqi CAO ; Ruiyin ZENG ; Baoguo JIANG ; Peifu TANG ; Xinbao WU ; Bin YU ; Zhiyong HOU ; Jian LI ; Jiacan SU ; Guodong LIU ; Baoqing YU ; Zhi YUAN ; Jiangdong NI ; Yanxi CHEN ; Dehao FU ; Peijian TONG ; Dongliang WANG ; Dianying ZHANG ; Peng ZHANG ; Yunfei ZHANG ; Feng NIU ; Lei YANG ; Qiang YANG ; Zhongmin SHI ; Qiang ZHOU ; Junwen WANG ; Yong WANG ; Chengjian HE ; Biao CHE ; Meng ZHAO ; Ping XIA ; Liming XIONG ; Liehu CAO ; Xiao CHEN ; Hui LI ; Yun SUN ; Liangcong HU ; Yan HU ; Mengfei LIU ; Bobin MI ; Yuan XIONG ; Hang XUE ; Ze LIN ; Yingze ZHANG ; Yu HU ; Guohui LIU
Chinese Journal of Trauma 2022;38(1):23-31
		                        		
		                        			
		                        			Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.
		                        		
		                        		
		                        		
		                        	
6.Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology.
Zhen-Hua BIAN ; Wen-Ming ZHANG ; Jing-Yue TANG ; Qian-Qian FEI ; Min-Min HU ; Xiao-Wei CHEN ; Lian-Lin SU ; Cheng-Hao FEI ; De JI ; Chun-Qin MAO ; Huang-Jin TONG ; Tu-Lin LU ; Xiao-Hang YUAN
China Journal of Chinese Materia Medica 2022;47(1):188-202
		                        		
		                        			
		                        			This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Chromatography, High Pressure Liquid
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		                        			Drugs, Chinese Herbal/chemistry*
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		                        			Metabolomics
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		                        			Network Pharmacology
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		                        			Rats
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		                        			Seeds/chemistry*
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		                        			Sleep Initiation and Maintenance Disorders/drug therapy*
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		                        			Tandem Mass Spectrometry
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		                        			Ziziphus/chemistry*
		                        			
		                        		
		                        	
7.Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract
Yuting ZHAO ; Ying WANG ; Shunan QI ; Yong YANG ; Xia HE ; Yujing ZHANG ; Huiqiang HUANG ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Tao WU ; Suyu ZHU ; Mei SHI ; Liming XU ; Zhiyong YUAN ; Hang SU ; Yuqin SONG ; Jun ZHU ; Yexiong LI
Chinese Journal of Oncology 2021;43(7):787-794
		                        		
		                        			
		                        			Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.
		                        		
		                        		
		                        		
		                        	
8.Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type
Xiaodan WANG ; Xin LIU ; Tao WU ; Yong YANG ; Shunan QI ; Xia HE ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Suyu ZHU ; Mei SHI ; Hang SU ; Ximei ZHANG ; Huilai ZHANG ; Huiqiang HUANG ; Yujing ZHANG ; Yuqin SONG ; Jun ZHU ; Ying WANG ; Yexiong LI
Chinese Journal of Oncology 2021;43(10):1105-1113
		                        		
		                        			
		                        			Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.
		                        		
		                        		
		                        		
		                        	
9.Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract
Yuting ZHAO ; Ying WANG ; Shunan QI ; Yong YANG ; Xia HE ; Yujing ZHANG ; Huiqiang HUANG ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Tao WU ; Suyu ZHU ; Mei SHI ; Liming XU ; Zhiyong YUAN ; Hang SU ; Yuqin SONG ; Jun ZHU ; Yexiong LI
Chinese Journal of Oncology 2021;43(7):787-794
		                        		
		                        			
		                        			Objective:To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL).Methods:The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis.Results:Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% ( P=0.281), while the PFS rates were 24.8% and 48.3%, respectively ( P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival ( P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival( P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions:Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.
		                        		
		                        		
		                        		
		                        	
10.Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type
Xiaodan WANG ; Xin LIU ; Tao WU ; Yong YANG ; Shunan QI ; Xia HE ; Liling ZHANG ; Gang WU ; Baolin QU ; Liting QIAN ; Xiaorong HOU ; Fuquan ZHANG ; Xueying QIAO ; Hua WANG ; Gaofeng LI ; Yuan ZHU ; Jianzhong CAO ; Junxin WU ; Suyu ZHU ; Mei SHI ; Hang SU ; Ximei ZHANG ; Huilai ZHANG ; Huiqiang HUANG ; Yujing ZHANG ; Yuqin SONG ; Jun ZHU ; Ying WANG ; Yexiong LI
Chinese Journal of Oncology 2021;43(10):1105-1113
		                        		
		                        			
		                        			Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.
		                        		
		                        		
		                        		
		                        	
            
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