1.Efficacy of focal radiofrequency ablation in the treatment of low-to-intermediate risk localized prostate cancer
Shu GAO ; Zhen JIANG ; Jiyuan SUN ; Haifeng HUANG ; Qing ZHANG ; Hongqian GUO
Journal of Modern Urology 2025;30(2):143-147
		                        		
		                        			
		                        			Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery,in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate,surgery related complications,postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months,the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy,little impact on urinary control and sexual function recovery,and few postoperative complications,which can be used as one of the treatment options for these patients.
		                        		
		                        		
		                        		
		                        	
2.Electro-acupuncture for Vascular Cognitive Impairment:A Visualized Data Mining Analysis
Hai-Zhen GUO ; Han WU ; Mei-Kang YAO ; Jiang-Wei SHI ; Tao YU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):161-168
		                        		
		                        			
		                        			Objective To summarize the acupoints and parameters commonly used in the treatment of vascular cognitive impairment(VCI)by electro-acupuncture(EA)through the visual data mining technique to provide a reference basis for clinical treatment.Methods The clinical studies of EA on the treatment of VCI were searched in CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases.The literature is managed by Note Express and the database is established by Excel.The frequency of selected acupoints,frequency,meridian tropism,parameter frequency and frequency of used acupoints are counted.Factor analysis is carried out by SPSS 21.0 software.SPSS Modeler 18.3 software is used to analyze association rules and co-occurrence network,and the analysis results are visualized by Cytoscape 3.9.1 software.Results Finally,155 papers were included,containing 155 acupoint prescriptions and 157 parameter prescriptions.Acupoint prescriptions involved 100 acupoints with a total frequency of 856 times;parameter prescriptions involved 33 parameters with a total frequency of 788 times.Conclusion At present,there is a big difference between the clinical studies,and there is no recognized acupoint and parameter for EA treatment of VCI.By further summarizing the law of EA acupuncture point and parameter,the study has sorted out the law of commonly used acupoints,meridian tropism,compounding and parameter selection for EA treatment of VCI.It was concluded that the selection of acupoints mainly started from the three aspects of deficiency,phlegm and stasis,focusing on the combination of local and distal selection of acupoints,through the identification of internal organs and meridians,to achieve the simultaneous regulation of the heart,spleen and kidney,and to take into account both the symptoms and the root cause,and to play the roles of opening the orifices to wake up mind,calming mind and benefiting intellect,strengthening the spleen and tonifying the kidneys,and invigorating blood circulation to remove stasis.The parameters of EA are recommended to be sparse and dense wave,low frequency,as tolerated by the patient,30 minutes/times,1 time/day,5 times/week as the main combinations,which can provide a certain reference basis for clinical decision-making.
		                        		
		                        		
		                        		
		                        	
3.Regulatory Mechanism of Drug-Containing Serum of Jinghou Zengzhi Prescription on GDF9 Expression and Apoptosis of Ovarian Granulosa Cells in Rats with Controlled Ovarian Hyperstimulation
Zhen YANG ; Xiao-Yan CHEN ; Shao-Ru JIANG ; Shu-Zhu YE ; Xiao-Hong FANG ; Wei-Min DENG ; Xin-Yu GUO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):735-741
		                        		
		                        			
		                        			Objective To observe the regulatory mechanism of drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method on the expression of growth and differentiation factor 9(GDF9)and apoptosis of ovarian granulosa cells in rats with controlled ovarian hyperstimulation(COH).Methods Serum of COH rats(blank serum)and serum of COH rats gavaged by the Jinghou Zengzhi Prescription were prepared.A COH rat model was established and ovarian granulosa cells were collected.The experiment was divided into 5 groups:blank serum group,drug-containing serum group,drug-containing serum+SB203580[p38 mitogen-activated protein kinase(p38MAPK)inhibitor]group,drug-containing serum + PDTC[nuclear transcription factor κB(NF-κB)inhibitor]group,drug-containing serum + SB203580 + PDTC group.The mRNA expression levels of p38MAPK,casein kinase 2(CK2),nuclear transcription factor κB inhibitor α(IκBα),NF-κB and GDF9 were detected by real-time quantitative polymerase chain reaction(qRT-PCR),and GDF9 protein expression level was detected by Western Blot,and ovarian granulosa cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Results The drug-containing serum of Jinghou Zengzhi Prescription decreased the mRNA expressions of p38MAPK and NF-κB,elevated the mRNA expressions of CK2 and IκBα,increased the mRNA and protein expression levels of GDF9,and decreased the apoptosis rate of ovarian granulosa cells in COH rats.The addition of p38MAPK inhibitor SB203580 alone and the addition of NF-κB inhibitor PDTC alone both promoted the mRNA and protein expressions of GDF9 and reduced the apoptosis rate of granulosa cells.Conclusion The drug-containing serum of Jinghou Zengzhi Prescription based on qi and blood replenishing method can promote the expression of GDF9 and inhibit the apoptosis of ovarian granulosa cells in rats with COH,and its mechanism may be related to the regulation of the expression of genes of the dual signaling pathways of p38MAPK and NF-κB.
		                        		
		                        		
		                        		
		                        	
4.Effect of Jinghou Zengzhi Granules on ovarian GDF9 secretion and granulosa cells apoptosis in controlled ovarian hyperstimulation rats
Zhen YANG ; Shaoru JIANG ; Xiaoyan CHEN ; Xiaolin CHEN ; Weimin DENG ; Xinyu GUO
The Journal of Practical Medicine 2024;40(7):918-923
		                        		
		                        			
		                        			Objective To explore the effects of Jinghou Zengzhi Granules(JHZZG),on ovarian GDF9 secretion and granulosa cells(GCs)apoptosis in controlled ovarian hyperstimulation(COH)rats through p38MAPK/CK2/IκBα/NF-κB pathway.Methods A model of COH rats was prepared and 18 rats were randomly divided into 3 groups,including natural ovulation group(NO group),COH group,and COH+JHZZG group.The expression of p38MAPK,CK2,IκBα,NF-κB,GDF9 mRNA and protein were detected by qRT-PCR and Western blot,and the apoptosis rate of ovarian GCs by TUNEL.Results Compared with the NO group,the expression of p38MAPK and NF-κB in the ovarian tissue of rats in the COH group increased,while the expression of CK2,IκBα and GDF9 decreased,and the apoptosis rate of ovarian GCs increased(all P<0.01).Compared with the COH group,the expression of p38MAPK and NF-κB in the ovarian tissue of rats in the COH+JHZZG group decreased,while the expression of CK2,IκBα and GDF9 increased(all P<0.01),and the apoptosis rate of ovarian GCs decreased(P<0.05).Conclusion Jinghou Zengzhi Granules could promote the secretion of ovarian GDF9 and inhibit the apoptosis of ovarian GCs of COH rats through p38MAPK/CK2/IκBα/NF-κB signaling pathway,which thereby improve the quality of COH oocytes.
		                        		
		                        		
		                        		
		                        	
5.Interleukin-12 participate in liver diseases of Sj?gren's syndrome through promoting oxidative stress
Jie ZHA ; Tingting JIANG ; Junqiao GUO ; Zhen XIAO ; Genhong YAO
Chinese Journal of Immunology 2024;40(3):461-465
		                        		
		                        			
		                        			Objective:To investigate the effect of interleukin-12(IL-12)on liver lesions and oxidative stress pathway in Sjo-gren's syndrome mice,and to clarify the possible mechanism of liver lesions in Sjogren's syndrome.Methods:Saliva flow rate,liver function,liver pathology and IL-12 level were measured in NOD,IL-12 knockout(IL-12KO)NOD and C57BL/6(B6)mice.Different concentrations of IL-12 and JAK2,TYK2 inhibitors were applied to mouse hepatoma cells.The oxidative stress index of mouse serum and cell culture supernatants of each group were determined.Results:Compared with the other two groups of mice,the NOD mice had significantly higher GOT and GPT(P<0.05),and decreased serum GSH-PX,SOD and CAT(P<0.05).CAT,GSH,GSH-PX and SOD were decreased,while MDA was increased in mice treated with different concentrations of IL-12.JAK2/TYK2 inhibitors reversed regulatory effects of IL-12 on SOD,GSH and MDA in hepatoma cells(P<0.05).Conclusion:IL-12 may aggravated liver damage of Sj?gren's syndrome through promoting oxidative stress of hepatocytes.
		                        		
		                        		
		                        		
		                        	
6.Impact of serum vitamin A levels on all-cause mortality risk in diabetes patients:a prospective study
Zhuo LI ; Baoyuan JIANG ; Yu OUYANG ; Yaxin XIANG ; Zhen YANG ; Lianying GUO
Journal of Shenyang Medical College 2024;26(6):575-581
		                        		
		                        			
		                        			Objective:To investigate the impact of serum vitamin A levels on all-cause mortality risk in diabetes patients.Methods:Diabetes patients aged 20 years and above who participated in the US National Health and Nutrition Examination Survey during 2003-2004 and 2005-2006 were enrolled as the study population,with death data up to 2019 as the endpoint.Cox proportional hazards regression models were employed to calculate the hazard ratios of all-cause mortality in diabetes patients with different serum vitamin A levels,both unadjusted and adjusted for confounders.Restricted cubic spline methods were used to analyze the dose-response relationship between serum vitamin A levels and all-cause mortality risk in diabetes patients.Results:A total of 484 diabetes patients were included,with a median follow-up period of 13.7 years,during which 211 deaths occurred.Cox proportional hazards analysis showed that compared to the lowest quartile of serum vitamin A,higher quartiles of serum vitamin A were not associated with all-cause mortality risk in diabetes patients without adjusting for confounders.However,after adjusting for confounders,higher quartiles of serum vitamin A significantly reduced the all-cause mortality risk.The dose-response analysis indicated a significantly increased risk of all-cause mortality in diabetes patients with lower serum vitamin A levels.As the vitamin A levels increased,the mortality risk gradually decreased.A significant reduction in all-cause mortality risk was observed when serum vitamin A levels were between 2.17 and 2.50 μmol/L.Beyond this range,there was a tendency for increased all-cause mortality risk with further increases in vitamin A levels.Conclusion:Lower serum vitamin A levels increase the all-cause mortality risk in diabetes patients,while moderate serum vitamin A levels help reduce the all-cause mortality risk in diabetes patients.
		                        		
		                        		
		                        		
		                        	
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
		                        		
		                        			
		                        			Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
		                        		
		                        		
		                        		
		                        	
8.Survival of patients with brain metastases from small cell lung cancer under different intracranial radiotherapy modalities
Fangfang CHANG ; Xiaodong XIA ; Mengni LI ; Ziwen GUO ; Jia LIU ; Hao JIANG ; Zhen CUI
Chinese Journal of Radiological Medicine and Protection 2024;44(11):924-930
		                        		
		                        			
		                        			Objective:To explore the prognostic impact of different intracranial radiotherapy modalities in patients with a limited number (≤10) of brain metastases from small cell lung cancer (SCLC-BM).Methods:The data of 143 cases with SCLC-BM that received intracranial radiotherapy at the First Affiliated Hospital of Bengbu Medical University in 2019-2022 were analyzed. The patients were grouped by radiotherapy modalities: whole brain radiotherapy (WBRT, 58 cases), WBRT combined with simultaneous integrated boost (WBRT+ SIB, 53 cases), and WBRT combined with sequential integrated boost (WBRT+ SEB, 32 cases). The overall survival (OS) and intracranial progression-free survival (IPFS) were calculated using the Kaplan-Meier method, and the Cox proportional hazard model was used for prognostic analysis.Results:In the whole group, the median OS and IPFS were 11.9 and 9.9 months, and the 1-, 2-, and 3-year survival rates were 49.7%, 15.3%, and 2.9%, respectively. The difference in OS among patients in the WBRT+ SIB, WBRT+ SEB, and WBRT groups was not significant (median OS: 13.0 months vs. 12.5 months vs. 11.2 months, P>0.05). The WBRT+ SIB and WBRT+ SEB groups were preferred over the WBRT group in terms of IPFS (median IPFS: 11.7 months vs. 10.4 months vs. 8.1 months, χ2=21.69, P<0.001). For patients with few brain metastases (≤3) analyzed separately, the WBRT+ SIB and WBRT+ SEB groups were preferred over the WBRT group in terms of OS and IPFS (median OS: 14.4 months vs. 13.7 months vs. 11.5 months, χ2=8.72, P=0.013; median IPFS: 12.6 months vs. 10.4 months vs. 8.9 months, χ2=12.37, P=0.002). Evaluation of the central nervous system as well as hematological acute radiological reactions reaching grade 2 and above showed no significant differences among the three groups ( P>0.05). Multivariate analysis showed that subsequent chemotherapy, targeted therapy, and immunotherapy were common independent influencing factors for patients′ OS and IPFS. Body mass index (BMI) level was an independent influencing factor for patients′ OS, and the number of brain metastases, lymph node metastasis, and radiotherapy modality were independent influencing factors for patients′ IPFS. Conclusions:BMI level and subsequent treatment (chemotherapy, targeted therapy, and immunotherapy) are independent influencing factors for patients' prognosis. WBRT+ SIB and WBRT+ SEB modalities are associated with increased IPFS.
		                        		
		                        		
		                        		
		                        	
9.Rapid Determination of Paraquat and Diquat Residues in Tea by QuEChERS/Ultra-High Performance Liquid Chromatography-Tandem Quadrupole Mass Spectrometry
Yan-Hua TANG ; Ying-Nan GAO ; Jiang-Yan CHEN ; Xin-Yi GUO ; Shao-Yong LI ; Yue LI ; Zhen ZHOU ; Wei GAO
Chinese Journal of Analytical Chemistry 2024;52(10):1619-1627
		                        		
		                        			
		                        			A rapid analytical method for determination of paraquat and diquat in tea samples was established by improving the QuEChERS pre-treatment method combined with ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry(UPLC-MS/MS).Four kinds of tea powder were extracted by using acetonitrile-0.1%formic acid solution(3∶7,V/V)and ultrasonic treatment,and the supernatant was purified with 400 mg C18 and 400 mg PSA and separated on hydrophilic HILIC(100 mm×2.1 mm,1.8 μm)column by using 0.1%formic acid aqueous solution(Containing 5 mmol/L ammonium formate)and acetonitrile as mobile phases.In the electrospray ion source positive ion mode(ESI+),multiple reaction monitoring scanning technology(MRM)was used for determination,and the matrix-matched standard solution external standard method was used for quantitative analysis.The results showed that paraquat obtained good linear relationship in the content range of 0.18-200 μg/kg and diquat obtained good linear relationship in the content range of 0.36-200 μg/kg,and the correlation coefficients(R2)were 0.9939-0.9976 and 0.9959-0.9987,respectively.The limits of detection(LODs)were 0.06 and 0.12 μg/kg,and the limits of quantitation(LOQs)were 0.18 and 0.36 μg/kg,respectively.The average spiked recoveries for tea samples varied from 84.4%to 128.8%,with the relative standard deviations(RSDs)from 0.6%to 13.5%.The method was simple and efficient,with accurate quantification ability and low detection limit,which could realize efficient determination of paraquat and diquat in tea samples.
		                        		
		                        		
		                        		
		                        	
10.Research on face mask recognition based on YOLOv5 lightweight network
Liang WEN ; Jiang WANG ; Guo-Biao LIANG ; Zhen-Ni LI
Chinese Medical Equipment Journal 2024;45(9):7-13
		                        		
		                        			
		                        			Objective To propose a YOLOv5 lightweight network-based face mask recognition method to solve the problems due to limited storage and computation resources of edge and mobile devices.Methods A YOLOv5 model composed of a backbone network(Backbone),a neck module(Neck)and a head module(Head)was selected as the base framework.Firstly,the Backbone part was modified and replaced using the ShuffleNetv2 lightweight network;secondly,a Ghost module and a C3_S module were introduced in the Neck part;finally,a Shuffle_Yolo_GS_CBAM model was formed by incorporating a convolutional block attention module(CBAM)to improve the detection accuracy.The model was trained and verified with the AIZOO dataset,which was evaluated for face mask recognition by mean average precision(mAP),frames per second(FPS),giga floating-point operations per second(GFLOPS)and parameters.Results The model proposed recognized face masks with the mAP being 89.5%,FPS being 158.7 frames/s,parameters being 2.38 M and and GFLOPS being 4.5 GFLOPS,which had the detection speed enhanced by 39.7%,parameters decreased by 67.3%and operations reduced by73.8%when compared with the YOLOv5s model.Conclusion The method proposed behaves well in increasing detection speed,decreasing parameters and operations and ensuring detection precision,and thus is worthy promoting for face mask recognition on edge and mobile devices.[Chinese Medical Equipment Journal,2024,45(9):7-13]
		                        		
		                        		
		                        		
		                        	
            
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