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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao general surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of Hepatobiliary Pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model liver transplantation

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Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer

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World Journal of Gastrointestinal surgery 2024年第6期16卷 1601-1608页

作者： Guo-Feng Wang Chang-Xin Shu Xiao-Dong Cai Hong-Bo Wang Jian-Hong Xu Yu-Qing Jia Department of general surgery Yangzhou Friendship Hospital Affiliated to Medical College of Yangzhou UniversityYangzhou 225000Jiangsu ProvinceChina

BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver *** To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver *** Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively *** patients underwent Gamma Knife®treatment combined with TACE and *** clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were *** The last follow-up for this study was conducted on October 31,*** evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths *** Gamma Knife®combined with TACE and immune-targeted th

关键词： Gamma Knife® Transarterial chemoembolization Immunotherapy Primary liver cancer liver function

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Integrative analysis of the transcriptome and metabolome reveals the importance of hepatokine FGF21 in liver aging

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Genes & Diseases 2024年第5期11卷 407-427页

作者： Wenchao Wang Junjie Qian Mingge Shang Yiting Qiao Jiacheng Huang Xinxin Gao Zhou Ye Xinyu Tong Kangdi Xu Xiang Li Zhengtao Liu Lin Zhou Shusen Zheng Division of Hepatobiliary and Pancreatic surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310003China NHC Key Laboratory of Combined Multi-organ transplantation HangzhouZhejiang 310003China Key Laboratory of the Diagnosis and Treatment of Organ transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical Sciences(2019RU019)HangzhouZhejiang 310003China Key Laboratory of Organ transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiang 310003China Shulan International Medical College Zhejiang Shuren UniversityHangzhouZhejiang 310015China Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College HangzhouZhejiang 310000China

Aging is a contributor to liver ***,the concept of liver aging has become prominent and has attracted considerable interest,but its underlying mechanism remains poorly *** our study,the internal mechanism of liver aging was explored via multi-omics analysis and molecular experiments to support future targeted *** aged rat liver model was established with D-galactose,and two other senescent hepatocyte models were established by treating HepG2 cells with D-galactose and *** then performed transcriptomic and metabolomic assays of the aged liver model and transcriptome analyses of the senescent hepatocyte *** livers,genes related to peroxisomes,fatty acid elongation,and fatty acid degradation exhibited down-regulated expression with aging,and the hepatokine Fgf21 expression was positively correlated with the down-regulation of these *** senescent hepatocytes,similar to the results found in aged livers,FGF21 expression was also ***,the expressions of cell cycle-related genes were significantly down-regulated,and the down-regulated gene E2F8 was the key cell cycle-regulating transcription *** then validated that FGF21 overexpression can protect against liver aging and that FGF21 can attenuate the declines in the antioxidant and regenerative capacities in the aging *** successfully validated the results from cellular and animal experiments using human liver and blood *** study indicated that FGF21 is an important target for inhibiting liver aging and suggested that pharmacological prevention of the reduction in FGF21 expression due to aging may be used to treat liver aging-related diseases.

关键词： Antioxidant capability FGF21 liver aging liver regeneration Multiomics analysis

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Early-onset and later-onset cancer:trends,risk factors,and prevention in Northern China

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Science China(Life Sciences) 2024年第9期67卷 1928-1940页

作者： Tong Liu Chen-An Liu Qing-Song Zhang Qi Zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling Wu Han-Ping Shi Department of Gastrointestinal surgery Department of Clinical NutritionBeijing Shijitan HospitalCapital Medical UniversityBeijing 100038China National Clinical Research Center for Geriatric Diseases Xuanwu HospitalCapital Medical UniversityBeijing 100053China Key Laboratory of Cancer FSMP for State Market Regulation Beijing 100038China Laboratory for Clinical Medicine Capital Medical UniversityBeijing 100038China Department of general surgery Kailuan General HospitalTangshan 063000China Department of Genetics Yale School of MedicineNew Haven 06510USA Department of Hepatobiliary surgery Kailuan General HospitalTangshan 063000China Cardiovascular Research Institute University of CaliforniaSan Francisco 94158USA Department of Cardiology Kailuan General HospitalTangshan 063000China

The characteristics of early-onset(onset age<50 years)and later-onset(onset age≥50 years)cancers differ *** novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for... 详细信息

The characteristics of early-onset(onset ageliver cancer,incidence rates for nearly all types of cancer increased during the study ***,alcohol consumption,lipid metabolism disorders,hypertension,diabetes mellitus,fatty liver,and inflammation were associated with a significantly increased risk of cancer at multiple sites,but risk factors for cancer incidence differed by ***,alcohol consumption,inflammation,and hypertension were the major contributors to preventable *** incidence of several different types of cancer,including earlyonset cancer,is increasing in northeastern *** in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

关键词： cancer early-onset later-onset trend risk factor prevention

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Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 52-63页

作者： Li Zhang Sai He Hao Guan Yao Zhao Di Zhang Department of general surgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004China Department of Breast Cancer Shaanxi Provincial Cancer HospitalXi’an 710000China

Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths *** evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC ***,the molecular mechanism of circZFR in HCC is ***:Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was employed to detect the expression of circZFR,microRNA-624-3p(miR-624-3p)and WEE1 in HCC tissues and *** R assay and actinomycin D treatment assay were used to analyze the characteristics of *** functional analysis,the capacities of colony formation,cell proliferation,cell apoptosis,migration and invasion were assessed by colony formation assay,5-ethynyl-2-deoxyuridine(EdU)assay,flow cytometry assay and transwell *** blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related *** interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)*** models were established to determine the role of circZFR in ***:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and *** could sponge miR-624-3p,and WEE1 was a downstream gene of *** of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this *** of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC ***,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting ***,in vivo studies have illustrated that circZFR knockdown inhibited tumor ***:circZFR knockdown reduced HCC cell proliferation,migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis,suggesting that the circZFR/miR-624-3p/WEE1 axis might

关键词： Hepatocellular carcinoma circZFR miR-624-3p WEE1 liver cancer

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Radiofrequency ablation versus microwave ablation for colorectal liver metastases:long-term results of a retrospective cohort surgical experience

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Hepatobiliary surgery and Nutrition 2024年第5期13卷 759-770,I0001页

作者： Ali Gunduz Sarioglu Chase J.Wehrle Ege Akgun Arturan Ibrahimli James F.Bena Eren Berber Department of Endocrine surgery Cleveland ClinicClevelandOHUSA Department of general surgery Cleveland ClinicClevelandOHUSA Department of Quantitative Health Sciences Cleveland ClinicClevelandOHUSA

Background:Ablation is an alternative treatment modality for selected patients with colorectal liver metastases(CRLMs).Although initially widely performed via radiofrequency ablation(RFA),more recently,microwave ablation(MWA)is being preferred due to its perceived superiority in creating the ablation *** aim of this study is to compare the long-term efficacy of these two modalities performed ***:Patients undergoing surgical liver ablation from 2005-2023 at a tertiary center by a single surgeon for CRLM were included in a retrospective institutional review board-approved *** were compared using Wilcoxon,Chi-square,Kaplan-Meier,and Cox multivariate regression *** data are presented as median(interquartile range).Results:There were a total of 242 *** RFA was done in 121 patients with 303 lesions and laparoscopic MWA in 121 patients with 300 *** was no difference between the groups regarding operative time(161 vs.147 minutes,respectively,P=0.4),perioperative morbidity(3%vs.8%,respectively,P=0.2)or hospital stay(1 vs.1 day,P=0.05).Local recurrence(LR)per lesion with at least 1 year of imaging follow-up was 29%in the RFA and 13%in the MWA group(P<0.001).Based on univariate survival analysis,tumor size,blood vessel proximity,ablation margin,and ablation modality were independent predictors of *** control these variables,direct matching was *** cohort included 189 ***-Meier analysis of these cohorts showed increased LR-free survival in the MWA group *** RFA group(P=0.005).Conclusions:This large study confirms our initial observation that local tumor control rate is better after MWA ***.

关键词： Colorectal cancer liver metastasis liver ablation radiofrequency ablation(RFA) microwave ablation(MWA) local recurrence(LR)

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Should we resect distant metastases?-reconsidering radical resection of pancreatic cancer with liver metastases

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Hepatobiliary surgery and Nutrition 2024年第5期13卷 905-907页

作者： Niv Pencovich Ido Nachmany Department of general surgery and transplantation Sheba Medical CenterTel-HashomerIsrael Faculty of Medicine and Health Sciences Tel-Aviv UniversityTel-AvivIsrael

The mechanism of cancer metastasis is far more complex than the mere mechanical shedding of tumor cells into the circulation,followed by cell proliferation within an organ where they accidentally get *** spread is also not random;different primary tumors exhibit predilections for specific organs they metastasize *** notion dates back to 1889 when Stephen Paget described the“seed and soil”hypothesis,suggesting that the spread of tumor cells is governed by close interactions between specific cancer cells(seed)and the host organ(soil).Other crucial processes of metastatic spread,such as cell intravasation,extravasation,tumor latency,metastatic niche formation,and the development of micrometastasis and macrometastasis,have been delineated over the last few decades.

关键词： Metastasis oligometastases systemic disease chemotherapy local disease

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Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： Kevin Tak-Pan Ng Li Pang Jia-Qi Wang Wong Hoi She Simon Hing-Yin Tsang Chung Mau Lo Kwan Man Tan To Cheung Department of surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of liver Research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not *** study was to find out whether systemic inflammation plays an important ***:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex *** relationships of the cytokines and the postoperative outcomes were compared between LLR and ***:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative *** to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly *** POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during *** levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital ***,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver ***:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

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Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults:30 years’overview and forecasted trends

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4177-4193页

作者： De-Sheng Chen Ze-Ping Chen Dong-Zi Zhu Lv-Xin Guan Qi Zhu Yi-Chao Lou Ze-Ping He Hao-Nan Chen Hong-Cheng Sun Department of general surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of general surgery Shanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Shenzhen Institute of Translational Medicine The First Affiliated Hospital of Shenzhen UniversityShenzhen 518035Guangdong ProvinceChina Department of general surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016Zhejiang ProvinceChina

BACKGROUND Hepatobiliary and pancreatic(HBP)cancers impose a considerable burden on young populations(aged 15 to 49 years),resulting in a substantial number of new cases and fatalities each *** young populations,the HBP cancers shows extensive variance worldwide and the updated data in China is *** To investigate the current status,trends,projections,and underlying risk factors of HBP cancers among young populations in *** The Global Burden of Disease Study 2019 provided data on the annual incidence,mortality,disability-adjusted life years(DALYs),age-standardized incidence rate(ASIR),mortality rate(ASMR),and DALYs rate(ASDR)of HBP cancers in young Chinese adults between 1990 and *** trends were assessed using estimated annual percentage change and hierarchical ***-specific mortality and DALYs caused by various risks were analyzed across China and other regions,with future trends until 2035 projected using the Bayesian age-period-cohort *** From 1990 to 2019,incident cases,deaths,DALYs,ASIR,ASMR,and ASDR for liver cancer(LC)in young Chinese individuals decreased,classified into'significant decrease'***,cases of gallbladder and biliary tract cancer and pancreatic cancer rose,categorized as either'significant increase'or'minor increase'*** contribution of risk factors to mortality and DALYs for HBP tumors increased to varying *** lifestyle behaviors,such as tobacco control,weight management,alcohol moderation,and drug avoidance,could lower HBP cancers ***,except for LC in females,which is likely to initially decline slightly and then rise,the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young *** HBP cancers burden among young adults in China is expected to increase until 2035,necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these

关键词： Hepatobiliary and pancreatic cancers Burden landscape Young adults Projection China

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Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

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World Journal of Gastrointestinal surgery 2024年第1期16卷 205-214页

作者： Gao-Yuan Yang Zhi-Wei He Yong-Chang Tang Feng Yuan Ming-Bo Cao Yu-Peng Ren Yu-Xuan Li Xiao-Rui Su Zhi-Cheng Yao Mei-Hai Deng Department of Hepatobiliary surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of general surgery Qilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina Department of general surgery The First Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436Guangdong ProvinceChina Department of Hepatobiliary and Pancreatic surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient *** adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer ***,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further *** To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal *** This study involved network meta-analyses and followed the PRISMA *** data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane *** included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary *** magnitudes of the effects were determined using risk ratios with 95%confidential *** results were analyzed using R software and STATA *** A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this *** was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and *** analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest *** who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent ***

关键词： Primary liver cancer Hepatocellular carcinoma Network meta-analysis External beam radiation therapy Stereotactic body radiotherapy Intensity modulated radiotherapy

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