1.In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum
Leijia CHEN ; Mengyi CUI ; Xiangyu SONG ; Kai WANG ; Zhibo JIA ; Liupu YANG ; Yanghui DONG ; Haochen ZUO ; Jiaxiang DU ; Dengke PAN ; Wenjing XU ; Hongbo REN ; Yaqun ZHAO ; Jiang PENG
Organ Transplantation 2024;15(3):415-421
		                        		
		                        			
		                        			Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.
		                        		
		                        		
		                        		
		                        	
2.Study on the effect of synaptic nuclear protein γ on migration and invasion of oral squamous cell carcinoma cells
Zuo-Dong REN ; Zhao-Wei ZHUANG ; Juan ZHAO ; Wu-Mei YUAN ; Yan ZENG
The Chinese Journal of Clinical Pharmacology 2024;40(9):1267-1271
		                        		
		                        			
		                        			Objective Lentivirus-mediated interference with synaptic nuclear protein γ(SNCG)in human oral squamous cell carcinoma was established to study the role of SNCG in the migration and invasion of oral squamous cell carcinoma.Methods Oral cancer CAL27 cells were infected with LV-shNC and LV-shSNCG constructed by lentivirus vector,respective,and then selected with puromycin to obtain cell lines stably interfering with SNCG,which were named NC group and experimental group,respectively.Detect the expression of SNCG through real-time quantitative polymerase chain reaction(qRT-PCR)and Western blot experiments;Transwell and scratch experiments were used to detect changes in migration and invasion ability.Results Compared with the NC group,the experimental group showed an 80%reduction in SNCG mRNA expression(P<0.01).The relative expression level of SNCG protein was also decreased in the experimental group compared to the NC group(P<0.01).In the NC group and the experimental group,the migration area percentages at 36 hours were 0.54±0.06 and 0.40±0.02,respectively;and at 48 hours were 0.83±0.01 and 0.47±0.05,respectively.The experimental group showed decrease in migration area compared to the NC group,and these differences were statistically significant(P<0.05,P<0.001).Compared to the NC group,the migration and invasion cell numbers in the experimental group(98.00±13.49 and 88.00±5.72)were significantly reduced to(48.00±2.16 and 49.00±2.94),and these differences were statistically significant(P<0.01,P<0.001).Conclusion Interference of SNCG expression can significantly reduce the migration and invasion ability of oral squamous cell carcinoma cells.
		                        		
		                        		
		                        		
		                        	
3.Clinical profiles and outcomes of acute type A aortic dissection and intramural hematoma in the current era: lessons from the first registry of aortic dissection in China.
Wei-Xun DUAN ; Wei-Guang WANG ; Lin XIA ; Chao XUE ; Bo YU ; Kai REN ; Wei YI ; Hong-Liang LIANG ; Xiao-Chao DONG ; Jian ZUO ; Jin-Cheng LIU ; Shi-Qiang YU ; Ding-Hua YI
Chinese Medical Journal 2021;134(8):927-934
		                        		
		                        			BACKGROUND:
		                        			Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases.
		                        		
		                        			METHODS:
		                        			All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test.
		                        		
		                        			RESULTS:
		                        			A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%).
		                        		
		                        			CONCLUSIONS
		                        			Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.
		                        		
		                        		
		                        		
		                        			Acute Disease
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		                        			Aneurysm, Dissecting/diagnosis*
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		                        			China
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		                        			Hematoma
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		                        			Humans
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		                        			Male
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		                        			Middle Aged
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		                        			Registries
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		                        			Retrospective Studies
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		                        			Time Factors
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		                        			Treatment Outcome
		                        			
		                        		
		                        	
4.Value of 18F-FDG PET/CT in diagnosis of prosthetic vascular graft infection after endovascular aortic repair
Fangyuan REN ; Changjing ZUO ; Jianhua WANG ; Gaofeng SUN ; Chao CHENG ; Aisheng DONG ; Jian YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(3):138-141
		                        		
		                        			
		                        			Objective To study the features and clinical value of 18F-fluorodeoxyglucose (FDG) PET/CT in prosthetic vascular graft infections (PVGIs) after endovascular aortic repair (EVAR).Methods Data of 27 patients (22 males and 5 females,age range:21-77 years,average age:42 years) who underwent PET/CT imaging after EVAR from October 2011 to January 2017 were studied retrospectively.A total of 11 cases were finally diagnosed as PVGIs (PVGIs group),and the remaining 16 cases were defined as the negative group.PET/CT imaging features were compared between two groups.The detection rates of PET/CT and aortic CT angiography (CTA) for PVGIs were calculated and compared.Two-sample t test and Fisher exact test were used for data analysis.Results Significant uptake of FDG around the stents was detected by PET/CT in all patients in PVGIs group.The maximum standardized uptake value (SUVmax) of 11 patients in early imaging was 14.9±3.3 (10.8-21.8) and that of 9 patients in delayed imaging was 13.8±3.4 (10.6-19.1).Six patients of the negative group underwent the delayed imaging.No uptake or mild uptake of FDG around the stents was observed in negative group,with the SUVmax of 1.7±0.8(1.0--2.9) in early imaging and 1.6±0.7(1.1-2.5) in delayed imaging.SUVmax in negative group was significantly lower than that in PVGIs group (t values:12.6 and 11.8,both P<0.001).Five patients in PVGIs group were diagnosed as graft infections by the aortic CTA,while the remaining 6 cases showed no definitive infection signs on aortic CTA.The detection rate of aortic CTA was 5/11,which was significantly lower than that of PET/CT (P<0.05).In negative group,6 patients had abnormal FDG uptakes in other areas and were finally confirmed as infectious lesions (n=3) or malignant tumors (n=3).Conclusion Compared with aortic CTA,18F-FDG PET/CT is more sensitive and accurate in detection and diagnosis of PVGIs after EVAR.
		                        		
		                        		
		                        		
		                        	
5.Roles of flotillins in tumors.
Xu-Xu LIU ; Wei-Dong LIU ; Lei WANG ; Bin ZHU ; Xiao SHI ; Zi-Xuan PENG ; He-Cheng ZHU ; Xing-Dong LIU ; Mei-Zuo ZHONG ; Dan XIE ; Mu-Sheng ZENG ; Cai-Ping REN
Journal of Zhejiang University. Science. B 2018;19(3):171-182
		                        		
		                        			
		                        			The identification and use of molecular biomarkers have greatly improved the diagnosis and treatment of malignant tumors. However, a much deeper understanding of oncogenic proteins is needed for the benefit to cancer patients. The lipid raft marker proteins, flotillin-1 and flotillin-2, were first found in goldfish retinal ganglion cells during axon regeneration. They have since been found in a variety of cells, mainly on the inner surface of cell membranes, and not only act as a skeleton to provide a platform for protein-protein interactions, but also are involved in signal transduction, nerve regeneration, endocytosis, and lymphocyte activation. Previous studies have shown that flotillins are closely associated with tumor development, invasion, and metastasis. In this article, we review the functions of flotillins in relevant cell processes, their underlying mechanisms of action in a variety of tumors, and their potential applications to tumor molecular diagnosis and targeted therapy.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Cell Differentiation
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		                        			Endocytosis
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		                        			Humans
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		                        			Membrane Proteins/physiology*
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		                        			Neoplasms/etiology*
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		                        			Nerve Regeneration
		                        			
		                        		
		                        	
6.Changes and significance of serum levels of VEGF, ES, TKLK, TSP and sICAM-1 in patients with diabetic retinopathy
Hu LI-MEI ; Yan WU-CHAO ; Ren WEI-DONG ; Liu HUI-YING ; Deng WEN-JUAN ; Xu ZHENG-RONG ; Zuo LI-JUAN ; Gu JUN ; Shi LI
International Eye Science 2017;17(12):2304-2307
		                        		
		                        			
		                        			·AIM: To investigate the changes of serum levels of vascular endothelial growth factor ( VEGF ) , Endostatin (ES), thrombospondin (TSP), tissue kallikrein (TKLK) and soluble intercellular adhesion molecule-1 ( sICAM-1) in patients with diabetic retinopathy ( DR ) and its clinical significance.·METHODS:Selected 60 patients with non-proliferative diabetic retinopathy ( NPDR group ) , 60 patients with proliferative diabetic retinopathy ( PDR group ) were enrolled in this study. Sixty diabetic patients without diabetic retinopathy ( DM group ) and 60 healthy people ( control group) were also enrolled. Collection time was from January 2014 to December 2016. Serum levels of VEGF, ES, TSP, TKLK and sICAM-1 were measured and compared.·RESULTS: The levels of serum VEGF, TKLK and sICAM-1 in PDR group were significantly higher than those in NPDR group, DM group and control group ( P<0. 05). The ES of PDR group was significantly lower than that of NPDR group, DM group and control group ( P<0. 05). The levels of VEGF, TKLK and ES in the NPDR group were significantly higher than those in the DM group and the control group (P<0. 05). The serum VEGF in the NPDR group was positively correlated with the levels of ES, TKLK and sICAM-1 (P<0. 05). The serum VEGF of PDR group was positively related to the levels of TKLK and sICAM-1 (P<0. 05). There was no significant relationship between serum VEGF with ES and TSP in PDR group (P>0. 05).·CONCLUSION: The levels of serum ES, TSP, TKLK and sICAM - 1 in patients with DR have changed significantly, and the process of retinopathy has been affected by regulating the level of VEGF.
		                        		
		                        		
		                        		
		                        	
7. Effects of different radiation on chromosome aberration in human lymphoblastoid cells
Ruifeng ZHANG ; Yayi YUAN ; Yue REN ; Zhongxin ZHANG ; Juancong DONG ; Xuhong DANG ; Lihong XING ; Yahui ZUO ; Zhikai DUAN
China Occupational Medicine 2017;44(03):341-344
		                        		
		                        			
		                        			 OBJECTIVE: To compare the effects of ~(56)Fe~(17+),~(12)C~(6+)ion beams and~(60)Co γ rays on chromosome aberration in human lymphoblastoid cells. METHODS: The human lymphoblastoid cells were divided into 0. 1,0. 3,0. 5,0. 7,1. 0,2. 0 Gy irradiated groups and 0. 0 Gy control group. They were separately exposed to ~(56)Fe~(17+)ion beams( linear energy transfer was 400. 0 ke V/μm),~(12)C~(6+)ion beams( linear energy transfer was 26. 0 ke V/μm) and~(60)C γ rays. Chromosome specimens were harvested 48 hours after irradiation. The effects of different radiation on dicentric plus centric ring( “d + r”) aberration rate and chromosome aberration in human lymphoblastoid cells were detected by light microscope with artificial counting. RESULTS: The “d + r”aberration rates induced by 0. 3-2. 0 Gy ~(12)C~(6+)ion beams were significantly higher than those of ~(56)Fe~(17+)ion beams and~(60)Co γ rays at the same dose( P < 0. 017). Chromosome aberration cell rates of 0. 1-2. 0 Gy ~(12)C~(6+)ion beams were significantly higher than those of ~(56)Fe~(17+)ion beams and~(60)C γ rays at the same dose( P < 0. 017). At the dose range of 0. 0-2. 0 Gy,chromosome aberration effects of three kinds of radiations were gradually increased( P < 0. 01). The relative biological effectiveness of ~(56)Fe~(17+)ion beams was lower than that of ~(12)C~(6+)ion beams.CONCLUSION: The chromosome aberration induced by ~(12)C~(6+)ion beams was more serious than that of~(60)Co γ rays and ~(56)Fe~(17+)ion beams. 
		                        		
		                        		
		                        		
		                        	
8.Diagnostic value of 18F-FDG PET/CT in differentiating pancreatic lymphoma and pancreatic carcinoma
Shengnan REN ; Jian ZHANG ; Yban YUAN ; Shengping HU ; Chao CHENG ; Aisheng DONG ; Changjing ZUO
Chinese Journal of Pancreatology 2016;16(4):243-247
		                        		
		                        			
		                        			Objective To evaluate the differential diagnostic value of 18F-FDG PET/CT between pancreatic lymphoma (PL) and pancreatic carcinoma (PC).Methods The 18 F-FDG PET-CT data of 16 patients who were pathological diagnosed with PL were retrospectively reviewed and compared with those of 32 consecutive pancreatic cancer patients who were pathologically diagnosed and randomly enrolled.The age,location,diameter and the maximum standard uptake values (SUVmax) of pancreatic lesions,pancreatic ductal dilatation,distal pancreatic atrophy,serum CA19-9 level and extrapancreatic organs involvement were analyzed.Results The 16 patients with PL included 8 men and 8 women,the mean age was (46 ± 17)year,and 11.1% (1/9) patients had elevated CA19-9.The 32 patients with PC included 15 men and 17 women,the mean age was (61 ± 12)year,and 81.3% patients had elevated CA19-9.There were no significant differences on gender between the two groups,while the mean age of PL patients was younger than that of PC,elevated CA19-9 was less common than that in PC,and the differences were statistically significant (all P<0.05).There were 12 cases of diffusive large B cell lymphoma,2 cases of B lymphoblastic lymphoma/leukaemia,1 case of follicular lymphoma and 1 case of dysplastic large T cell lymphoma in 16 PL patients.There was no significant difference on the site of pancreatic lesions between the two groups,but long diameter of PL lesions was larger than that of PC [(6.6 ± 3.3) vs (4.3 ± 1.8) cm,P =0.038].Dilated pancreatic duct and distal parenchyma atrophy in PL were less than those in PC (3/16 vs 17/32,1/16 vs 13/32),and SUVmax of PL lesions was significantly higher than that of PC (12.0 ± 5.5 vs 8.6 ± 3.8),indicating that the differences were statistically significant (all P < 0.05).The cut-off value of SUVmax was 9.95,and Youden's index was 0.406 with the sensitivity and specificity of 68.8% and 71.9% for differentiating PL from PC.The incidence of extrapancreatic lesions including bone marrow and kidney and spleen infiltration was significantly more frequent in patients with PL than that in patients with PC(56.3% vs 6.25%,43.8% vs 3.1%,50.0% vs 6.3%),while the incidence of liver metastases was significantly lower than that in PC (12.5% vs 5.0%),indicating that the differences were statistically significant (all P <0.01).There were no significant differences on the incidence of other extrapancreatic lesions.Conclusions PL should be considered in relatively younger patients and manifested as a bulky mass with significant FDG uptake and extrapancreatic involvement of bone,kidney and spleen but without distinct pancreatic ductal dilation or distal parenchymal atrophy or liver metastasis.
		                        		
		                        		
		                        		
		                        	
9.Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced Acute Lung Injury in Mice.
Dong-Dong WU ; Pin-Hua PAN ; Ben LIU ; Xiao-Li SU ; Le-Meng ZHANG ; Hong-Yi TAN ; Zu CAO ; Zuo-Ren ZHOU ; Hai-Tao LI ; Hao-Si LI ; Li HUANG ; Yuan-Yuan LI
Chinese Medical Journal 2015;128(19):2638-2645
BACKGROUNDPyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.
METHODSC57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.
RESULTSThe expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.
CONCLUSIONSThis study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.
Acute Lung Injury ; chemically induced ; prevention & control ; Amino Acid Chloromethyl Ketones ; pharmacology ; Animals ; Lipopolysaccharides ; toxicity ; Macrophages, Alveolar ; drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Pyroptosis ; drug effects
10.Study of relationship between the state of sugar metabolic regulation and serum 25-hydroxyl Vitamin D3 levels of healthy adults
Ming-Xia LI ; Li SHI ; Yi-Feng ZHAO ; Wei-Fang HAO ; Li-Juan ZUO ; Ming-Hui ZHANG ; Wei-Dong REN ; Jun GU
The Chinese Journal of Clinical Pharmacology 2015;(21):2105-2107
		                        		
		                        			
		                        			Objective To investigate the relationship between the state of sugar metabolic regulation and serum 25 -hydroxyl Vitamin D3[25(OH)D] levels of healthy adult. Methods A total of 102 healthy adults who were received health examination in our hospital were enroll for the study.Their state of sugar metabolic regulation were evalua-ted through the homeostasis model assessment B cell function index ( HOMA-B) , secretion index ( IS ) , the sensitive index ( IAI ) , and insulin resistance index ( HOMA-IR).Healthy adults cases were divid-ed into the 25( OH) D reduction group and normal group according to the serum 25 ( OH ) D level. Clinical data were compared between two groups.25 ( OH ) D, HOMA-B, IS, HOMA -IR followed abnormal distribution were analyzed by logarithmic transformation. Pearson correlation analysis and multiple linear regression analysis were performed to investigate the relationship between the index of sugar metabolic regulation and serum 25-hydroxyl Vitamin D3 levels. Results The serum 25(OH)D level of 64 cases (62.7%) decreased.Lg(HOMA-B), Lg(IS), IAI of the 25(OH)D reduction group were significantly higher than those of normal group ( P<0.05 ) , and Lg ( HOMA -IR ) was significantly lower than that of normal group(P<0.05).Lg[25(OH)D] was positively correlated with Lg(HOMA-B), Lg(IS),IAI(P<0.05),andnegativelycorrelatedwithLg(HOMA-IR)(P<0.05).Conclusion 25(OH)D could improve the function of pancreatic islet B cell and sensitivity of insulin, thus the adults with decreased serum 25 ( OH) D level are advised to receive appropriate VD supplement.
		                        		
		                        		
		                        		
		                        	
            
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