This study was conducted to explore the feasibility of partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of benign tumors of the pancreatic head(BTPH). From November 2006 to Febr...This study was conducted to explore the feasibility of partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of benign tumors of the pancreatic head(BTPH). From November 2006 to February 2009, four patients(three female and one male) with a mean age of 34.3 years(range: 21-48 years) underwent partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of BTPH(diameters of 3.2-4.5 cm) using small incisions(5.1-7.2 cm). Preoperative symptoms include one case of repeated upper abdominal pain, one case of drowsiness and two cases with no obvious preoperative symptoms. All four surgeries were successfully performed. The mean operative time was 196.8 min(range 165-226 min), and average blood loss was 138.0 m L(range: 82-210 m L). The mean postoperative hospital stay was 7.5 d(range: 7-8 d). In one case, the main pancreatic duct was injured. Pathological examination confirmed that one patient suffered from mucinous cystadenoma, one exhibited insulinoma, and two patients had solid-pseudopapillary neoplasms. There were no deaths or complications observed during the perioperative period. All patients had no signs of recurrence of the BTPH within a follow-up period of 48-76 mo and had good quality of life without diabetes. Partial pancreatic head resection with Roux-en-Y pancreatic jejunostomy is feasible in selected patients with BTPH.展开更多
Mammals exhibit limited heart regeneration ability,which can lead to heart failure after myocardial infarction.In contrast,zebrafish exhibit remarkable cardiac regeneration capacity.Several cell types and signaling pa...Mammals exhibit limited heart regeneration ability,which can lead to heart failure after myocardial infarction.In contrast,zebrafish exhibit remarkable cardiac regeneration capacity.Several cell types and signaling pathways have been reported to participate in this process.However,a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable.We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration.We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes,and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration.Furthermore,we identified a regeneration-induced cell(RIC)population in the epicardium-derived cells(EPDC),and demonstrated Angiopoietin 4(Angpt4)as a specific regulator of heart regeneration.angpt4 expression is specifically and transiently activated in RIC,which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway,and further induces activation of cathepsin K in cardiomyocytes through RA signaling.Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation,while overexpression of angpt4 accelerates regeneration.Furthermore,we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes,and promote cardiac repair in mice after myocardial infarction,indicating that the function of Angpt4 is conserved in mammals.Our study provides a mechanistic understanding of heart regeneration at single-cell precision,identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration,and offers a novel therapeutic target for improved recovery after human heart injuries.展开更多
Dear Editor,Myocardial infarction(MI)is one of the leading causes of cardiovascular-related mortality worldwide.Timely restoration of the blood supply to ischemic my-ocardium by thrombolysis or percuta-neous coronary ...Dear Editor,Myocardial infarction(MI)is one of the leading causes of cardiovascular-related mortality worldwide.Timely restoration of the blood supply to ischemic my-ocardium by thrombolysis or percuta-neous coronary intervention is a com-mon clinical practice and decreases the mortality risk for MI patients(Heusch,2020).展开更多
Gaining cellular and molecular insights into heart development and regeneration will likely provide new therapeutic targets and opportunities for cardiac regenerative medicine,one of the most urgent clinical needs for...Gaining cellular and molecular insights into heart development and regeneration will likely provide new therapeutic targets and opportunities for cardiac regenerative medicine,one of the most urgent clinical needs for heart failure.Here we present a review on zebrafish heart development and regeneration,with a particular focus on early cardiac progenitor development and their contribution to building embryonic heart,as well as cellular and molecular programs in adult zebrafish heart regeneration.We attempt to emphasize that the signaling pathways shaping cardiac progenitors in heart development may also be redeployed during the progress of adult heart regeneration.A brief perspective highlights several important and promising research areas in this exciting field.展开更多
Dear Editor: Gao et al. published data in Nature Biotechnology (Nat Biotechnol. 2016 May 2) showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute (NgAgo) protein targeted 47 mammali...Dear Editor: Gao et al. published data in Nature Biotechnology (Nat Biotechnol. 2016 May 2) showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute (NgAgo) protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo's utility in various cells and organisms such as mouse and zebrafish for gene editing.展开更多
Heart regeneration is a fascinating and complex biological process. Decades of intensive studies have revealed asophisticated molecular network regulating cardiac regeneration in the zebrafish and neonatal mouse heart...Heart regeneration is a fascinating and complex biological process. Decades of intensive studies have revealed asophisticated molecular network regulating cardiac regeneration in the zebrafish and neonatal mouse heart. Here,we review both the classical and recent literature on the molecular and cellular mechanisms underlying heartregeneration, with a particular focus on how injury triggers the cell-cycle re-entry of quiescent cardiomyocytes toreplenish their massive loss after myocardial infarction or ventricular resection. We highlight several importantsignaling pathways for cardiomyocyte proliferation and propose a working model of how these injury-inducedsignals promote cardiomyocyte proliferation. Thus, this concise review provides up-to-date research progresses onheart regeneration for investigators in the field of regeneration biology.展开更多
Myocardial infarction is a devastating disease worldwide.At present,nearly 40 million patients suffer from heart failure.Owing to a lack of adequate blood supply,25%of cardiomyocytes are subjected to apoptosis and nec...Myocardial infarction is a devastating disease worldwide.At present,nearly 40 million patients suffer from heart failure.Owing to a lack of adequate blood supply,25%of cardiomyocytes are subjected to apoptosis and necrosis within a few hours after infarction.It remains challenging to find effective therapeutic methods for heart failure.On the other hand,zebrafish and neonatal mouse hearts have a strong ability to regenerate(Poss et al.,2002;Raya et al.,2003;Porrello et al.,2011),and their regeneration derives from existing cardiomyocytes(Jopling et al.,2010;Kikuchi et al..展开更多
Organ regeneration is an important, fascinating, and old topic while much remains unknown in spite of extensiveinvestigations for decades. From March 25th to 27th, 2021, the Third Chinese Symposium on Organ Regenerati...Organ regeneration is an important, fascinating, and old topic while much remains unknown in spite of extensiveinvestigations for decades. From March 25th to 27th, 2021, the Third Chinese Symposium on Organ Regenerationtook place in the beautiful ocean city of Zhoushan, Zhejiang, China. This biennial conference attracted ~ 300 academicattendees: students, postdoctoral fellows, and principal investigators, in addition to few industrial investigators.The mixed live and virtual talks covered the broad field of organ regeneration from different animal organisms tohuman organoids, and concluded with some impressive advances on inflammatory signaling, regenerative signalingmechanisms, new technologies, and applications for organ regeneration.展开更多
Some lower vertebrates such as zebrafish and axolotl have incredible cardiac regenerative potential while mammals have very limited ones.Comparative studies among species have revealed that cardiomyocyte polyploidy,en...Some lower vertebrates such as zebrafish and axolotl have incredible cardiac regenerative potential while mammals have very limited ones.Comparative studies among species have revealed that cardiomyocyte polyploidy,endothermy,and injury-induced activation of certain transcriptional factors including AP1 complexes are critical for cardiomyocyte proliferation and heart regeneration during animal evolution.Gaining insights into these evolutionarily conserved mechanisms will likely lead to achieving heart regeneration in non-regenerative mammals including humans.展开更多
基金Supported by Capital Medical Science Development Funds of China,No.2009-3027
文摘This study was conducted to explore the feasibility of partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of benign tumors of the pancreatic head(BTPH). From November 2006 to February 2009, four patients(three female and one male) with a mean age of 34.3 years(range: 21-48 years) underwent partial pancreatic head resection and Roux-en-Y pancreatic jejunostomy for the treatment of BTPH(diameters of 3.2-4.5 cm) using small incisions(5.1-7.2 cm). Preoperative symptoms include one case of repeated upper abdominal pain, one case of drowsiness and two cases with no obvious preoperative symptoms. All four surgeries were successfully performed. The mean operative time was 196.8 min(range 165-226 min), and average blood loss was 138.0 m L(range: 82-210 m L). The mean postoperative hospital stay was 7.5 d(range: 7-8 d). In one case, the main pancreatic duct was injured. Pathological examination confirmed that one patient suffered from mucinous cystadenoma, one exhibited insulinoma, and two patients had solid-pseudopapillary neoplasms. There were no deaths or complications observed during the perioperative period. All patients had no signs of recurrence of the BTPH within a follow-up period of 48-76 mo and had good quality of life without diabetes. Partial pancreatic head resection with Roux-en-Y pancreatic jejunostomy is feasible in selected patients with BTPH.
基金the National Key Research and Development Program of China and the National Natural Science Foundation of China(NSFC)(Grant Nos.2018YFA0801001,32070824,31871458,2019YFA0802800,2016YFA0100500,31671500,81371264,31671177,and 2018YFA0800501).
文摘Mammals exhibit limited heart regeneration ability,which can lead to heart failure after myocardial infarction.In contrast,zebrafish exhibit remarkable cardiac regeneration capacity.Several cell types and signaling pathways have been reported to participate in this process.However,a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable.We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration.We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes,and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration.Furthermore,we identified a regeneration-induced cell(RIC)population in the epicardium-derived cells(EPDC),and demonstrated Angiopoietin 4(Angpt4)as a specific regulator of heart regeneration.angpt4 expression is specifically and transiently activated in RIC,which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway,and further induces activation of cathepsin K in cardiomyocytes through RA signaling.Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation,while overexpression of angpt4 accelerates regeneration.Furthermore,we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes,and promote cardiac repair in mice after myocardial infarction,indicating that the function of Angpt4 is conserved in mammals.Our study provides a mechanistic understanding of heart regeneration at single-cell precision,identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration,and offers a novel therapeutic target for improved recovery after human heart injuries.
基金supported by grants from the National Key R&D Program of China(2018YFA0800501,2019YFA0801602)the National Natural Science Foundation of China(32230032,31730061,31430059,81870198)and Synogen Biopharma Co.,Nanjing,China.
文摘Dear Editor,Myocardial infarction(MI)is one of the leading causes of cardiovascular-related mortality worldwide.Timely restoration of the blood supply to ischemic my-ocardium by thrombolysis or percuta-neous coronary intervention is a com-mon clinical practice and decreases the mortality risk for MI patients(Heusch,2020).
基金supported by the grants from the National Basic Research Program of China(Nos.2010CB529503 and 2012CB944501)the National Science Foundation of China(Nos.30971662 and 31000644)
文摘Gaining cellular and molecular insights into heart development and regeneration will likely provide new therapeutic targets and opportunities for cardiac regenerative medicine,one of the most urgent clinical needs for heart failure.Here we present a review on zebrafish heart development and regeneration,with a particular focus on early cardiac progenitor development and their contribution to building embryonic heart,as well as cellular and molecular programs in adult zebrafish heart regeneration.We attempt to emphasize that the signaling pathways shaping cardiac progenitors in heart development may also be redeployed during the progress of adult heart regeneration.A brief perspective highlights several important and promising research areas in this exciting field.
文摘Dear Editor: Gao et al. published data in Nature Biotechnology (Nat Biotechnol. 2016 May 2) showing that DNA-guided genome editing using the Natronobacterium gregoryi Argonaute (NgAgo) protein targeted 47 mammalian genomic loci with a 100% success rate and an efficiency of 21.3%-41.3% at various targets. This report led us to test NgAgo's utility in various cells and organisms such as mouse and zebrafish for gene editing.
基金This paper was supported by grants from the National Key Research&Development Program of China(2018YFA080051)the National Natural Science Foundation of China(31730061 and 81870198).
文摘Heart regeneration is a fascinating and complex biological process. Decades of intensive studies have revealed asophisticated molecular network regulating cardiac regeneration in the zebrafish and neonatal mouse heart. Here,we review both the classical and recent literature on the molecular and cellular mechanisms underlying heartregeneration, with a particular focus on how injury triggers the cell-cycle re-entry of quiescent cardiomyocytes toreplenish their massive loss after myocardial infarction or ventricular resection. We highlight several importantsignaling pathways for cardiomyocyte proliferation and propose a working model of how these injury-inducedsignals promote cardiomyocyte proliferation. Thus, this concise review provides up-to-date research progresses onheart regeneration for investigators in the field of regeneration biology.
基金supported by grants from the National Natural Science Foundation of China(Nos.31730061,81870198 and 31821091)the National Key R&D Program of China(2018YFA080050 and 2019YFA0801602)
文摘Myocardial infarction is a devastating disease worldwide.At present,nearly 40 million patients suffer from heart failure.Owing to a lack of adequate blood supply,25%of cardiomyocytes are subjected to apoptosis and necrosis within a few hours after infarction.It remains challenging to find effective therapeutic methods for heart failure.On the other hand,zebrafish and neonatal mouse hearts have a strong ability to regenerate(Poss et al.,2002;Raya et al.,2003;Porrello et al.,2011),and their regeneration derives from existing cardiomyocytes(Jopling et al.,2010;Kikuchi et al..
基金The authors were supported by grants from the National Key R&D Program of China(2018YFA0800501 and 2019YFA0801602)the National Natural Science Foundation of China(31730061 and 31430059)。
文摘Organ regeneration is an important, fascinating, and old topic while much remains unknown in spite of extensiveinvestigations for decades. From March 25th to 27th, 2021, the Third Chinese Symposium on Organ Regenerationtook place in the beautiful ocean city of Zhoushan, Zhejiang, China. This biennial conference attracted ~ 300 academicattendees: students, postdoctoral fellows, and principal investigators, in addition to few industrial investigators.The mixed live and virtual talks covered the broad field of organ regeneration from different animal organisms tohuman organoids, and concluded with some impressive advances on inflammatory signaling, regenerative signalingmechanisms, new technologies, and applications for organ regeneration.
文摘Some lower vertebrates such as zebrafish and axolotl have incredible cardiac regenerative potential while mammals have very limited ones.Comparative studies among species have revealed that cardiomyocyte polyploidy,endothermy,and injury-induced activation of certain transcriptional factors including AP1 complexes are critical for cardiomyocyte proliferation and heart regeneration during animal evolution.Gaining insights into these evolutionarily conserved mechanisms will likely lead to achieving heart regeneration in non-regenerative mammals including humans.