Over the past three decades,there has been increasing interest in miniaturized percutaneous nephrolithotomy(mPCNL)techniques featuring smaller tracts as they offer potential solutions to mitigate complications associa...Over the past three decades,there has been increasing interest in miniaturized percutaneous nephrolithotomy(mPCNL)techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL(sPCNL).However,despite this growing acceptance and recognition of its benefits,unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks.In response to these challenges,an international panel comprising experts from the International Alliance of Urolithiasis(IAU)took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice.This endeavor involved conducting a systematic literature review to identify research gaps(RGs),which formed the foundation for developing a structured questionnaire survey.Subsequently,a two-round modified Delphi survey was implemented,culminating in a group meeting to generate final evidence-based comments.All 64 experts completed the second-round survey,resulting in a response rate of 100.0%.Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains,including general information(13 questions),preoperative work-up(13 questions),procedural tips and tricks(19 questions),and postoperative evaluation and follow-up(13 questions).Additionally,9 questions evaluated the experts’experience with PCNLs.Consensus was reached on 30 questions after the second-round survey,while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting.mPCNL,characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique,has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics.It offers several advantages over sPCNL including reduced bleeding,fewer requirements for nephrostomy tubes,decreased pain,and shorter hospital stays.The series of detailed techniques presented here serve as a comprehensive guide for urologists,aiming to improve their procedural understanding and optimize patient outcomes.展开更多
Identifying prognostic indicators of clear cell renal cell carcinoma(ccRCC)and elucidating the mechanisms underlying ccRCC progression are crucial for improving ccRCC patient prognosis.This study investigated the clin...Identifying prognostic indicators of clear cell renal cell carcinoma(ccRCC)and elucidating the mechanisms underlying ccRCC progression are crucial for improving ccRCC patient prognosis.This study investigated the clinical significance and biological role of Ring finger protein 43(RNF43)in ccRCC.Two independent cohorts of patients with ccRCC were employed to determine the prognostic significance of RNF43 by immunohistochemistry and statistical analyses.In vitro and in vivo experiments,RNA-seq,and other techniques were used to determine the biological role of RNF43 in ccRCC and related molecular mechanisms.RNF43 expression was commonly decreased in ccRCC specimens,and low expression of RNF43 indicated a higher TNM stage,SSIGN score,and WHO/ISUP grade and short survival in patients with ccRCC.Additionally,RNF43 overexpression suppressed the proliferation,migration,and targeted drug resistance of ccRCC cells,while the knockdown of RNF43 enhanced these characteristics of ccRCC.RNF43 knockdown activated YAP signaling by decreasing YAP phosphorylation by p-LATS1/2 and increasing the transcription and nuclear distribution of YAP.By contrast,RNF43 overexpression showed the opposite effects.Decreasing YAP abolished the effect of RNF43 knockdown in promoting the malignant features of ccRCC.Additionally,restoring RNF43 expression suppressed the resistance of the targeted drug pazopanib in in vivo orthotopic ccRCC.Furthermore,combining the expression of RNF43 and YAP with TNM stage or the SSIGN score exhibited greater accuracy than any of these indicators alone in assessing the postoperative prognosis of ccRCC patients.In summary,our study identified a novel tumor suppressor,RNF43,which is also a prognostic indicator and potential target for ccRCC.展开更多
文摘Over the past three decades,there has been increasing interest in miniaturized percutaneous nephrolithotomy(mPCNL)techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL(sPCNL).However,despite this growing acceptance and recognition of its benefits,unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks.In response to these challenges,an international panel comprising experts from the International Alliance of Urolithiasis(IAU)took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice.This endeavor involved conducting a systematic literature review to identify research gaps(RGs),which formed the foundation for developing a structured questionnaire survey.Subsequently,a two-round modified Delphi survey was implemented,culminating in a group meeting to generate final evidence-based comments.All 64 experts completed the second-round survey,resulting in a response rate of 100.0%.Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains,including general information(13 questions),preoperative work-up(13 questions),procedural tips and tricks(19 questions),and postoperative evaluation and follow-up(13 questions).Additionally,9 questions evaluated the experts’experience with PCNLs.Consensus was reached on 30 questions after the second-round survey,while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting.mPCNL,characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique,has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics.It offers several advantages over sPCNL including reduced bleeding,fewer requirements for nephrostomy tubes,decreased pain,and shorter hospital stays.The series of detailed techniques presented here serve as a comprehensive guide for urologists,aiming to improve their procedural understanding and optimize patient outcomes.
基金supported by the Top-Level Clinical Discipline Project of Shanghai Pudong (PWYgf2018-03)National Natural Science Foundation of China (Nos.81773154,81902565,81772747,81974391)+4 种基金Shanghai Natural Science Foundation (No.20ZR1449600)Pudong New Area Science and Technology Development Fund Special Fund for People’s Livelihood Research (Medical and Health) (PKJ2019-Y19)Young Scientists Foundation of Changzhou No.2 People’s Hospital (2019K008)Changzhou Sci&Tech Program (CJ20190100)the Program of Shanghai Academic/Technology Research Leader (No.19XD1405100).
文摘Identifying prognostic indicators of clear cell renal cell carcinoma(ccRCC)and elucidating the mechanisms underlying ccRCC progression are crucial for improving ccRCC patient prognosis.This study investigated the clinical significance and biological role of Ring finger protein 43(RNF43)in ccRCC.Two independent cohorts of patients with ccRCC were employed to determine the prognostic significance of RNF43 by immunohistochemistry and statistical analyses.In vitro and in vivo experiments,RNA-seq,and other techniques were used to determine the biological role of RNF43 in ccRCC and related molecular mechanisms.RNF43 expression was commonly decreased in ccRCC specimens,and low expression of RNF43 indicated a higher TNM stage,SSIGN score,and WHO/ISUP grade and short survival in patients with ccRCC.Additionally,RNF43 overexpression suppressed the proliferation,migration,and targeted drug resistance of ccRCC cells,while the knockdown of RNF43 enhanced these characteristics of ccRCC.RNF43 knockdown activated YAP signaling by decreasing YAP phosphorylation by p-LATS1/2 and increasing the transcription and nuclear distribution of YAP.By contrast,RNF43 overexpression showed the opposite effects.Decreasing YAP abolished the effect of RNF43 knockdown in promoting the malignant features of ccRCC.Additionally,restoring RNF43 expression suppressed the resistance of the targeted drug pazopanib in in vivo orthotopic ccRCC.Furthermore,combining the expression of RNF43 and YAP with TNM stage or the SSIGN score exhibited greater accuracy than any of these indicators alone in assessing the postoperative prognosis of ccRCC patients.In summary,our study identified a novel tumor suppressor,RNF43,which is also a prognostic indicator and potential target for ccRCC.
