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Marcello Ceccaroni,Giovanni Roviglione,Mario Malzoni,Francesco Cosentino,Emanuela Spagnolo,Roberto Clarizia,Paolo Casadio,Renato Seracchioli,Fabio Ghezzi,Daniele Mautone,Francesco Bruni,Stefano Uccell 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.1
Objective: Total laparoscopic nerve-sparing radical hysterectomy (TL-NSRH) has beenconsidered a promising approach, however, surgical, clinical, oncological and functionaloutcomes have not been systematically addressed. We present a large retrospective multi center experience comparing TL-NSRH vs. open abdominal NSRH (OA-NSRH) for early andlocally-advanced cervical cancer, with particular emphasis on post-surgical pelvic function. Methods: All consecutive patients who underwent class C1-NSRH plus bilateral pelvic + para aortic lymphadenectomy for stage IA2–IIB cervical cancer at 4 Italian gynecologic oncologiccenters (Negrar, Varese, Bologna, Avellino) were enrolled. Patients were divided into TL NSRH and OA-NSRH groups and were investigated with preoperative questionnaires onurinary, rectal and sexual function. Postoperatively, patients filled a questionnaire assessingquality of life, taking into account sexual function and psychological status. Oncologicaloutcomes were analyzed using Kaplan-Meyer method. Results: 301 consecutive patients were included in this study: 170 in the TL-NSRH group and131 in the OA-NSRH group. Patients in the OA-NSRH group were more likely to experienceurinary incontinence and (after 12-months follow-up) urinary retention. No patient in theTL-NSRH group vs. 5 (5.5%) in the OA-NSRH group had complete urinary retention (at the>24-month follow-up [p=0.02]). A total of 20 (11.8%) in the TL-NSRH and 11 (8.4%) patientsin the OA-NSRH had recurrence of disease (p=0.44) and 14 (8.2%) and 9 (6.9%) died ofdisease during follow-up, respectively (p=0.83). Conclusion: Our study shows that TL-NSRH is feasible, safe and effective and conjugatesadequate radicality and improvement in post-operative functional outcomes. Oncologicaloutcomes of laparoscopic procedures deserve further investigation.
Wilson, William C.,Hornig-Do, Hue-Tran,Bruni, Francesco,Chang, Jeong Ho,Jourdain, Alexis A.,Martinou, Jean-Claude,Falkenberg, Maria,Spå,hr, Henrik,Larsson, Nils-Gö,ran,Lewis, Richard J.,Hewit Oxford University Press 2014 Human Molecular Genetics Vol.23 No.23
<P>The p.N478D missense mutation in human mitochondrial poly(A) polymerase (mtPAP) has previously been implicated in a form of spastic ataxia with optic atrophy. In this study, we have investigated fibroblast cell lines established from family members. The homozygous mutation resulted in the loss of polyadenylation of all mitochondrial transcripts assessed; however, oligoadenylation was retained. Interestingly, this had differential effects on transcript stability that were dependent on the particular species of transcript. These changes were accompanied by a severe loss of oxidative phosphorylation complexes I and IV, and perturbation of <I>de novo</I> mitochondrial protein synthesis. Decreases in transcript polyadenylation and in respiratory chain complexes were effectively rescued by overexpression of wild-type mtPAP. Both mutated and wild-type mtPAP localized to the mitochondrial RNA-processing granules thereby eliminating mislocalization as a cause of defective polyadenylation. <I>In vitro</I> polyadenylation assays revealed severely compromised activity by the mutated protein, which generated only short oligo(A) extensions on RNA substrates, irrespective of RNA secondary structure. The addition of LRPPRC/SLIRP, a mitochondrial RNA-binding complex, enhanced activity of the wild-type mtPAP resulting in increased overall tail length. The LRPPRC/SLIRP effect although present was less marked with mutated mtPAP, independent of RNA secondary structure. We conclude that (i) the polymerase activity of mtPAP can be modulated by the presence of LRPPRC/SLIRP, (ii) N478D mtPAP mutation decreases polymerase activity and (iii) the alteration in poly(A) length is sufficient to cause dysregulation of post-transcriptional expression and the pathogenic lack of respiratory chain complexes.</P>