Strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate for benign prostate hyperplasia / 中华男科学杂志

Objective@#To explore the strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate (PKEP) for benign prostate hyperplasia (BPH).@*METHODS@#We treated 65 BPH patients by PKEP with preservation of urinary continence (UC-PKEP), which involved protection of the external urethral sphincter in the beginning of surgery, proper preservation of the anterior lobe of the prostate to protect the internal urethral sphincter in the middle, and preservation of the integrity of the bladder neck towards the end. We compared the postoperative status of urinary continence of the patients with that of the 54 BPH cases treated by complete plasmakinetic enucleation of the prostate (Com-PKEP).@*RESULTS@#All the operations were performed successfully with the urinary catheters removed at 5 days after surgery. In comparison with Com-PKEP, UC-PKEP achieved evidently lower incidence rates of urinary incontinence at 24 hours (31.49% vs 13.85%, P 0.05), and 3 months (3.70% vs 0%, P >0.05) after catheter removal. Compared with the baseline, the maximum urinary flow rate (Qmax) was significantly improved postoperatively in both the Com-PKEP (［7.43 ± 3.26］ vs ［20.58 ± 3.22］ ml, P <0.05) and the UC-PKEP group (［8.04 ± 2.28］ vs ［20.66 ± 3.08］ ml, P <0.05).@*CONCLUSIONS@#Transurethral PKEP is a safe and effective method for the management of BPH, during which the strategies of avoiding blunt or sharp damage to the external urethral sphincter in the beginning, properly preserving the anterior lobe of the prostate in the middle and preserving the integrity of the bladder neck towards the end may help to achieve rapid recovery of urinary continence.

Virtual mutagenesis of isocitrate dehydrogenase 1 involved in glioblastoma multiforme / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT), consequently reducing the production of α-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway. However, given that the roles of other active sites in IDH1 substrate binding remain unclear, we aimed to investigate IDH1 mutation pattern and its influence on enzyme function.</p><p><b>METHODS</b>Fifteen IDH1 catalytic active site candidates were selected for in silico mutagenesis and protein homology modeling. Binding free energy of the IDH1/ICT complexes with single-site mutations was compared with that of the wild type. The affinity of 10 IDH1 catalytic active sites for the ICT substrate was further calculated.</p><p><b>RESULTS</b>The IDH1 active site included seven residues from chain A (A77Thr, A94Ser, A100Arg, A132Arg, A109Arg, A275Asp, and A279Asp) and three residues from chain B (B214Thr, B212Lys, and B252Asp) that constituted the substrate ICT-binding site. These residues were located within 0.5 nm of ICT, indicating a potential interaction with the substrate. IDH1 changes of binding free energy (ΔE) suggested that the A132Arg residue from chain A contributes three hydrogen bonds to the ICT α-carboxyl and β-carboxyl groups, while the other nine residues involved in ICT binding form only one or two hydrogen bonds. Amino acid substitutes at A132Arg, A109Arg, and B212Lys sites, had the greatest effect on enzyme affinity for its substrate.</p><p><b>CONCLUSIONS</b>Mutations at sites A132Arg, A109Arg, and B212Lys reduced IDH1 affinity for ICT, indicating these active sites may play a central role in substrate binding. Mutations at sites A77Thr, A94Ser, and A275Asp increased the affinity of IDH1 for ICT, which may enhance IDN1 catalytic activity. Mutant IDH1 proteins with higher catalytic activity than the wild-type IDH1 could potentially be used as a novel gene therapy for glioblastoma multiforme.</p>

Evidence grading system and its usage in clinical decision-making analysis / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore feasibility of applying evidence grading system in clinical decision-making analysis.</p><p><b>METHODS</b>Using grading system as well as a quantitative approach to generate the threshold NNT((T)), and conducting clinical decision-making analysis through one study on Asymptomatic carotid atherosclerosis.</p><p><b>RESULTS</b>NNT((T)) was 12, comparing with no-intervention in the ACA study that NNT = 6. NNT < NNT((T)) indicated the benefits of intervention outweigh the risks and costs.</p><p><b>CONCLUSION</b>To obtain the rate of adverse event and the specifying approximate cost were vital in the process of applying grading system in clinical decision-making.</p>