The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective:To investigate the long term outcome of artificial urinary sphincter implantation for patients with stress urinary incontinence.Methods:The data of 46 patients who underwent artificial urethral sphincter implantation in China Rehabilitation Research Center from April 2002 to April 2022 were retrospectively analyzed.The patients’ age ranged from 19-80 years old (median 45.6 years). There were 45 males and 1 female. The history of illness was 8 months to 33 years. The patients category were urethral injuries associated urinary incontinence ( n=24), neurogenic urinary incontinence ( n=9) and post-prostatectomy incontinence ( n=13). Preoperative daily pad usage was 3.5±1.0. The impact of incontinence on the quality of life (QOL)measured by the visual analogue scale (VAS)was 7.1±1.2. All 46 patients underwent artificial urethral sphincter implantation, of which 20 patients were treated with anticholinergic drugs (5 cases) or urinary tract related surgery (urethral stenosis incision in 2 cases, sphincterectomy in 3 cases, urethral dilation in 5 cases, urethral calculus lithotripsy in 1 case, and augmentation cystoplasty in 4 cases) before artificial urethral sphincter implantation. Of the 45 male patients, 25 patients had the transperineal approach and 20 had the trans-scrotal approach. The female case had a trans-retropubic approach. Different cuffs size was used based on individual circumference of bulbar urethra (45 male cases: 4.5cm in 16 cases, 4.0cm in 29 cases; one female case: 8.0cm). Long-term surgical efficacy was evaluated. Assessments included postoperative urinary continence (socially continent: one pad per day or less; complete dry: wearing no pads), artificial urinary sphincter status and complications. The influences of patients of different etiologies, surgical approaches and cuff size on surgical results were compared. Results:The mean follow-up time was 7.1 years ranged from 6 months to 19 years. At the latest visit, 32 patients (69.6%) maintained the primary functional artificial urinary sphincter. Three patients (6.5%) had artificial urinary sphincter revisions and maintained continence with the new device. 11 patients (23.9%) removed the artificial urinary sphincter because of post-complications. Thirty-five patients were socially continent, of which 16 patients were totally dry, leading to the overall social continent rate as 76.1%(35/46). There was a significant reduction in pad usage to 1.2±0.6 diapers per day ( P<0.001). The impact of incontinence on the QOL measured by the VAS dropped to 2.6±1.9 ( P<0.001). The complication rate was 32.6%(15/46), including infections ( n=4), erosions ( n=5), mechanical failure ( n=3), dysurie ( n=2) and urethral atrophy ( n=1). There were no significant differences in social continent rate between patients with different etiologies[75.0%(18/24)vs. 66.7%(6/9) vs. 84.6%(11/13)], perioperative complications [37.5%(9/24)vs. 33.3%(3/9) vs. 23.1%(3/13)] and device re-intervention rate[37.5%(9/24) vs. 33.3%(3/9)vs. 15.4%(2/13)]. There were no statistically significant differences in postoperative complete dry rate [32%(8/25)vs. 40%(8/20), P=0.76] and postoperative device failure free rate [60%(15/25)vs. 80%(16/20), P=0.20] between trans-perineal group and trans-scrotal group. There was no statistically significant difference in postoperative social continent rate between 4.5cm cuff and 4.0 cuff[75%(12/16) vs. 65.5%(19/29), P=0.74]. Conclusions:Artificial urethral sphincter implantation is an effective treatment for stress urinary incontinence due to intrinsic sphincter deficiency. There was no difference in the continent rate and complication rate between patients of different etiologies, different surgical approaches and cuff size selection.

The minimally invasive cardiovascular surgery developed rapidly in last decades. In order to promote the development of minimally invasive cardiovascular surgery in China, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) has gradually standardized the collection and report of the data of Chinese minimally invasive cardiovascular surgery since its establishment. The total operation volume of minimally invasive cardiovascular surgery in China has achieved substantial growth with a remarkable popularization of concepts of minimally invasive medicine in 2019. The data of Chinese minimally invasive cardiovascular surgery in 2019 was reported as a paper for the first time, which may provide reference to cardiovascular surgeons and related professionals.

Objective To assess clinical and urodynamic results of augmentation enterocystoplasty (AE) in patients with ncurogcnic hladdcr dysfunction (NBD).Methods Retrospectively reviewed our database between 2005-2011 to identify 77 patients who underwent AE ( sigmoid 74 patients,ileum 3 patients).Postoperativc complications,renal function,urodynamics parameters and quality of daily life were evaluated.Results The mean follow-up length was 24 months.Compared with pre-operative condition,the mean bladder capacity significantly increased from (160.6 ± 128.3) to (468.5 ± 60.6) ml (P ＜0.001 ) and the maximum detrusor pressure decreased from ( 31.1 ± 26.4) to ( 10.9 ± 4.5 ) cm H2O ( P =0.002 ).Serum creatinine level decreased from (270.3 ± 113.6 ) to ( 174.4 ± 81.3 ) μmol/(l) ( P =0.00 1 ).There were significant decrease on mean number of incontinence episodes and pads used per day ( P ＜0.01 ).Post-operative complications included metabolic acidosis in two patients (2.6％),adhesive intestinal obstruction in four patients (5.2％),deteriorating renal function in one patients ( 1.2％ ) and recurrence of vesicoureteral reflux in three patients (3.9％).Conclusions The results suggest that AE is safe and effective in treating patients with NBD.Concomitant URI is considerèd on patients with long illness history,vesicoureteral reflux at low intravesical pressures and upper urinary tract dilation.Patients with moderate and severe upper urinary tract deteriorations benefit from this procedure and the benefit can maintain a long time.

Objective To evaluate the long-term outcome of reconstruction for urinary conti-nence function by using implantation of artificial urinary sphincter (AUS). Methods From 2002 to 2005,15 incontinent patients (14 men and 1 woman) with age range of 19-75 years treated with im-plantation of AUS were followed up. In 15 eases, there were 5 cases with traumatic urinary inconti-nence, 1 with neurogenic stress incontinence, 1 with neurogenic urgent incontinence,6 with postpros-tatectomy incontinence and 2 with neurogenie voiding dysfunction. Three eases had taken urethro-stenotomy, 3 had sphineterotomy and 1 had enterocystoplasty and ureterovesieostomy before the im-plantation for AUS. The patients were followed up for 13-55 months with mean of 37 months. The information about the continence status and pads usage, also the complications were collected. Results After implantation, 13 cases(87%)used AUS device normally, 12(92%)beeame dry and 1 (8%) got social continence. Eleven cases (85%) got continence depending on the original implanted AUS and 15% did continence by reoperation. There were 4 cases(27%) with complications including erosion of skin and urethral in 1, graft rejection in 1, urethral atrophy in 1, and voiding dysfunction in 1. Durability of 11 cases with original implanted devices was 13-55 months with mean of 38 months.Conclusion The implantation of AUS is a long-term reliable method in reconstruction for lower uri-nary tract function.

Objective To investigate the effect of Holmium laser urethrotomy under ureteroscopy on urethral stricture.Methods 30 men with urethral stricture who accepted urethrotomy with Holmium laser under ureteroscopy were observed.Results Operation was performed successfully in 21 cases;7 cases underwent 2～3 endoscopic surgical treatments.Endoscopic surgical treatment failed in 2 cases,and open surgery were performed on them.21 cases were followed up for 3～37 months,and 8 of them need urethral dilatation termly.Conclusion Endoscopic surgery with ureteroscopy and Holmium laser may be effective on urethral stricture with slight trauma.

Objective To evaluate the effectiveness and safety of Botulinum toxin-A (BTX-A) injection into detrusor to treat neurogenic detrusor overactivity in patients with spinal cord injury (SCI).Methods A total of 78 patients with SCI were treated with transurethral injection of BTX-A (300 IU dissolved in 15 ml of saline) into 30 different points of detrusor with 15 ml in every patients. Urodynamic parameters and voiding diary were assessed at baseline and 3 weeks and 3 months after the injections. Adverse events were recorded after the injection if present.Results After the first injection, 78 patients showed that the mean frequencies of incontinence decreased from 13.5 to 2.7 times per day, the mean volume of intermittent catheterization (IC) increased from 131 ml to 389 ml per time, the mean volume of incontinence decreased from 1 690 ml to 281 ml per day, the mean getting effect time was 7.6 days. 10 patients received second injection at 8.9 months after first injection, the results showed that the mean frequencies of incontinence decreased from 9.7 to 3.7 times per day, the mean IC volume increased from 108 ml to 387 ml. 6 patients received third injection at 5.8 months after second injection, the results showed that the mean frequencies of incontinence decreased from 9.2 to 3.9 times per day, the mean IC volume increased from 116 ml to 364 ml. No side effects were observed during the follow-up.Conclusion BTX-A injection into detrusor to treat neurogenic detrusor overactivity in patients with SCI seems to be an effective, safe and miniinvasive solution.

ObjectiveTo study the videourodynamic characteristics in spina bifida patients and to discuss the urodynamic risk factors causing the upper urinary tract deterioration.Methods33 cases with spina bifida were evaluated with non-complete synchronized videourodynamic test.Filling-phase function of bladder was evaluated with bladder sensation,detrusor activity,compliance,relative safe capacity,detrusor leak point pressure and presence of vesicoureteral reflux;voiding phase function was evaluated with detrusor pressure,the synergy between detrusor and external sphincter,the pressure-flow study.Patients were classified into upper urinary tract damage group and non-damage group according to the imaging and renal function test.The urodynamic parameters between the two groups were compared statistically.Results17 cases were found upper urinary tract damage(51%)in which 11 with vesicoureteral reflux and 6 was non-reflux hydronephrosis.Bladder compliance and relative safe capacity were significantly different between the two groups.ConclusionSpina bifida patients complicate a high incidence of upper urinary damage,especially vesicoureteral reflux.Low compliance and small relative safe capacity may be the major urodynamic risk factors causing upper urinary tract damage.

ObjectiveTo evaluate the effects of Botulinum toxin type A(BTX-A) repeated injection into detrusor to treat detrusor hyperreflexia and neurogenic incontinence in spinal cord injury(SCI) patients.Methods6 patients with SCI were included into the study.300 U of BTX-A was dissolved in saline 15 ml,and injected into 30 different sites in detrusor using a flexible cystoscopic needle.BTX-A injection was repeated 3 times for all the patients.Urodynamic examination,voiding diary and toxic effects were recorded.ResultsThe improvement for symptoms was observed within 5 to 21 days.The effects of injections lasted averagely 8.9 and 5.8 months for each injection.After the first injection,the mean frequency of incontinence decreased from 10.1 /d to 3.3 /d.The mean volume of intermittent catheterization(IC) increased from 98.5 ml to 404.2 ml each time.Mean cystometric volume increased from 95.4 ml to 385.6 ml,mean maximum storage detrusor pressure decreased from 105.8 cmH2O to 31 cmH2O.After the second injection,the mean frequency of incontinence decreased from 9.7/d to 3.7/d.The mean volume of IC increased from 108.3 ml to 387.2 ml each time.Mean cystometric bladder storage volume increased from 105.4 ml to 375.6 ml.Mean maximum storage detrusor pressure decreased from 97.8 cmH2O to 33 cmH2O.After the third injection,the mean frequency of incontinence decreased from 9.2/d to 3.9/d.The mean volume of IC increased from 115.7 ml to 363.9 ml each time.Mean cystometric volume increased from 102 ml to 357.6 ml.Mean maximum storage detrusor pressure decreased from 98.1 cmH2O to 36.9 cmH2O.The patients were followed up for 6 months.No adverse and toxic effect was observed.ConclusionBotulinum toxin type A repeated injection into detrusor is effective,safe,feasible and mini-invasive to treat detrusor hyperreflexia and neurogenic incontinence in patients with SCI.Botulinum toxin type A repeated injection into detrusor is effective,safe,feasible and mini-invasive to treat detrusor hyperreflexia and neurogenic incontinence in patients with SCI.

ObjectiveTo explore the effects of sacral neuromodulation using a new tined-lead electrode on neurogenic bladder.MethodsThe use of a new tined-lead electrode for sacral neuromodulation was evaluated in a study including 5 consecutive patients with neurogenic bladder.The tined leads were implanted at the S3 foramen under the X-ray screening.Subjects completed the recording of detailed voiding diary pre-and post-operation including fluid intake,voided volume,leaked volume,catheterized volume,frequency,accompanying symptoms and sensation.Vesicourethral function was assessed by video-urodynamics.ResultsUrinary frequency and voided volume were improved 22% and 49% respectively in one patient with spinal bifida.Urinary frequency,voided volume and residual volume were improved 0.7%,11% and 46% respectively in another one.Urinary frequency,voided volume and residual volume were improved 0.4%,18% and 44% respectively in the third one.Frequency of leakage and leaked volume were improved 36% and 54% respectively in the patient with brain trauma.Frequency of CIC and catheterized volume were improved 42% and 54% respectively,and indexes of urodynamics were improved 37%～45% in the patient with spinal cord injury.ConclusionA new tined-lead electrode for sacral neuromodulation provide a new alterative and minimally invasive procedure to treat neurogenic bladder.