Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

BACKGROUND: At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI. METHODS: Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups. RESULTS: Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs . 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs . 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs . 5.6, P <0.001). CONCLUSIONS It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.
Humans ; Male ; Prostatectomy/methods* ; Prostatic Neoplasms/diagnosis* ; Middle Aged ; Aged ; Positron Emission Tomography Computed Tomography/methods* ; Biopsy ; Multiparametric Magnetic Resonance Imaging ; Prostate-Specific Antigen/metabolism*

Objective To explore the efficacy and adverse events of antibody-drug conjugate(ADC)combined with PD-1 inhibitors in neoadjuvant therapy for muscle-invasive bladder cancer.Methods A retrospective study included 22 patients with bladder cancer who received neoadjuvant therapy with ADC combined with PD-1 inhibitors and gemcitabine+cisplatin(GC)regimen combined with PD-1 inhibitors in the Department of Urology,Cancer Hospital,Chinese Academy of Medical Sciences from Nov.2020 to Jan.2025.The patients were divided into the vedotinumab combined with toripalimab group and the GC combined with toripalimab group.The clinical complete response rate(cCR)of the two groups of patients was compared and analyzed,and the adverse events(AEs)that occurred during the medication period were evaluated simultaneously.Results The cCR in the vedotinmab combined with toripalimab group was higher than that in the GC combined with toripalimab group(54.5％vs.27.3％),but the difference was not statistically significant(P=0.387).In the vedotinumab combined with toripalimab group,one patient(9.1％)developed grade 3-4 AEs,presenting with peripheral sensory nerve function decline,nausea,loss of appetite and fatigue.Two patients(18.2％)in the GC combined with toripalimab group developed grade 3-4 AEs,presenting with leukopenia and nausea.Conclusion In neoadjuvant therapy for bladder cancer,ADC(vedotinumab)combined with PD-1 inhibitors(toripalimab)has better clinical complete remission and adverse events compared with the traditional GC combined with PD-1 inhibitors regimen.

Objective To explore the efficacy and adverse events of antibody-drug conjugate(ADC)combined with PD-1 inhibitors in neoadjuvant therapy for muscle-invasive bladder cancer.Methods A retrospective study included 22 patients with bladder cancer who received neoadjuvant therapy with ADC combined with PD-1 inhibitors and gemcitabine+cisplatin(GC)regimen combined with PD-1 inhibitors in the Department of Urology,Cancer Hospital,Chinese Academy of Medical Sciences from Nov.2020 to Jan.2025.The patients were divided into the vedotinumab combined with toripalimab group and the GC combined with toripalimab group.The clinical complete response rate(cCR)of the two groups of patients was compared and analyzed,and the adverse events(AEs)that occurred during the medication period were evaluated simultaneously.Results The cCR in the vedotinmab combined with toripalimab group was higher than that in the GC combined with toripalimab group(54.5％vs.27.3％),but the difference was not statistically significant(P=0.387).In the vedotinumab combined with toripalimab group,one patient(9.1％)developed grade 3-4 AEs,presenting with peripheral sensory nerve function decline,nausea,loss of appetite and fatigue.Two patients(18.2％)in the GC combined with toripalimab group developed grade 3-4 AEs,presenting with leukopenia and nausea.Conclusion In neoadjuvant therapy for bladder cancer,ADC(vedotinumab)combined with PD-1 inhibitors(toripalimab)has better clinical complete remission and adverse events compared with the traditional GC combined with PD-1 inhibitors regimen.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

Objective:To investigate the effect of modified Retzius-sparing robot-assisted radical prostatectomy(RS-RARP) and " Sandwich" technique of total urethral reconstruction on the early postoperative urinary continence.Methods:The clinical data of 70 consecutive patients who underwent RS-RARP by the same operator at the Cancer Hospital of the Chinese Academy of Medical Sciences from October 2021 to November 2023 were retrospectively analyzed. The age was (65.1±8.0) years old, the body mass index (BMI) was (25.6±3.1) kg/m 2, the prostate volume was (31.9±18.1)ml and the preoperative prostate specific antigen(PSA) was (16.3±16.1)ng/ml. Four patients treated with neoadjuvant hormonal therapy before radical prostatectomy. Eleven patients underwent radical prostatectomy without prostate biopsy, while the remaining 59 patients underwent prostate biopsy. There were 10, 23, 14, 10 and 2 patients with Gleason scores of 6, 7, 8, 9 and 10 respectively.There were 48 patients with clinical stage cT 2 and 22 with cT 3. The surgical method was RS-RARP and "Sandwich" technique of total urethral reconstruction. The operation time, intraoperative blood loss, postoperative drain tube preservation time, postoperative hospitalization time, pathological staging and positive margin rate, and recovery of urinary continence immediately after postoperative catheter removal were recorded. Results:In this study, all 70 surgeries were successfully completed, with no cases converted to anterior approach radical surgery or open surgery, and no serious intraoperative complications such as post-shamus hemorrhage or ureteric/rectal injury. The median postoperative follow-up was 14(3, 28) months, and there were no cases of readmission for surgical complications. The duration of surgery was (89.8±19.5) min, and the blood loss volume was (53.7±25.2)ml. The duration of drainage tube after surgery was (6.7±1.8)d, the duration of hospitalization after surgery was (7.1±1.9)d, and the duration of urinary catheter was (8.9±3.0)d. Immediate urinary continence was achieved in 50 cases when the catheter was removed, and the rate of immediate urinary continence was 71.4%(50/70). Postoperative urinary continence rate was 81.4% (57/70) at 1 month after surgery, and 90.0% (63/70) at 3 months after surgery.At 1 month postoperatively, 94.3% (66/70) of patients had a PSA <0.2 ng/ml. At 3 months postoperatively, 98.5% (69/70) of patients had a PSA <0.2 ng/ml.Conclusions:The RS-RARP and "Sandwich" technique of total urethral reconstruction is technically feasible for patients with localized prostate cancer.The short-term follow-up effect of tumor control and urinary continence are satisfactory.

Objective:To investigate the effect of modified Retzius-sparing robot-assisted radical prostatectomy(RS-RARP) and " Sandwich" technique of total urethral reconstruction on the early postoperative urinary continence.Methods:The clinical data of 70 consecutive patients who underwent RS-RARP by the same operator at the Cancer Hospital of the Chinese Academy of Medical Sciences from October 2021 to November 2023 were retrospectively analyzed. The age was (65.1±8.0) years old, the body mass index (BMI) was (25.6±3.1) kg/m 2, the prostate volume was (31.9±18.1)ml and the preoperative prostate specific antigen(PSA) was (16.3±16.1)ng/ml. Four patients treated with neoadjuvant hormonal therapy before radical prostatectomy. Eleven patients underwent radical prostatectomy without prostate biopsy, while the remaining 59 patients underwent prostate biopsy. There were 10, 23, 14, 10 and 2 patients with Gleason scores of 6, 7, 8, 9 and 10 respectively.There were 48 patients with clinical stage cT 2 and 22 with cT 3. The surgical method was RS-RARP and "Sandwich" technique of total urethral reconstruction. The operation time, intraoperative blood loss, postoperative drain tube preservation time, postoperative hospitalization time, pathological staging and positive margin rate, and recovery of urinary continence immediately after postoperative catheter removal were recorded. Results:In this study, all 70 surgeries were successfully completed, with no cases converted to anterior approach radical surgery or open surgery, and no serious intraoperative complications such as post-shamus hemorrhage or ureteric/rectal injury. The median postoperative follow-up was 14(3, 28) months, and there were no cases of readmission for surgical complications. The duration of surgery was (89.8±19.5) min, and the blood loss volume was (53.7±25.2)ml. The duration of drainage tube after surgery was (6.7±1.8)d, the duration of hospitalization after surgery was (7.1±1.9)d, and the duration of urinary catheter was (8.9±3.0)d. Immediate urinary continence was achieved in 50 cases when the catheter was removed, and the rate of immediate urinary continence was 71.4%(50/70). Postoperative urinary continence rate was 81.4% (57/70) at 1 month after surgery, and 90.0% (63/70) at 3 months after surgery.At 1 month postoperatively, 94.3% (66/70) of patients had a PSA <0.2 ng/ml. At 3 months postoperatively, 98.5% (69/70) of patients had a PSA <0.2 ng/ml.Conclusions:The RS-RARP and "Sandwich" technique of total urethral reconstruction is technically feasible for patients with localized prostate cancer.The short-term follow-up effect of tumor control and urinary continence are satisfactory.

Objective:To evaluate the clinical value of Xing's ureteroileal anastomosis technique in radical cystectomy.Methods:The data of 38 patients who underwent radical cystectomy with Xing's ureteroileal anastomosis technique at Cancer Hospital, Chinese Academy of Medical Sciences and Beijing Chaoyang Hospital from July 2013 to June 2021 were retrospectively reviewed. There were 30 males and 8 females. The mean age was 61.6±15.1 years old. The mean body mass index (BMI) was 25.1±2.7 kg/m 2. The American Society of Anesthesiology (ASA) graded 25 cases as grade 1, 10 cases as grade 2 and 3 cases as grade 3. There were 35 cases with stage cT 2N 0M 0 and 3 cases with cT 3N 0M 0. All patients underwent radical cystectomy and ileal conduit, and the ureteroileal anastomosis was performed using the Xing's ureteroileal anastomosis technique. Afferent loop entry was divided equally into two lumens. After 1.5 cm-long lengthwise incisions, each ureter was directly and end-to-end anastomosed to the aforementioned lumens. Postoperative information was recorded, including ureteric stricture, ureteric reflux, hydronephrosis, anastomotic leakage, renal calculus, urinary tract infection, and pyelonephritis. Results:Ureteroileal anastomosis was performed successfully in 38 cases with 76 units. The median follow-up time was 35.6 (17.0, 46.3) months. Three patients developed unilateral anastomotic stenosis after operation. Five patients had unilateral ureteral reflux. Two patients had unilateral hydronephrosis. No anastomotic leakage, urinary tract infection, or pyelonephritis occurred after the operation. Renal calculus appeared in 3 cases, all on the left unit.Conclusions:Xing's ureteroileal anastomosis technique is a simple method with few postoperative and good functional outcomes.

Objective:To explore the effect of enhanced recovery after surgery (ERAS) protocols in patients undergoing laparoscopic radical cystectomy (LRC) and intracorporeal urinary diversion (ICUD).Methods:A total of 83 patients who received LRC+ ICUD in Beijing Chaoyang Hospital from March 2014 to September 2020, were divided into 2 groups based on different perioperative management, including 29 ERAS cases and 54 conventional recovery after surgery (CRAS) cases. The ERAS group included 26 males and 3 females , with an average age of (62.07 ± 9.26) years. There were 26 patients with ASA class Ⅰ-Ⅱ, 3 patients with ASA class Ⅲ, 4 patients received neoadjuvant chemotherapy, and 7 patients had a history of abdominal surgery in ERAS group. The CRAS group included 44 males and 10 females , with an average age of (61.59 ± 10.16) years. There were 50 patients with ASA class Ⅰ-Ⅱ, 4 patients with ASA class Ⅲ, 9 patients received neoadjuvant chemotherapy, and 10 patients had a history of abdominal surgery in CRAS group. There were no statistically significant differences in the baseline characteristics between the two groups. The patients in both groups underwent LRC+ ICUD procedures. The perioperative results and complications between the two groups were compared.Results:In the ERAS group, there were 20 patients who underwent Bricker ileal conduit surgery and 9 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 3, 3, 7, 7, 5 and 4 cases in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 23, 2, 3 and 1 patient with pathological stage N 0, N 1, N 2 and N 3, respectively. Pathological diagnosis included 3 cases of low-grade urothelial carcinoma, 24 cases of high-grade urothelial carcinoma, and 2 cases of other histological subtypes. In the CRAS group, there were 31 patients who underwent Bricker ileal conduit surgery and 23 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 5, 3, 12, 9, 15 and 10 patients in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 35, 6, 7 and 6 patients with pathological stage N 0, N 1, N 2, and N 3, respectively. Pathological diagnoses included 6 cases of low-grade urothelial carcinoma, 45 cases of high-grade urothelial carcinoma, and 3 cases of other histological subtypes. There were no statistically significant differences ( P>0.05) in surgical methods, pathological staging, or pathological types between the ERAS and CRAS groups. ERAS group presented less albumin loss [(25.73±8.63)% vs. (32.63±9.05)%, P=0.001], shorter hospital stay [9(7, 13)d vs. 12(9, 16)d, P=0.006], less 30-day overall complications [55.2% (16/29) vs. 83.3% (45/54), P=0.009]. In multivariable analysis, maximum albumin loss≥20% was independently associated with 30-day minor complications ( P=0.049), and maximum albumin loss ≥25% was independently associated with hospital of stay≥10 days ( P=0.038), respectively. Conclusions:For patients who received LRC+ ICUD, ERAS was associated with reduced perioperative albumin loss, shorter length of stay, less 30-day complications, accelerated recovery time, improved clinical outcome and less albumin injection.

【Objective】 To investigate the effects of diabetes and/or obesity on the incidence of acute kidney injury (AKI) and long-term renal function recovery in patients undergoing laparoscopic partial nephrectomy. 【Methods】 A retrospective analysis was performed on 221 patients who underwent laparoscopic partial nephrectomy in Beijing Chaoyang Hospital during Jan.2018 and Dec.2019. Baseline data, incidence of AKI, and renal function recovery after 12 months were analyzed in the diabetic, non-diabetic, diabetic + obese and diabetic + non-obese groups, with estimated glomerular filtration rate (eGFR) reaching 90% of the preoperative level as the standard. Risk factors of AKI were analyzed with univariate and multivariate regression analyses. 【Results】 Compared with the non-diabetic group, the diabetic group had lower preoperative eGFR [ (79.1±12.1)mL/ (min·1.73 m² )vs. (85.3±10.7)mL/ (min·1.73 m² ), P=0.01] , higher incidence of AKI (14.0% vs. 11.8%), and lower proportion of patients whose renal function recovered to at least 90% of the preoperative level (73.1% vs.83.5%). Patients with diabetes and obesity were more likely to develop AKI (31.3% vs.3.7%, P=0.039), and diabetic patients without obesity had better renal function recovery (81.3% vs. 60.0%). Multivariate analysis showed gender and operation time were the independent risk factors of AKI. 【Conclusion】 There were no significant differences between diabetic and non-diabetic patients in the incidence of postoperative AKI, or rate of renal function recovery 12 months after surgery. The incidence of AKI significantly increased in diabetic patients with obesity, and the renal function recovery rate decreased one year after surgery. Gender and operation time were the independent risk factors of AKI.