ObjectiveTo evaluate the effect of Ningying Formula （宁瘿方） combined with low-dose antithyroid drugs （ATDs） on the relapse risk for patients with Graves' hyperthyroidism （GH） during the remission phase， and to analyze the related factors between GH relapse and thyrotropin receptor antibody （TRAb） negativity， so as to provide evidence for the standardized management of GH in remission stage. MethodsA single-center retrospective cohort study was conducted， including 269 GH patients in the remission stage. After propensity score matching （PSM）， 102 matched pairs （204 patients） were established. The control group received low-dose ATDs as maintenance therapy， while the exposure group received the core Ningying Formula in addition to low-dose ATDs. The primary outcome was the GH recurrence rate； the secondary outcome was the thyrotropin receptor antibody （TRAb） negativity rate （TRAb＜1.75 IU/L）. Safety outcomes included treatment-related adverse events. Differences between groups were assessed using Cox regression models and Kaplan-Meier curves， with sensitivity analysis performed using inverse probability of treatment weighting （IPTW）. ResultsThe median follow-up in the matched cohort was 28.07 months. Regarding the GH recurrence outcome， the recurrence rate in the exposure group （18/102， 17.6%） was significantly lower than that in the control group （31/102， 30.4%； χ²=4.539， P=0.033）； regarding the TRAb negativity outcome， the TRAb negativity rate in the exposure group （50/102， 49.0%） was significantly higher than that in the control group （23/102， 22.5%； χ²=15.551， P＜0.001）. Multivariate Cox regression analysis for recurrence showed that Ningying Formula treatment reduced the risk of recurrence ［HR=0.324， 95%CI（0.170， 0.617）， P＜0.001］. Male ［HR=2.209， 95%CI（1.079， 4.520）， P=0.030］， higher initial TRAb level ［per 1 IU/L increase： HR=1.033， 95%CI（1.003， 1.064）， P=0.032］， and larger thyroid volume ［per 1 ml increase： HR=1.045， 95%CI（1.003， 1.088）， P=0.035］ were identified as independent risk factors for recurrence； multivariate Cox regression analysis for TRAb negativity indicated that Ningying Formula treatment promoted TRAb negativity ［HR=1.826， 95%CI（1.091， 3.056）， P=0.022］， while a higher initial TRAb level was associated with a lower probability of negativity ［HR=0.974， 95%CI（0.950， 0.998）， P=0.032］. Survival analysis showed significant differences in relapse rate between groups （Log-Rank P=0.003） and in TRAb outcomes （Log-Rank P=0.034）. The incidence of treatment-related adverse events was similar between groups （P=0.757）. The IPTW sensitivity analysis was consistent with the primary analysis， indicating robust results. ConclusionThe Ningying Formula combined with low-dose ATDs can significantly reduce the risk of recurrence and can improve the TRAb negativity rate in GH patients during the remission stage， without increasing common adverse events， making it an optional strategy for reducing relapse risk during remission. Male gender， higher baseline TRAb level， and larger thyroid volume indicate a higher risk of recurrence， warranting focused follow-up and stratified management.

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 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 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.

Objective:To investigate the clinical effect and demonstrate the techniques of single position laparoscopic nephroureterectomy.Methods:The clinical data of 84 upper urinary tract urothelial carcinoma patients admitted to the Cancer Hospital Chinese Academy of Medical Sciences from September 2018 to July 2022 were retrospectively analyzed, including 39 males and 45 females, with a median age of (64.9±9.3)years and mean BMI of(24.7±3.4)kg/m 2. The tumor was located on the left side in 47 cases and the right side in 37 cases. All 84 patients received single position laparoscopic nephroureterectomy. According to different treatment methods, they were divided into two groups, including 67 cases undergoing nephrectomy first, and then bladder cuff excision was performed along ureter(traditional group), 17 cases undergoing bladder cuff excision before clamping the ureter below the tumor, and then nephrectomy was performed along the ureter to the head side (modified group). There was no statistically significant in the comparison of age [(65.5±9.4)years vs.(62.7±8.9)years], BMI[(24.9±3.5)kg/m 2vs.(23.9±3.3)kg/m 2], left/right side tumor of(38/29 cases vs. 9/8 cases), tumor location (in renal pelvis or calyx or upper/middle/lower ureter being 46/9/12 cases vs. 13/2/2 cases)and tumor stage(T 1-2/T 3-4: 54/13 cases vs. 15/2 cases) between traditional group and modified group ( P>0.05). The operation time, estimate blood loss, postoperative intestinal function recovery time and postoperative drainage time were recorded and compared. Results:All 84 cases were successfully completed without conversion to open surgery. The mean operation time was (160.4±50.1)min, the mean estimated blood loss was(59.4±24.4)ml, the median postoperative intestinal function recovery time was 1(1, 2)d and the mean postoperative drainage time was (4.8±1.9)d(No drainage tube was placed in 4 patients). No Clavien Dindo >grade 3 complications occured. There was no significant difference in the comparison of operation time [(159.2±52.9)min vs. (164.7±38.1)min], estimate blood loss [(60.5±26.2)ml vs. (55.0±17.5)ml], postoperative intestinal function recovery time [1(1-2)d vs. 2(1-2)d] and drainage removal time [(4.8±1.8)d vs. (5.2±2.0)d] between traditional group and modified group ( P>0.05). The postoperative pathology of 84 cases was urothelial carcinoma, and the pathological results of the resection margin were negative. The median follow-up of 84 upper tract urothelial carcinoma patients was 13(3, 28)months. Five patients were lost to follow-up. In traditional group, 5 patients had bladder tumor recurrence, and 5 patients had distant metastasis. In modified group, no bladder tumor recurrence occurred and 1 patient had distant metastasis. Conclusions:Laparoscopic nephroureterectomy in single position is a safe and effective minimally invasive technique for the treatment of upper urinary tract urothelial carcinoma. Treatment of the bladder cuff excision firstly is more in line with the principle of tumor-free and increase surgical space.