Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the relationship between general demographic characteristics,inflammatory indicators,nutritional indicators,pathological data and lymph node metastasis in endometrial cancer(EC)pa-tients,and to construct and validate a model for preoperative prediction of lymph node status in endometrial canc-er patients.Methods:The preoperative clinical data of 473 patients with EC who underwent surgical treatment in the Zhu Jiang Hospital of Southern Medical University from January 2010 to April 2024 were retrospectively ana-lyzed.The independent risk factors of lymph node metastasis of endometrial cancer were screened by univariate and multivariate Logistic regression analyses,and the nomogram prediction model was constructed by R soft-ware.The performance of the model was evaluated by the receiver operating characteristic(ROC)curve,calibra-tion curve and clinical decision curve.Results:Menopausal status,high grade biopsy pathology,CA125 ≥24.47U/ml,systemic immune inflammatory index(SII)≥710.91,and prognostic nutritional index(PNI)＜52.90 were in-dependent risk factors for lymph node metastasis in endometrial cancer(OR＞1,P＜0.05).The nomogram model constructed based on these five factors had an AUC of 0.853 in the training set and 0.871 in the test set.The cali-bration curve fitted well,and the clinical decision curve shows a positive benefit.Conclusions:The endometrial cancer lymph node metastasis prediction model constructed based on menopausal status,biopsy pathology,CA125,SII,and PNI has good accuracy and fit,with certain clinical application value.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

Objective:To explore the relationship between general demographic characteristics,inflammatory indicators,nutritional indicators,pathological data and lymph node metastasis in endometrial cancer(EC)pa-tients,and to construct and validate a model for preoperative prediction of lymph node status in endometrial canc-er patients.Methods:The preoperative clinical data of 473 patients with EC who underwent surgical treatment in the Zhu Jiang Hospital of Southern Medical University from January 2010 to April 2024 were retrospectively ana-lyzed.The independent risk factors of lymph node metastasis of endometrial cancer were screened by univariate and multivariate Logistic regression analyses,and the nomogram prediction model was constructed by R soft-ware.The performance of the model was evaluated by the receiver operating characteristic(ROC)curve,calibra-tion curve and clinical decision curve.Results:Menopausal status,high grade biopsy pathology,CA125 ≥24.47U/ml,systemic immune inflammatory index(SII)≥710.91,and prognostic nutritional index(PNI)＜52.90 were in-dependent risk factors for lymph node metastasis in endometrial cancer(OR＞1,P＜0.05).The nomogram model constructed based on these five factors had an AUC of 0.853 in the training set and 0.871 in the test set.The cali-bration curve fitted well,and the clinical decision curve shows a positive benefit.Conclusions:The endometrial cancer lymph node metastasis prediction model constructed based on menopausal status,biopsy pathology,CA125,SII,and PNI has good accuracy and fit,with certain clinical application value.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective:To investigate the function and mechanism of exosomes in bladder cancer cell growth and metastasis regulating by NETs.Methods:The exosomes secreted by SV-HUC-1,MGH-U3 and 253J cells were extracted.PBS and the above exo-somes incubated with PMN,recorded as PBS group,SV-HUC-1 exo group,MGH-U3 exo group,253J exo group.The generation of NETs was detected by Sytox green staining,and the expressions of NETs marker proteins CIT-H3,NE and MPO were detected by Western blot.MGH-U3 and 253J cells were divided into Control group,PMN group,MGH-U3 exo group,253J exo group MGH-U3 exo+PMN group,253J exo+PMN group.The PMN culture supernatant of MGH-U3 exo group and 253J exo group were added with 1.5 U/ml DNAse,after incubation for 30 min,the collected mixture to co-incubate with MGH-U3 and 253J cells,recorded as MGH-U3 exo+PMN+DNAse group and 253J exo+PMN+DNAse group.The proliferation ability of MGH-U3 and 253J cells were detected by CCK8,the migration and invasion of cells were detected by Transwell,and the phosphorylation levels of PI3K and AKT were detected by Western blot.Results:Compared with PBS group,the formation of NETs and the expressions of CIT-H3,NE and MPO in MGH-U3 exo group and 253J exo group increased significantly(P<0.001).There was no significant change of the above indexes in SV-HUC-1 exo group.Compared with Control group,MGH-U3 exo+PMN group and 253J exo+PMN group had significantly increased cell prolifer-ation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT increased significantly(P<0.001).Com-pared with MGH-U3 exo+PMN group,MGH-U3 exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability(P<0.05),the phosphorylation levels of PI3K and AKT decreased significantly(P<0.001).Compared with 293J exo+PMN group,293J exo+PMN+DNAse group had significantly decreased cell proliferation,migration and invasion ability,the phosphor-ylation levels of PI3K and AKT decreased significantly(P<0.001).Conclusion:The exosomes of bladder cancer cells can promote the proliferation,migration and invasion of tumor cells by inducing the generation of NETs.

Objective:Analyze the influencing factors of postoperative recurrence of common bile duct stones in patients with gallstones and multiple common bile duct stones,and evaluate the application value of nomogram predic-tion models.Methods:Collected clinical data of 587 patients with gallstones and multiple common bile duct stones who underwent surgical treatment at Beijing Fengtai Hospital from January 2022 to January 2024.They were divided into a training cohort(n=410)and a validation cohort(n=177)according to a 7∶3 ratio.Analyzed the influencing factors of postoperative recurrence of common bile duct stones in patients with gallstones and multiple common bile duct stones,and constructed a nomogram prediction model based on this.Results:The recurrence rate of postoperative common bile duct stones in the training queue was 38.05％(156/410).Age,BMI,intrahepatic bile duct stones,initial course of dis-ease,duodenal diverticulum,biliary tract infection,history of biliary surgery,thickness of the common bile duct wall,num-ber of multiple stones in the common bile duct,diameter of the common bile duct,and dysfunction of the Oddis sphincter in the duodenal papilla during ERCP examination are independent risk factors for postoperative recurrence in patients with gallbladder stones combined with multiple stones in the common bile duct(P＜0.05).The AUC of the constructed nomo-gram prediction model in the training queue and validation queue were 0.854 and 0.889,respectively.The Hosmer Lem-eshow fitting test results showed that there was no statistically significant difference between the predicted probability and the actual probability of the prediction model(x2=3.952,P=0.865),indicating that this model has good predictive abil-ity.Conclusion:The nomogram prediction model based on various risk factors can effectively predict the risk of post-operative common bile duct stone recurrence in patients with gallstones and multiple common bile duct stones.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.