A retrospective study of paraganglioma of the urinary bladder and literature review.

Objective: To review and summarize the characteristics and therapy of paraganglioma of the urinary bladder (PUB). Method: Patients who underwent the operation in Peking Union Medical College Hospital between January 2012 and December 2021 were reviewed for this retrospective study. Results: A total of 29 patients, comprising 9 (31%) men and 20 (69%) women, were included. The main manifestations were hypertension, palpitation, and micturition syncope. Eight patients had an increased 24-h urinary catecholamine, and seven of them had increased norepinephrine. Normetanephrine in seven patients was increased. Six of 18 metaiodobenzylguanidine and 8 of 22 octreotide scans were positive. In total, 15 cases underwent laparoscopic partial cystectomy and 14 underwent transurethral resection of bladder tumor. In all patients, the immunohistochemical index of Melan-A, AE1/AE3, and α-inhibin were negative, and chromogranin A, S-100, and succinate dehydrogenase were positive. The Ki-67 of 28/29 cases was under 5%, and 1 case with a Ki-67 of 20% was diagnosed with malignant PUB. A total of 27 patients had a regular follow-up, 2 patients were lost during the follow-up, 3 patients had a recurrence, and 1 of these patients died within 1 year of surgery. The symptoms all disappeared or were relieved after the surgery. Conclusion: The transurethral surgery approach fits PUB tumors with a size <3 cm or that protrudes into the bladder and can significantly reduce the postoperative hospital stay. Early detection and treatment are effective, and regular review is necessary after the surgery.

The role of antimicrobial prophylaxis in laparoscopic nephrectomy for renal cell carcinoma.

BACKGROUND: To investigate the role of antimicrobial prophylaxis in laparoscopic nephrectomy for renal cell carcinoma. METHODS: We retrospectively enrolled 1000 patients who underwent laparoscopic nephrectomy from August 2019 to November 2021 in the Peking Union Medical College Hospital. Patients were divided into group without antimicrobial prophylaxis (n = 444) and group with antimicrobial prophylaxis (n = 556). Outcomes including 30-day postoperative infection rate, the increase rate of pre- and post-operative white blood cell counts and hospital stay were analyzed. RESULTS: The overall infection rate was 5.0% (28/556) in the group with antimicrobial prophylaxis, which was similar to 4.1% (18/444) in the group without antimicrobial prophylaxis (P = 0.461). The increase rate of pre- and post-operative white blood cell counts was significantly lower (85.5% versus 97.0%) in the group with antimicrobial prophylaxis (P = 0.004). The postoperative hospital stay was 5 (4, 6) days in both groups (P = 0.483). Logistic regression analyses identified the use of antimicrobial prophylaxis had no influence on the occurrence of infection events (odds ratio = 0.797; 95% confidence interval, 0.435-1.460; P = 0.462). Hemoglobin (odds ratio = 0.430; 95% confidence interval, 0.257-0.719; P = 0.001) and partial nephrectomy (odds ratio = 2.292; 95% confidence interval, 1.724-3.046; P < 0.001) influenced the use of antimicrobial prophylaxis independently. CONCLUSIONS: The use of antimicrobial prophylaxis had no impact on postoperative infection in patients receiving laparoscopic nephrectomy for renal cell carcinoma.

Comparison of AirSeal versus conventional insufflation system for retroperitoneal robot-assisted laparoscopic partial nephrectomy: a randomized controlled trial.

PURPOSE: AirSeal is a valve-less trocar insufflation system which is widely used in robotic urologic surgeries. More evidence is needed concerning the application and cost of AirSeal in retroperitoneal robot-assisted laparoscopic partial nephrectomy. METHODS: We conducted a randomized controlled trial enrolling 62 patients who underwent retroperitoneal robot-assisted laparoscopic partial nephrectomy from February 2022 to February 2023 in the Peking Union Medical College Hospital. Patients were randomly assigned into AirSeal insufflation (AIS) group and conventional insufflation (CIS) group. The primary outcome was the rate of subcutaneous emphysema (SCE). RESULTS: The SCE rate in the AIS group (12.9%) was significantly lower than that in the CIS group (35.5%) (P = 0.038). Lower maximum end-tidal carbon dioxide (CO2) (41 vs 45 mmHg, P = 0.011), PaCO2 at the end of the operation (40 vs 45 mmHg, P < 0.001), maximum tidal volume (512 vs 570 ml, P = 0.003), frequency of lens cleaning (3 vs 5, P < 0.001), pain score at 8 h (3 vs 4, P = 0.025), 12 h (2 vs 3, P = 0.029) postoperatively and at time of discharge (1 vs 2, P = 0.002) were observed in the AIS group, despite a higher hospitalization cost (68,197 vs 64658RMB, P < 0.001). Logistic regression analysis identified insufflation approach was the only influencing factor for the occurrence of SCE events. CONCLUSION: AirSeal insufflation system exhibited similar efficacy and improved safety for retroperitoneal robot-assisted laparoscopic partial nephrectomy than conventional insufflation system, despite an affordable increase of hospitalization costs.

Plural molecular and cellular mechanisms of pore domain KCNQ2 encephalopathy.

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as keystone of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal cell KCNQ2 and KCNQ3 immunolabeling was significantly shifted from axon initial segments to neuronal somata. Despite normal mRNA levels, G256W/+ mouse KCNQ2 protein levels were reduced by about 50%. Our findings indicate that G256W pathogenicity results from multiplicative effects, including reductions in intrinsic conduction, subcellular targeting, and protein stability. These studies reveal pore "turret arch" bonding as a KCNQ structural novelty and introduce a valid animal model of KCNQ2 encephalopathy. Our results, spanning structure to behavior, may be broadly applicable because the majority of KCNQ2 encephalopathy patients share variants near the selectivity filter.

POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer.

RNA Polymerase III Subunit G (POLR3G) promotes tumorigenesis, metastasis, cancer stemness, and chemoresistance of breast cancer and lung cancer; however, its biological function in bladder cancer (BLCA) remains unclear. Through bioinformatic analyses, we found that POLR3G expression was significantly elevated in BLCA tumor tissues and was associated with decreased survival. Multivariate Cox analysis indicated that POLR3G could serve as an independent prognostic risk factor. Our functional investigations revealed that POLR3G deficiency resulted in reduced migration and invasion of BLCA cells both in vitro and in vivo. Additionally, the expressions of EMT-related mesenchymal markers were also downregulated in POLR3G knockdown cells. Mechanistically, we showed that POLR3G could activate the PI3K/AKT signaling pathway. Inhibition of this pathway with LY294002 reduced the enhanced migration and invasion of BLCA cells induced by POLR3G overexpression, whereas the activation of this pathway using 740Y-P restored the abilities that were inhibited by POLR3G knockdown. Taken together, our findings suggested that POLR3G is a prognostic predictor for BLCA and promotes EMT of BLCA through activation of the PI3K/AKT signaling pathway.

Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials.

PURPOSE: To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti-human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E, in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC) refractory to standard or regular therapies. PATIENTS AND METHODS: The data analyzed and reported are from two phase II, open-label, multicenter, single-arm studies (RC48-C005 and RC48-C009) in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic UC who have progressed on at least one previous line of systemic chemotherapy. Patients received DV treatment (2 mg/kg IV infusion, once every 2 weeks). The primary end point was objective response rate (ORR) assessed by a blinded independent review committee (BIRC). Progression-free survival (PFS), overall survival (OS), and safety were also assessed. RESULTS: One hundred and seven patients were enrolled in total. The overall confirmed ORR by BIRC was 50.5% (95% CI, 40.6 to 60.3). Consistent results were observed in prespecified subgroups including patients with liver metastasis and patients previously treated with anti-PD-1/L1 therapies. By the cutoff date of May 10, 2022, the median duration of response was 7.3 months (95% CI, 5.7 to 10.8). The median PFS and OS were 5.9 months (95% CI, 4.3 to 7.2) and 14.2 months (95% CI, 9.7 to 18.8), respectively. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (68.2%), leukopenia (50.5%), AST increased (42.1%), and neutropenia (42.1%). Fifty-eight (54.2%) patients experienced grade ≥3 TRAEs, including peripheral sensory neuropathy (18.7%) and neutropenia (12.1%). CONCLUSION: DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who had progressed on at least one line of systemic chemotherapy.

SHOX2 promotes prostate cancer proliferation and metastasis through disruption of the Hippo-YAP pathway.

The transcription factor SHOX2 gene is critical in regulating gene expression and the development of tumors, but its biological role in prostate cancer (PCa) remains unclear. In this study, we found that SHOX2 expression was significantly raised in PCa tissues and was associated with clinicopathological features as well as disease-free survival (DFS) of PCa patients. Phenotypic tests showed that the absence of SHOX2 inhibited PCa growth and invasion, while SHOX2 overexpression promoted these effects. Mechanistically, SHOX2 was found to activate the transcription of nephronophthisis type 4 (NPHP4), a gene located downstream of SHOX2. Further analysis revealed that SHOX2 could potentially interfere with the Hippo-YAP signaling pathway through NPHP4 activation, facilitating the oncogenic behavior of PCa cells. These findings highlight SHOX2 as an oncogene in PCa and provide a basis for developing potential therapeutic approaches against this disease.

Machine-learning based integrating bulk and single-cell RNA sequencing reveals the SLC38A5-CCL5 signaling as a promising target for clear cell renal cell carcinoma treatment.

Cancer-associated fibroblasts paly critical roles in regulating cancer cell biological properties by intricate and dynamic communication networks. But the mechanism of CAFs in clear cell renal cell carcinoma (ccRCC) is not clear. In our study, we identified CAFs and malignant cells from the integrated scRNA-seq datasets and establish a CAF-derived communication signature based on the highly activated regulons ETS1 and MEF2C. We stratified the ccRCC TME into two molecular subtypes with distinct prognoses, immune cell infiltration landscapes, and immune-related characteristics. The model derived from signature demonstrated high accuracy and robustness in predicting prognosis and ICIs therapy responses. Subsequently, the SLC38A5 of the model was found upregulated in CAFs and was related to decreased survival probabilities, inflamed TME, and upregulated inhibitory checkpoints. SLC38A5 inhibition could attenuate the pro-tumoral abilities of CAFs in terms of proliferation, migration, and invasion. Mechanically, CCL5 could restore these properties induced by SLC38A5 inhibition. In conclusion, our communication signature and its derived model enabled a more precise selection of ccRCC patients who were potential beneficiaries of ICIs. Besides, the SLC38A5-CCL5 axis may serve as a promising target for ccRCC treatment.

Laparoscopic resection of a paraganglioma behind the retrohepatic segment of the inferior vena cava: a case report and literature review.

Background: Due to the location of paragangliomas (PGLs) behind the retrohepatic segment of inferior vena cava (IVC), it is difficult to expose and resect the tumor. Case presentation: A tumor measuring 50×45×62cm behind the retrohepatic portion of IVC was found in a 51-year-old female with hypertention and diabetes mellitus. Although the test for catecholamines revealed no signs of disease, the enhanced computed tomography (CT) scan, somatostatin receptor imaging and iodine-131-labeled metaiiodo-benzylguanidine (131I-MIBG) imaging revealed that the tumor was PGL. A three-dimensional printing was performed to visualize the tumor. The laparoscpic surgery for the PGL behind the retrohepatic segment of IVC was performed and the tumor was resected completely without causing any tissues injury. The pathologic diagnosis was PGL and the patient was able to recover well. Conclusions: This case demonstrates that laparoscopic surgery may be helpful in tumor accessibility, and could be used in the appropriate cases to remove PGLs that are located behind the retrohepatic segment of the IVC.

PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling.

PLAGL2 is upregulated in various tumors, including bladder cancer (BCa). However, the mechanisms underlying the tumorigenic effects of PLAGL2 in BCa remain unclear. In our study, we proved that PLAGL2 was overexpressed in BCa tissues and correlated with decreased survival. Functionally, PLAGL2 deficiency significantly suppressed the proliferation and metastasis of BCa cells in vitro and in vivo. RNA sequencing, qRT‒PCR, immunoblotting, immunofluorescence staining, luciferase reporter, and ChIP assays revealed that overexpressed PLAGL2 disrupted the Hippo pathway and increased YAP1/TAZ activity by transactivating RACGAP1. Further investigations demonstrated that PLAGL2 activated YAP1/TAZ signaling via RACGAP1-mediated RhoA activation. Importantly, the RhoA inhibitor simvastatin or the YAP1/TAZ inhibitor verteporfin abrogated the proproliferative and prometastatic effects of BCa enhanced by PLAGL2. These findings suggest that PLAGL2 promotes BCa progression via RACGAP1/RhoA GTPase/YAP1 signaling. Hence, the core nodes of signaling may be promising therapeutic targets for BCa.

Long-term partial response in a patient with liver metastasis of primary adrenocortical carcinoma with adjuvant mitotane plus transcatheter arterial chemoembolization and microwave ablation: a case report.

Adrenocortical carcinoma (ACC) is a rare, heterogeneous, and aggressive malignancy with a generally poor prognosis. Surgical resection is the optimal treatment plan. After surgery, both mitotane treatment or the etoposide-doxorubicin-cisplatin (EDP) protocol plus mitotane chemotherapy have a certain effect, but there is still an extremely high possibility of recurrence and metastasis. The liver is one of the most common metastatic targets. Therefore, techniques such as transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA) for liver tumors can be attempted in a specific group of patients. We present the case of a 44-year-old female patient with primary ACC, who was diagnosed with liver metastasis 6 years after resection. During mitotane treatment, we performed four courses of TACE and two MWA procedures in accordance with her clinical condition. The patient has maintained the partial response status and has currently returned to normal life to date. This case illustrates the value of the practical application of mitotane plus TACE and MWA treatment.

Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients.

Background: Disulfidptosis is a recently discovered form of cell death. However, its biological mechanisms in bladder cancer (BCa) are yet to be understood. Methods: Disulfidptosis-related clusters were identified by consensus clustering. A disulfidptosis-related gene (DRG) prognostic model was established and verified in various datasets. A series of experiments including qRT-PCR, immunoblotting, IHC, CCK-8, EdU, wound-healing, transwell, dual-luciferase reporter, and ChIP assays were used to study the biological functions. Results: We identified two DRG clusters, which exhibited distinct clinicopathological features, prognosis, and tumor immune microenvironment (TIME) landscapes. A DRG prognostic model with ten features (DCBLD2, JAM3, CSPG4, SCEL, GOLGA8A, CNTN1, APLP1, PTPRR, POU5F1, CTSE) was established and verified in several external datasets in terms of prognosis and immunotherapy response prediction. BCa patients with high DRG scores may be characterized by declined survival, inflamed TIME, and elevated tumor mutation burden. Besides, the correlation between DRG score and immune checkpoint genes and chemoradiotherapy-related genes indicated the implication of the model in personalized therapy. Furthermore, random survival forest analysis was performed to select the top important features within the model: POU5F1 and CTSE. qRT-PCR, immunoblotting, and immunohistochemistry assays showed the enhanced expression of CTSE in BCa tumor tissues. A series of phenotypic assays revealed the oncogenetic roles of CTSE in BCa cells. Mechanically, POU5F1 can transactivate CTSE, promoting BCa cell proliferation and metastasis. Conclusions: Our study highlighted the disulfidptosis in the regulation of tumor progression, sensitivity to therapy, and survival of BCa patients. POU5F1 and CTSE may be potential therapeutic targets for the clinical treatment of BCa.

LC-MS based urine untargeted metabolomic analyses to identify and subdivide urothelial cancer.

Introduction: Urine metabolomics has been a promising technique in the liquid biopsy of urothelial cancer (UC). The comparison of upper tract urothelial cancer (UTUC), lower tract urothelial cancer (BCa), and healthy controls (HCs) need to be performed to find related biomarkers. Methods: In our investigation, urine samples from 35 UTUCs, 44 BCas, and 53 gender- and age-matched HCs were analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS). In different groups, the differential metabolites and the disturbed metabolism pathways were explored. Transcriptomics and urine metabolomics are combined to identify the probably disturbed gene in BCa. Results: With an area under the curve (AUC) of 0.815, the panel consisting of prostaglandin I2, 5-methyldeoxycytidine, 2,6-dimethylheptanoyl carnitine, and deoxyinosine was able to discriminate UC from HCs. With an AUC of 0.845, the validation group also demonstrated strong predictive ability. UTUC and BCa without hematuria could be distinguished using the panel of 5'-methylthioadenosine, L-beta-aspartyl-L-serine, dehydroepiandrosterone sulfate, and N'-formylkynurenine (AUC=0.858). The metabolite panel comprising aspartyl-methionine, 7-methylinosine, and alpha-CEHC glucuronide could discriminate UTUC from BCa with hematuria with an AUC of 0.83. Fatty acid biosynthesis, purine metabolism, tryptophan metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism were dysregulated when comparing UC with HCs. PTGIS and BCHE, the genes related to the metabolism of prostaglandin I2 and myristic acid respectively, were significantly associated with the survival of BCa. Discussion: Not only could LC-HRMS urine metabolomic investigations distinguish UC from HCs, but they could also identify UTUC from BCa. Additionally, urine metabolomics combined with transcriptomics can find out the potential aberrant genes in the metabolism.

Preclinical and pilot clinical evaluation of a small-molecule carbonic anhydrase IX targeting PET tracer in clear cell renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC. METHODS: The in vivo and ex vivo biodistribution of 68Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied. RESULTS: NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, 68Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative 68Ga-NY104 uptake. CONCLUSION: 68Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate 68Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC. TRIAL REGISTRATION: The clinical evaluation part of this study was retrospectively registered at ClinicalTrial.gov (NCT05728515) as NYPILOT on 6 Feb, 2023.

Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle-invasive bladder cancer: A multi-center, single-arm, phase 2 study.

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD-1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. METHODS: This was a multi-center, single-arm study that enrolled MIBC patients with a clinical stage of T2-4aN0-1M0, and scheduled for RC. Patients received three 21-day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). RESULTS: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune-related AEs were all grade 1 or 2. Pathologic response was not correlated with PD-L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. CONCLUSIONS: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti-tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.

Insight into over Repair of Hot Carrier Degradation by GIDL Current in Si p-FinFETs Using Ultra-Fast Measurement Technique.

In this article, an experimental study on the gate-induced drain leakage (GIDL) current repairing worst hot carrier degradation (HCD) in Si p-FinFETs is investigated with the aid of an ultra-fast measurement (UFM) technique (~30 µs). It is found that increasing GIDL bias from 3 V to 4 V achieves a 114.7% VT recovery ratio from HCD. This over-repair phenomenon of HCD by UFM GIDL is deeply discussed through oxide trap behaviors. When the applied gate-to-drain GIDL bias reaches 4 V, a significant electron trapping and interface trap generation of the fresh device with GIDL repair is observed, which greatly contributes to the approximate 114.7% over-repair VT ratio of the device under worst HCD stress (-2.0 V, 200 s). Based on the TCAD simulation results, the increase in the vertical electric field on the surface of the channel oxide layer is the direct cause of an extraordinary electron trapping effect accompanied by the over-repair phenomenon. Under a high positive electric field, a part of channel electrons is captured by oxide traps in the gate dielectric, leading to further VT recovery. Through the discharge-based multi-pulse (DMP) technique, the energy distribution of oxide traps after GIDL recovery is obtained. It is found that over-repair results in a 34% increment in oxide traps around the conduction energy band (Ec) of silicon, which corresponds to a higher stabilized VT shift under multi-cycle HCD-GIDL tests. The results provide a trap-based understanding of the transistor repairing technique, which could provide guidance for the reliable long-term operation of ICs.

Machine learning-based identification of tumor-infiltrating immune cell-associated model with appealing implications in improving prognosis and immunotherapy response in bladder cancer patients.

Background: Immune cells are crucial components of the tumor microenvironment (TME) and regulate cancer cell development. Nevertheless, the clinical implications of immune cell infiltration-related mRNAs for bladder cancer (BCa) are still unclear. Methods: A 10-fold cross-validation framework with 101 combinations of 10 machine-learning algorithms was employed to develop a consensus immune cell infiltration-related signature (IRS). The predictive performance of IRS in terms of prognosis and immunotherapy was comprehensively evaluated. Results: The IRS demonstrated high accuracy and stable performance in prognosis prediction across multiple datasets including TCGA-BLCA, eight independent GEO datasets, our in-house cohort (PUMCH_Uro), and thirteen immune checkpoint inhibitors (ICIs) cohorts. Additionally, IRS was superior to traditional clinicopathological features (e.g., stage and grade) and 94 published signatures. Furthermore, IRS was an independent risk factor for overall survival in TCGA-BLCA and several GEO datasets, and for recurrence-free survival in PUMCH_Uro. In the PUMCH_Uro cohort, patients in the high-IRS group were characterized by upregulated CD8A and PD-L1 and TME of inflamed and immunosuppressive phenotypes. As predicted, these patients should benefit from ICI therapy and chemotherapy. Furthermore, in the ICI cohorts, the high-IRS group was related to a favorable prognosis and responders have dramatically higher IRS compared to non-responders. Conclusions: Generally, these indicators suggested the promising application of IRS in urological practices for the early identification of high-risk patients and potential candidates for ICI application to prolong the survival of individual BCa patients.

Feasibility, safety and effectiveness of robot-assisted retroperitoneal partial adrenalectomy with a new robotic surgical system: A prospective clinical study.

Objectives: To evaluate the feasibility, safety and efficacy of the newly developed KD-SR-01® robotic system for retroperitoneal partial adrenalectomy. Subjects and Methods: We prospectively enrolled patients with benign adrenal mass undergoing KD-SR-01® robot-assisted partial adrenalectomy in our institution from November 2020 to May 2022. Surgeries were performed via a retroperitoneal approach using the KD-SR-01® robotic system. The baseline, perioperative and short-term follow-up data were prospectively collected. A descriptive statistical analysis was performed. Results: A total of 23 patients were enrolled, including nine (39.1%) patients with hormone-active tumors. All patients received partial adrenalectomy via the retroperitoneal approach without conversions to other procedures. The median operative time was 86.5 min [interquartile range (IQR), 60.0-112.5] and the median estimated blood loss was 50 ml (range, 20-400). Three (13.0%) patients developed Clavien-Dindo grade I-II postoperative complications. The median postoperative stay was 4.0 days (IQR, 3.0-5.0). All surgical margins were negative. The short-term follow-up demonstrated complete or partial clinical and biochemical success as well as absence of imaging recurrence in all patients with hormone-active tumors. Conclusions: Initial results illustrate that the KD-SR-01® robotic system is safe, feasible and effective for the surgical management of benign adrenal tumors.

Understanding the Effect of Top Electrode on Ferroelectricity in Atomic Layer Deposited Hf0.5Zr0.5O2 Thin Films.

It is commonly believed that the impact of the top electrodes on the ferroelectricity of hafnium-based thin films is due to strain engineering. However, several anomalies have occurred that put existing theories in doubt. This work carries out a detailed study of this issue using both theoretical and experimental approaches. The 10 nm Hf0.5Zr0.5O2 (HZO) films are prepared by atomic layer deposition, and three different top capping electrodes (W/MO/ITO) are deposited by physical vapor deposition. The electrical testing finds that the strain does not completely control the ferroelectricity of the devices. The results of further piezoelectric force microscopy characterization exclude the potential interference of the top capping electrodes and interface for electrical testing. In addition, through atomic force microscopy characterization and statistical analysis, a strong correlation between the grain size of the top electrode and the grain size of the HZO film has been found, suggesting that the grain size of the top electrode can induce the formation of the grain size in HZO thin films. Finally, the first-principles calculation is carried out to understand the impact of the strain and grain size on the ferroelectric properties of HZO films. The results show that the strain is the dominant factor for ferroelectricity when the grain size is large (>10 nm). However, when the grain size becomes thinner (<10 nm), the regulation effect of grain sizes increases significantly, which could bring a series of benefits for device scaling, such as device-to-device variations, film uniformity, and domain switch consistency. This work not only completes the understanding of ferroelectricity through top electrode modulation but also provides strong support for the precise regulation of ferroelectricity of nanoscale devices and ultrathin HZO ferroelectric films.