RC48-Antibody-Drug Conjugate in Metastatic Urothelial Carcinoma: A Multicenter Real-World Study in China.

OBJECTIVES: RC48 is an antibody-drug conjugate (ADC) that targets HER2. In China, RC48 is approved for patients with HER-2-positive metastatic urothelial carcinoma (mUC) who have failed at least platinum-based chemotherapy. This study aimed to evaluate RC48 for mUC in a cohort of real-world patients. MATERIALS AND METHODS: We retrospectively collected data from 103 mUC patients from 12 centers between July 2021 and August 2023 in China. RC48 alone or with immunotherapy was administered until disease progression, intolerable toxicity, death, or other reasons. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of treatment-related adverse events (TRAEs) were evaluated. RESULTS: The median age of the patients was 68 years, and 68.0% were men. Twenty-nine (28.2%) patients received RC48 alone; 73 (70.9%) received RC48 combination therapy. The response rates were as follows: complete response in 2 (1.9%) patients, partial response in 50 (48.5%) patients, stable disease in 30 (29.1%) patients. The ORR was 50.5%. In patients with ≥80 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 and creatinine clearance rate (CCr) <30 mL/min, the ORR was 75%, 48.6%, and 40.0%, respectively. The median PFS was 6 (3.9-8.1) months, and the median OS was not reached. The most reported TRAEs were peripheral sensory neuropathy (53.4%), alopecia (42.7%), asthenia (38.8%), decreased appetite (35.9%) and weight loss (35.9%) and TRAE did not increase in patients with poor condition or impaired renal function. CONCLUSION: Administration of RC48 for real-world patients is both effective and safe. mUC patients can benefit from RC48-based therapy, regardless of their poor condition or impaired renal function.

The identification of a N6-methyladenosin-modifed immune pattern to predict immunotherapy response and survival in urothelial carcinoma.

BACKGROUND: Dysregulation of the immune system and N6-methyladenosine (m6A) contribute to immune therapy resistance and cancer progression in urothelial carcinoma (UC). This study aims to identify immune-related molecules, that are m6A-modified, and that are associated with tumor progression, poor prognosis, and immunotherapy response. METHODS: We identified prognostic immune genes (PIGs) using Cox analysis and random survival forest variable hunting algorithm (RSF-VH) on immune genes retrieved from the Immunology Database and Analysis Portal database (ImmPort). The RM2Target database and MeRIP-seq analysis, combined with a hypergeometric test, assessed m6A methylation in these PIGs. We analyzed the correlation between the immune pattern and prognosis, as well as their association with clinical factors in multiple datasets. Moreover, we explored the interplay between immune patterns, tumor immune cell infiltration, and m6A regulators. RESULTS: 28 PIGs were identified, of which the 10 most significant were termed methylated prognostic immune genes (MPIGs). These MPIGs were used to create an immune pattern score. Kaplan-Meier and Cox analyses indicated this pattern as an independent risk factor for UC. We observed significant associations between the immune pattern, tumor progression, and immune cell infiltration. Differential expression analysis showed correlations with m6A regulators expression. This immune pattern proved effective in predicting immunotherapy response in UC in real-world settings. CONCLUSION: The study identified a m6A-modified immune pattern in UC, offering prognostic and therapeutic response predictions. This emphasizes that immune genes may influence tumor immune status and progression through m6A modifications.

TR4 worsen urosepsis by regulating GSDMD.

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

Enhanced Proximity of Rh1,2-Rhn Ensembles Encaged in UiO-67 Boosting Catalytic Conversion of Syngas to Oxygenates.

Maintaining high conversion under the premise of high oxygenates selectivity in syngas conversion is important but a formidable challenge in Rh catalysis. Monometallic Rh catalysts provide poor oxygenate conversion efficiency, and efforts have been focused on constructing adjacent polymetallic sites; however, the one-pass yields of C2+ oxygenates over the reported Rh-based catalysts were mostly <20 %. In this study, we constructed a monometallic Rh catalyst encapsulated in UiO-67 (Rh/UiO-67) with enhanced proximity to dual-site Rh1,2-Rhn ensembles. Unexpectedly, this catalyst exhibited high efficacy for oxygenate synthesis from syngas, giving a high oxygenate selectivity of 72.0 % with a remarkable CO conversion of 50.4 %, and the one-pass yield of C2+ oxygenates exceeded 25 %. The state-of-the-art characterizations further revealed the spontaneous formation of an ensemble of Rh single atoms/dimers (Rh1,2) in the proximity of ultrasmall Rh clusters (Rhn) confined within the nanocavity of UiO-67, providing adjacent Rh+-Rh0 dual sites dynamically during the reaction that promote the relay of the undissociated CHO species to the CHx species. Thus, our results open a new route for designing highly efficient Rh catalysts for the conversion of syngas to oxygenates by precisely tuning the ensemble and proximity of the dual active sites in a confined space.

ParaCM-PNet: A CNN-tokenized MLP combined parallel dual pyramid network for prostate and prostate cancer segmentation in MRI.

The precise prostate gland and prostate cancer (PCa) segmentations enable the fusion of magnetic resonance imaging (MRI) and ultrasound imaging (US) to guide robotic prostate biopsy systems. This precise segmentation, applied to preoperative MRI images, is crucial for accurate image registration and automatic localization of the biopsy target. Nevertheless, describing local prostate lesions in MRI remains a challenging and time-consuming task, even for experienced physicians. Therefore, this research work develops a parallel dual-pyramid network that combines convolutional neural networks (CNN) and tokenized multi-layer perceptron (MLP) for automatic segmentation of the prostate gland and clinically significant PCa (csPCa) in MRI. The proposed network consists of two stages. The first stage focuses on prostate segmentation, while the second stage uses a prior partition from a previous stage to detect the cancerous regions. Both stages share a similar network architecture, combining CNN and tokenized MLP as the feature extraction backbone to creating a pyramid-structured network for feature encoding and decoding. By employing CNN layers of different scales, the network generates scale-aware local semantic features, which are integrated into feature maps and inputted into an MLP layer from a global perspective. This facilitates the complementarity between local and global information, capturing richer semantic features. Additionally, the network incorporates an interactive hybrid attention module to enhance the perception of the target area. Experimental results demonstrate the superiority of the proposed network over other state-of-the-art image segmentation methods for segmenting the prostate gland and csPCa tissue in MRI images.

Ligand-dependent CD36 functions in cancer progression, metastasis, immune response, and drug resistance.

CD36, a multifunctional glycoprotein, has been shown to play critical roles in tumor initiation, progression, metastasis, immune response, and drug resistance. CD36 serves as a receptor for a wide range of ligands, including lipid-related ligands (e.g., long-chain fatty acid (LCFA), oxidized low-density lipoprotein (oxLDL), and oxidized phospholipids), as well as protein-related ligands (e.g., thrombospondins, amyloid proteins, collagens I and IV). CD36 is overexpressed in various cancers and may act as an independent prognostic marker. While it was initially identified as a mediator of anti-angiogenesis through its interaction with thrombospondin-1 (TSP1), recent research has highlighted its role in promoting tumor growth, metastasis, drug resistance, and immune suppression. The varied impact of CD36 on cancer is likely ligand-dependent. Therefore, we focus specifically on the ligand-dependent role of CD36 in cancer to provide a critical review of recent advances, perspectives, and challenges.

Comprehensive analysis of subtypes and risk model based on complement system associated genes in ccRCC.

BACKGROUND: Immune therapy is widely used in treating clear cell renal cell carcinoma (ccRCC), yet identifying patient subgroups that are expected to response remains challenging. As complement system can mediate immune effects, including the progression of tumors, a correlation between complement system and immune therapy may exist. METHODS: Based on 11 complement system associated genes (CSAGs) identified from The Cancer Genome Atlas (TCGA), we performed unsupervised clustering and classified the tumors into two different complement system (CS) patterns. The clinical significance, tumor microenvironment (TME), functional enrichment, and immune infiltration were further analyzed. A novel scoring system named CSscore was developed based on the expression levels of the 11 CSAGs. RESULTS: Two distinct CS patterns were identified, classified as Cluster1 and Cluster2, and Cluster1 showed poor clinical outcome. Further analysis of functional enrichment, immune cell infiltration, and genetic variation revealed that Cluster1 had high infiltration of TME immune cells, but also exhibited high immune escape. The novel prognostic model, CSscore could act as an independent prognostic factor and effectively predict patients' prognosis and distinguish the therapeutic efficacy of different immune treatment strategies. The pan-cancer analysis of the CSscore indicates its potential to be further generalized to other types of cancer. CONCLUSIONS: Two distinct CS patterns were identified and were further analyzed in terms of infiltration of TME immune cells and immune escape, providing potential explanations for the impact on prognosis of ccRCC. Our CSscore prognostic model may offer a novel perspective in the management of ccRCC patients, and potentially other types of cancer as well.

HIF1A-repressed PUS10 regulates NUDC/Cofilin1 dependent renal cell carcinoma migration by promoting the maturation of miR-194-5p.

BACKGROUND: Renal cell carcinoma (RCC) is characterized by a high rate of distant metastasis, which leads to poor prognosis in patients with advanced RCC. PUS10 has been recognized as a member of the pseudouridine synthase family, and recently other functions beyond the synthesis of the RNA modification have been uncovered. However, little is known about its role in diseases such as cancer. METHODS: RT-qPCR, western blot and immunohistochemistry were used to measure the expression of PUS10 in RCC tissues. Transwell assay, wound healing assay, and in vivo metastasis model were conducted to determine the function of PUS10 in RCC progression. MicroRNA sequencing and GEO database were used to screen for the downstream microRNAs of PUS10. RNA immunoprecipitation, dual luciferase reporter assay, immunostaining, and rescue experiments were employed to establish the PUS10/miR-194-5p/nuclear distribution protein C(NUDC)/Cofilin1 axis in RCC migration. Chromatin immunoprecipitation and dual luciferase reporter assay were used to verify its upstream transcriptional regulator. RESULTS: The expression of PUS10 was significantly decreased in RCC tissues, and low expression predicted poor prognosis. In vitro and in vivo experiments showed that PUS10 suppressed RCC migration, which, however, was independent of its classical pseudouridine catalytic function. Mechanically, PUS10 promoted the maturation of miR-194-5p, which sequentially inhibited RCC migration via disrupting NUDC-dependent cytoskeleton. Furthermore, hypoxia and HIF-1 A were found involved in the downregulation of PUS10. CONCLUSION: We unraveled PUS10 restrained RCC migration via the PUS10/miR-194-5p/NUDC/Cofilin1 pathway, which independent of its classical catalytic function. Furthermore, a linkage between the critical tumor microenvironment hallmark with malfunction of the forementioned metastasis inhibition mechanism was presented, as demonstrated by repressed expression of PUS10 due to hypoxia and HIF-1A.

The predictive value of perioperative circulating markers on surgical complications in patients undergoing robotic-assisted radical prostatectomy.

BACKGROUND: The occurrence of postoperative complications was associated with poor outcomes for patients undergoing robotic-assisted radical prostatectomy. A prediction model with easily accessible indices could provide valuable information for surgeons. This study aims to identify novel predictive circulating biomarkers significantly associated with surgical complications. METHODS: We consecutively assessed all multiport robotic-assisted radical prostatectomies performed between 2021 and 2022. The clinicopathological factors and perioperative levels of multiple circulating markers were retrospectively obtained from the included patients. The associations of these indices with Clavien-Dindo grade II or greater complications, and surgical site infection were assessed using univariable and multivariable logistic regression models. Further, the models were validated for the overall performance, discrimination, and calibration. RESULTS: In total, 229 patients with prostate cancer were enrolled in this study. Prolonged operative time could independently predict surgical site infection (OR, 3.39; 95% CI, 1.09-10.54). Higher RBC (day 1-pre) implied lower risks of grade II or greater complications (OR, 0.24; 95% CI, 0.07-0.76) and surgical site infection (OR, 0.23; 95% CI, 0.07-0.78). Additionally, RBC (day 1-pre) independently predicted grade II or greater complications of obese patients (P value = 0.005) as well as those in higher NCCN risk groups (P value = 0.012). Regarding the inflammatory markers, NLR (day 1-pre) (OR, 3.56; 95% CI, 1.37-9.21) and CRP (day 1-pre) (OR, 4.16; 95% CI, 1.69-10.23) were significantly associated with the risk of grade II or greater complications, and both the indices were independent predictors in those with higher Gleason score, or in higher NCCN risk groups (P value < 0.05). The NLR (day 0-pre) could also predict the occurrence of surgical site infection (OR, 5.04; 95% CI, 1.07-23.74). CONCLUSIONS: The study successfully identified novel circulating markers to assess the risk of surgical complications. Postoperative increase of NLR and CRP were independent predictors for grade II or greater complications, especially in those with higher Gleason score, or in higher NCCN risk groups. Additionally, a marked decrease of RBC after the surgery also indicated a higher possibility of surgical complications, especially for the relatively difficult procedures.

Immunotherapy with or without targeted therapy for metastatic upper tract urothelial carcinoma: case report and literature review.

Background: Immune checkpoint inhibitors (ICIs) have been proved having a better safety profile compared to platinum-based chemotherapy and have demonstrated encouraging anti-tumor therapeutic effects for patients with metastatic urothelial carcinoma (mUC). However, few studies have evaluated the efficacy of ICIs in patients with metastatic upper tract urothelial carcinoma (mUTUC). Case reports: Case 1 was a 71-year-old male patient diagnosed with left renal pelvic carcinoma, accompanied by a metastasis to the second lumbar spine. As the patient became refractory to chemotherapy, four cycles of camrelizumab, one of the ICIs, were administered, which helped to control the metastases and extend the patient's progression-free survival to five months. Case 2 was an 88-year-old female with middle and lower right ureter carcinoma with right iliac arteriovenous invasion. The patient received five cycles of camrelizumab plus vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors and achieved stable disease. Conclusion: For patients who are ineligible for chemotherapy, immunotherapy might be a feasible treatment, regardless of whether or not they are given VEGFR2 inhibitors.

Development of prediction models to estimate extubation time and midterm recovery time of ophthalmic patients undergoing general anesthesia: a cross-sectional study.

BACKGROUND: To develop prediction models for extubation time and midterm recovery time estimation in ophthalmic patients who underwent general anesthesia. METHODS: Totally 1824 ophthalmic patients who received general anesthesia at Joint Shantou International Eye Center were included. They were divided into a training dataset of 1276 samples, a validation dataset of 274 samples and a check dataset of 274 samples. Up to 85 to 87 related factors were collected for extubation time and midterm recovery time analysis, respectively, including patient factors, anesthetic factors, surgery factors and laboratory examination results. First, multiple linear regression was used for predictor selection. Second, different methods were used to develop predictive models for extubation time and midterm recovery time respectively. Finally, the models' generalization abilities were evaluated using a same check dataset with MSE, RMSE, MAE, MAPE, R-Squared and CCC. RESULTS: The fuzzy neural network achieved the highest R-Squared of 0.956 for extubation time prediction and 0.885 for midterm recovery time, and the RMSE value was 6.637 and 9.285, respectively. CONCLUSION: The fuzzy neural network developed in this study had good generalization performance in predicting both extubation time and midterm recovery time of ophthalmic patients undergoing general anesthesia. TRIAL REGISTRATION: This study is prospectively registered in the Chinese Clinical Trial Registry, registration number: CHiCRT2000036416, registration date: August 23, 2020.

Single-port robot-assisted perineal radical prostatectomy with the da Vinci XI system: initial experience and learning curve using the cumulative sum method.

BACKGROUND: To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method. METHODS: The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time. RESULTS: All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into "early phase" and "late phase." In "late phase" cases, there was less time spent on each step of the operation and less EBL. CONCLUSIONS: Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.

Exosome-derived circTFDP2 promotes prostate cancer progression by preventing PARP1 from caspase-3-dependent cleavage.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play a significant role in tumorigenesis. However, the detailed function of circRNA in prostate cancer (PCa) is still largely unknown. METHODS: We quantified circTFDP2 expression in PCa tissues and adjacent normal tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, transwell, and in vivo progression and metastasis assays were applied to reveal the proliferation and metastatic abilities of circTFDP2 in PCa cells. Mass spectrometry, RNA pulldown, RNA-immunoprecipitation (RIP), western blotting and immunofluorescence were used for the mechanistic studies. qRT-PCR and RIP assays were used to explore the regulatory role of eIF4A3 in the biogenesis of circTFDP2. Finally, functional assays showed the effect of circTFDP2-containing exosomes on PCa cell progression. RESULTS: circTFDP2 was upregulated in PCa tissues compared with adjacent normal tissues. Furthermore, high circTFDP2 expression was positively correlated with the Gleason score. Functionally, circTFDP2 promoted PCa cell proliferation and metastasis both in vivo and in vitro. Mechanistically, circTFDP2 interacted with poly(ADP-ribose) polymerase 1 (PARP1) protein in its DNA-binding domain to prevent it from active caspase-3-dependent cleavage, and finally relieved PCa cells from DNA damage. In addition, RNA-binding protein eIF4A3 can interact with the flanking region of circTFDP2 and promote the biogenesis of circTFDP2. Moreover, exosome-derived circTFDP2 promoted PCa cell progression. CONCLUSIONS: In general, our study demonstrated that circTFDP2 promoted PCa cell progression through the PARP1/DNA damage axis, which may be a promising therapeutic target for PCa.

Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation.

Testicular nuclear receptor 4 (TR4) modulates the transcriptional activation of genes and plays important roles in many diseases. The regulation of TR4 on target genes involves direct interactions with DNA molecules via the DNA-binding domain (DBD) and recruitment of coregulators by the ligand-binding domain (LBD). However, their regulatory mechanisms are unclear. Here, we report high-resolution crystal structures of TR4DBD, TR4DBD-DNA complexes and the TR4LBD-JAZF1 complex. For DNA recognition, multiple factors come into play, and a specific mutual selectivity between TR4 and target genes is found. The coactivators SRC-1 and CREBBP can bind at the interface of TR4 originally occupied by the TR4 activation function region 2 (AF-2); however, JAZF1 suppresses the binding through a novel mechanism. JAZF1 binds to an unidentified surface of TR4 and stabilizes an α13 helix never reported in the nuclear receptor family. Moreover, the cancer-associated mutations affect the interactions and the transcriptional activation of TR4 in vitro and in vivo, respectively. Overall, our results highlight the crucial role of DNA recognition and a novel mechanism of how JAZF1 reinforces the autorepressed conformation and influences the transcriptional activation of TR4, laying out important structural bases for drug design for a variety of diseases, including diabetes and cancers.

Exosomes in Genitourinary Cancers: Emerging Mediators of Drug Resistance and Promising Biomarkers.

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy.

circPHF16 suppresses prostate cancer metastasis via modulating miR-581/RNF128/Wnt/ß-catenin pathway.

Circular RNAs (circRNAs) have been recognized as important regulators in tumorigenesis. However, the specific role of circRNAs in prostate cancer is still largely unknown. Here, we identified that circPHF16 was downregulated in prostate cancer (PCa) tissues compared with normal tissues. Functionally, circPHF16 restrained prostate cancer metastasis both in vivo and in vitro. Mechanistically, circPHF16 directly interacted with miR-581, leading to the downregulation of ring finger protein 128 (RNF128) and inhibiting the metastatic ability of PCa. Furthermore, circPHF16-dependent upregulation of RNF128 inactivated Wnt/ß-catenin signaling. In total, our findings revealed that circPHF16 suppressed prostate cancer metastasis through the circPHF16/miR-581/Wnt/ß-catenin pathways.

Adding fuel to the fire: The lipid droplet and its associated proteins in cancer progression.

A lipid droplet (LD) is an organelle that consists of a phospholipid monolayer and a neutral lipid core, with proteins embedded in or attached to its surface. Until recently, cancers had long been regarded as genetic disorders with the abnormal activation of oncogenes and inactivation of tumor suppressor genes before their quality of a metabolic disorder began to be recognized. The last decade has witnessed the recognition of several metabolic characteristics of cancer cells, among which one is the accumulation of lipid droplets; therefore, attention has been given to exploring the role of LDs in carcinomas. In addition, there has been a remarkable expansion in understanding the complexity of LD's function in cellular homeostasis, including but not limited to energy supply, endoplasmic reticulum (ER) stress and oxidative stress management, or lipotoxicity alleviation. Thus, lipid droplet-associated proteins, which to a great extent determine the dynamics of a lipid droplet, have attracted the interest of numerous cancer researchers and their potential as cancer diagnostic biomarkers and therapeutic targets has been affirmed by emerging evidence. In this review, we systematically summarize the critical role of LDs in cancer and then focus on four categories of lipid droplet-associated proteins having the most direct influence on LD biosynthesis (diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2)), degradation (adipose triglyceride lipase (ATGL)), and two renowned protein families on the LD surface (perilipins and cell death-inducing DNA fragmentation factor alpha-like effectors (CIDEs)). In this way, we aim to highlight their important role in tumor progression and their potential in clinical applications.

Erratum: Excretable IR-820 for in vivo NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor: Erratum.

[This corrects the article DOI: 10.7150/thno.31332.].

METTL1 drives tumor progression of bladder cancer via degrading ATF3 mRNA in an m7G-modified miR-760-dependent manner.

7-methylguanosine (m7G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m7G modification, METTL1 has been reported in certain human cancers. However, the role of internal m7G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m7G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m7G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m7G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.

Acute respiratory distress syndrome secondary to carbon dioxide gas embolism after single-port robotic-assisted perineal radical prostatectomy: a case report.

Background: Single-port robotic-assisted perineal radical prostatectomy (spRAPP) can provide oncologic outcomes similar to those with a traditional approach and is especially indicated for patients with prostate cancer who have a history of major abdominopelvic surgery. Few complications associated with this procedure have been reported. Case Description: A 64-year-old man underwent a spRAPP with a sudden decrease in the percutaneous oxygen saturation (SpO2) and the end-tidal carbon dioxide (ETCO2) partial pressure after accidental injury to the right prostatic venous plexus. And the diagnosis of carbon dioxide (CO2) gas embolism was confirmed by transesophageal echocardiography (TEE). By reducing the pneumoperitoneal pressure, closing the venous rupture, increasing the end-expiratory pressure, and elevating the concentration of inhaled oxygen, the patient's oxygenation improved until the end of the operation. However, he progressed to adult acute respiratory distress syndrome (ARDS) postoperatively. The patient was treated with intensive care and recovered well after treatment with pulmonary protective ventilation. This article reports a case of CO2 embolism confirmed by TEE during spRAPP and resulting in postoperative ARDS, which is the first report in the literature. Conclusions: Anesthesiologists' and surgeons' early detection of CO2 embolism was the key to effective treatment. ARDS secondary to CO2 embolism is rare but cannot be ignored and requires intensive care intervention and comprehensive treatment based on a protective pulmonary ventilation strategy.