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PURPOSE: To compare the efficacy and safety of micropercutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS) in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters. METHODS: This study is a retrospective analysis that combines a review of medical records with an outcomes management database. A total of 163 patients who underwent MPCNL and 137 patients who had FURS were identified between January 2017 and December 2021. Demographic data, operation time, hospitalization time, stone-free rate, and complication rate were collected and analyzed. RESULTS: Preoperative general data of sex, age, BMI, serum creatinine, time of stone existence, stone hardness, stone diameter, preoperative hydronephrosis, and preoperative infection of the MPCNL group have no statistically significant difference with that of the FURS group. All MPCNL or FURS operations in both groups were successfully completed without any instances of reoperation or conversion to another surgical procedure. Patients who underwent MPCNL had a considerably reduced operation time (49.6 vs. 72.4 min; P<0.001), but a higher duration of hospitalization (9.1 vs. 3.9 days; P<0.001) compared to those who underwent FURS. The stone-free rate in the MPCNL group was superior to that of the FURS group, with a percentage of 90.8% compared to 71.5% (P<0.001). There was no statistically significant disparity in the rate of complications between the two groups (13.5% vs. 15.3%; P = 0.741). CONCLUSION: Both MPCNL and FURS are viable and secure surgical choices for individuals with solitary upper ureteral calculi measuring 1 to 2 cm. The FURS procedure resulted in a shorter duration of hospitalization compared to MPCNL. However, it had a comparatively lower rate of successfully removing the stones and required a longer duration for the operation.There were no substantial disparities observed in the complication rate between the two groups.FURS is the preferable option for treating uncomplicated upper ureteral calculi, whereas MPCNL is the preferable option for treating complicated upper ureteral calculi.Prior to making treatment options, it is crucial to take into account the expertise of surgeons, the quality of the equipment, and the preferences of the patient. TRIAL REGISTRATION: No.
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Cálculos Renais , Nefrolitotomia Percutânea , Cálculos Ureterais , Humanos , Cálculos Renais/cirurgia , Cálculos Renais/etiologia , Nefrolitotomia Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Ureterais/cirurgia , Cálculos Ureterais/etiologia , Ureteroscopia/métodos , Masculino , FemininoRESUMO
BACKGROUND: The introduction of multiparameter MRI and novel biomarkers has greatly improved the prediction of clinically significant prostate cancer (csPCa). However, decision-making regarding prostate biopsy and prebiopsy examinations is still difficult. We aimed to establish a quick and economic tool to improve the detection of csPCa based on routinely performed clinical examinations through an automated machine learning platform (AutoML). METHODS: This study included a multicenter retrospective cohort and two prospective cohorts with 4747 cases from 9 hospitals across China. The multimodal data, including demographics, clinical characteristics, laboratory tests, and ultrasound reports, of consecutive participants were retrieved using extract-transform-load tools. AutoML was applied to explore potential data processing patterns and the most suitable algorithm to build the Prostate Cancer Artificial Intelligence Diagnostic System (PCAIDS). The diagnostic performance was determined by the receiver operating characteristic curve (ROC) for discriminating csPCa from insignificant prostate cancer (PCa) and benign disease. The clinical utility was evaluated by decision curve analysis (DCA) and waterfall plots. RESULTS: The random forest algorithm was applied in the feature selection, and the AutoML algorithm was applied for model establishment. The area under the curve (AUC) value in identifying csPCa was 0.853 in the training cohort, 0.820 in the validation cohort, 0.807 in the Changhai prospective cohort, and 0.850 in the Zhongda prospective cohort. DCA showed that the PCAIDS was superior to PSA or fPSA/tPSA for diagnosing csPCa with a higher net benefit for all threshold probabilities in all cohorts. Setting a fixed sensitivity of 95%, a total of 32.2%, 17.6%, and 26.3% of unnecessary biopsies could be avoided with less than 5% of csPCa missed in the validation cohort, Changhai and Zhongda prospective cohorts, respectively. CONCLUSIONS: The PCAIDS was an effective tool to inform decision-making regarding the need for prostate biopsy and prebiopsy examinations such as mpMRI. Further prospective and international studies are warranted to validate the findings of this study. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048428. Registered on 06 July 2021.
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Inteligência Artificial , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Algoritmos , Aprendizado de MáquinaRESUMO
PURPOSE: This study aims to establish and validate a new diagnosis model called P.Z.A. score for clinically significant prostate cancer (csPCa). METHODS: The demographic and clinical characteristics of 956 patients were recorded. Age, prostate-specific antigen (PSA), free/total PSA (f/tPSA), PSA density (PSAD), peripheral zone volume ratio (PZ-ratio), and adjusted PSAD of PZ (aPSADPZ) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The nomogram was established, and discrimination abilities of the new nomogram were verified with a calibration curve and area under the ROC curve (AUC). The clinical benefits of P.Z.A. score were evaluated by decision curve analysis and clinical impact curves. External validation of the model using the validation set was also performed. RESULTS: The AUCs of aPSADPZ, age, PSA, f/tPSA, PSAD and PZ-ratio were 0.824, 0.672, 0.684, 0.715, 0.792 and 0.717, respectively. The optimal threshold of P.Z.A. score was 0.41. The nomogram displayed excellent net benefit and better overall calibration for predicting the occurrence of csPCa. In addition, the number of patients with csPCa predicted by P.Z.A. score was in good agreement with the actual number of patients with csPCa in the high-risk threshold. The validation set provided better validation of the model. CONCLUSION: P.Z.A. score (including PIRADS(P), aPSADPZ(Z) and age(A)) can increase the detection rate of csPCa, which may decrease the risk of misdiagnosis and reduce the number of unnecessary biopsies. P.Z.A. score contains data that is easy to obtain and is worthy of clinical replication.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico/análise , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Nomogramas , Imageamento por Ressonância MagnéticaRESUMO
In this paper, a Cr(OH)3NSs@ZIF67 (NSs = nanosheets) electrocatalyst is prepared on foam Ni via a simple and rapid electrochemical deposition method. Excellent electrocatalytic activity of Cr(OH)3NSs@ZIF67 is demonstrated. It can use the overpotential of 281 mV and 390 mV respectively to drive 10 mA cm-2and 50 mA cm-2. It is observed that the Cr(OH)3NSs@ZIF67 electrode has the highest initial current density at 1.57 V compared with the other two monomer electrodes and shows excellent stability at the end of 60â¯000 s. It has the largest electrochemical activity specific surface and lowest charge-transfer resistance, and M-O bonds (M = Co, Cr) and shifting of binding energy peaks at the interface lead to more active sites and more efficient electron transfer for oxygen evolution reaction. This work highlights the construction of highly efficient composite electrocatalysts composted of low-dimensional non-precious transition metal compounds and metalorganic frameworks, promoting the development of low-cost non-noble metal composites in energy chemistry.
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Herein, the effect of long noncoding RNA forkhead box D1 antisense RNA 1 (FOXD1-AS1) on malignant phenotypes of prostate cancer (PCa) cells was investigated. FOXD1-AS1 presented high expression in PCa cells according to the results of RT-qPCR. As shown by cell counting kit-8 assays, colony formation assays, wound-healing assays, Transwell assays and flow cytometry analyses, silenced FOXD1-AS1 suppressed PCa cell viability, proliferation, migration and invasion and enhanced cell apoptosis. Additionally, FOXD1-AS1 was primarily localised in cytoplasm of PCa cells. RNA immunoprecipitation assays and luciferase reporter assays revealed that FOXD1-AS1 interacted with miR-3167 in PCa cells. MiR-3167 functioned as an anti-oncogene in PCa and miR-3167 overexpression suppressed cell proliferation while promoted cell apoptosis. Moreover, the downstream target of miR-3167 is mRNA YWHAZ. FOXD1-AS1 elevated the expression of YWHAZ by binding with miR-3167. The suppressive effect of miR-3167 on YWHAZ expression was reversed by FOXD1-AS1 overexpression. Furthermore, overexpressed YWHAZ reversed the suppressive effect of FOXD1-AS1 deficiency on malignant behaviours of PCa cells. Overall, FOXD1-AS1 facilitates malignant phenotypes of PCa cells by up-regulating YWHAZ via miR-3167. The study first reveals the molecular mechanism of FOXD1-AS1 in PCa, suggesting that FOXD1-AS1 and its downstream molecules might be prognostic biomarkers before medical treatment.
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MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Proteínas 14-3-3 , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Antissenso , RNA Longo não Codificante/genéticaRESUMO
The landscape and characteristics of circulating exosomal messenger RNAs (emRNAs) are poorly understood, which hampered the accurate detection of circulating emRNAs. Through comparing RNA sequencing data of circulating exosomes with the corresponding data in tissues, we illustrated the different characteristics of emRNAs compared to tissue mRNAs. We then developed an improved strategy for emRNA detection based on the features of circulating emRNAs. Using the optimized detection strategy, we further validated prostate cancer (PCa) associated emRNAs discovered by emRNA-seq in a large cohort of patients and identified emRNA signatures for PCa screening and diagnosis using logistic regression analysis. The receiver operating characteristic curve (ROC) analysis showed that the circulating emRNA-based screening signature yielded an area under the ROC curve (AUC) of 0.948 in distinguishing PCa patients from healthy controls. The circulating emRNA-based diagnostic signature also showed a great performance in predicting prostate biopsy results (AUC: 0.851). In conclusion, our study developed an optimized emRNA detection strategy and identified novel emRNA signatures for the detection of PCa.
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Biomarcadores Tumorais , Ácidos Nucleicos Livres , Exossomos/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Mensageiro/genética , Detecção Precoce de Câncer/métodos , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/diagnóstico , Curva ROC , TranscriptomaRESUMO
BACKGROUND: Preoperative prediction of extracapsular extension (ECE) of prostate cancer (PCa) is important to guide clinical decision-making and improve patient prognosis. PURPOSE: To investigate the value of multiparametric magnetic resonance imaging (mpMRI)-based peritumoral radiomics for preoperative prediction of the presence of ECE. STUDY TYPE: Retrospective. POPULATION: Two hundred eighty-four patients with PCa from two centers (center 1: 226 patients; center 2: 58 patients). Cases from center 1 were randomly divided into training (158 patients) and internal validation (68 patients) sets. Cases from center 2 were assigned to the external validation set. FIELD STRENGTH/SEQUENCE: A 3.0 T MRI scanners (three vendors). Sequence: Pelvic T2-weighted turbo/fast spin echo sequence and diffusion weighted echo planar imaging sequence. ASSESSMENT: The peritumoral region (PTR) was obtained by 3-12 mm (half of the tumor length) 3D dilatation of the intratumoral region (ITR). Single-MRI radiomics signatures, mpMRI radiomics signatures, and integrated models, which combined clinical characteristics with the radiomics signatures were built. The discrimination ability was assessed by area under the receiver operating characteristic curve (AUC) in the internal and external validation sets. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U-test, DeLong test. RESULTS: The PTR radiomics signatures demonstrated significantly better performance than the corresponding ITR radiomics signatures (AUC: 0.674 vs. 0.554, P < 0.05 on T2-weighted, 0.652 vs. 0.546, P < 0.05 on apparent diffusion coefficient, 0.682 vs. 0.556 on mpMRI in the external validation set). The integrated models combining the PTR radiomics signature with clinical characteristics performed better than corresponding radiomics signatures in the internal validation set (eg. AUC: 0.718 vs. 0.671, P < 0.05 on mpMRI) but performed similar in the external validation set (eg. AUC: 0.684, vs. 0.682, P = 0.45 on mpMRI). DATA CONCLUSION: The peritumoral radiomics can better predict the presence of ECE preoperatively compared with the intratumoral radiomics and may have better generalization than clinical characteristics. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 2.
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Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Extensão Extranodal , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
Composite electrocatalysts of carbon and metals or metal compounds with homogeneous active sites can be obtained through the carbonization of metal organic framework (MOF) materials under inert atmosphere. In this work, a three-phase composite electrocatalysts NiFe2O4/Ni@C were prepared via pyrolysis from self-assembled MOF nanosheets aggregates. The excellent electrocatalytic activity of the obtained electrocatalysts with various Ni:Fe ratios is demonstrated. Especially, the NiFe2O4/Ni@C sample with the mole ratio of Ni:Fe = 1:1 can use the overpotential (η) of 330 and 423 mV to drive 10 and 50 mA cm-2 respectively. After 80 000 s/22 h, the current density could retained 90% of the initial current density. The excellent activity and stability of the electrocatalysts are attributed to nickel and iron ions with uniform dispersion at atomic level in the NiFe2O4 phase and the synergistic effect of nickel and NiFe2O4 nanoparticles with amorphous carbon atoms or nanoparticles around.
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HLA donor-specific antibodies (DSAs) binding to vascular endothelial cells of the allograft trigger inflammation, vessel injury, and antibody-mediated rejection (AMR). Accumulation of intragraft-recipient macrophages is a histological characteristic of AMR, which portends worse outcome. HLA class I (HLA I) DSAs enhance monocyte recruitment by activating endothelial cells and engaging FcγRs, but the DSA-activated donor endothelial influence on macrophage differentiation is unknown. In this study, we explored the consequence of DSA-activated endothelium on infiltrating monocyte differentiation. Here we show that cardiac allografts from murine recipients treated with MHC I DSA upregulated genes related to monocyte transmigration and Fc receptor stimulation. Human monocytes co-cultured with HLA I IgG-stimulated primary human endothelium promoted monocyte differentiation into CD68+ CD206+ CD163+ macrophages (M(HLA I IgG)), whereas HLA I F(ab')2 stimulated endothelium solely induced higher CD206 (M(HLA I F(ab')2 )). Both macrophage subtypes exhibited significant changes in discrete cytokines/chemokines and unique gene expression profiles. Cross-comparison of gene transcripts between murine DSA-treated cardiac allografts and human co-cultured macrophages identified overlapping genes. These findings uncover the role of HLA I DSA-activated endothelium in monocyte differentiation, and point to a novel, remodeling phenotype of infiltrating macrophages that may contribute to vascular injury.
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Células Endoteliais , Rejeição de Enxerto , Aloenxertos , Animais , Rejeição de Enxerto/etiologia , Antígenos HLA , Humanos , Inflamação/etiologia , Isoanticorpos , Macrófagos , Camundongos , Fenótipo , Doadores de TecidosRESUMO
Prostate cancer (PCa) is a common malignant tumor with increasing incidence and high heterogeneity among males worldwide. In the era of big data and artificial intelligence, the paradigm of biomarker discovery is shifting from traditional experimental and small data-based identification toward big data-driven and systems-level screening. Complex interactions between genetic factors and environmental effects provide opportunities for systems modeling of PCa genesis and evolution. We hereby review the current research frontiers in informatics for PCa clinical translation. First, the heterogeneity and complexity in PCa development and clinical theranostics are introduced to raise the concern for PCa systems biology studies. Then biomarkers and risk factors ranging from molecular alternations to clinical phenotype and lifestyle changes are explicated for PCa personalized management. Methodologies and applications for multi-dimensional data integration and computational modeling are discussed. The future perspectives and challenges for PCa systems medicine and holistic healthcare are finally provided.
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Inteligência Artificial , Neoplasias da Próstata , Biomarcadores , Humanos , Masculino , Medicina de Precisão , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Pesquisa Translacional BiomédicaRESUMO
BACKGROUND: To evaluate the prognostic value of Lymphovascular Invasion (LVI) in patients with squamous cell carcinoma of the penis (SCCP) following surgery. PATIENTS AND METHODS: This retrospective study analyzed the data of 891 eligible patients with SCCP who were diagnosed between 2010 and 2014, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were categorized by LVI, age, grade, T stage, lymph nodes status, distant metastasis, regional lymph nodes removed, and surgery. Overall survival (OS) and penile carcinoma-specific survival (PCSS) were evaluated by Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: The presence of LVI was significantly associated with increased risk of advanced T stage, high grade, lymph node metastasis, and distant metastasis (P < 0.001 for all). In Kaplan-Meier analyses, patients with the presence of LVI had significantly lower OS and PCSS than those with the absence of LVI (P < 0.001 for both,). The presence of LVI was also significantly associated with poorer OS and worse PCSS in patients with Tx + Ta + T1 stage (P = 0.007, P < 0.001), N0 stage (P < 0.001, P = 0.040), grade 1 (P = 0.001, P < 0.001), grade 2 (P = 0.001, P = 0.014), no distant metastasis (P < 0.001 for both), no regional lymph nodes removed (P < 0.001 for both), Non-radical surgery (P < 0.001 for both) and radical surgery(P = 0.037, P = 0.002). In multivariate analyses, the presence of LVI in patients with SCCP following surgery was found to be a significant independent predictor of decreased OS (hazard ratio 1.403, P = 0.039). CONCLUSIONS: The LVI status might be a crucial prognostic indicator for overall survival in patients with SCCP.
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Carcinoma de Células Escamosas/cirurgia , Metástase Linfática/patologia , Neoplasias Penianas/cirurgia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Prognóstico , Estudos Retrospectivos , Programa de SEERRESUMO
OBJECTIVES: To examine the association between endometrial/subendometrial vasculature and in vitro fertilization-embryo transfer (IVF-ET) and frozen embryo transfer (FET) outcomes. METHODS: A meta-analysis of studies using endometrial/subendometrial 3-dimensional ultrasound and power Doppler angiography was performed to examine the vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in pregnant and nonpregnant women. Ten articles were analyzed, including 895 pregnant women and 882 nonpregnant women. RESULTS: A subgroup analysis of the measuring time showed that the endometrial VI (standardized mean difference [SMD], 0.57; 95% confidence interval [CI], 0.40, 0.74; P < .00001), FI (SMD, 0.56; 95% CI, 0.33, 0.78; P < .00001), and VFI (SMD, 0.45; 95% CI, 0.28, 0.61; P < .00001) measured on the ET day, but not on the human chorionic gonadotropin (hCG) trigger day, were significantly higher in pregnant than nonpregnant women. Additionally, the subendometrial FI was significantly increased in pregnant women on the both hCG day (SMD, 0.68; 95% CI, 0.31, 1.06; P = .004) and ET day (SMD, 0.30; 95% CI, 0.08, 0.52; P = .007). A subgroup analysis of cycle type showed that the endometrial VI (SMD, 0.52; 95% CI, 0.30, 0.74; P < .00001), FI (SMD, 0.44; 95% CI, 0.22, 0.66; P = .0001), and VFI (SMD, 0.45; 95% CI, 0.23, 0.67; P = .03) on the ET day were significantly increased in pregnant women in the FET subgroup. CONCLUSIONS: The subendometrial FI on the hCG day and endometrial VI, FI, and VFI on the ET day are potentially associated with pregnancy occurrence during IVF-ET. The endometrial VI, FI, and VFI could help identify appropriate timing for FET. However, the accuracy of these indices in predicting pregnancy occurrence must be further evaluated in additional large-scale studies.
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Transferência Embrionária/estatística & dados numéricos , Endométrio/irrigação sanguínea , Endométrio/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Feminino , Humanos , Gravidez , Ultrassonografia Doppler/métodosRESUMO
BACKGROUND: B7-H3, a member of the B7 family of the Ig superfamily of proteins, has been detected in the epididymis, which is a storage organ related to sperm maturation. However, the characteristics of its expression in different regions of the epididymis remain unknown. Our aim was to investigate the expression of B7-H3 in the caput, corpus, and cauda of the epididymis. METHODS: We extracted epididymis specimens from adult male C57BL/6 mice. The expression of B7-H3 was then measured with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: B7-H3 protein was predominantly detected on the membrane and in the cytoplasm of the principal cells in the epididymis. Moreover, the level of B7-H3 in the corpus of the mouse epididymis was significantly higher than that in the caput (p < 0.05) or the cauda of the epididymis (P < 0.05). However, there was no remarkable difference in the level of B7-H3 between the caput and the cauda (p > 0.05). CONCLUSIONS: The caput, corpus, and cauda of the mouse epididymis all expressed B7-H3 protein. However, the levels of B7-H3 were different in the three regions of the epididymis.
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Antígenos B7/análise , Epididimo/química , Animais , Antígenos B7/metabolismo , Epididimo/anatomia & histologia , Epididimo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
In this study, 4 different spermatic vein ligation procedures for varicocele (VC) treatment were compared based on recurrence rate, postoperative complications, and semen quality. Between January 2012 and May 2013, a total of 345 male patients with VC were recruited at The First Affiliated Hospital of Soochow University. Patients were performed by different ligation procedures, and they were divided into 4 groups: laparoscopic varicocelectomy group (LV group: n = 84), microscopic inguinal varicocelectomy group (MIV group: n = 85), microscopic retroperitoneal varicocelectomy group (MRV group: n = 86), and microscopic subinguinal varicocelectomy group (MSV group: n = 90). In MSV group, the operative time was 55 ± 6.9 minutes, which was significantly longer than LV, MIV, and MRV groups (P < 0.05). Recurrence rate in LV group was at 11.9%, the highest rate observed compared with the MIV, MRV, and MSV groups (P < 0.05). Scrotal edema and testicular atrophy in MSV group were markedly decreased (P < 0.05), and scrotal pain was relieved in almost all patients in the MSV group at a significantly higher rate than LV, MIV, and MRV groups (P < 0.05). Sperm concentration, sperm count of grades a + b, and sperm motility (%) in the MSV group were sharply higher than LV, MIV, and MRV groups (all P < 0.05). Our study indicates that MSV is the most beneficial of the 4 spermatic vein ligation procedures and may be offered as the first-line treatment for VC in infertile men.
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Laparoscopia/métodos , Microcirurgia/métodos , Escroto/patologia , Varicocele/cirurgia , Adolescente , Adulto , Atrofia , Humanos , Ligadura , Masculino , Duração da Cirurgia , Dor/epidemiologia , Dor/etiologia , Recidiva , Espaço Retroperitoneal , Estudos Retrospectivos , Análise do Sêmen , Contagem de Espermatozoides , Testículo/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.
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Imunoterapia , Piroptose , Humanos , Apoptose , Morte Celular , Desenho de FármacosRESUMO
Prostate cancer (PCa) is commonly occurred with high incidence in men worldwide, and many patients will be eventually suffered from the dilemma of castration-resistance with the time of disease progression. Castration-resistant PCa (CRPC) is an advanced subtype of PCa with heterogeneous carcinogenesis, resulting in poor prognosis and difficulties in therapy. Currently, disorders in androgen receptor (AR)-related signaling are widely acknowledged as the leading cause of CRPC development, and some non-AR-based strategies are also proposed for CRPC clinical analyses. The initiation of CRPC is a consequence of abnormal interaction and regulation among molecules and pathways at multi-biological levels. In this study, CRPC-associated genes, RNAs, proteins, and metabolites were manually collected and integrated by a comprehensive literature review, and they were functionally classified and compared based on the role during CRPC evolution, i.e., drivers, suppressors, and biomarkers, etc. Finally, translational perspectives for data-driven and artificial intelligence-powered CRPC systems biology analysis were discussed to highlight the significance of novel molecule-based approaches for CRPC precision medicine and holistic healthcare.
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Medicina de Precisão , Neoplasias de Próstata Resistentes à Castração , Humanos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias de Próstata Resistentes à Castração/patologia , Masculino , Medicina de Precisão/métodos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , PrognósticoRESUMO
OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.
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Laparoscopia , Imageamento por Ressonância Magnética , Margens de Excisão , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Prostatectomia/métodos , Laparoscopia/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Idoso , Antígeno Prostático Específico/sangue , Fatores de Risco , Medição de Risco/métodos , Gradação de Tumores , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Nuclear cap-binding protein 2 (NCBP2), as the component of the cap-binding complex, participates in a number of biological processes, including pre-mRNA splicing, transcript export, translation regulation and other gene expression steps. However, the role of NCBP2 on the tumor cells and immune microenvironment remains unclear. To systematically analyze and validate functions of NCBP2, we performed a pan-cancer analysis using multiple approaches. METHODS: The data in this study were derived from sequencing, mutation, and methylation data in the TCGA cohort, normal sample sequencing data in the GTEx project, and cell line expression profile data in the CCLE database. RESULTS: Survival analyses including the Cox proportional-hazards model and log-rank test revealed the poor prognostic role of NCBP2 in multiple tumors. We further validated the oncogenic ability of NCBP2 in prostate cancer cell lines, organoids and tumor-bearing mice. A negative correlation was observed between NCBP2 expression and immune score by the ESTIMATE algorithm. Simultaneously, the NCBP2-induced immunosuppressive microenvironment might be related to the decline in CD8+T cells and the increase in regulatory T cells and neutrophils, examined by flow cytometry experiments for NCBP2 overexpressed tumor-bearing mice. CONCLUSION: This research offered strong proof supporting NCBP2 as the prognostic marker and the therapeutic target in the future.
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PURPOSE: Machine learning (ML) models presented an excellent performance in the prognosis prediction. However, the black box characteristic of ML models limited the clinical applications. Here, we aimed to establish explainable and visualizable ML models to predict biochemical recurrence (BCR) of prostate cancer (PCa). MATERIALS AND METHODS: A total of 647 PCa patients were retrospectively evaluated. Clinical parameters were identified using LASSO regression. Then, cohort was split into training and validation datasets with a ratio of 0.75:0.25 and BCR-related features were included in Cox regression and five ML algorithm to construct BCR prediction models. The clinical utility of each model was evaluated by concordance index (C-index) values and decision curve analyses (DCA). Besides, Shapley Additive Explanation (SHAP) values were used to explain the features in the models. RESULTS: We identified 11 BCR-related features using LASSO regression, then establishing five ML-based models, including random survival forest (RSF), survival support vector machine (SSVM), survival Tree (sTree), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and a Cox regression model, C-index were 0.846 (95%CI 0.796-0.894), 0.774 (95%CI 0.712-0.834), 0.757 (95%CI 0.694-0.818), 0.820 (95%CI 0.765-0.869), 0.793 (95%CI 0.735-0.852), and 0.807 (95%CI 0.753-0.858), respectively. The DCA showed that RSF model had significant advantages over all models. In interpretability of ML models, the SHAP value demonstrated the tangible contribution of each feature in RSF model. CONCLUSIONS: Our score system provide reference for the identification for BCR, and the crafting of a framework for making therapeutic decisions for PCa on a personalized basis.
RESUMO
Kidney transplantation is the gold standard for the treatment of end-stage renal diseases (ESRDs). However, the scarcity of donor kidneys has caused more and more ESRD patients to be stuck on the waiting list for transplant surgery. Improving the survival rate for renal grafts is an alternative solution to the shortage of donor kidneys. Therefore, real-time monitoring of the surgical process is crucial to the success of kidney transplantation, but efficient methods and techniques are lacking. Herein, a fluorescence technology based on bright, photostable and long-circulating aggregation-induced emission (AIE) active NIR-II nano-contrast agent DIPT-ICF nanoparticles for the whole-process monitoring and evaluation of renal transplantation has been reported. In the aggregated state, DIPT-ICF exhibits superior photophysical properties compared with the commercial dyes IR-26 and IR-1061. Besides, the long-circulating characteristic of the AIE nano-contrast agent helps to achieve renal angiography in kidney retrieval surgery, donor kidney quality evaluation, diagnosing vascular and ureteral complications, and assessment of renal graft reperfusion beyond renovascular reconstruction, which considerably outperforms the clinically approved indocyanine green (ICG).