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The study of the dominant factors influencing moisture content is essential for investigating vacuum filtration mechanisms. In view of the present situation where there is insufficient experimental data and the dominant factors influencing the moisture content of a filter cake have not been identified, in this study a vacuum filtration apparatus was designed and constructed. Quartz sand particles were used as the filtration material. 300 datasets of moisture contents of a filter cake were obtained under different experimental conditions. Multiple Linear Regression, artificial neural network, decision tree, random forest, and extreme gradient boosting were used to establish a prediction model for moisture content during vacuum screening. By comprehensively analyzing the feature importance rankings and the effects of positive and negative correlations, the dominant factors influencing the moisture content of the filter cake during vacuum screening were the particle ratio, screen mesh, and airflow rate. This finding not only provides a scientific basis for the optimization of vacuum screening technology but also points the way for improving screening efficiency in practical applications. It is of significant importance for deepening the understanding of the vacuum screening mechanism and promoting its extensive application.
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Chitin has garnered significant attention due to its renewable, biocompatibility and biodegradability, while its practical application seriously hindered as the functionality of chitin itself can no longer meet people's increasing requirements for materials. Here, an effective method is successfully built for high-performance chitin fibers fabrication through a multi-step strategy that involved chemical pre-crosslinking, followed by wet-twisting and wet-stretching techniques, combined with physical cross-linking. The as-prepared chitin fiber exhibited a smooth surface, adjustable diameter, and mechanical strong properties (144.6 MPa). More importantly, functional chitin fiber with magnetic or conductive abilities can be easily obtained by spraying Fe3O4 particles or Ag nanowire on the chemical pre-crosslinking chitin gel film before stretching and twisting. The doped functional inorganic particles exist in a continuous ribbon structure in the fiber reduced the decrease in material strength caused by uneven particles dispersion, resulting 88.4 % of stress and 91.6 % of strain retention. This work not only bestow invaluable insights into the fabrication of functional chitin fibers but also provide a novel approach to solve the problem of poor compatibility between organic and inorganic composite materials.
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Desmoplastic small round cell tumour (DSRCT) is a highly aggressive soft-tissue sarcoma with distinctive morphological features and characteristic EWSR1::WT1 gene fusion. DSRCT occurs in a variety of anatomic sites, with abdominal cavity being the most common location. Primary DSRCTs arising in the male genital system are exceedingly rare, with no documented definitive cases of primary DSRCT of the prostate to date, although 28 cases of DSRCT in the testicular or paratesticular regions have been reported. We here present two cases of primary DSRCT of the prostate. Both cases demonstrated the distinct morphology and the typical multiphenotypic immunohistochemical profile, and the characteristic EWSR1::WT1 fusion verified by fluorescent in situ hybridisation. Our cases expand the anatomic distribution of primary DSRCT and highlight the importance of considering this rare tumour in the differential diagnoses of small cell malignancies of the prostate.
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ABSTRACT: ß-thalassemia is a condition characterized by reduced or absent synthesis of ß-globin resulting from genetic mutations, leading to expanded and ineffective erythropoiesis. Mitoxantrone has been widely used clinically as an antitumor agent considering its ability to inhibit cell proliferation. However, its therapeutic effect on expanded and ineffective erythropoiesis in ß-thalassemia is untested. We found that mitoxantrone decreased α-globin precipitates and ameliorated anemia, splenomegaly, and ineffective erythropoiesis in the HbbTh3/+ mouse model of ß-thalassemia intermedia. The partially reversed ineffective erythropoiesis is a consequence of effects on autophagy as mitochondrial retention and protein levels of mTOR, P62, and LC3 in reticulocytes decreased in mitoxantrone-treated HbbTh3/+ mice. These data provide significant preclinical evidence for targeting autophagy as a novel therapeutic approach for ß-thalassemia.
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Modelos Animales de Enfermedad , Eritropoyesis , Mitoxantrona , Talasemia beta , Animales , Talasemia beta/tratamiento farmacológico , Eritropoyesis/efectos de los fármacos , Ratones , Mitoxantrona/farmacología , Mitoxantrona/uso terapéutico , Autofagia/efectos de los fármacos , Globinas alfa/genética , Reticulocitos/efectos de los fármacos , Reticulocitos/metabolismoRESUMEN
INTRODUCTION: It is important to explore strategies reducing the number of SB cores taken to minimize biopsy-related morbidity and patient's discomfort during biopsy. This study aims to optimize prostate biopsy procedures by reducing the number of systematic biopsy (SB) cores while preserving cancer detection rates in the era of combined biopsy. PATIENTS AND METHODS: We prospectively recruited patients with ≥1 magnetic resonance imaging (MRI) lesions and they underwent transperineal combined 12-core SB+3-core targeted prostate biopsy (TB, reference standard). New strategy was defined as a laterally 6-core SB+3-core TB. Patients were served as their own control. Detection rates for overall prostate cancer (PCa) and clinically significant PCa (csPCa) were compared among the standard SB, MRI-TB, 6-core SB +3-core TB, and reference standard. Pathology consistency was assessed using the Kappa test. RESULTS: A total of 204 men were included, of which 111 (54.41%) and 92 (45.10%) harbored overall PCa and csPCa. Referenced combined biopsy detected significantly 6.86% (P = .0005) or 4.90% (P = .0044) more csPCa than performing only SB or 3-core TB, but was comparable to the new biopsy strategy. (45.10% vs. 43.14%, P = .1336) Similar results persisted when limiting patients in biopsy-naïve men or stratified by Prostate Imaging Reporting and Data System scores, PSAD, and index lesion parameters. Additionally, performing 6-core SB+3-core TB demonstrated high consistency with reference standard in grade group distribution (Kappa coefficient: 0.952 for all, 0.961 for biopsy-naïve men) and achieved superior sensitivity of 95.7% (All: 95% CI: 89.2%-99.8%) and 96.9% (Biopsy-naïve: 95% CI: 91.1%-99.7%), respectively. CONCLUSIONS: The 6-core SB+3-core TB approach maintains expected detection rates while reducing the total core count, offering a promising alternative to the reference standard, which may help to tailor transperineal combined biopsy procedures.
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Biopsia Guiada por Imagen , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Persona de Mediana Edad , Biopsia Guiada por Imagen/métodos , Estudios Prospectivos , Biopsia con Aguja Gruesa/métodos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Próstata/patología , Próstata/diagnóstico por imagen , Ultrasonografía Intervencional/métodosRESUMEN
Bronchial papillomas are benign tumors, which can be divided into different subtypes based on the cellular features. So far, no bronchial papilloma with basaloid cell features has been reported. We report a bronchial basaloid papillary tumor in a 67-year-old woman. Tumor recurrence and malignant transformation were observed after a long-term follow-up. The clinical, histological, immunohistochemical, and genetic features were reappraised. The primary tumor was characterized by papillary growth pattern and basaloid neoplastic cells, only a small amount of neoplastic cells showed mature characteristics. The tumor originated from respiratory epithelium and had a low proliferation index by Ki-67. Keratin (KRT) 5/6 and KRT7 showed patchy or partial positivity. Myoepithelial markers were negative. P63 was diffusely positive, but it was negative in the small amount of tumor cells with mature characteristics. The common genetic alterations (EGFR, KRAS, BRAF V600E, HER2, and ALK) of lung cancers were not detected. However, tumor recurrence was observed in the mediastinum and esophagus 12 years after surgery. The recurrent tumor had a morphology overlapping with that of the primary tumor; however, it displayed significantly malignant characteristics. The recurrent tumor was not related to high-risk HPV. A high variant allele frequency was observed in tumor suppressor gene BRCA1, TP53, oncogene GNA11, and KIT, which were all missense mutations. Considering the bland features of the primary tumor and the fact of tumor recurrence and undisputed malignant transformation, the basaloid papillary tumor was considered a tumor with uncertain malignant potential.
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OBJECTIVES: The study aims to identify the outcome and the related factors of unvaccinated patients with end-stage kidney disease during the Omicron pandemic. DESIGN: A multicentre retrospective study of patients with end-stage kidney disease undergone maintenance haemodialysis (HD) in China. SETTING: 6 HD centres in China. PARTICIPANTS: A total of 654 HD patients who tested positive for SARS-CoV-2 were ultimately included in the study. OUTCOME MEASURES: The primary outcomes of interest were adverse outcomes, including hospitalisation due to COVID-19 and all-cause mortality. RESULTS: The average age of the patients was 57 years, with 33.6% of them being over 65 years. Among the patients, 57.5% were male. During the follow-up period, 158 patients (24.2%) experienced adverse outcomes, and 93 patients (14.2%) died. The majority of patients (88/158) developed adverse outcomes within 30 days, and most deaths (77/93) occurred within 1 month. An advanced multivariable Cox regression analysis identified that adverse outcomes were associated with various factors while all-cause mortality was related to advanced age, male gender, high levels of C reactive protein (CRP) and low levels of prealbumin. The Kaplan-Meier curves demonstrated significantly higher all-cause mortality rates in the older, male, high CRP and low prealbumin subgroups. CONCLUSIONS: Among unvaccinated HD patients with confirmed Omicron infections, various factors were found to be linked to adverse outcomes. Notably, age, sex, CRP and prealbumin had a substantial impact on the risk of all-cause mortality.
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COVID-19 , Fallo Renal Crónico , Diálisis Renal , SARS-CoV-2 , Humanos , Masculino , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/complicaciones , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/complicaciones , China/epidemiología , Factores de Riesgo , Anciano , Adulto , Hospitalización/estadística & datos numéricos , PandemiasRESUMEN
The conventional von Neumann architecture has proven to be inadequate in keeping up with the rapid progress in artificial intelligence. Memristors have become the favored devices for simulating synaptic behavior and enabling neuromorphic computations to address challenges. An artificial synapse utilizing the perovskite structure PbHfO3 (PHO) has been created to tackle these concerns. By employing the sol-gel technique, a ferroelectric film composed of Au/PHO/FTO was created on FTO/glass for the purpose of this endeavor. The artificial synapse is composed of Au/PHO/FTO and exhibits learning and memory characteristics that are similar to those observed in biological neurons. The recognition accuracy for both MNIST and Fashion-MNIST data sets saw an increase, reaching 92.93% and 76.75%, respectively. This enhancement resulted from employing a convolutional neural network architecture and implementing an improved stochastic adaptive algorithm. The presented findings showcase a viable approach to achieve neuromorphic computation by employing artificial synapses fabricated with PHO.
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BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.
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Androstenos , Biomarcadores de Tumor , Antígeno Ki-67 , Neoplasias de la Próstata , Humanos , Masculino , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Anciano , Androstenos/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Proliferación Celular/efectos de los fármacos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Anciano de 80 o más Años , Antineoplásicos/uso terapéuticoRESUMEN
The fabrication of reliable, reusable and efficient catalyst is crucial for the conversion of nitroaromatic compounds into more chemically valuable amine-based molecules. In this study, a series of chitin supported platinum (Pt) catalysts with high catalytic activity, stability, and reusability were developed by using chitin derived from seafood waste as raw materials. The catalytic performance differences among these catalysts activated by different methods were investigated by hydrogenation of nitroaromatic compounds. The results showed that the multilayer hierarchical pore structure and abundance of hydroxyl and acetamido groups in chitin provided ample anchoring sites for Pt nanoparticles (NPs), ensuring the high dispersion of Pt NPs. Moreover, the interconnected channels between chitin nanofibrous microspheres facilitated rapid transport of reaction substrates. The best Pt/Chitin catalyst exhibited excellent catalytic activity and broad substrate applicability in hydrogenation of nitroaromatic compounds. Significantly, even after 20 runs, no discernible deactivation of activity was observed, demonstrating exceptional catalytic reusability. The application of seafood waste-based catalysts is conducive to the development of a green/sustainable society.
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Quitina , Nanopartículas , Platino (Metal)/química , Hidrogenación , Nanopartículas/química , Alimentos MarinosRESUMEN
PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. RESULTS: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.
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Carcinoma de Células Renales , Fumarato Hidratasa , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Fumarato Hidratasa/deficiencia , Fumarato Hidratasa/genética , Masculino , Femenino , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Persona de Mediana Edad , Anciano , Adulto , Activación de Linfocitos/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Memoria Inmunológica , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inmunoterapia/métodos , Células T de Memoria/inmunología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells. METHODS: The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin ß8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. RESULTS: Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts. CONCLUSIONS: The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.
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Cadenas beta de Integrinas , Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Vejiga Urinaria , Animales , Ratones , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Actinas/metabolismo , Recurrencia Local de Neoplasia , Serina-Treonina Quinasas TOR/metabolismo , Glucólisis , Línea Celular Tumoral , Proliferación Celular , Mamíferos/metabolismo , Proteínas de Motivos Tripartitos/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
Esophageal basaloid squamous cell carcinoma (BSCC) is a heterogenous entity with multilineage differentiation. It lacks systematical analysis on submucosal gland differentiation (SGD) due to the histological diversity and low incidence of esophageal BSCC. This study aims to find the correlation of SGD and clinicopathological features. A total of 152 esophageal BSCCs were separated into three histological groups: pure, mixed, and borderline group. The clinicopathological features were compared between different groups. The prevalence of SGD was also compared between cases of different groups. A panel of antibodies were used to identify SGD. The pure group differed from the mixed and borderline groups in many aspects, lymph node metastasis (LNM), cancer embolus, perineural invasion, and advanced stage occurred less frequently in the pure group (P<0.01). The pure group had a better but statistically insignificant overall survival (P=0.097). The squamous cell carcinoma (SCC) component or focal squamous differentiation was present in metastatic lymph nodes in almost all mixed BSCCs (95.7%, 22/23) with LNM. The LNM rate of superficial (T1b) BSCCs (17.6%, 6/34) was comparable to that of superficial (T1b) SCCs (18.5%, 57/308). However, LNM exclusively occurred in superficial mixed (3/5) and borderline (3/10) BSCCs. The IHC results demonstrated a prevalence of SGD in pure group (77%, 43/56). SGD is considered to be a favorable factor, while the squamous differentiation or invasive SCC component is an adverse factor in esophageal BSCCs. Refinement of classification is a promising way to improve patient management.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/patología , Diferenciación CelularRESUMEN
Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.
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Adenocarcinoma , Carcinoma Intraductal no Infiltrante , Neoplasias de la Próstata , Masculino , Humanos , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/patología , Próstata/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Neoplasias de la Próstata/patología , Genómica , Clasificación del TumorRESUMEN
To clarify the characteristics in immunogenicity and safety of inactivated SARS-Cov-2 vaccines among HIV-infected individuals, a longitudinal cohort study was performed on HIV-infected and HIV-uninfected participants with no history of COVID-19 infection and COVID-19 vaccine inoculation. Participants information and adverse events were collected. Blood samples were collected on the same day before vaccination, 21 days after the first shot, 28 days after the second shot, 6 months after the second vaccination and 14 days after the third dose to test anti-receptor-binding domain IgG antibody, viral load, CD4+, CD8+ T cell count. Our result showed that although HIV-infected adults with low nadir CD4+ T cell count ≤ 350 cells/mm3 generate significantly lower immune response after three shots of vaccine compared with HIV-negative controls, 100% of all the HIV-infected and healthy controls were seroconverted after the third shot. Seroconversion ratio and antibody level of 190 days after two shots of vaccination for HIV-infected with nadir CD4+ T cell count ≤ 350 were significantly lower than that of healthy controls. No significant difference was found in viral load among blood samples collected at each time points. CD4 and CD4/CD8 ratio value were found increased greatly after each shot of inoculation in HIV-infected individuals with nadir CD4+ T cell count ≤ 350. Multiple logistic regression analysis showed that among HIV-infected individuals, PLWH with CD4+ T cell count ≤ 350 were less likely experience seroconversion 21 days after the first shot, and less likely maintained antibody immunity 6 months post 2nd dose. Adverse events after each inoculation were not serious and recovered within 1 week. In conclusion, inactivated COVID-19 vaccine was safe and effective in people living with HIV after three shots of vaccination. HIV-infected individuals with low nadir CD4+ T cell count ≤ 350 was associated with a nonoptimal antibody response. Further vaccination strategies could be developed for those with low CD4+ T cell counts.
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COVID-19 , Infecciones por VIH , Adulto , Humanos , Estudios Longitudinales , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , SARS-CoV-2 , Estudios de Cohortes , Anticuerpos Antivirales , Vacunas de Productos Inactivados/efectos adversosRESUMEN
Colorectal clear cell adenocarcinomas are rare tumors. They can be divided into two types: intestinal- and Müllerian-type. Most intestinal-type clear cell adenocarcinomas show a composite morphology, and most early-stage (T1) intestinal-type clear cell adenocarcinomas have an adenoma component. We report an additional early-stage (T1) colonic clear cell adenocarcinoma that was a de novo adenocarcinoma without any adenoma component. It had a pure morphology and the smallest size (0.6â cm) ever reported. Immunohistochemical results demonstrated an intestinal phenotype (KRT20+, KRT7-, CEA+, and CDX2+). Periodic acid-schiff and alcian blue stains were both negative, which demonstrated decrease in mucin expression in the clear tumor cells. Enteroblastic differentiation was observed in a few colorectal clear cell adenocarcinomas in the literature, while it had not been observed in the present tumor. The tumor did not have deep submucosal invasion and cancer embolus, endoscopic submucosal dissection with regular follow-up was an appropriate treatment for the patient. Due to the rarity and diversity of primary colorectal clear cell adenocarcinomas, the cause of clear cytoplasm change and the impact on patient prognosis remain unknown. Accumulating evidence indicates that clear cell adenocarcinomas of intestinal-type is a histological variant of colorectal adenocarcinoma.
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Introduction: The aim of the present study was to evaluate the diagnostic efficacy of different tendon reflexes in detecting diabetic peripheral neuropathy (DPN). Material and methods: According to the changes in tendon reflexes, all patients with diabetes were divided into three strata: impaired Achilles reflex only, impaired lower extremity reflexes, and impaired lower and upper extremity reflexes. Taking nerve conduction studies (NCS) as the gold standard, the sensitivity, specificity, and predictive ability of the tendon reflexes of these three strata, as well as the Toronto clinical scoring system (TCSS) and Michigan Neuropathy Screening Instrument (MNSI), were calculated. Then, the electrophysiological characteristics of diabetic patients with different tendon reflexes were analysed. Results: Among the 240 patients studied, 92 (38.3%) presented evidence of neuropathy, which was confirmed by abnormal NCS, while 148 (61.7%) had normal NCS results. Taking NCS as the gold standard, stratum 1 yielded a sensitivity and specificity of 93.5% and 54.7%, respectively, while stratum 3 had higher specificity (96.6%) and lower sensitivity (34.8%) when compared to stratum 1. However, stratum 2 had the highest specificity (75.7%). Conclusions: The assessment of tendon reflexes can be proposed as a test for screening diabetic polyneuropathy.
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The impact of vaccination on the outcomes of dialysis patients with Omicron infections in China remains unknown. This study aimed to examine the relationship between vaccination and hospitalization as well as all-cause mortality. We included patients who had undergone maintenance hemodialysis (HD) for at least three months at our center. The follow-up period spanned from December 2022 to February 2023. We assessed the connections between vaccination and hospitalization as well as all-cause mortality using univariable and multivariable logistic regression models. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy for hospitalization and all-cause mortality. Ultimately, a total of 427 HD patients with confirmed SARS-CoV-2 infections were included. The patients had a mean age of 54 years, and 59.4% of them were male. Prior to the investigation, 108 patients had received vaccinations, with 81 of them having completed or received booster vaccinations. Throughout the follow-up period, 81 patients were admitted to the hospital, and 39 patients died. Multivariable logistic regression revealed that vaccination significantly decreased all-cause mortality (OR 0.25, 95% CI 0.07-1.94, P = .04). Moreover, completed or booster vaccinations were effective in reducing the hospitalization rate (OR 0.41, 95%CI 0.17-0.99, P = .047). It is noteworthy that both unvaccinated and vaccinated individuals experienced mild symptoms, and the hospitalization rates were relatively low in both groups. Despite the reduced pathogenicity of Omicron compared to previous strains in dialysis patients, both vaccinated and unvaccinated, vaccination still provides benefits for improving the prognosis.
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COVID-19 , Diálisis Renal , Humanos , Masculino , Persona de Mediana Edad , Femenino , COVID-19/prevención & control , SARS-CoV-2 , Vacunación , Hospitalización , China/epidemiologíaRESUMEN
Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on immunohistochemistry can be used to screen for FH-deficient RCC, but their sensitivity and specificity are not perfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. We compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. We included genetically confirmed FH-deficient RCCs (n = 58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC) (n = 83), clear cell RCCs (n = 188), chromophobe RCCs (n = 128), and papillary RCCs (pRCC) (n = 97). AKR1B10, 2SC, and FH were informative diagnostic markers. AKR1B10 had 100% sensitivity and 91.4% specificity for FH-deficient RCC. The nonspecificity of AKR1B10 was shown in 26.5% of TFE3-tRCCs and 21.6% of pRCCs. 2SC showed 100% sensitivity and 88.9% specificity. However, nonspecificity for 2SC was evident in multiple RCCs, including pRCC, TFE3-tRCC, clear cell RCCs, and chromophobe RCCs. FH was 100% specific but 84.5% sensitive. AKR1B10 served as a highly sensitive and specific diagnostic biomarker. Our findings suggest the value of combining AKR1B10 and 2SC to screen for FH-deficient RCC. AKR1B10+/2SC+/FH- cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious of FH-deficient RCC and should be referred for FH genetic tests.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Fumarato Hidratasa/genética , Fumarato Hidratasa/metabolismo , Neoplasias Renales/patología , Factores de Transcripción , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Aldo-Ceto ReductasasRESUMEN
Neuroendocrine differentiation (NED) characterized by the expression of neuroendocrine markers, such as chromogranin A (CgA), is frequently observed in advanced prostate cancer (PCa), the prognostic significance of which is still controversial. Here we specifically addressed the issue of the potential prognostic value of CgA expression in advanced-stage PCa patients with distant metastases and its change over time from metastatic hormone-sensitive (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC). CgA expression was assessed immunohistochemically in initial biopsies of mHSPC, as well as in second biopsies of mCRPC in sixty-eight patients, and its correlation with prognosis (together with conventional clinicopathologic parameters) was analyzed using the Kaplan-Meier method and Cox proportional hazard model. We found that CgA expression was an independent adverse prognostic factor for both mHSPC (CgA positivity ≥ 1%, HR = 2.16, 95% CI: 1.04-4.26, p = 0.031) and mCRPC (CgA ≥ 10%, HR = 20.19, 95% CI: 3.04-329.9, p = 0.008). CgA positivity generally increased from mHSPC to mCRPC and was a negative prognosticator. The assessment of CgA expression may help with the clinical evaluation of advanced-stage patients with distant metastases.