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BACKGROUND: The response to everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML) varies among individuals. This study aims to identify potential factors associated with the response to everolimus. METHOD: We retrospectively examined data encompassing age, gender, tumor size, computed tomography attenuation value (CT value), CT enhancement, and tumor reduction rate in patients with TSC-RAML undergoing everolimus in two previously registered clinical trials. RESULT: A total of 33 participants (29.33 ± 6.63 years old, 20 females) were included. The correlation analysis conducted separately for tumors located in the left and right kidneys revealed significant negative correlations (P < 0.05) between tumor reduction rate and age, as well as tumor size. While significant positive correlations (P < 0.05) were observed between tumor reduction rate and unenhanced CT value as well as CT enhancement. Nonetheless, based on multiple linear regression analysis, unenhanced CT value emerged as the sole-independent predictor of tumor reduction rate among age, gender, tumor size, unenhanced CT value and CT enhancement for both left (coefficient = 0.00319, P < 0.0001) and right kidneys (coefficient = 0.00315, P = 0.0104). Notable reductions were observed in unenhanced CT value (- 3.81 vs - 24.70HU, P < 0.0001) and CT enhancement (48.16 vs 33.56HU, P < 0.0001) following a 3-month administration of everolimus. The decline in both unenhanced CT value and tumor size predominantly occurred within the initial 3 months, subsequently maintaining a relatively stable level throughout the treatment. CONCLUSION: The unenhanced CT value of TSC-RAML showed an independent correlation with the response to everolimus, suggesting its potential as a predictor of everolimus efficacy in patients with TSC-RAML.
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Angiomiolipoma , Neoplasias Renales , Esclerosis Tuberosa , Femenino , Humanos , Adulto Joven , Adulto , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/tratamiento farmacológico , Angiomiolipoma/complicaciones , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/tratamiento farmacológico , Everolimus/uso terapéutico , Estudios Retrospectivos , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/tratamiento farmacológico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: We aimed to launched new staging criteria to predict mTOR inhibitors treatment effect of renal angiomyolipomas (r-AMLs) in TSC patients. METHODS: 40 TSC patients with 69 r-AMLs were divided into two groups based on the efficacy of 6-month mTOR inhibitor treatment. Epidemiological data, therapeutic response, and predictive factors of enrolled patients were collected and analyzed. Age, sex, maximum diameter, maximum cross-sectional area (CSAmax), unenhanced mean CT value, enhanced mean CT value, and added value of enhanced CT of largest r-AML at baseline were assessed as potential influencing factors. Receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) was used to estimate prediction power. RESULTS: After 6 months of mTOR inhibitor treatment, the tumor reduction rates in the two groups were 55.87% and 16.44% (P < 0.001). At the start of treatment, the maximum diameters, CSAmax, added value of enhanced CT of the target lesion in two groups were 7.70 ± 0.73 cm vs. 13.18 ± 1.23 cm(P = 0.028), 57.40 ± 10.76cm2 vs. 167.29 ± 33.09cm2 (P = 0.015), and 62.32 ± 5.03HU vs. 33.06 ± 3.13HU (P = 0.009), respectively. AUCs of CSAmax, added value of enhanced CT, and combination of both were 0.8024, 0.7672, and 0.8116, respectively (P < 0.001). Cut-off values of CSAmax combined with the added value of enhanced CT were 40cm2 and 46HU. AUCs of maximum diameters, combination of maximum diameters and added value of enhanced CT were 0.7600 and 0.8100, respectively (P < 0.001), with cut-off values of 6.6 cm and 46 HU. CONCLUSION: New staging criteria, based on CSAmax and added value of enhanced CT, can predict the treatment efficiency of m-TOR inhibitors for r-AMLs in TSC patients. A simplified version based on maximum diameter and added value of enhanced CT of lesion has also been proposed.
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Angiomiolipoma , Neoplasias Renales , Inhibidores mTOR , Estadificación de Neoplasias , Esclerosis Tuberosa , Humanos , Angiomiolipoma/tratamiento farmacológico , Angiomiolipoma/patología , Angiomiolipoma/diagnóstico por imagen , Femenino , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/tratamiento farmacológico , Masculino , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Adulto , Inhibidores mTOR/uso terapéutico , Resultado del Tratamiento , Estudios Retrospectivos , Adulto Joven , Persona de Mediana Edad , Adolescente , Valor Predictivo de las PruebasRESUMEN
PURPOSE OF REVIEW: To review the role of the immune cells and their interaction with cells found in gingiva, periodontal ligament, and bone that leads to net bone loss in periodontitis or bone remodeling in orthodontic tooth movement. RECENT FINDINGS: Periodontal disease is one of the most common oral diseases causing inflammation in the soft and hard tissues of the periodontium and is initiated by bacteria that induce a host response. Although the innate and adaptive immune response function cooperatively to prevent bacterial dissemination, they also play a major role in gingival inflammation and destruction of the connective tissue, periodontal ligament, and alveolar bone characteristic of periodontitis. The inflammatory response is triggered by bacteria or their products that bind to pattern recognition receptors that induce transcription factor activity to stimulate cytokine and chemokine expression. Epithelial, fibroblast/stromal, and resident leukocytes play a key role in initiating the host response and contribute to periodontal disease. Single-cell RNA-seq (scRNA-seq) experiments have added new insight into the roles of various cell types in the response to bacterial challenge. This response is modified by systemic conditions such as diabetes and smoking. In contrast to periodontitis, orthodontic tooth movement (OTM) is a sterile inflammatory response induced by mechanical force. Orthodontic force application stimulates acute inflammatory responses in the periodontal ligament and alveolar bone stimulated by cytokines and chemokines that produce bone resorption on the compression side. On the tension side, orthodontic forces induce the production of osteogenic factors, stimulating new bone formation. A number of different cell types, cytokines, and signaling/pathways are involved in this complex process. Inflammatory and mechanical force-induced bone remodeling involves bone resorption and bone formation. The interaction of leukocytes with host stromal cells and osteoblastic cells plays a key role in both initiating the inflammatory events as well as inducing a cellular cascade that results in remodeling in orthodontic tooth movement or in tissue destruction in periodontitis.
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Resorción Ósea , Periodontitis , Humanos , Osteoclastos/metabolismo , Técnicas de Movimiento Dental , Resorción Ósea/metabolismo , Periodontitis/metabolismo , Citocinas/metabolismo , Inflamación/metabolismoRESUMEN
PURPOSE: Growing evidence proved the efficacy of multi-parametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided targeted biopsy (TB) in prostate cancer (PCa) diagnosis, but there is no direct comparison between mpMRI-TB and PSMA PET/CT-TB. Gastrin-releasing peptide receptor (GRPR) is highly expressed in PCa, which can compensate for the unstable expression of PSMA in PCa. Therefore, we designed a study to compare the efficiency of mpMRI-TB, dual-tracer (GRPR and PSMA) PET/CT-TB, systematic biopsy, and combined biopsy for the diagnosis of prostate cancer. METHODS: One hundred twelve suspicious PCa patients were enrolled from September 2020 to June 2021. Patients with anyone of positive dual-tracer PET/CT or mpMRI underwent TB, and all enrolled patients underwent systematic biopsy (SB) after TB. The primary outcome was the detection rates of PCa in different biopsy strategies. Secondary outcomes were the performance of three imaging methods, omission diagnostic rates, and upgrading and downgrading of biopsy samples relative to those of prostatectomy specimens in different biopsy strategies. McNemar's tests and Bonferroni correction in multiple comparisons were used to compare the primary and secondary outcomes. RESULTS: In 112 men, clinically significant PCa (grade group[GG] ≥ 2) accounted for 34.82% (39/112), and nonclinically significant PCa (GG = 1) accounted for 4.46% (5/112). 68 Ga-PSMA PET/CT-TB achieved higher PCa detection rate (69.77%) and positive ratio of biopsy cores (0.44) compared with SB (39.29% and 0.12) and mpMRI-TB (36.14% and 0.23), respectively (P < 0.005). Dual-tracer PET/CT screen out patients for avoiding 52.67% (59/112) unnecessary biopsy, whereas dual-tracer PET/CT-TB plus SB achieved high detection rate (77.36%) without misdiagnosis of csPCa. CONCLUSION: Dual-tracer PET/CT might screen patients for avoiding unnecessary biopsy. Dual-tracer PET/CT-TB plus SB might be a more effective and promising strategy for the definite diagnosis of clinically significant PCa than mpMRI-TB.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Biopsia , Radioisótopos de Galio , Humanos , Biopsia Guiada por Imagen , Masculino , Proyectos Piloto , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/patología , Receptores de BombesinaRESUMEN
To investigate the characteristic of neuromyelitis optica spectrum disorder (NMOSD) in plasma and cerebrospinal fluid, UHPLC-MS was used to identify metabolites by metabolite extraction and on-machine detection. Multivariate analysis methods were used to complete differential metabolite screening and metabolic pathway analysis. The content of eight substances, such as tryptophan and l-glutamic acid in the plasma of NMOSD patients, was higher than that of the healthy control group. Moreover, no differential metabolite was found in the plasma of patients with AQP-4 antibody-positive and antibody-negative NMOSD. The content of five substances including 3-hydroxybutyric acid in cerebrospinal fluid of patients with NMOSD was reduced. We demonstrated that the distribution of metabolites in plasma between NMOSD patients and healthy counterparts was significantly different. However, there is no significant difference in plasma metabolites between AQP-4 antibody positive and negative NMOSD. There were some differences in metabolites between the cerebrospinal fluid of NMOSD patients and that of healthy controls. A variety of amino-acid abnormalities, sphingomyelin dysfunction, energy metabolism and mitochondrial dysfunction are involved in the pathogenesis of NMOSD.
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Metaboloma/fisiología , Metabolómica/métodos , Neuromielitis Óptica/sangre , Neuromielitis Óptica/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Humanos , Análisis de los Mínimos Cuadrados , Espectrometría de MasasRESUMEN
Early brain biopsy may be indicated in HIV patients with focal brain lesion. This study aimed to evaluate and compare the safety and diagnostic value of brain biopsy in HIV patients in the pre-highly active antiretroviral therapy (HAART) versus post-HAART era via meta-analysis. Appropriate studies were identified per search criteria. The local database was retrospectively reviewed to select a similar patient cohort. Patient demographics, brain biopsy technique, histopathology and patient outcomes were extracted from each study. Study-specific outcomes were combined per random-effects model. Outcomes were compared between the pre-HAART and post-HAART era. Correlations between outcomes and baseline characteristics were assessed via meta-regression analysis. The proportions of histopathological diagnosis were tabulated and compared between the pre- and post-HAART era. Survival analysis was performed for patients in the post-HAART era. A total of 26 studies (including the local database) with 1209 patients were included in this meta-analysis. The most common indications for brain biopsy were diagnosis unlikely to be toxoplasmosis (n=8, 42.1%), focal brain lesion (n=5, 26.3%) or both (n=3, 15.8%). The weighted proportions for diagnostic success were 92% (95% CI 90.0% to 93.8%), change in management 57.7% (45.9% to 69.1%) and clinical improvement 36.6% (26.3% to 47.5%). Morbidity and mortality were 5.7% (3.6% to 8.3%) and 0.9% (0.3% to 1.9%), respectively. Diagnostic success rate was significantly higher in the post-HAART than the pre-HAART era (97.5% vs 91.9%, p=0.047). The odds ratio (OR) for diagnostic success in patients with contrast-enhanced lesions was 2.54 ((1.25 to 5.15), p<0.01). The median survival for HIV patients who underwent biopsy in the post-HAART era was 225â days (90-2446). Brain biopsy in HIV patients is safe with high diagnostic yield. Early brain biopsy should be considered in patients without classic presentation of toxoplasmosis encephalitis.
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Complejo SIDA Demencia/patología , Biopsia , Encéfalo/patología , Infecciones por VIH/patología , Leucoencefalopatía Multifocal Progresiva/patología , Toxoplasmosis Cerebral/patología , Complejo SIDA Demencia/tratamiento farmacológico , Complejo SIDA Demencia/mortalidad , Estudios de Cohortes , Adhesión a Directriz , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Humanos , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Leucoencefalopatía Multifocal Progresiva/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Estadística como Asunto , Análisis de Supervivencia , Toxoplasmosis Cerebral/tratamiento farmacológico , Toxoplasmosis Cerebral/mortalidad , Resultado del TratamientoRESUMEN
In-stent restenosis (ISR), caused by aggressive vascular smooth muscle cell (VSMC) proliferation, is a serious complication of stenting. Therefore, developing therapeutic approaches that target VSMC inhibition is imperative. Our previous study showed that VSMC hyperplasia was attenuated after iron stent degradation, and VSMC proliferation around the stented section was arrested. The corrosion products of the iron stents were primarily Fe3O4 particles. Therefore, we hypothesized that Fe3O4 particles generated by iron stents would prevent neointimal hyperplasia by inhibiting VSMC proliferation. To test this hypothesis, culture assays and flow cytometry were performed to investigate the proliferation of VSMC. Global gene sequencing and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to investigate the underlying mechanisms. Fe3O4-coated stents were implanted into rabbit carotid arteries to evaluate the inhibitory effects of Fe3O4 on neointimal hyperplasia. The major findings of the study were as follows: 1) Fe3O4 attenuated neointimal hyperplasia by preventing VSMC proliferation after stenting; 2) Fe3O4 exerted inhibitory effects on VSMCs by downregulating proliferative genes such as SOX9, EGR4, and TGFB1, but upregulated inhibitory genes such as DNMT1, TIMP3, and PCNA; 3) Fe3O4 inhibited VSMCs by preventing phenotypic transformation from the contractile to the synthetic phase; and 4) Fe3O4-coated stents achieved satisfactory hemocompatibility in a rabbit model. Our study highlights the additional benefits of Fe3O4 particles in inhibiting VSMC proliferation, indicating that Fe3O4 coated stent potentially served as an attractive therapeutic approach for ISR prevention.
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Wood fiber as a natural and renewable material has low cost and plenty of functional groups, which owns the ability to adsorb dyes. In order to improve the application performance of wood fiber in dye-pollution wastewater, Eucalyptus wood fiber loaded nanoscale zero-valent iron (EWF-nZVI) was developed to give EWF magnetism and the ability to degrade dyes. EWF-nZVI was characterized via FTIR, XRD, zeta potential, VSM, SEM-EDS and XPS. Results showed that EWF-nZVI owned a strong magnetism of 96.51 emu/g. The dye removal process of EWF-nZVI was more in line with the pseudo-second-order kinetics model. In addition, the Langmuir isotherm model fitting results showed that the maximum removal capacities of Congo red and Rhodamine B by EWF-nZVI were 714.29 mg/g and 68.49 mg/g at 328 K, respectively. After five adsorption-desorption cycles, the regeneration efficiencies of Congo red and Rhodamine B were 74 % and 42 % in turn. The dye removal mechanisms of EWF-nZVI included redox degradation (Congo red and Rhodamine B) and electrostatic adsorption (Congo red). In summary, EWF-nZVI is a promising biomass-based material with high dye removal capacities. This work is beneficial to promote the large-scale application of wood fiber in water treatment.
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Colorantes , Eucalyptus , Hierro , Aguas Residuales , Contaminantes Químicos del Agua , Purificación del Agua , Madera , Eucalyptus/química , Aguas Residuales/química , Madera/química , Colorantes/química , Colorantes/aislamiento & purificación , Hierro/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Purificación del Agua/métodos , Cinética , Nanopartículas del Metal/química , Concentración de Iones de Hidrógeno , Rojo Congo/química , Rojo Congo/aislamiento & purificación , Rodaminas/químicaRESUMEN
Background: We aimed to demonstrate the function of premelanosome protein (PMEL) as a biomarker to predict the effectiveness of mammalian target of rapamycin complex 1 (mTORC1) inhibitor treatment in renal angiomyolipomas (RAMLs) in tuberous sclerosis complex (TSC) patients. Methods: 95 whole blood samples from 49 patients diagnosed with TSC-RAMLs were collected. PMEL, N4BP2, and PCSK1N expression in the plasma samples were tested by quantitative sandwich ELISA. The target tumor volume assessed by maximum cross-sectional area (CSAmax) in CT scans. Correlation analysis was used to determine the relationship between PMEL expression and target tumors, as well as the tumor reduction rate. Results: The tumor size of TSC-RAMLs positivity correlated with PMEL expression (r = 0.30, p = 0.036) and PCSK1N expression (r = 0.23, p = 0.027), but had no significant relationship with N4BP2 (r = 0.06, p = 0.89). The positive correlation between TSC-RAML tumor volume and PMEL expression still existed in TSC patients before (r = 0.30, p = 0.026) and after mTORC1 inhibitor treatment (r = 0.41, p = 0.0017), but the correlation between tumor volume and PCSK1N expression no longer existed. Further analysis found that PMEL expression negatively correlated with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment (r = -0.50, p = 0.0022), both after 3 months (r = -0.47, p = 0.048) and 6 months of treatment (r = -0.52, p = 0.028). Conclusion: PMEL expression positively correlated with the tumor size of TSC-RAMLs, and inversely with the reduction rate of TSC-RAMLs after mTORC1 inhibitor treatment, which may suggest that PMEL may serve as a predictive biomarker for the efficacy of mTORC1 inhibitor treatment.
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BACKGROUND: Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. METHODS: Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. RESULT: A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P < 0.05). However, the decline in hemoglobin, WBC, and neutrophils attenuated by the 12th month (P ≥ 0.05). Aspartate transaminase (AST), Alanine transferase (ALT), total cholesterol (TC), and triglyceride (TG) increased significantly during everolimus treatment (P < 0.05), and these increases persisted throughout the year-long treatment. Hemoglobin decreased significantly more in male patients (- 15 vs - 6, P = 0.010), and AST showed a more significant increase in males (7.0 vs 3.0, P = 0.041). Platelet counts decreased significantly more in younger patients (≤ 30 years old) compared to older patients (- 50 vs - 14, P = 0.020). CONCLUSION: Everolimus administration in TSC-RAML patients may increase hematologic risks, with male and younger patients potentially exhibiting greater susceptibility to these effects.
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The endothelialization of drug-eluting stents is delayed after implantation in patients with diabetes. Although numerous factors were implicated in hyperglycemia-induced endothelial dysfunction, the effects of stent drug coating degradation on endothelial dysfunction remains unclear. We hypothesized that diabetic conditions promote drugcoating degradation and enhance antiproliferative agent release, but that the rapid release of these antiproliferative agents inhibits endothelial cell proliferation leading to poor reendothelialization post-stenting. To verify this hypothesis, a dynamic hyperglycemic circulation system was introduced to measure the profile of drugcoating degradation in vitro. Flow cytometry and RNA sequencing were performed to evaluate endothelial cell proliferation. Moreover, a Type 1 diabetic rabbit model was generated and a rescue experiment conducted to evaluate the effects of rapid drugcoating elution on endothelial coverage in vivo. The main findings were as follows: 1) diabetic conditions promoted drugcoating degradation and increased antiproliferative agent release; 2) this increase in antiproliferative agent release inhibited endothelial cell proliferation and delayed endothelial coverage; and 3) strict glycemic control attenuated drugcoating degradation and promoted endothelial coverage post-stenting. This is the first study to illustrate rapid drugcoating degradation and its potential effects on endothelial recovery under diabetic conditions, highlighting the importance of strict glycemic management in patients with diabetes after drug-eluting stent implantation. STATEMENT OF SIGNIFICANCE: Diabetic conditions promote drug coating degradation and increase the release of antiproliferative agents. Rapid drug coating degradation under diabetic conditions inhibits endothelial cell proliferation and delays endothelialization. Strict glycemic control attenuates drug coating degradation and promotes endothelialization.
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Antineoplásicos , Diabetes Mellitus , Stents Liberadores de Fármacos , Animales , Humanos , Conejos , Stents , EndotelioRESUMEN
[This corrects the article DOI: 10.3389/fgene.2020.616988.].
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BACKGROUND: Adult pure androgen-secreting adrenal tumors (PASATs) are rarely reported and the malignancy of such tumor are difficult to confirm before surgery. Here we report a PASAT demonstrating extremely 18F-FDG uptake turned out to benign tumor by postoperative pathology examination. CASE PRESENTATION: A 19-year-old adolescent found a tumor measuring 7.2 cm located in the right adrenal region on enhanced CT during the routine physical examination. Signs of virilization and elevated testosterone and dehydroepiandrosterone (DHEA) were verified during preoperative examination. 18F-FDG PET/CT revealed the tumor had an extremely high 18F-FDG uptake with a SUVmax reaching 42.7, which turned out to be oncocytic adrenocortical adenoma by pathological examination. CONCLUSIONS: 18F-FDG PET/CT may be limited in assessing the malignancy of PASAT.
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6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P < 0.05). To validate these findings, clinical data and immunohistochemistry staining were performed on specimens obtained from 89 BLCA patients who underwent radical cystectomy at either Qingdao University Affiliated Hospital or Peking Union Medical College Hospital. The findings from this verification process confirmed that high expression of PFKFB3 serves as a biomarker for predicting worse prognosis in BLCA patients (OR: 2.462, 95 % CI: 1.202-5.042, P = 0.012). To facilitate clinical application, we developed a nomogram based on four variables, including PFKFB3 expression, to predict the survival of BLCA patients. Importantly, this nomogram demonstrated a low mean prediction error of 0.03. Taken together, our findings suggest that PFKFB3 has the potential to serve as both a prognostic biomarker and a therapeutic target for BLCA patients.
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Poststent restenosis is caused by insufficient endothelialization and is one of the most serious clinical complications of stenting. We observed a rapid endothelialization rate and increased fibrin deposition on the surfaces of the corroded iron stents. Thus, we hypothesized that corroded iron stents would promote endothelialization by increasing fibrin deposition on rough surfaces. To verify this hypothesis, we conducted an arteriovenous shunt experiment to analyze fibrin deposition in the corroded iron stents. We implanted a corroded iron stent in both the carotid and iliac artery bifurcations to elucidate the effects of fibrin deposition on endothelialization. Co-culture experiments were conducted under dynamic flow conditions to explore the relationship between fibrin deposition and rapid endothelialization. Our findings indicate that, from the generation of corrosion pits, the surface of the corroded iron stent was rough, and numerous fibrils were deposited in the corroded iron stent. Fibrin deposition in corroded iron stents facilitates endothelial cell adhesion and proliferation, which, in turn, promotes endothelialization after stenting. Our study is the first to elucidate the role of iron stent corrosion in endothelialization, pointing to a new direction for preventing clinical complications caused by insufficient endothelialization.
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Background: There are some limitations in the commonly used methods for the detection of prostate cancer. There is a lack of nomograms based on multiparametric magnetic resonance imaging (mpMRI) and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) for the prediction of prostate cancer. The study seeks to compare the performance of mpMRI and 68Ga-PSMA PET-CT, and design a novel predictive model capable of predicting clinically significant prostate cancer (csPCa) before biopsy based on a combination of 68Ga-PSMA PET-CT, mpMRI, and patient clinical parameters. Methods: From September 2020 to June 2021, we prospectively enrolled 112 consecutive patients with no prior history of prostate cancer who underwent both 68Ga-PSMA PET-CT and mpMRI prior to biopsy at our clinical center. Univariate and multivariate regression analyses were used to identify predictors of csPCa, with a predictive model and its nomogram incorporating 68Ga-PSMA PET-CT, mpMRI, and the clinical predictors then being generated. The constructed model was evaluated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis, and further validated with the internal and external cohorts. Results: The model incorporated prostate-specific antigen density (PSAd), Prostate Imaging Reporting and Data System (PI-RADS) category, and maximum standardized uptake value (SUVmax), and it exhibited excellent predictive efficacy when applying to evaluate both training and validation cohorts [area under the curve (AUC): 0.936 and 0.940, respectively]. Compared with SUVmax alone, the model demonstrated excellent diagnostic performance with improved specificity (0.910, 95% CI: 0.824-0.963) and positive predictive values (0.811, 95% CI: 0.648-0.920). Calibration curve and decision curve analysis further confirmed that the model exhibited a high degree of clinical net benefit and low error rate. Conclusions: The constructed model in this study was capable of accurately predicting csPCa prior to biopsy with excellent discriminative ability. As such, this model has the potential to be an effective non-invasive approach for the diagnosis of csPCa.
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Objective: To determine the different clinical features of patients with vertigo attacks alone and of those with weakness accompanying vertigo attacks before the vertebrobasilar ischemic stroke. Methods: In this 4-year retrospective study, we manually screened the medical records of 209 patients, hospitalized with vertigo attack as the main complaint who were finally diagnosed with acute vertebrobasilar ischemic stroke. Patients were divided into two groups according to their symptoms: patients who only experienced vertigo attacks prior to the vertebrobasilar stroke (VO group) and patients who had both vertigo and weakness attacks (VW group) prior to the stroke. Clinical parameters, such as infarction site and volume, relative risk factors, ABCD2 score, and medical intervention, were compared between the two groups. Results: The prevalence of hypertension was higher in the Vertigo attacks only (VO) group (42.2 vs. 29.0%, p < 0.05). The total cerebral infarction volume in the VO group was larger than the Vertigo and weakness attacks (VW) group (4.44 vs. 2.12 cm3, p < 0.05). Additionally, the cerebellum was more likely to be affected in the VO group. In contrast, patients in the VW group had higher carotid stenosis (14.2 vs. 27.2%, p < 0.05) and ABCD2 score (2.1 ± 1.2 vs. 3.6 ± 1.5, p = 0.02). The percentage of patients with medullary infarctions also increased in the VW group. Vertigo attack events occurred more frequently in the VW group (median 2.4 vs. 4.3, p < 0.04). We also found that the patients in the VW group were more likely to seek medical intervention after vertigo. Conclusions: Clinical parameters, such as infarction location, relative risk factors, and ABCD2 score, differed between patients with vertigo symptoms with or without weakness attacks. These findings highlight the different clinical features of patients with vertigo attack only and those with weakness attacks accompanying vertigo prior to vertebrobasilar ischemic stroke.
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Objectives: To evaluate a new deep neural network (DNN)-based computer-aided diagnosis (CAD) method, namely, a prostate cancer localization network and an integrated multi-modal classification network, to automatically localize prostate cancer on multi-parametric magnetic resonance imaging (mp-MRI) and classify prostate cancer and non-cancerous tissues. Materials and methods: The PROSTAREx database consists of a "training set" (330 suspected lesions from 204 cases) and a "test set" (208 suspected lesions from 104 cases). Sequences include T2-weighted, diffusion-weighted, Ktrans, and apparent diffusion coefficient (ADC) images. For the task of abnormal localization, inspired by V-net, we designed a prostate cancer localization network with mp-MRI data as input to achieve automatic localization of prostate cancer. Combining the concepts of multi-modal learning and ensemble learning, the integrated multi-modal classification network is based on the combination of mp-MRI data as input to distinguish prostate cancer from non-cancerous tissues through a series of operations such as convolution and pooling. The performance of each network in predicting prostate cancer was examined using the receiver operating curve (ROC), and the area under the ROC curve (AUC), sensitivity (TPR), specificity (TNR), accuracy, and Dice similarity coefficient (DSC) were calculated. Results: The prostate cancer localization network exhibited excellent performance in localizing prostate cancer, with an average error of only 1.64 mm compared to the labeled results, an error of about 6%. On the test dataset, the network had a sensitivity of 0.92, specificity of 0.90, PPV of 0.91, NPV of 0.93, and DSC of 0.84. Compared with multi-modal classification networks, the performance of single-modal classification networks is slightly inadequate. The integrated multi-modal classification network performed best in classifying prostate cancer and non-cancerous tissues with a TPR of 0.95, TNR of 0.82, F1-Score of 0.8920, AUC of 0.912, and accuracy of 0.885, which fully confirmed the feasibility of the ensemble learning approach. Conclusion: The proposed DNN-based prostate cancer localization network and integrated multi-modal classification network yielded high performance in experiments, demonstrating that the prostate cancer localization network and integrated multi-modal classification network can be used for computer-aided diagnosis (CAD) of prostate cancer localization and classification.
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In-stent restenosis after interventional therapy remains a severe clinical complication. Current evidence indicates that neointimal hyperplasia induced by vascular smooth muscle cell (VSMC) proliferation is a major cause of restenosis. Thus, inhibiting VSMC proliferation is critical for preventing in-stent restenosis. The incidence of restenosis was reduced in nitrided iron-based stents (hereafter referred to as iron stents). We hypothesized that the corroded granules produced by the iron stent would prevent in-stent restenosis by inhibiting VSMC proliferation. To verify this hypothesis, we introduced a dynamic circulation device to analyze the components of corroded granules. To investigate the effects of corroded granules on VSMC proliferation, we implanted the corroded iron stent into the artery of the atherosclerotic artery stenosis model. Moreover, we explored the mechanism underlying the inhibition of VSMC proliferation by iron corroded granules. The results indicated that iron stent produced the corroded granules after implantation, and the main component of the corrosion granules was iron oxide. Remarkably, the corroded granules reduced the neointimal hyperplasia in an atherosclerotic artery stenosis model, and iron corroded granules decreased the neointimal hyperplasia by inhibiting VSMC proliferation. In addition, we revealed that corroded granules reduced VSMC proliferation by activating autophagy through the AMPK/mTOR signaling pathway. Importantly, safety of iron corroded granules was evaluated and proved to be satisfactory hemocompatibility in rabbit model. Overall, the role of corroded granules in restenosis prevention was described for the first time. This finding highlighted the implication of corroded granules produced by iron stent in inhibiting VSMC proliferation, pointing to a new direction to prevent in-stent restenosis.
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BACKGROUND: To compare intracorporeal urinary diversion (ICUD) with extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC) for surgery safety, postoperative recovery, complication, and prognosis. METHODS: We performed a literature search on PubMed, Embase, Medline and the Cochrane Library based on all randomized controlled trials (RCTs) and observational comparative studies related to study topics published before July 14th, 2020. Then systematic review and meta-analysis was performed. RESULTS: 13 retrospective studies containing 4,755 patients were identified. In terms of surgery safety, with similar operative time, ICUD group showed less estimated blood loss (EBL) (P<0.0001) and lower blood transfusion rate (P=0.006). In terms of postoperative recovery, with similar hospital stay, ICUD group showed earlier recovery on flatus (P<0.001) and oral intake (P<0001). In aspect of complications, there were no significant differences between ICUD and ECUD groups, except for gastrointestinal system complications. ICUD group had lower gastrointestinal complications rate than ECUD group (P=0.002). In aspect of prognosis outcomes, with similar mortality, ICUD group had lower recurrence rate than ECUD group (P=0.004). CONCLUSIONS: Based on the current evidence, ICUD procedure is excellence in surgery safety, postoperative recovery, complications, and prognosis. However, the observational studies reduced the level of evidence, larger randomized trials are needed to confirm these findings.