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Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.
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Neurocognitive disorders, such as Alzheimer's disease, vascular dementia, and postoperative cognitive dysfunction, are non-psychiatric brain syndromes in which a significant decline in cognitive function causes great trauma to the mental status of the patient. The lack of effective treatments for neurocognitive disorders imposes a considerable burden on society, including a substantial economic impact. Over the past few decades, the identification of resveratrol, a natural plant compound, has provided researchers with an opportunity to formulate novel strategies for the treatment of neurocognitive disorders. This is because resveratrol effectively protects the brain of those with neurocognitive disorders by targeting some mechanisms such as inflammation and oxidative stress. This article reviews the status of recent research investigating the use of resveratrol for the treatment of different neurocognitive disorders. By examining the possible mechanisms of action of resveratrol and the shared mechanisms of different neurocognitive disorders, treatments for neurocognitive disorders may be further clarified.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia Vascular , Humanos , Resveratrol/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico , Demencia Vascular/tratamiento farmacológico , EncéfaloRESUMEN
Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis and severe economic losses to salmon and trout aquaculture worldwide. Currently, the only commercial vaccine against IHNV is a DNA vaccine with some biosafety concerns. Hence, more effective vaccines and antiviral drugs are needed to prevent IHNV infection. In this study, 1,483 compounds were screened from a traditional Chinese medicine monomer library, and bufalin showed potential antiviral activity against IHNV. The 50% cytotoxic concentration of bufalin was >20 µM, and the 50% inhibitory concentration was 0.1223 µΜ against IHNV. Bufalin showed the inhibition of diverse IHNV strains in vitro, which confirmed that it had an inhibitory effect against all IHNV strains, rather than random activity against a single strain. The bufalin-mediated block of IHNV infection occurred at the viral attachment and RNA replication stages, but not internalization. Bufalin also inhibited IHNV infection in vivo and significantly increased the survival of rainbow trout compared with the mock drug-treated group, and this was confirmed by in vivo viral load monitoring. Our data showed that the anti-IHNV activity of bufalin was proportional to extracellular Na+ concentration and inversely proportional to extracellular K+ concentration, and bufalin may inhibit IHNV infection by targeting Na+/K+-ATPase. The in vitro and in vivo studies showed that bufalin significantly inhibited IHNV infection and may be a promising candidate drug against the disease in rainbow trout. IMPORTANCE: Infectious hematopoietic necrosis virus (IHNV) is the pathogen of infectious hematopoietic necrosis (IHN) which outbreak often causes huge economic losses and hampers the healthy development of salmon and trout farming. Currently, there is only one approved DNA vaccine for IHN worldwide, but it faces some biosafety problems. Hence, more effective vaccines and antiviral drugs are needed to prevent IHNV infection. In this study, we report that bufalin, a traditional Chinese medicine, shows potential antiviral activity against IHNV both in vitro and in vivo. The bufalin-mediated block of IHNV infection occurred at the viral attachment and RNA replication stages, but not internalization, and bufalin inhibited IHNV infection by targeting Na+/K+-ATPase. The in vitro and in vivo studies showed that bufalin significantly inhibited IHNV infection and may be a promising candidate drug against the disease in rainbow trout.
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Bufanólidos , Enfermedades de los Peces , Virus de la Necrosis Hematopoyética Infecciosa , Oncorhynchus mykiss , Vacunas de ADN , Animales , Virus de la Necrosis Hematopoyética Infecciosa/genética , Medicina Tradicional China , Antivirales/farmacología , Antivirales/uso terapéutico , Adenosina Trifosfatasas , Necrosis , Enfermedades de los Peces/tratamiento farmacológico , Enfermedades de los Peces/prevención & controlRESUMEN
The clinical significance and prognostic role of whole-blood EBV-DNA in EBV-associated nasopharyngeal carcinoma (NPC) have not been thoroughly investigated. This study aims to explore the diagnostic and prognostic value of EBV-DNA for NPC in a non-endemic region of China. We enrolled patients with chronic active EBV infection (CAEBV), nasopharyngitis (NA), extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), and NPC. Demographic and clinical data were collected and the diagnostic and prognostic values of EBV-DNA were analyzed. Immunohistochemistry was performed to detect EBV-encoded small ribonucleic acids (EBER), as well as the expression of p53, Ki-67, and epidermal growth factor receptor (EGFR). The levels of pretreatment Epstein-Barr virus DNA (preEBV-DNA) in new NPC cases were found to differ from those in other diseases and exhibited varying age distributions. The threshold value of preEBV-DNA for distinguishing NPC from CAEBV and NA was determined. We confirmed that epistaxis, diabetes mellitus, T3N2 or T4N0-2 stage, and IgM positivity were associated with higher levels of preEBV-DNA, and identified risk factors associated with the prognosis of locoregionally advanced NPC (La-NPC). Patients with intermittently or persistently positive EBV-DNA (IPCP), higher preEBV-DNA levels, and positive Epstein-Barr virus-encoded small RNA (EBER) status (EBERpos) had worse survival. New cases of NPC with elevated levels of EBV in the whole-blood and positive EBER status were shown to have a poor prognosis upon progression to La-NPC. EBV-DNA was found to be an indicator for predicting prognosis in La-NPC and could also be used to distinguish new NPC cases.
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[This corrects the article DOI: 10.7150/jca.39760.].
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OBJECTIVE: This study aimed to evaluate the effects on the dislocation and misalignment of the cuffed end of a double-lumen endobronchial tube (DLT) when a patient moves from a horizontal to a lateral position without fixation. METHODS: A total of 148 patients who had undergone video-assisted thoracoscope surgery were enrolled and randomly divided into two groups: a group in which the periportal end of the DLT was fixed with tape (group I; n = 74) and a group in which the periportal end of the DLT remained unfixed (group II; n = 74). Both groups were given an intravenous induction for double-lumen endobronchial intubation and then moved from a horizontal position to a lateral position, after which the alignment of the bronchial cuffed end of the DLT was assessed using a fiberoptic bronchoscope. RESULTS: After lateral position, the dislocation rate of group I and group II was 44.6% and 20.2%, and the misalignment rate was 27.0% and 8.1%, respectively, the incidence of dislocation and misalignment was significantly lower in group II than in group I after the change to a lateral position (p < 0.05). After lateral position, the total rate of airway injury was 25.7% in group I and 5.4% in group II, the incidence of airway injury was significantly lower in group II than in group I (p < 0.05), as was the incidence of sore throat, hoarseness, and cough on postoperative day 1 (p < 0.05). The average outward dislocation of the periportal end of the DLT in group II was 1.5 cm. CONCLUSION: A DLT without periportal fixation is less likely to be displaced and poorly aligned when the patient moves from a horizontal to a lateral position, which could facilitate intra-operative management and reduce the incidence of postoperative complications.
Through a randomized controlled trial, this study innovatively found that no double-lumen endobronchial tube (DLT) peripheral tape binding can prevent the dislocation and misalignment of the DLT bronchial cuffed end in patients undergoing thoracic surgery from horizontal to lateral position.
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Tos , Dolor , Humanos , Administración Intravenosa , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Periodo PosoperatorioRESUMEN
OBJECTIVE: The purpose of this study is to verify the correlation between medium and low radiation doses of the pelvic-bone marrow and the incidence of lymphocytic toxicity during concurrent chemoradiotherapy for cervical cancer. MATERIALS AND METHODS: This research included 117 cervical cancer patients, who received concurrent chemoradiotherapy. Radiotherapy included external-beam radiation therapy and brachytherapy. The dosimetry parameters include the Volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and the mean dose (D mean) of the bone marrow. Lymphocytic toxicity was calculated from lowest lymphocytic count after two cycles of concurrent chemotherapy. RESULTS: During concurrent chemoradiotherapy, the incidence of lymphocytic toxicity is 94.88%. The incidence of grade 3-4 toxicity is 68.38%. Multivariate analysis findings show that the dosimetry parameters V5, V10, V20, and V30 are significantly correlated with lymphocytic toxicity. The patients are divided into small-volume subgroups and large-volume subgroups based on the cutoff values. The relative risk of both grade 1-4 and grade 3-4 lymphocytic toxicity is significantly lower in the small-volume subgroups than in the large-volume subgroups (P < 0.05). Kaplan-Meier analysis shows that the incidence of both grade 1-4 and grade 3-4 lymphocytic toxicity of the small-volume subgroups is significantly lower than that of the large-volume subgroups (P < 0.05). CONCLUSION: There is a significant correlation between a medium and low dose of pelvic-bone-marrow radiation and incidence of lymphocytic toxicity. Reducing the volume of medium and low radiation doses could effectively reduce incidence of lymphocytic toxicity.
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Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Femenino , Humanos , Médula Ósea , Radioterapia de Intensidad Modulada/efectos adversos , Dosificación Radioterapéutica , Neoplasias del Cuello Uterino/radioterapia , Quimioradioterapia/efectos adversos , Dosis de RadiaciónRESUMEN
BACKGROUND: The resistance to radiotherapy remains a major obstacle that limits the efficacy of radiotherapy in non-small cell lung cancer (NSCLC). This study aims to illustrate the molecular mechanism underlying the role of LINC00665 in the radiosensitivity of NSCLC, which involves ubiquitin C-terminal hydrolase L3 (UCHL3). METHODS AND RESULTS: The expression of UCHL3 was determined in clinical tissue samples collected from NSCLC patients and NSCLC cell lines. We found that UCHL3 overexpression occurred in both NSCLC tissues and cells, associated with poor prognosis in NSCLC patients. Mechanistically, UCHL3 stabilized aryl hydrocarbon receptor (AhR) protein through deubiquitination, thereby promoting PD-L1 expression. UCHL3 reduced the radiosensitivity of NSCLC cells by stabilizing AhR protein. Upstream microRNAs (miRNAs) and lncRNAs of UCHL3 were predicted by microarray profiling and validated by functional experiments. LINC00665 functioned as a sponge of miR-582-5p and thus up-regulated the expression of the miR-582-5p target UCHL3. Gain- and loss- of function assays were performed to assess the effects of LINC00665, UCHL3 and miR-582-5p on the in vitro cell malignant behaviors and immune escape as well as on the in vivo tumor growth. Silencing LINC00665 or overexpressing miR-582-5p enhanced the sensitivity of NSCLC cells to radiotherapy. LINC00665 augmented the immune escape of NSCLC cells in vitro and in vivo through stabilizing AhR protein via the miR-582-5p/UCHL3 axis. CONCLUSIONS: Overall, LINC00665 reduced the radiosensitivity of NSCLC cells via stabilization of AhR through the miR-582-5p/UCHL3 axis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , MicroARNs/genética , MicroARNs/metabolismo , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Ubiquitina TiolesterasaRESUMEN
DDX3, a member of the DEAD-box RNA helicase family and has highly conserved ATP-dependent RNA helicase activity, has important roles in RNA metabolism and innate anti-viral immune responses. In this study, five transcript variants of the DDX3 gene were cloned and characterized from rainbow trout (Oncorhynchus mykiss). These five transcript variants of DDX3 encoded proteins were 74.2 kDa (686 aa), 76.4 kDa (709 aa), 77.8 kDa (711 aa), 78.0 kDa (718 aa), and 78.8 kDa (729 aa) and the predicted isoelectric points were 6.91, 7.63, 7.63, 7.18, and 7.23, respectively. All rainbow trout DDX3 proteins contained two conserved RecA-like domains that were similar to the DDX3 protein reported in mammals. Phylogenetic analysis showed that the five cloned rainbow trout DDX3 were separate from mammals but clustered with fish, especially Northern pike (Esox lucius) and Nile tilapia (Oreochromis niloticus). RT-qPCR analysis showed that the DDX3 gene was broadly expressed in all tissues studied. The expression of DDX3 after infectious hematopoietic necrosis virus (IHNV) infection increased gradually after the early stage of IHNV infection, decreased gradually with the proliferation of IHNV in vivo (liver, spleen, and kidney), and was significantly decreased after the in vitro infection of epithelioma papulosum cyprini (EPC) and rainbow trout gonad cell line-2 (RTG-2) cell lines. We also found that rainbow trout DDX3 was significantly increased by a time-dependent mechanism after the poly I:C treatment of EPC and RTG cells; however no significant changes were observed with lipopolysaccharide (LPS) treatment. Knockdown of DDX3 by siRNA showed significantly increased IHNV replication in infected RTG cells. This study suggests that DDX3 has an important role in host defense against IHNV infection and these results may provide new insights into IHNV pathogenesis and antiviral drug research.
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Enfermedades de los Peces , Virus de la Necrosis Hematopoyética Infecciosa , Oncorhynchus mykiss , Infecciones por Rhabdoviridae , Animales , Antivirales , ARN Helicasas DEAD-box/genética , Virus de la Necrosis Hematopoyética Infecciosa/fisiología , Mamíferos , Filogenia , Proteínas/genéticaRESUMEN
MicroRNAs play significant roles in various malignancies, with breast cancer (BC) being no exception. Consequently, we explored the functional mechanism of miR-135 in the progression of BC. In total, 55 pairs of BC and matched adjacent normal tissues were clinically collected from patients, followed by quantification of miR-135 and zinc finger protein 217 (ZNF217) expression patterns in BC tissues and cells. Accordingly, high ZNF217 expression and low miR-135 expression levels were identified in BC tissues and cells. Subsequently, the expressions of miR-135 and ZNF217 were altered to evaluate their effects on BC cell migration, invasion and EMT initiation. It was found that when ZNF217 was silenced or miR-135 was elevated, BC cell malignant behaviors were significantly inhibited, which was reproduced in nude mice for in vivo evidence. Furthermore, dual-luciferase reporter gene assay revealed the presence of direct binding between miR-135 and ZNF217. Subsequent co-immunoprecipitation, methylated-RNA binding protein immunoprecipitation and photoactivatable ribonucleoside enhanced-crosslinking and immunoprecipitation assays further revealed that ZNF217 could upregulate NANOG by reducing N6-methyladenosine levels via methyltransferase-like 13 (METTL3). Collectively, our findings highlighted the role of the miR-135/ZNF217/METTL3/NANOG axis in the progression of BC, emphasizing potential therapeutic targets ZNF217 silencing and miR-135 upregulation in preventing or treating BC.
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Neoplasias de la Mama , MicroARNs , Proteína Homeótica Nanog , Transactivadores , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metiltransferasas/metabolismo , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Proteína Homeótica Nanog/genética , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
Infectious hematopoietic necrosis virus (IHNV) is the causative pathogen of infectious hematopoietic necrosis, outbreaks of which are responsible for significant losses in rainbow trout aquaculture. Strains of IHNV isolated worldwide have been classified into five major genogroups, J, E, L, M, and U. To date, comparative transcriptomic analysis has only been conducted individually for the J and M genogroups. In this study, we compared the transcriptome profiles in U genogroup and J genogroup IHNV-infected RTG-2 cells with mock-infected RTG-2 cells. The RNA-seq results revealed 17,064 new genes, of which 7,390 genes were functionally annotated. Differentially expressed gene (DEG) analysis between U and J IHNV-infected cells revealed 2,238 DEGs, including 1,011 downregulated genes and 1,227 upregulated genes. Among the 2,238 DEGs, 345 new genes were discovered. The DEGs related to immune responses, cellular signal transduction, and viral diseases were further analyzed. RT-qPCR validation confirmed that the changes in expression of the immune response-related genes trpm2, sting, itgb7, ripk2, and irf1, cellular signal transduction-related genes irl, cacnb2, bmp2l, gadd45α, and plk2, and viral disease-related genes mlf1, mtor, armc5, pik3r1, and c-myc were consistent with the results of transcriptome analysis. Taken together, our findings provide a comprehensive transcriptional analysis of the differential virulence of the U and J genogroups of IHNV, and shed new light on the pathogenic mechanisms of IHNV strains.
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BACKGROUND: Sepsis is a critical challenge for the older adults as the immune function is less responsive by aging. Although cell numbers seem preserved in the older adults, macrophages present age-related function decline, which including reduced chemokines, phagocytosis, and autophagy. ABT-263, an inhibitor of the anti-apoptotic protein Bcl-2, is reported had a senolytic effect which can selectively clear the senescent cells in vivo and rejuvenate the aged tissues. METHODS: We treated the aged (12-16 months) and young (4-6 months) C57BL/6 mouse with ABT-263, then gave the animals cecal slurry injection to induce sepsis to observe the effect of senolytic compound ABT-263 on the survival rate of sepsis. Additionally, we isolated peritoneal macrophages from the aged mouse to investigate the cell function and molecular mechanism. 3-methyladenine (3-MA), a phosphatidylinositol 3-kinases (PI3K) inhibitor, and rapamycin, an autophagy-enhancer, were used to block or mimic the autophagy, respectively. RT-PCR and Western Blot were used to detect autophagy related gene and protein changes in sepsis. EGFP-expressing E. coli was used as a marker to evaluate the phagocytic ability of macrophages. RESULTS: The results showed ABT-263 treatment improved the survival rate of sepsis in the aged mouse which related to autophagy, while blocking the autophagy can eliminate this effect. It is revealed that ABT-263 enhanced the phagocytic ability of the peritoneal macrophages by increasing the Trem-2 receptor. Additionally, ABT-263 blocked the binding of Bcl-2 to Beclin-1, thus induced Beclin-1-dependent autophagy. CONCLUSION: ABT-263 enhanced the macrophage function in aged mouse by increasing the Trem-2 receptors and inducing a beclin-1-dependent autophagy, consequently, protected the aged mouse from sepsis.
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Escherichia coli , Fosfatidilinositol 3-Quinasas , Anciano , Compuestos de Anilina , Animales , Autofagia , Beclina-1 , Humanos , Macrófagos , Ratones , Ratones Endogámicos C57BL , Fagocitosis , SulfonamidasRESUMEN
Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9-81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34-2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.
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Linfoma Extranodal de Células NK-T/mortalidad , Adulto , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.
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Toma de Decisiones Clínicas , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Linfoma Extranodal de Células NK-T/mortalidad , Nomogramas , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Área Bajo la Curva , Manejo de la Enfermedad , Femenino , Humanos , Linfoma Extranodal de Células NK-T/diagnóstico , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Análisis de SupervivenciaRESUMEN
BACKGROUND: Radioresistance is a major challenge in the use of radiotherapy for the treatment of lung cancer while microRNAs (miRs) have been reported to participate in multiple essential cellular processes including radiosensitization. This study was conducted with the main objective of investigating the potential role of miR-320a in radioresistance of non-small cell lung cancer (NSCLC) via the possible mechanism related to HIF1α, KDM5B, and PTEN. METHODS: Firstly, NSCLC radiosensitivity-related microarray dataset GSE112374 was obtained. Then, the expression of miR-320a, HIF1α, KDM5B, and PTEN was detected in the collected clinical NSCLC samples, followed by Pearson's correlation analysis. Subsequently, ChIP assay was conducted to determine the content of the PTEN promoter fragment enriched by the IgG antibody and H3K4me3 antibody. Finally, a series of in vitro and in vivo assays were performed in order to evaluate the effects of miR-320a on radioresistance of NSCLC with the involvement of HIF1α, KDM5B, and PTEN. RESULTS: The microarray dataset GSE112374 presented with a high expression of miR-320a in NSCLC radiosensitivity samples, which was further confirmed in our clinical samples with the use of reverse transcription-quantitative polymerase chain reaction. Moreover, miR-320a negatively targeted HIF1α, inhibiting radioresistance of NSCLC. Interestingly, miR-320a suppressed the expression of KDM5B, and KDM5B was found to enhance the radioresistance of NSCLC through the downregulation of PTEN expression. The inhibition of miR-320a in radioresistance of NSCLC was also reproduced by in vivo assay. CONCLUSION: Taken together, our findings were suggestive of the inhibitory effect of miR-320a on radioresistance of NSCLC through HIF1α-suppression mediated methylation of PTEN.
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Acute ischemic stroke is one of the leading causes of death in developed countries and the most common cause of disability in adults worldwide. Despite advances in the understanding of stroke pathophysiology, therapeutic options remain limited. In this study, we explored the interaction of Shrm4 and the metabotropic gamma-aminobutyric acid (GABA) receptors (GABAB ) in ischemic stroke. A transient middle cerebral artery occlusion (MCAO) model was induced by filament insertion in Shrm4+/+ and wild-type C57BL/6J mice, followed by reperfusion for up to 7 days. Baclofen was administered was used to activate GABAB in vivo during reperfusion. Neurological deficits, motor and memory functions, and infarct volume were determined in the various mouse groups. Furthermore, we also developed an oxygen-glucose deprivation (OGD) cell model in primary neurons to test Shrm4/GABAB interactions in vitro. Shrm4 was observed to decrease infarct volume and neuronal cell loss in penumbra, and rescue neurological deficits in MCAO mice. Notably, Shrm4 also increased pole climbing speed, reduced foot faults, and increased escape latency in the Morris water maze test, while reducing neuron autophagy through an interaction with GABAB receptors. GABAB activation using baclofen further reduced OGD-induced neuron damage in culture and stroke outcomes of MCAO, relative to Shrm4 alone. Taken together, Shrm4-mediated GABAB activation confers neuroprotection by reducing neuronal autophagy in acute ischemic stroke.
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Autofagia/fisiología , Isquemia Encefálica/metabolismo , Proteínas del Citoesqueleto/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Proteínas de Microfilamentos/metabolismo , Neuroprotección/fisiología , Ácido gamma-Aminobutírico/metabolismo , Animales , Células Cultivadas , Glucosa/metabolismo , Células HEK293 , Humanos , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Ratones Endogámicos C57BL , Neuronas/metabolismo , Oxígeno/metabolismoRESUMEN
Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson's disease. In this study, we aimed to identify the gut microbiome associated with Parkinson's disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson's disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson's disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson's disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer's disease. We developed the first gut microbial gene catalogue associated with Parkinson's disease. Twenty-five gene markers were identified that distinguished Parkinson's disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1-96.1%). A highly accurate Parkinson's disease index, which was not influenced by disease severity or Parkinson's disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson's disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4-98.0%), but also in an independent group of 78 patients with Parkinson's disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0-95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson's disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer's disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson's disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson's disease.
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Microbioma Gastrointestinal/genética , Marcadores Genéticos , Metagenómica/métodos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/microbiología , Anciano , Estudios de Casos y Controles , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Lung cancer is a type of malignant tumor with high morbidity and mortality. Due to its complicated etiology and clinical manifestations, no significant therapeutic advance has been made. Lung squamous cell carcinoma (LSCC) is the most common type of lung cancer. To combat this disease, novel therapeutic targets are badly requirement. ASPM (Abnormal spindle-like microcephaly-associated protein) is involved in multiple cellular or developmental processes, such as neurogenesis and brain growth. ASPM is also reported widely expressed in multiple tumor tissues and involved in the development and progression of several cancers including lung cancer. However, the potential role on ASPM on LSCC is still unclear. In this study, we reported that ASPM was related to the poor prognosis of patients with lung squamous cell carcinoma. Our results further showed that ASPM depletion dramatically inhibited the proliferation of LSCC cells, consistent with the obviously decreased of cyclin D1(CCND1) and cyclin dependent kinases 4 (CDK4) expression. In vivo assays further confirmed ASPM ablation markedly blocked tumor growth in vivo compared with control. In addition, a co-expression was found between ASPM and CDK4 in human tumor tissues. Taken together, our data provides strong evidence that ASPM promotes lung squamous cell carcinoma proliferation in vitro and in vivo, and indicates its potential role as a LSCC therapeutic target.