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BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease characterized by sacroiliitis and spondylitis, with a few hematological abnormalities. Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders with frequent autoimmune phenomena. The relationship between AS and MDS remains unknown. CASE SUMMARY: We describe a rare case of concurrent AS and MDS. An 18-year-old man with low back pain and anemia was diagnosed with AS; however, the cause of anemia could not be determined by the first bone marrow examination. He recovered from anemia and the symptoms of AS resolved after treatment with etanercept, glucocorticoid, and blood transfusion, but he developed pancytopenia with an increased myeloblast count (from 2.5% to 9%). Chromosome analysis revealed del(7q) and trisomy 8. Refractory anemia with excess of blasts-1 (RAEB-1)/MDS was confirmed by repeating the bone marrow examination. He became blood transfusion-dependent and received decitabine-based chemotherapy but eventually died. CONCLUSION: We suspect that AS may be an early autoimmune phenomenon related to MDS. However, a condition of coexistence cannot be excluded.
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Objective@#To explore epidemiological characteristics and diagnosis delay among tuberculosis patients, and to provide reference basis for pulmonary tuberculosis prevention and control in schools.@*Methods@#Retrospective data of school based tuberculosis patients information and cluster epidemiological information in Hefei during Jan. 2019 to Dec. 2020 was collected. Changes of the epidemiological characteristics and diagnosis delay of school tuberculosis epidemic and possible role were explored.@*Results@#The reported incidence of Hefei school pulmonary tuberculosis was 14.04/10 5 in 2020. Two peaks of cases occurred during May to Jun. and Oct. to Nov. Teacher account for 8.00% of pulmonary tuberculosis cases in school, a significant increase was observed compared with 2019 ( χ 2=4.30, P <0.05). In 2020, the median length of treatment for cases reported by local medical institutions was 5.14 days, and the median length of diagnosis was 18 days, both of which were shorter than those in 2019 ( Z =22.45, 4.52, P <0.05). In multiple cases sporadic of school pulmonary tuberculosis, strong positive rate of PPD test was 13.50% among close contacts, and new case detectable rate was 0.62%. The median duration from exposure to symptoms onset among close contacts was 132 days, which significant increased compared to 2019 ( Z =251.50, P <0.05). The diagnosis delay among tuberculosis patients diagnosed by chest CT was 12.10%, and was 16.15% through supervision by school or parents. Chest radiograph was associated with higher risk of delayed diagnosis ( OR=4.34, P <0.05) compared to chest CT as the first medical radiology option. Low delayed diagnosis rate was associated with supervision of tuberculosis by school or parents than control ( OR=0.26, P <0.05).@*Conclusion@#Factors such as the selection of diagnostic radiology and case supervision are associated with delay diagnosis. It s necessary to strengthen the management and monitoring of the pulmonary tuberculosis epidemic in school.
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BACKGROUND: Malignant obstructive jaundice (MOJ) is a common pathologic manifestation of malignant biliary obstruction. Recently, several clinical trials have explored the clinical effectiveness of intraluminal 125I seed-based brachytherapy for MOJ patients, and various outcomes have been reported. AIM: To assess the efficacy and safety of percutaneous biliary stents with 125I seeds compared to conventional metal stents in patients with unresectable MOJ. METHODS: A systematic search of English-language databases (PubMed, Embase, Cochrane Library, and Web of Science) was performed to identify studies published prior to June 2020 that compared stents with or without 125I seeds in the treatment of unresectable MOJ. The outcomes analyzed included primary outcomes (stent patency and overall survival) and secondary outcomes (complications and liver function parameters). RESULTS: Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis. Of the 875 included patients, 404 were treated with 125I seed stents, while 471 were treated with conventional stents. Unadjusted pooled analysis demonstrated that compared to conventional stents, 125I seed stents extended the stent patency time [hazard ratio (HR) = 0.36, 95% confidence interval (CI) = 0.28-0.45, P < 0.0001] and overall survival period (HR = 0.52, 95%CI = 0.42-0.64, P < 0.00001). Subgroup analyses based on the type of 125I seed stent and type of study design showed consistent results. However, there were no significant differences in the occurrence of total complications [odds ratio (OR) = 1.12, 95%CI = 0.75-1.67, P = 0.57], hemobilia (OR = 1.02, 95%CI = 0.45-2.3, P = 0.96), pancreatitis (OR = 1.79, 95%CI = 0.42-7.53, P = 0.43), cholangitis (OR = 1.13, 95%CI = 0.60-2.13, P = 0.71), or pain (OR = 0.67, 95%CI = 0.22-2, P = 0.47). In addition, there were no reductions in the levels of serum indices, including total bilirubin [mean difference (MD) = 10.96, 95%CI = -3.56-25.49, P = 0.14], direct bilirubin (MD = 7.37, 95%CI = -9.76-24.5, P = 0.4), alanine aminotransferase (MD = 7.52, 95%CI = -0.71-15.74, P = 0.07), and aspartate aminotransferase (MD = -4.77, 95%CI = -19.98-10.44, P = 0.54), after treatment. Publication bias was detected regarding the outcome overall survival; however, the conclusions were not changed after the adjustment. CONCLUSION: Placement of stents combined with brachytherapy using 125I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage. Thus, it can be considered an effective and safe treatment for unresectable MOJ.
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Background: An increasing number of patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and develop progressive disease after receiving conventional treatments. In recent years, several novel therapies have been approved for later lines of therapy of previously treated NSCLC. Erlotinib, an EGFR tyrosine kinase inhibitor, was recommended as the second-line therapy for pre-treated patients. However, the use of erlotinib has been reported to represent different clinical effects and adverse effects. Objectives: The current study was aim to investigate the efficacy and safety of erlotinib versus chemotherapy in pre-treated patients with advanced NSCLC. Methods: Electronic databases were searched for eligible literatures updated on June 2018. Randomized-controlled trials assessing the efficacy and safety of erlotinib in pre-treated NSCLC were included, of which the main outcomes were ORR (objective response rate), PFS (progression-free survival), OS (overall survival) and AEs (adverse events). All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated. Results: A total of 11 randomized controlled trials were included in this analysis. The group of erlotinib did not achieved benefit in progression-free survival (OR = 0.61, 95%CI = 0.33-1.12, P = 0.11), overall survival (OR = 0.98, 95%CI = 0.84-1.15, P = 0.81) as well with the objective response rate (OR = 0.77, 95%CI = 0.36-1.63, P = 0.49), respectively. In the results of subgroup analysis among the patients with EGFR wild-type, there is also no significant differences in overall survival with erlotinib (OR = 0.90, 95%CI = 0.78-1.04, P = 0.15) and progression-free survival (OR = 0.33, 95%CI = 0.09-1.18, P = 0.09). The most common treatment-related adverse events in the erlotinib group is rash (OR = 5.79, 95%CI = 2.12-15.77, P = 0.0006), and neutropenia (OR = 0.02, 95%CI = 0.01-0.10, P ≤ 0.00001) is more found in the control group. In addition, fatigue (P = 0.09) and diarrhea (P = 0.52), the difference between the two groups had no statistical significance. Conclusions: There was no significant difference noted with regard to efficacy and safety between erlotinib vs. chemotherapy as the later-line therapy for previously treated patients with NSCLC, even with subgroup patients who have wild-type EGFR tumors. While, erlotinib might increase the risk of rash, and decrease the risk of neutropenia, compared with the chemotherapy. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Clorhidrato de Erlotinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptores ErbB/genética , Clorhidrato de Erlotinib/efectos adversos , Exantema/inducido químicamente , Humanos , Mutación , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Oportunidad Relativa , Seguridad del Paciente , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Hypoxic pulmonary arterial hypertension is characterized by elevated pulmonary vascular resistance and remodelling. Transforming growth factor-ß1 (TGF-ß1 ) is the master regulator in cellular response to hypoxia which can directly target lysyl oxidase (LOX). This study aimed to determine whether hypercapnia attenuates hypoxic pulmonary hypertension via regulating TGF-ß1 and LOX signalling. We found that exposure to hypercapnia ameliorated the increase in mean pulmonary artery pressure (mPAP) and ratio of right ventricle to left ventricle plus septum (RV/(LV + S)) induced by hypoxia but had no effect on mPAP and RV/(LV + S) in normoxia-exposed control. In addition, exposure to hypoxia upregulated the mRNA and protein levels of LOX and TGF-ß1 in rat PASMCs both in vivo and in vitro, but these effects were abrogated by concurrent exposure to hypercapnia. The downregulation of LOX in rat PASMCs induced by hypercapnia was reversed by the administration with TGF-ß1 , while TGF-ß1 knockdown repressed the upregulation of LOX in hypoxia-exposed rat PASMCs. In conclusion, hypoxia upregulates LOX and TGF-ß1 expression in PASMCs and contributes to pulmonary hypertension. Hypercapnia downregulates hypoxia-induced LOX expression and alleviates hypoxia-associated pulmonary hypertension via inhibiting TGF-ß1 signalling. SIGNIFICANCE OF THE STUDY: Hypoxia-induced upregulation of TGF-ß1 , PDGF, and HIF-1α plays a pivotal role in PAH, but molecular mechanism of how hypoxia regulates LOX expression is not clear. In the present study, we showed that mRNA and protein expression levels of LOX were substantially increased when TGF-ß1 was induced by hypoxia, and the effects were reversed by TGF-ß1 knockdown. Our study indicates that TGF-ß1 is implicated in the regulation of LOX.
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Regulación hacia Abajo , Hipercapnia/metabolismo , Hipertensión Pulmonar/metabolismo , Proteína-Lisina 6-Oxidasa/biosíntesis , Transducción de Señal , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Animales , Apoptosis , Hipoxia de la Célula , Supervivencia Celular , Células Cultivadas , Hipertensión Pulmonar/patología , Masculino , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Proteína-Lisina 6-Oxidasa/metabolismo , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: This study investigates the therapeutic potential of urothelin A in attenuating atherosclerotic lesion in wistar rat models and explore the role of Scavenger receptor-class B type I (SR-BI) and activation of Nrf-2 singling pathway. METHODS: Wistar rats (n=48) were feed with high cholesterol diet supplemented with Vitamin D3 and subjected to balloon injury of the aorta. Three days prior to the aortal injury, rats (n=16) were administered urothelin A (3mg/kg/d; po). Positive control were rats receiving high cholesterol diet and balloon injury of the aorta (n=16). The sham group (n=16) consisted of rats fed on basal diet. After twelve weeks blood was collected from all animals for estimation of lipid and angiotensin II (Ang II) levels along, subsequently all animals were sacrificed and morphologic analysis of the aorta was performed. Expression of SR-BI and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein were evaluated by Western blot. RESULTS: After twelve weeks of treatment with urolithin A, there was a significant decrease in the plasma lipid and Ang II levels and improvement of aortic lesion compared with the sham group. There was an increased expression of SR-BI and inhibition of p-ERK1/2 (p<0.05). The expression of SR-BI was inversely correlated with levels of Ang II. CONCLUSION: From the results it can be safely concluded that administration of urolithin A attenuates atherosclerosis via upregulation of SR-BI expression and inhibition of p-ERK1/2 levels.
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Aterosclerosis/tratamiento farmacológico , Cumarinas/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Receptores Depuradores/metabolismo , Transducción de Señal/efectos de los fármacos , Angiotensina II/sangre , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aterosclerosis/sangre , Aterosclerosis/metabolismo , Antígenos CD36/metabolismo , Hipercolesterolemia/sangre , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/metabolismo , Lípidos/sangre , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Nowadays, there is a high demand for supersensitive contrast agents for the early diagnostics of hepatocarcinoma. It has been recognized that accurate imaging information is able to be achieved by constructing hepatic tumor specific targeting probes, though it still faces challenges. Here, a AGKGTPSLETTP peptide (A54)-functionalized superparamagnetic iron oxide (SPIO)-loaded nanostructured lipid carrier (A54-SNLC), which can be specifically uptaken by hepatoma carcinoma cell (Bel-7402) and exhibited ultralow imaging signal intensity with varied Fe concentration on T2-weighted imaging (T2WI), was first prepared as an effective gene carrier. Then, an endogenous ferritin reporter gene for magnetic resonance imaging (MRI) with tumor-specific promoter (AFP-promoter) was designed, which can also exhibit a decrease in signal intensity on T2WI. At last, using protamine as a cationic mediator, novel ternary nanoparticle of A54-SNLC/protamine/DNA (A54-SNPD) as an active dual-target T2-weighted MRI contrast agent for imaging hepatic tumor was achieved. Owing to the synergistic effect of A54-SNLC and AFP-promoted DNA targeting with Bel-7402 cells, T2 imaging intensity values of hepatic tumors were successfully decreased via the T2 contrast enhancement of ternary nanoparticles. It is emphasized that the novel A54-SNPD ternary nanoparticle as active dual-target T2-weighted MRI contrast agent were able to greatly increase the diagnostic sensitivity and specificity of hepatic cancer.
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Neoplasias Hepáticas , Medios de Contraste , Ferritinas , Genes Reporteros , Humanos , Lípidos , Imagen por Resonancia Magnética , Nanopartículas de MagnetitaRESUMEN
Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.
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Artritis Reumatoide/patología , Receptor Smoothened/antagonistas & inhibidores , Sinoviocitos/patología , Apoptosis/genética , Proliferación Celular/genética , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Receptor Smoothened/agonistas , Receptor Smoothened/metabolismoRESUMEN
MicroRNA-126 (miR-126) has been found to promote angiogenesis, but the underlying mechanisms are still unclear. So, we conducted this study to explore the effect of miR-126 expression on angiogenesis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The expression levels of miR-126 and sprouty-related, EVH1 domain containing protein (Spred)1 in surgically resected HCC tissue, HCC tissue with TACE + operation, and tumor-adjacent tissues were determined by quantitative real-time polymerase chain reaction. The expression levels of miR-126, Spred1, and vascular endothelial growth factor were found by quantitative real-time polymerase chain reaction and Western blot. The microvessel density (MVD) of tumor tissues was determined by immunohistochemical staining. The miR-126 and Spred1 expressions in HCC tissue with TACE + operation were elevated and decreased, respectively, as compared to those in surgically resected HCC tissues and tumor-adjacent tissues (all P<0.001), which indicated that the expression of Spred1 was negatively correlated with miR-126 (P<0.001, r=-0.6224). Based on the bioinformatics analysis and luciferase reporter gene activity detection, Spred1 was found to target miR-126 (P<0.001). Inhibition of miR-126 expression reduces the degree of weight loss and tumor size in TACE model rats. The MVD in TACE + operation group was increased compared to that in the control group; inhibition of miR-126 expression had a reversal effect, to a certain extent, on MVD increase after TACE (all P<0.05). Inhibition of miR-126 expression increased Spred1 expression and decreased vascular endothelial growth factor expression (P<0.01). In summary, this study unveiled the potential mechanism by which miR-126 regulates angiogenesis in HCC tissues through embolization treatment by targeting Spred1, and also showed that the feasibility of TACE with the miR-126 inhibitor has a certain value in the medical treatment of HCC.
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OBJECTIVES: CD200 is expressed on various cell types, including T cells, while the CD200 receptor (CD200R) is expressed on myeloid cells such as monocytes-derived macrophages (MDMs). The CD200-CD200R interaction has been shown to play an important role in the prevention of autoimmune disease. Thus, we hypothesized that CD200/CD200R1 is involved in the pathogenesis of rheumatoid arthritis (RA). METHODS: In total, 35 RA patients and 17 healthy controls (HCs) were enrolled in this study. CD200/CD200R1 expression and Th17/Treg were examined by flow cytometry. Serum levels of interleukin (IL)-2, interferon-γ (IFN-γ), IL-4 and IL-10 were detected by ELISA. Disease activity was evaluated according to the C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR) and 28-joint disease activity score (DAS28) scores. RESULTS: Compared with HCs, RA patients exhibited a significantly decreased level of CD200R1 on MDMs. CD200R1 expression correlated negatively with DAS28, ESR, and CRP levels. This abnormal expression was associated with Th17/Treg imbalance in the active RA patients. However, expression of CD200R1 was not correlated with Th1 (IL-2, IFN-γ) or Th2 (IL-4, IL-10) cytokine responses. CONCLUSION: In this study, we demonstrate a significant correlation between CD200R1(+) cells and disease severity in RA patients, thus indicating the relevance of the CD200/CD200R1 signaling pathway's potential involvement in the pathogenesis of RA.