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1.
Leuk Res ; 107: 106607, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33957372

RESUMO

The study investigated pretreatment Epstein-Barr virus (EBV) DNA status and its prognostic values in 96 patients newly diagnosed Hodgkin lymphoma (HL). With 13.5 % patients in positive EBV DNA status before therapy, the positive group had inferior progression-free survival (PFS) (P = 0.023) as well as overall survival (OS) (P = 0.001). Pretreatment EBV DNA positivity was observed as an independent prognostic factor in OS (P = 0.036) while a trend to predict PFS (P = 0.064). By monitoring changes of EBV DNA copies in 13 patients with positive pretreatment EBV DNA status, 5 of 6 patients with complete response (CR) had their copies undetectable after 3 cycles of first-line treatment and 7 patients with progressive disease (PD) all had elevated EBV DNA copies during their relapsed period. Whole blood EBV DNA may be an adjunctive biomarker to reflect treatment response, risk of disease relapse as well as prognosis in HL patients.

2.
Drug Des Devel Ther ; 15: 1915-1930, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976541

RESUMO

Background: S. baicalensis, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer's disease. Aim of the Study: To elucidate the mechanism by which S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. Materials and Methods: The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking. Results: Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which S. baicalensis acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which S. baicalensis is involved to regulate lipid metabolism. Conclusion: According to our metabolomics results, S. baicalensis may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of S. baicalensis, may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of S. baicalensis on lipid metabolism using network pharmacology and lipidomics.

3.
Yi Chuan ; 43(4): 362-374, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33972210

RESUMO

The emerging cleavage under target and tagment (CUT&Tag) technology uses Tn5 transposase to cleavage near the DNA binding site of target protein and study the generated DNA fragments by the next-generation sequencing. It can quickly identify protein-DNA interactions, which greatly simplifies the experimental process of ChIP-Seq. After CUT&Tag tagment reaction, DNA recovery or other post-processing is required to perform library construction PCR. Different recovery methods have significant impact respectively. By establishing Streptavidin beads recovery CUT&Tag(srCUT&Tag), we can quickly and conveniently complete the product recovery of CUT&Tag. We carried out CUT&Tag assay of H3K4me3, RNA Polymerase II (RNA polymerase II, RNAPII), transcription factor CTCF and HMGA1 in K562 cells with different recovery methods, including ethanol precipitation, fragment separation magnetic beads (SPRI) Magnetic bead recovery, direct PCR method, as well as our srCUT&Tag recovery method. The results show that among the CUT&Tag results of four different targets, the SPRI magnetic bead recovery and our srCUT&Tag methods have higher recovery efficiency than the direct PCR method and ethanol precipitation method. All CUT&Tag results showed that the recovery of SPRI magnetic beads would lose most of the product fragments less than 150 bp. In the recovery of CTCF and HMGA1, direct PCR lost most of the fragments larger than 300 bp and has significant difference from result of other recovery method. This enables srCUT&Tag to provide more real and higher-resolution information than other recovery method. In summary, the newly established srCUT&Tag recovery method can improve the efficiency of CUT&Tag library construction and obtain better data quality compared with the existing CUT&Tag product recovery method, providing a better technical choice for epigenetics research.

4.
Small ; : e2100378, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33870644

RESUMO

An integrated molecular probe for combined tumor-targeted multimodal imaging and therapy in the era of precision medicine requires a multiplexed platform that simultaneously has high targeting specificity, versatile conjugation capability, and biocompatibility. Here, a novel biocompatible melanin nanoprobe (PMNs-II-813) coupled with a highly specific prostate-specific membrane antigen small molecule inhibitor is developed for the targeted multimodal diagnosis and treatment of prostate cancer. The melanin nanoparticles demonstrate photoacoustic imaging and photothermal therapy (PTT) functionalities via strong near-infrared absorption. The imaging contrast agents 89 Zr and Mn2+ are stably conjugated to the nanoparticles for positron emission tomography (PET) and magnetic resonance imaging (MRI). Fusion PET/MRI with PMNs-II-813 enables the monitoring of treatment effects in real time and lasts for more than 1 week, demonstrating the capability for multimodal theranostics in prostate cancer. Labeling with a therapeutic radionuclide, 131 I, simultaneously endows the nanoprobe with the capability for radioisotope therapy (RIT) and PTT under triple-modal imaging guidance. Combined PTT and RIT has an inhibitory effect on prostate cancer growth (tumor inhibition rate of ≈93% 20 days after treatment), which is significantly better than that with the single treatment. Overall, it is believed that PMNs-II-813 has potential for clinical translation to treat prostate cancer.

5.
World J Pediatr ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844176

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development. METHODS: This multicenter observational study was conducted at two designated maternal and children's hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age. RESULTS: Of 72 neonates born to mothers with COVID-19, 8 (11%) were diagnosed with COVID-19, 8 (11%) were critically ill, and no deaths were reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among these five neonates, three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2, delayed myelination and brain dysplasia in newborn 3, and abnormal signal in the bilateral periventricular in newborn 5. The other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age (P > 0.05). Physical growth parameters for weight, length, and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all neonates. CONCLUSIONS: Some of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical growth. These findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2, but further study is required to evaluate the association between the abnormal MRI findings and the exposure to SARS-CoV-2.

6.
Phys Rev Lett ; 126(11): 112003, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33798370

RESUMO

Collimated sprays of hadrons, called jets, are an emergent phenomenon of quantum chromodynamics (QCD) at collider experiments, whose detailed internal structure encodes valuable information about the interactions of high energy quarks and gluons and their confinement into color-neutral hadrons. The flow of energy within jets is characterized by correlation functions of energy flow operators, with the three-point correlator being the first correlator with nontrivial shape dependence, playing a special role in unraveling the dynamics of QCD. In this Letter, we initiate a study of the three-point energy correlator to all orders in the strong coupling constant, in the limit where two of the detectors are squeezed together. We show that, by rotating the two squeezed detectors with respect to the third by an angle ϕ, a cos(2ϕ) dependence arising from the quantum interference between intermediate virtual gluons with +/- helicity is imprinted on the detector. This can be regarded as a double slit experiment performed with jet substructure, and it provides a direct probe of the ultimately quantum nature of the substructure of jets and of transverse spin physics in QCD. To facilitate our all-orders analysis, we adopt the operator product expansion (OPE) for light-ray operators in conformal field theory and develop it in QCD. Our application of the light-ray OPE in real world QCD establishes it as a powerful theoretical tool with broad applications for the study of jet substructure.

7.
Proc Natl Acad Sci U S A ; 118(16)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33846242

RESUMO

Precision medicine in oncology leverages clinical observations of exceptional response. Toward an understanding of the molecular features that define this response, we applied an integrated, multiplatform analysis of RNA profiles derived from clinically annotated glioblastoma samples. This analysis suggested that specimens from exceptional responders are characterized by decreased accumulation of microglia/macrophages in the glioblastoma microenvironment. Glioblastoma-associated microglia/macrophages secreted interleukin 11 (IL11) to activate STAT3-MYC signaling in glioblastoma cells. This signaling induced stem cell states that confer enhanced tumorigenicity and resistance to the standard-of-care chemotherapy, temozolomide (TMZ). Targeting a myeloid cell restricted an isoform of phosphoinositide-3-kinase, phosphoinositide-3-kinase gamma isoform (PI3Kγ), by pharmacologic inhibition or genetic inactivation disrupted this signaling axis by reducing microglia/macrophage-associated IL11 secretion in the tumor microenvironment. Mirroring the clinical outcomes of exceptional responders, PI3Kγ inhibition synergistically enhanced the anti-neoplastic effects of TMZ in orthotopic murine glioblastoma models. Moreover, inhibition or genetic inactivation of PI3Kγ in murine glioblastoma models recapitulated expression profiles observed in clinical specimens isolated from exceptional responders. Our results suggest key contributions from tumor-associated microglia/macrophages in exceptional responses and highlight the translational potential for PI3Kγ inhibition as a glioblastoma therapy.

8.
Leuk Res ; 105: 106580, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33836479

RESUMO

The study investigated serum 25-Hydroxy vitamin D (25-(OH)D) deficiency and its prognostic values of patients newly diagnosed Hodgkin lymphoma (HL). With seventy-seven patients enrolled, the median level of 25-(OH)D was 44.5 nmol/L (range, 15.5-100.9 nmol/L) and 16 (20.8 %) of them were considered as 25-(OH)D deficiency. With a median follow-up of 28 months (range, 4-56 months), the 2-year progression-free survival (PFS) and overall survival (OS) rate were 75.3 %±5.5 % and 94.7 %±3.0 %, respectively. Patients with deficient 25-(OH)D level had inferior PFS (P<0.001) as well as OS (P<0.001). In multivariate Cox analysis, 25-(OH)D deficiency was observed as an independent prognostic factor for both PFS (hazard ratio (HR) 3.323, 95 % CI 1.527-7.229, P = 0.002) and OS (HR 5.819, 95 % CI 1.322-25.622, P = 0.020). Receiver-operator characteristic (ROC) curve showed International Prognostic Score (IPS) plus 25-(OH)D deficiency (IPS-D) predicted more accurately than IPS in PFS (AUC: 0.735 (95 % CI 0.622-0.829) vs. 0.701 (95 % CI 0.586-0.800), P = 0.033) and OS (AUC: 0.864 (95 % CI 0.767-0.932) vs. 0.825 (95 % CI 0.722-0.902), P = 0.028). All these findings suggest that serum 25-(OH)D level may be an adjunctive indicator to predict prognosis in HL patient.

9.
Anticancer Drugs ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33735117

RESUMO

Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3ß (GSK-3ß) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3ß was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3ß and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3ß signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.

10.
Clin Nucl Med ; 46(6): 474-476, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661191

RESUMO

ABSTRACT: 18F-FDG and 18F-(2S,4R)4-fluoroglutamine (18F-FGln) PET/CT were performed in a 58-year-old woman with suspected small intestinal malignancy for differential diagnosis and staging. 18F-FDG and 18F-FGln PET images showed consistent intense hypermetabolic lesion activity in part of the small intestine. Moreover, 18F-FDG/PET demonstrated a focal of increased radiotracer uptake in left adrenal lesion, which did not show abnormal activity on 18F-FGln/PET. The postoperative pathology confirmed that it was a peripheral T-cell lymphomas of the intestine, and the adrenal lesion was considered benign after continuous CT follow-up for more than 2 years.

11.
Acta Physiol (Oxf) ; : e13652, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752256

RESUMO

AIM: Highly prevalent diseases such as insulin resistance and heart failure are characterized by reduced metabolic flexibility and reserve. We tested whether Na/K-ATPase (NKA)-mediated regulation of Src kinase, which requires two NKA sequences specific to the α1 isoform, is a regulator of metabolic capacity that can be targeted pharmacologically. METHODS: Metabolic capacity was challenged functionally by Seahorse metabolic flux analyses and glucose deprivation in LLC-PK1-derived cells expressing Src binding rat NKA α1, non-Src-binding rat NKA α2 (the most abundant NKA isoform in the skeletal muscle), and Src binding gain-of-function mutant rat NKA α2. Mice with skeletal muscle-specific ablation of NKA α1 (skα1-/-) were generated using a MyoD:Cre-Lox approach and were subjected to treadmill testing and Western diet. C57/Bl6 mice were subjected to Western diet with or without pharmacological inhibition of NKA α1/Src modulation by treatment with pNaKtide, a cell-permeable peptide designed by mapping one of the sites of NKA α1/Src interaction. RESULTS: Metabolic studies in mutant cell lines revealed that the Src binding regions of NKA α1 are required to maintain metabolic reserve and flexibility. Skα1-/- mice had decreased exercise endurance and mitochondrial Complex I dysfunction. However, skα1-/- mice were resistant to Western diet-induced insulin resistance and glucose intolerance, a protection phenocopied by pharmacological inhibition of NKA α1-mediated Src regulation with pNaKtide. CONCLUSIONS: These results suggest that NKA α1/Src regulatory function may be targeted in metabolic diseases. Because Src regulatory capability by NKA α1 is exclusive to endotherms, it may link the aerobic scope hypothesis of endothermy evolution to metabolic dysfunction.

12.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33785590

RESUMO

Compelling evidence indicates that radiotherapy (RT) has a systemic inhibitory effect on nonirradiated lesions (abscopal effect) in addition to the ablation of irradiated tumors. However, this effect occurs only in rare circumstances in clinical practice, and mechanisms underlying the abscopal effect of RT are neither fully understood nor therapeutically utilized. Here we identified that intercellular adhesion molecule-1 (ICAM-1), an inducible glycoprotein of the immunoglobulin superfamily, is up-regulated in nonirradiated tumors responsive to RT. ICAM-1 expression in preclinical animal models can be noninvasively detected by optical imaging and positron emission tomography (PET) using near-infrared fluorescence dye- and 64Cu-labeled imaging probes that we synthesized, respectively. Importantly, the expression levels of ICAM-1 determined by quantitative PET imaging showed a strong negative linear correlation with the growth of nonirradiated tumors. Moreover, genetic or pharmacologic up-regulation of ICAM-1 expression by either an intratumoral injection of engineered recombinant adenovirus or systemic administration of a Toll-like receptor 7 agonist-capsulated nanodrug could induce markedly increased abscopal responses to local RT in animal models. Mechanistic investigation revealed that ICAM-1 expression can enhance both the activation and tumor infiltration of CD8+ T cells to improve the responses of the nonirradiated tumors to RT. Together, our findings suggest that noninvasive PET imaging of ICAM-1 expression could be a powerful means to predict the responses of nonirradiated tumors to RT, which could facilitate the exploration of new combination RT strategies for effective ablation of primary and disseminated lesions.

13.
Bioorg Med Chem Lett ; 40: 127901, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33705912

RESUMO

As an indicative biomarker for immunotherapy, PD-L1 plays an important role in the clinical decision-making of the immune checkpoint blockade therapy. PET imaging through radiotracer can real-timely, quantitatively, and non-invasively assess the expression of PD-L1 in tumors. Here, we reported a copper-64 radiolabeled NOTA-WL12, 64Cu-NOTA-WL12, and preliminarily evaluated its application in non-invasively detecting the PD-L1 expression.64Cu-NOTA-WL12 was produced with high radiochemical yield (>90%), radiochemical purity (>98%), and specific activity (20 MBq/nmol). 64Cu-NOTA-WL12 showed high in vitro stability and high binding affinity to the PD-L1 (KD ≈ 3.012 nM). The micro-positron emission tomography/computerized tomography (micro-PET/CT) imaging indicated that 64Cu-NOTA-WL12 was specifically accumulated in the tumor with PD-L1 expression. All results demonstrated that 64Cu-NOTA-WL12 holds great potential for noninvasive evaluation of PD-L1 expression levels.

14.
Catheter Cardiovasc Interv ; 97 Suppl 2: 988-995, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33734575

RESUMO

OBJECTIVES: This study sought to compare the efficacy and clinical safety of the LONGTY drug-coated balloon (DCB) with those of SeQuent Please DCB in patients with in-stent restenosis (ISR). BACKGROUND: Although DCB technologies have evolved, little is known about the clinical efficacy of the new-generation LONGTY DCB. METHODS: This was a prospective, multicenter, randomized, noninferiority trial comparing LONGTY DCB with SeQuent Please DCB in patients with ISR. The primary endpoint was target lesion late lumen loss at 9 months' follow-up. RESULTS: A total of 211 patients with ISR from 13 Chinese sites were included (LONGTY DCB, n = 105; SeQuent Please DCB, n = 106). Device success was achieved in all patients. At the 9 month angiographic follow-up, target lesion late lumen loss was 0.35 ± 0.42 mm with LONGTY and 0.38 ± 0.45 mm with SeQuent Please (p for noninferiority <.001). The target lesion revascularization rates at 1 year were similar in both DCB groups (15.24 vs. 13.21%; p = .673). Over an extended follow-up of 2 years, the clinical endpoints, including cardiac death, myocardial infarction, and thrombus rate, were extremely low and similar in both groups. CONCLUSIONS: In this multicenter, head-to-head, randomized trial, the new-generation LONGTY DCB was noninferior to the SeQuent Please DCB for the primary endpoint of target lesion late lumen loss at 9 months.

15.
Sci Total Environ ; 777: 146006, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33677283

RESUMO

Cadmium (Cd), a noxious heavy metal, is widespread in the living environment. Gestational exposure to Cd at environmental dose has been shown to cause fetal growth restriction (FGR). However, the long-term effects and the mechanisms underlying environmental Cd exposure on glucose metabolism in offspring remain unclear. Here, we established a murine model to study the impacts of gestational exposure to environmental Cd on glucose metabolism at different life stages of offspring. Results demonstrated that the offspring mice developed hyperglycemia in puberty and impaired glucose tolerance in adulthood following maternal Cd exposure during gestation. Further mechanistic investigation showed that Cd exposure upregulated the expression of key proteins in hepatic gluconeogenesis, including p-CREB, PGC-1α and G6PC, in pubertal and adult offspring. In addition, we demonstrated that Cd exposure during pregnancy markedly elevated the level of oxidative stress-related proteins, including NOX2, NOX4 and HO-1, in the fetal liver. The effects of gestational exposure to N-acetylcysteine (NAC), a free-radical scavenging antioxidant, presented that NAC supplementation alleviated hepatic oxidative stress in fetuses, and thereby reversed hyperglycemia and glucose intolerance in mouse offspring. Collectively, our data suggested that gestational exposure to environmental Cd caused diabetes-like phenotypes via enhancing hepatic gluconeogenesis, which is associated with oxidative stress in fetal livers. This work provides new insights into the protective effects of antioxidants on fetal-originated diabetes triggered by environmental toxicants.

16.
Ann Hematol ; 100(4): 995-1002, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33651193

RESUMO

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3+ T-lymphocyte count (ACD3C), CD4+ T-lymphocyte count (ACD4C), CD8+ T-lymphocyte count (ACD8C), and CD4+/CD8+ T-lymphocyte ratio (CD4+/CD8+) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4+/CD8+ ratio. And the lower level of ß2-microglobulin (<3 mg/L) was associated with a higher CD4+/CD8+ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4+/CD8+ ratio inversion (CD4+/CD8+<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4+/CD8+ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4+/CD8+ inversion patients but did not affect normal CD4+/CD8+ patients. We show that low circulating CD4+/CD8+ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4+/CD8+ ratio less than 1.5.


Assuntos
Relação CD4-CD8 , Macroglobulinemia de Waldenstrom/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/mortalidade , Microglobulina beta-2/análise
17.
Artigo em Inglês | MEDLINE | ID: mdl-33544201

RESUMO

PURPOSE: To explore the clinical features and immunological mechanisms of Castleman disease (CD) complicated with autoimmune diseases (AID). METHODS: We explored the prevalence and clinical manifestations of CD complicated with AID by reviewing clinical, pathological, and laboratory data of 40 CD patients retrospectively, and then explored abnormal immune mechanisms in the co-existence of the two entities by monitoring lymphocyte subsets in peripheral blood. RESULTS: Paraneoplastic pemphigus, autoimmune hemolytic anemia, Sjogren's syndrome, myasthenia gravis, and psoriasis were found to be coexisted with CD in 9/40 (22.5%) patients with different sequence of onset. No bias in the clinical and histological type of CD was observed for the occurrence of AID. CD patients with AID were more likely to have skin and/or mucous membrane damage and pulmonary complications, and presented elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and positive autoantibodies than those without AID (p < 0.05). Deregulated cellular and innate immune responses as indicated by decreased CD3+ T cells and increased natural killer cells were observed in peripheral blood of CD patients with AID (p < 0.05). UCD patients with AID were successfully treated with surgery and immunosuppressive therapy. MCD complicated by AID relieved with immunosuppressors, cytotoxic chemotherapy, and rituximab. CONCLUSION: Systemic inflammation/immunological abnormalities and organ dysfunction were associated with the occurrence of AID in CD. Impairment of cellular and innate immunity may be a candidate etiology for the coexistence of the two entities.

18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(1): 46-51, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33522176

RESUMO

In recent years, the application of stent intervention in the treatment of non-vascular stenosis caused by benign and malignant factors has been widely concerned by researchers at home and abroad. The high incidence of malignant tumor diseases, further promotes the development of stent intervention. The conventional bare stents are prone to irritate luminal mucosa and produce restenosis and other complications. The emergence of drug-eluting stent is expected to solve this problem and become one of the important development trends of non-vascular stents. In this paper, the drug loading materials, drug loading layer drugs, preparation technology and quality evaluation methods of non-vascular drugeluting stent are described based on the recent research and clinical application documents, so as to provide basis and direction for the follow-up research and development.


Assuntos
Stents Farmacológicos , Reestenose Coronária , Humanos , Desenho de Prótese , Resultado do Tratamento
19.
Cell Death Dis ; 12(2): 203, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608513

RESUMO

Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.

20.
Hum Brain Mapp ; 42(7): 1945-1951, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33522661

RESUMO

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation. We also share pointers to an associated data user agreement that is not only useful in the EU context, but also for any researchers dealing with personal (clinical) data elsewhere.

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