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1.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692057

RESUMO

Renal tubular epithelial cells may undergo epithelial-mesenchymal transition (EMT) in response to stimuli, such as transforming growth factor (TGF)-ß1, leading to myofibroblast activation and renal fibrosis. The formin mDia1 is required for nucleation and polymerization of actin and the microtubule cytoskeleton. The present study sought to explore the role of mDia1 in EMT of tubular epithelial cells. A rat model of unilateral ureteral obstruction (UUO) was established. The expression of TGF-ß1, collagen I, collagen III, and mDia1 in the kidneys was examined at day 7 after surgery. The effect of mDia1 on EMT was explored in NRK-52E cells by exposing them to TGF-ß1. Increased expression of TGF-ß1, collagen I, collagen III, and mDia1 was found in obstructive kidneys of UUO model rats. Exposing rat tubular epithelial cells to TGF-ß1 promoted collagen I and collagen III expression but had no effect on mDia1 expression. Silencing mDia1 expression impeded epithelial cell migration as well as reduced TGF-ß1, collagen, and Profilin1 expression, whereas mDia1 overexpression exerted an opposite effect. Furthermore, mDia1 regulated the expression of vimentin, α-smooth muscle actin, and E-cadherin and focal adhesion-kinase (FAK)/Src activation through Profilin1. Inhibition of the mDia1 activator RhoA by fasudil reversed EMT, and FAK/Src activation induced by mDia1. In conclusion, mDia1 regulated tubular epithelial cell migration, collagen expression, and EMT in NRK-52E cells exposed to TGF-ß1. Thus, suppression of mDia1 activation might be a strategy to counteract renal fibrosis.

2.
Plant Sci ; 289: 110282, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31623771

RESUMO

The metabolic profile of rice (Oryza sativa) during germination under low temperature (LT) has not been reported. In this study, the rice varieties 02428 (japonica) and YZX (indica) were subjected to experiments consisting of treatments including LT, normal temperature (NT) and a transition from LT to NT, and tissues were sampled at different time points during germination. A total of 730 metabolites were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based widely targeted metabolomics method. On the basis of the screening criteria of increased contents under LT and decreased contents under NT, we identified 35 different metabolites that responded to LT stress among the 730 metabolites. Furthermore, the content differences of the 35 metabolites were compared when the samples were transferred from LT to NT. According to a fold change <0.5 or a variable importance in projection (VIP) score>1 at the transition point, 7 out of the 35 metabolites responded significantly to LT stress and were defined as key metabolites. A partial least squares (PLS) regression model of seven key metabolites with seedling length (SL), seedling area (SSA), and seedling volume (SV) was constructed, and the fitting effect was good. These seven key metabolites participate in the biosynthesis of amino acids and phenylpropanoids and in the metabolism of glutathione and inositol phosphate. This study laid a foundation for an improved understanding of the LT-germination mechanism of rice seeds.

3.
Nano Lett ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31594301

RESUMO

Nanoscale photodynamic therapy (PDT) is an appealing antitumor modality for which apoptosis is the major mechanism of toxicity induction. It was postulated that the highly reactive singlet oxygen in PDT could deplete glutathione (GSH) and activate ferroptosis, the extent to which could be further manipulated by a redox-responsive nanocarrier. To validate this, a disulfide-bearing imidazole ligand coordinated with zinc to form an all-active metal organic framework (MOF) nanocarrier where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless of light irradiation, the Ce6-loaded nanocarrier caused the depletion of intracellular GSH via the disulfide-thiol exchange reaction in a murine mammary carcinoma cell line (4T1). The GSH depletion further caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement of cytotoxicity that was alleviated by ferroptosis inhibitors. The superior in vivo antitumor efficacy of the all-active nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression and animal survival rate. The coadministration of an iron chelator weakened the antitumor potency of the nanocarrier due to ferroptosis inhibition, which was supported by the fact of tumor growth upsurge and the recovered GPX4 activity. The current work highlights the contribution of ferroptotic machinery to antitumor PDT via an activatable, adaptable, all-active MOF nanocarrier.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31580250

RESUMO

BACKGROUND: Large-scale studies showed that the SNP rs1764391 of Cx37 gene plays a pivotal role in the occurrence and development of AMI. Published results, however, were highly controversial. OBJECTIVE: This study aimed to examine the association between SNP rs1764391 of Cx37 and disease-susceptibility, several risk factors, gene-environment interactions of AMI in Guangxi Han Chinese. METHODS: In this study, 344 healthy controls and 344 AMI patients of Han Chinese were enrolled. The TaqMan assay was implemented to confirm the genotypes. Differences in genotype and allele frequencies of SNP rs1764391 were compared in both the AMI and control groups. RESULTS: Significant differences in TT genotype frequencies of SNP rs1764391 between the AMI and control groups were detected (P < 0.05). In the context of gender stratification, the result was also statistically different in women (P < 0.05). Age, BMI, diabetes, high blood pressure, smoking and TC were closely correlated to the risk of AMI (P < 0.05 for each). HDL-C was negatively correlated to the risk of AMI (P < 0.001). Significant interactions were observed between presence of the SNP rs1764391 CC genotype and BMI, smoking or alcohol consumed (P < 0.017 for each). CONCLUSIONS: The TT genotype of Cx37 SNP rs1764391 was identified as a predisposing factor for AMI, especially in women. This genetic variant may prove to be an important tool for AMI risk stratification, and thus might be a useful target for therapeutic intervention to further improve prognosis in high-risk patients.

5.
Helicobacter ; : e12656, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571330

RESUMO

BACKGROUND & AIMS: Developing countries are making efforts to improve health management. Practice deviating from the guideline means inefficient control. The study aims to investigate the management of Helicobacter pylori (H pylori) infection from a developing country perspective. METHODS: An authoritative survey was conducted in 14th (2014) and 17th (2017) Congress of Gastroenterology China, respectively. The Maastricht V/Florence consensus report was invoked as the evaluation criterion. RESULTS: A total of 4182 valid samples were included in this study. Most of the respondents (94%) updated knowledge by lectures. Respondents had a different awareness rate of H pylori-related diseases, ranging from 45% to 95%. Up to 40% of the respondents did not follow the recommendations for the diagnosis. Choice accuracy of eradication regimens and antibiotic combinations was <70%. About 20% of the respondents did not pay attention to the confirmation after the eradication. The situation had been improved in 2017 when compared with that in 2014 (all P < .05). Multivariate logistic regression analysis revealed that influencing factors including nongastroenterologists, bachelor degree and below, the primary professional title, hospital location, and a small proportion of H pylori infection in daily practice related to the deviation of consensus (all P < .05). CONCLUSIONS: Although the management of H pylori infection has been improved in a developing country, there is still a gap between the real-world practices and the consensus. Influencing factors should be taken into account in decision-making, and the corresponding population should be strengthened with precision training during the promotion of the guideline.

6.
BMC Plant Biol ; 19(1): 395, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510917

RESUMO

BACKGROUND: Leaf morphology and spikelet number are two important traits associated with grain yield. To understand how genes coordinating with sink and sources of cereal crops is important for grain yield improvement guidance. Although many researches focus on leaf morphology or grain number in rice, the regulating molecular mechanisms are still unclear. RESULTS: In this study, we identified a prohibitin complex 2α subunit, NAL8, that contributes to multiple developmental process and is required for normal leaf width and spikelet number at the reproductive stage in rice. These results were consistent with the ubiquitous expression pattern of NAL8 gene. We used genetic complementation, CRISPR/Cas9 gene editing system, RNAi gene silenced system and overexpressing system to generate transgenic plants for confirming the fuctions of NAL8. Mutation of NAL8 causes a reduction in the number of plastoglobules and shrunken thylakoids in chloroplasts, resulting in reduced cell division. In addition, the auxin levels in nal8 mutants are higher than in TQ, while the cytokinin levels are lower than in TQ. Moreover, RNA-sequencing and proteomics analysis shows that NAL8 is involved in multiple hormone signaling pathways as well as photosynthesis in chloroplasts and respiration in mitochondria. CONCLUSIONS: Our findings provide new insights into the way that NAL8 functions as a molecular chaperone in regulating plant leaf morphology and spikelet number through its effects on mitochondria and chloroplasts associated with cell division.

7.
Int J Oncol ; 55(5): 1077-1089, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545408

RESUMO

Peripheral T­cell lymphomas (PTCLs) are heterogeneous malignancies that are types of non­Hodgkin lymphomas; patients with this disease have poor prognoses. The IL­2­inducible T­cell kinase­spleen tyrosine kinase (ITK­SYK) fusion gene, the first recurrent chromosome translocation in PTCL­not otherwise specified (NOS), can drive cellular transformation and the development of T­cell lymphoma in mouse models. The aim of the current study was to investigate the signal transduction pathways downstream of ITK­SYK. The authors constructed a lentiviral vector to overexpress the ITK­SYK fusion gene in Jurkat cells. By using Signal­Net and cluster analyses of microarray data, the authors identified the tyrosine­protein kinase JAK (JAK)3/STAT5 signalling pathway as a downstream pathway of ITK­SYK, activation of which mediates the effects of ITK­SYK on tumourigenesis. JAK3­selective inhibitor tofacitinib abrogated the phosphorylation of downstream signalling molecule STAT5, supressed cell growth, induced cell apoptosis and arrested the cell cycle at the G1/S phase in ITK­SYK+ Jurkat cells. In a xenograft mouse model, tumour growth was significantly delayed by tofacitinib. Since JAK3 associates with interleukin­2 receptor subunit γ (IL2RG) only, siRNA­specific knockdown of IL2RG showed the same effect as tofacitinib treatment in vitro. These results first demonstrated that the activation of the IL2RG/JAK3/STAT5 signalling pathway contributed greatly to the oncogenic progress regulated by ITK­SYK, supporting further investigation of JAK3 inhibitors for the treatment of PTCLs carrying the ITK­SYK fusion gene.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31546002

RESUMO

CONTEXT: Patients with advanced-stage cancer often suffer many physical and psychological symptoms. Exercise has been shown to improve quality of life (QoL), decrease cancer-related symptoms, and maintain or improve functional status in cancer survivors or patients with early stage cancer. However, the effect of exercise on these outcomes in patients with advanced-stage cancer is unclear. OBJECTIVES: This meta-analysis aimed to assess the effectiveness of exercise interventions for patients with advanced-stage cancer in improving cancer-related symptoms and functional status outcomes. METHODS: We conducted a comprehensive literature search in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science from their inception to February 3, 2019, to include randomized controlled trials (RCTs) comparing exercise and usual care for improving outcomes in patients with advanced-stage cancer. Two reviewers independently screened the studies, extracted data of interest, and assessed the risk of bias of individual RCTs using the Cochrane Handbook, Version 5.1.0. RESULTS: About 15 RCTs enrolling 1208 patients were included. Compared with usual care, exercise showed a significant improvement in QoL (standardized mean difference [SMD] 0.22; 95% CI 0.06-0.38; P = 0.009), fatigue (SMD -0.25; 95% CI -0.45 to -0.04; P = 0.02), insomnia (SMD -0.36; 95% CI -0.56 to -0.17; P = 0.0002), physical function (SMD 0.22; 95% CI 0.05-0.38; P = 0.009), social function (SMD 0.18; 95% CI 0.02-0.34; P = 0.03), and dyspnea reduction (SMD -0.18; 95% CI -0.34 to -0.01; P = 0.03). CONCLUSION: Exercise serves as an effective intervention to improve QoL and alleviate fatigue, insomnia, dyspnea, and physical and social functions for patients with advanced-stage cancer.

9.
Nat Biotechnol ; 37(9): 1038-1040, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31477924

RESUMO

We have developed a deep generative model, generative tensorial reinforcement learning (GENTRL), for de novo small-molecule design. GENTRL optimizes synthetic feasibility, novelty, and biological activity. We used GENTRL to discover potent inhibitors of discoidin domain receptor 1 (DDR1), a kinase target implicated in fibrosis and other diseases, in 21 days. Four compounds were active in biochemical assays, and two were validated in cell-based assays. One lead candidate was tested and demonstrated favorable pharmacokinetics in mice.


Assuntos
Aprendizado Profundo , Receptor com Domínio Discoidina 1/antagonistas & inibidores , Receptor com Domínio Discoidina 1/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Animais , Receptor com Domínio Discoidina 1/genética , Cães , Inibidores Enzimáticos , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Estrutura Molecular , Conformação Proteica , Ratos
11.
Eur J Pharm Sci ; 138: 105034, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382032

RESUMO

NLG919 is an effective small molecule inhibitor of indoleamine 2, 3-dioxygenase-1 (IDO-1) in anti-tumour immunotherapy, but the poor aqueous solubility limits its application for effective intravenous dosing. In this study a cyclodextrin (CD) complexation strategy has been systematically evaluated to achieve a simple and feasible method to prepare an NLG919 injectable formulation. From a series of CDs, HP-ß-CD proved to be the most conducive for NLG919 solubilization (approx 800-fold increase). Characterization studies using DSC, 1H NMR, XRPD and molecular simulation demonstrated that the NLG919/HP-ß-CD loading mechanism involved an increasing pH-dependent binding affinity. Importantly cell-based studies in vitro and anti-tumour activity in vivo demonstrated that the pharmacological activity of NLG919 as an IDO-1 inhibitor was not influenced by HP-ß-CD complexation. Furthermore, the combination of NLG919/HP-ß-CD with paclitaxel (PTX) significantly improved anti-tumour chemotherapy compared to PTX alone. In summary, NLG919/HP-ß-CD is shown to highly enhance the aqueous solubility of NLG919 with activity unaffected, greatly facilitating the intravenous use of this small molecule immunotherapeutic to improve the efficacy of PTX.

12.
Medicine (Baltimore) ; 98(34): e16964, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441901

RESUMO

BACKGROUND: Hysteroscopic procedures were widely applied but the clinical effects of antibiotic prophylaxis for these operations were not specifically addressed. In current study, we aimed to investigate the role of prophylactic antibiotics in hysteroscopic procedures by meta-analysis. METHODS: We conducted literature retrieval in electronic databases, including MEDLINE, EMBASE, and Cochrane Central, to identify relevant randomized controlled trials (RCTs) investigating the clinical effects of antibiotic prophylaxis for hysteroscopic procedures. The postoperative infection rate was selected for pooled estimation. The I index statistic was used to assess heterogeneity. Publication bias was evaluated using funnel plots and Egger test. Sensitivity analysis based on different subcategories was conducted to examine the stability of the main results. RESULTS: Four RCTs including 2221 patients were identified for the final quantitative analysis. Pooled estimation indicated no significant difference in infection rate between the antibiotic prophylaxis group and control group (test for OR: Z = 0.50, P = .616; 95% CI: 0.987-1.008). Sensitivity analysis based on surgical procedure, antibiotic application, follow-up time and administration time revealed similar results. CONCLUSION: Based on current objective evidence, we conclude that antibiotic prophylaxis exhibits no clinical benefit for hysteroscopic procedures. Therefore, it is not recommended. Meanwhile, more high-quality RCTs are needed to support our conclusion.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Histeroscopia/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos
13.
Int J Hematol ; 110(5): 575-583, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31440963

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by a dismal outcome. To enable better outcomes, it is necessary to develop individual therapies based on risk stratification. In the present study, we established two new comprehensive prognostic scoring systems (CPSS) for overall survival (OS) and relapse-free survival (RFS) using the Cox proportional hazards regression, CPSS integrated and weighted age, AML type, lactic dehydrogenase (LDH), ECOG score, cytogenetics, and gene mutations. We divided patients into three risk groups-low-, intermediate-, and high-risk-with 1-year OS rates of 100.0%, 82.9%, and 38.2%, respectively (p < 0.0001), and patients undergoing complete remission (CR) were also separated into low-risk, intermediate-risk, and high-risk groups, with 1-year RFS rates of 87.7%, 58.4%, and 30.2%, respectively (p < 0.0001). We conclude that CPSS that integrate clinical characteristics, cytogenetic abnormalities, and gene mutations may improve the stratification of AML patients.

14.
BMC Ophthalmol ; 19(1): 170, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382918

RESUMO

BACKGROUND: To assess bioactive transforming growth factor-ß2 (TGFß2) and secreted frizzled-related protein-1 (SFRP1) levels in aqueous humor (AH) of different types of glaucoma. METHODS: AH samples were obtained immediately before ophthalmic surgery with a 27-gauge needle attached to a microsyringe from 126 eyes (105 patients) divided into five groups: cataract (control), primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), primary angle-closure suspects (PACS), and acute angle-closure glaucoma (AACG). Bioactive TGFß2 and SFRP1 levels were assayed by ELISA. RESULTS: The concentration of TGFß2 in AH of POAG patients, but not CACG, PACS, or AACG patients, was significantly higher than control eyes. However, within the AACG group, although the TGFß2 levels in AH did not differ significantly from the control level when all AACG patients were grouped together, there were differences when the AACG patients were divided into high and normal intraocular pressure (IOP); TGFß2 of AACG patients with high IOP (> 21 mmHg) was significantly higher than those with normal IOP. AH levels of SFRP1 were not significantly different among the groups. However, a statistical significant, negative correlation between SFRP1 and IOP existed in the POAG group. POAG patients with high IOP had lower levels of SFRP1 than those with normal IOP. In contrast, a significant, positive correlation between SFRP1 level and IOP was detected in the AACG group. AACG patients with high IOP had a higher level of SFRP1 than those with normal IOP. Concentrations of TGFß2 and SFRP1 did not correlate significantly with each other, or with age. CONCLUSIONS: These results indicate that AH levels of TGFß2 and SFRP1 showed different profiles in different types of glaucomas.


Assuntos
Humor Aquoso/metabolismo , Glaucoma de Ângulo Fechado/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Pressão Intraocular/fisiologia , Proteínas/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Idoso , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Acta Paediatr ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393023

RESUMO

AIM: The aim of this study was to determine reference values for oxygen saturation (SpO2 ) in neonates at mild and moderate altitudes. METHODS: Our study included 41 097 consecutively born, asymptomatic neonates from 35 hospitals, located in Yunnan, China, with altitudes ranging from 267 to 2202 m. Pre-and post-ductal SpO2 of each neonate was measured at 24 hours of age and before hospital discharge. All study participants, according to the altitude of birth, were categorised into three groups: low (0-500 m), mild (500-1500 m) and moderate altitude (1500-2500 m). RESULTS: Every 1000-m increase in altitude was associated with a 1.54 per cent decrease in mean SpO2 . The means of pre-ductal SpO2 at low, mild and moderate groups were 97.9%, 96.4% and 95.5%, respectively. We used the 2.5th percentile of SpO2 distribution as the cut-off for neonatal SpO2 screening and defined new cut-off values of ≤93% for mild altitudes, ≤92% for moderate altitudes and no adjustment for low altitudes. CONCLUSION: We recommend revised cut-off values for neonatal SpO2 at mild and moderate altitudes and provide new values for paediatricians to refer to when screening neonates for severe congenital heart or lung diseases.

16.
Medicine (Baltimore) ; 98(26): e16241, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261586

RESUMO

BACKGROUND: The application of antibiotic prophylaxis for hepatectomy remains uncertain. This research aims to evaluate different antibiotic prophylaxis strategies for hepatectomy based on network meta-analysis. METHODS: Literature retrieval was conducted in globally recognized databases, namely, MEDLINE, EMBASE and Cochrane Central, to address relative randomized controlled trials (RCTs) investigating antibiotic prophylaxis strategies for hepatectomy. Relative parametric data, including surgical site infection (SSI), remote site infection (RSI) and total infection (TI), were quantitatively pooled and estimated based on the Bayesian theorem. The values of surface under the cumulative ranking curve (SUCRA) probabilities regarding each parameter were calculated and ranked. Node-splitting analysis was performed to test the inconsistency of the main results, and publication bias was assessed by examining the funnel plot symmetry. Additional pairwise meta-analyses were performed to validate the differences between respective strategies at the statistical level. RESULTS: After a detailed review, a total of 5 RCTs containing 4 different strategies were included for the network meta-analysis. The results indicated that the application of no antibiotics possessed the highest possibility of having the best clinical effects on SSI (SUCRA, 0.56), RSI (SUCRA, 0.46) and TI (SUCRA, 0.61). Moreover, node-splitting analysis and funnel plot symmetries illustrated no inconsistencies in the current study. Additional pairwise meta-analyses determined that additional and long-duration applications had no clinical benefit. CONCLUSION: Based on current evidence, we concluded that antibiotic prophylaxis did not reveal clinical benefit in hepatectomy. However, more relative trials and statistical evidence are still needed.


Assuntos
Antibioticoprofilaxia/métodos , Hepatectomia , Humanos , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
CNS Neurosci Ther ; 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31278861

RESUMO

AIMS: Cognitive impairment is a common symptom in the trajectory of Parkinson's disease (PD). However, the pathological underpinning is not fully known. We aimed to explore the critical structural alterations in the process of cognitive decline and its relationships with the dopaminergic deficit and the level of related cerebrospinal fluid (CSF) proteins. METHODS: Ninety-four patients with PD and 32 controls were included in this study. Neuropsychological tests were performed at baseline and after 28 months to identify which patients had normal cognition and which ones developed PD-MCI after follow-up ("converters"). Gray matter atrophy was assessed in cross-sectional and longitudinal analyses, respectively. The associations between altered GMV with dopamine transporter (DAT) results and the level of CSF proteins were assessed. RESULTS: Among the 94 patients with normal cognition at baseline, 24 (mean age, 63.1 years) developed PD-MCI after 28 months of follow-up, and 70 (mean age, 62.3 years) remained nonconverters. The converters showed significant right temporal atrophy at baseline and extensive atrophy in temporal lobe at follow-up. Progressive bilateral frontal lobe atrophy was found in the converters. Baseline right temporal atrophy was correlated with the striatal dopaminergic degeneration in the converters. No correlation was found between the right temporal atrophy and the alterations of CSF proteins. CONCLUSION: Early atrophy in temporal lobes and progressive atrophy in frontal lobes might be a biomarker for developing multidomain impairment of cognition and converting to PD-MCI. Furthermore, cognition-related temporal atrophy might be associated with dopaminergic deficit reflected by DAT scan but independent of CSF proteins in patients with PD who convert to PD-MCI.

18.
Am J Hematol ; 94(10): 1113-1122, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321805

RESUMO

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD- CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD- CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD- CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

19.
Int Heart J ; 60(4): 919-923, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31257330

RESUMO

Tenascin-C (TNC) is involved in aortic disease pathophysiology. This study aims to evaluate TNC's value for predicting in-hospital death in acute aortic dissection (AD).We prospectively enrolled consecutive patients with suspected acute AD within 48 hours from symptom onset. Serum TNC and C-reactive protein (CRP) levels were examined on admission. Their baseline clinical characteristics and serum D-Dimer (DD) were collected. The endpoint was in-hospital death from AD.In the study cohort,78 survivors and 31 non-survivors with acute AD were enrolled. Compared to survivors, elevated median levels of serum TNC (141.10 pg/mL versus 75.30 pg/mL, P < 0.001), DD (8.74 µg/mL versus 4.58 µg/mL, P < 0.001), and CRP (19.20 mg/L versus 13.40 mg/L, P < 0.001) were found in non-survivors. Multiple logistic regressions revealed TNC, DD, and CRP were independent predictors of in-hospital death from acute AD. The OR and 95% CI were 1.038, 1.017-1.055; 1.084, 1.009-1.165 and 1.386, 1.107-1.643, respectively. Furthermore, TNC's sensitivity and specificity in predicting in-hospital death in acute AD were 83.87% and 83.33%. The combination of TNC and DD can improve the sensitivity and specificity to 90.30% and 88.46%.TNC is a valuable biomarker for predicting in-hospital death from acute AD. The combination of TNC and DD can improve predictions of in-hospital death from acute AD.


Assuntos
Aneurisma Dissecante/mortalidade , Aneurisma da Aorta Torácica/mortalidade , Tenascina/sangue , Doença Aguda , Aneurisma Dissecante/sangue , Aneurisma da Aorta Torácica/sangue , Biomarcadores/sangue , China/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Taxa de Sobrevida/tendências
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 991-994, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204966

RESUMO

OBJECTIVE: To assess the analgesic efficacy of compound lidocaine cream in lumbar puncture of children with leukemia and lymphoma. METHODS: 312 leukemia and lymphoma children necessarily undergone lumbar puncture were divided into compound lidocaine cream (cream) group and compound lidocaine injection (injation) group as control with 156 cases respectively according to the will of inpatient children and their family. For cream group, compound lidocaine cream was smeared on the skin around the lumbar puncture point evenly and covered with sterile and transparent dressing for about one hour before lumbar puncture. Then the cream and transparent dressing were removed and lumbar puncture was performed after regular disinfection. For control group, 2% compound lidocaine was injected as local anesthesia before lumbar puncture. The extent of pain was evaluated by Wong-Baker Faces Pain Rating Scale and FLACC Scale as well as children's physiological indexes (heart rate, breathing, blood pressure). The lumbar puncture success rate and the discomfortableness as well as family satisfaction were recorded by special person. RESULTS: Compared with control group, the incidence of pain and discomfortableness in cream group significantly reduced, and the family satisfaction significantly increased (P<0.05). There were obviously differences in the physiological indexes (heart rate, breathing, systolic blood pressure) before and after lumbar puncture in control group (P<0.05). However, the physiological indexes in cream group had no obvious change. There was no difference on the success rate of lumbar puncture between the two methods of anesthesia. CONCLUSION: Compound lidocaine cream has significantly analgesic effect which can relieving pain caused by lumbar puncture for children.


Assuntos
Neoplasias Hematológicas , Analgésicos , Anestésicos Locais , Criança , Humanos , Lidocaína , Combinação Lidocaína e Prilocaína , Punção Espinal
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