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1.
J Immunol ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893171

RESUMO

NLRP3 inflammasome plays an important role in innate immune system through recognizing pathogenic microorganisms and danger-associated molecules. Deubiquitination of NLRP3 has been shown to be essential for its activation, yet the functions of Ubc13, the K63-linked specific ubiquitin-conjugating enzyme E2, in NLRP3 inflammasome activation are not known. In this study, we found that in mouse macrophages, Ubc13 knockdown or knockout dramatically impaired NLRP3 inflammasome activation. Catalytic activity is required for Ubc13 to control NLRP3 activation, and Ubc13 pharmacological inhibitor significantly attenuates NLRP3 inflammasome activation. Mechanistically, Ubc13 associates with NLRP3 and promotes its K63-linked polyubiquitination. Through mass spectrum and biochemical analysis, we identified lysine 565 and lysine 687 as theK63-linked polyubiquitination sites of NLRP3. Collectively, our data suggest that Ubc13 potentiates NLRP3 inflammasome activation via promoting site-specific K63-linked ubiquitination of NLRP3. Our study sheds light on mechanisms of NLRP3 inflammasome activation and identifies that targeting Ubc13 could be an effective therapeutic strategy for treating aberrant NLRP3 inflammasome activation-induced pathogenesis.

2.
Ecotoxicol Environ Saf ; 216: 112188, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33862439

RESUMO

The contamination of Cd and Cu in soil is a great threat to medicinal plant. Ground granulated blast furnace slag (GGBS) is a potential soil pH adjuster to reduce metal toxicity. However, how GGBS affects the quality and yield of herbal plants under the stress of Cd and Cu is not clear. This study aims to investigate the quality and yield of a medicinal plant (Pseudostellaria heterophylla) responding to GGBS treatment in Cd and Cu contaminated soil. GGBS with three mass percentages (0%, 3%, 5%) was added into contaminated lateritic soils for planting. Each condition had 21 replicated seedlings. The concentrations of Cd and Cu in plant, amounts of active ingredients (polysaccarides and saponins) in medicinal organ, and tuber properties were measured after harvest. The results showed that under 3% and 5% GGBS treatments, Cd and Cu accumulations in all plant organs (leaf, stem, root and tuber) were reduced by 69.4-86.0% and 10.3-30.1%, respectively. They were below the permissible limits (World Health Organization, WHO). Even though the concentrations of active ingredients in P. heterophylla tuber decreased by up to 35.8%, they still met Hong Kong Chinese Materia Medica standard. Besides, the biomass of root tuber increased by 9.8% and 46%, due to 3% and 5% GGBS treatments, respectively. The recommended 5% GGBS treatment in practice can balance the reduction of active ingredients and the increase of plant yield when minimizing Cd and Cu accumulation in tuber.

3.
Nephron ; : 1-12, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33915538

RESUMO

BACKGROUND: Growing data indicate a higher prevalence of cerebrovascular diseases in patients with ESRD. Cerebral small-vessel disease (CSVD) is an important risk factor of stroke and dementia. A comprehensive assessment of CSVD in a dialysis population is needed. METHODS: In this retrospective cross-sectional study, we enrolled 179 dialysis patients and 351 controls matched by sex and age with normal serum creatinine. The presence and locations of 3 main features of CSVD in dialysis patients, including lacunes, cerebral microbleeds (CMBs), and white matter hyperintensities (WMHs), were evaluated with brain magnetic resonance imaging and compared with controls. Univariate and multivariate analyses were performed to identify risk factors. RESULTS: Compared with controls, the prevalence of CSVD was significantly increased in dialysis patients (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.26-5.62). Among them, risks of CMBs and WMHs were increased in dialysis (OR 4.01, 95% CI 1.78-9.42; 3.91, 95% CI 1.67-9.15), except for lacunes. The age of subjects with CSVD detected was significantly younger in the dialysis group (p = 0.002). Unlike controls, basal ganglia were most affected by lacunes and CMBs in dialysis patients. In dialysis patients, multivariate analysis further revealed that aging, smoking, and hyperlipidemia were significantly associated with CSVD, while dialysis modality was not significant. CONCLUSION: We demonstrated a higher prevalence and early-onset tendency of CSVD in dialysis patients, especially for CMBs and WMHs. Dialysis patients showed different patterns and associated factors for CSVD.

4.
Stroke Vasc Neurol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903177

RESUMO

BACKGROUND AND PURPOSE: This study aimed to investigate the association of metabolic syndrome (MetS) with both intracranial atherosclerotic stenosis (ICAS) and imaging markers of cerebral small vessel disease (CSVD) in a community-based sample. METHODS: This study included 943 participants (aged 55.6±9.2 years, 36.1% male) from the community-based Shunyi cohort study. MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score. ICAS was evaluated by brain magnetic resonance angiography. The MRI markers of CSVD, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS), were assessed. Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers. RESULTS: We found that risk of ICAS (OR=1.75, 95% CI 1.39 to 2.21, p<0.001) increased consistently with MetS severity. MetS severity was significantly associated with higher risks of WMH volume (ß=0.11, 95% CI 0.01 to 0.20, p=0.02) and lacunes (OR=1.28, 95% CI 1.03 to 1.59, p=0.03) but not the presence of CMBs (OR=0.93, 95% CI 0.74 to 1.16, p=0.51) and PVS severity (EPVS in basal ganglia: OR=0.96, 95% CI 0.84 to 1.09, p=0.51 and EPVS in white matter: OR=1.09, 95% CI 0.96 to 1.23, p=0.21). CONCLUSIONS: Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery, whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

5.
Zhongguo Fei Ai Za Zhi ; 24(3): 141-160, 2021 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-33819964

RESUMO

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

6.
Theranostics ; 11(8): 3981-3995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664876

RESUMO

Salmonella typhimurium (S. typhimurium) infection of macrophage induces NLRC4 inflammasome-mediated production of the pro-inflammatory cytokines IL-1ß. Post-translational modifications on NLRC4 are critical for its activation. Sirtuin3 (SIRT3) is the most thoroughly studied mitochondrial nicotinamide adenine dinucleotide (NAD+) -dependent deacetylase. We wondered whether SIRT3 mediated-deacetylation could take part in NLRC4 inflammasome activation. Methods: We initially tested IL-1ß production and pyroptosis after cytosolic transfection of flagellin or S. typhimurium infection in wild type and SIRT3-deficient primary peritoneal macrophages via immunoblotting and ELISA assay. These results were confirmed in SIRT3-deficient immortalized bone marrow derived macrophages (iBMDMs) which were generated by CRISPR-Cas9 technology. In addition, in vivo experiments were conducted to confirm the role of SIRT3 in S. typhimurium-induced cytokines production. Then NLRC4 assembly was analyzed by immune-fluorescence assay and ASC oligomerization assay. Immunoblotting, ELISA and flow cytometry were performed to clarify the role of SIRT3 in NLRP3 and AIM2 inflammasomes activation. To further investigate the mechanism of SIRT3 in NLRC4 activation, co-immunoprecipitation (Co-IP), we did immunoblot, cellular fractionation and in-vitro deacetylation assay. Finally, to clarify the acetylation sites of NLRC4, we performed liquid chromatography-mass spectrometry (LC-MS) and immunoblotting analysis. Results: SIRT3 deficiency led to significantly impaired NLRC4 inflammasome activation and pyroptosis both in vitro and in vivo. Furthermore, SIRT3 promotes NLRC4 inflammasome assembly by inducing more ASC speck formation and ASC oligomerization. However, SIRT3 is dispensable for NLRP3 and AIM2 inflammasome activation. Moreover, SIRT3 interacts with and deacetylates NLRC4 to promote its activation. Finally, we proved that deacetylation of NLRC4 at Lys71 or Lys272 could promote its activation. Conclusions: Our study reveals that SIRT3 mediated-deacetylation of NLRC4 is pivotal for NLRC4 activation and the acetylation switch of NLRC4 may aid the clearance of S. typhimurium infection.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33682554

RESUMO

Objective: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.Results: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.Conclusions: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.

8.
Medicine (Baltimore) ; 100(11): e24909, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725963

RESUMO

INTRODUCTION: Botulinum toxin (BTX) injection is a widely used treatment option for dysphagia associated with cricopharyngeal (CP) muscle achalasia, but uniform standards and protocols for administration techniques and injection sites are still lacking. This case study suggests that a unique administration technique involving a combination of ultrasound, electromyography, and balloon guidance for injecting the CP muscle can reduce inadvertent migration of BTX to non-injected tissues and increase the effectiveness and safety of BTX treatment. PATIENT CONCERNS: We describe the case of a 74-year-old man who could not swallow food or saliva for 8 months. DIAGNOSIS: The patient showed signs of true bulbar paralysis, including dizziness, hoarseness, and dysphagia. The fiberoptic endoscopic evaluation of swallowing showed massive mucilage secretion and residual materials in the postcricoid region and aspiration when swallowing 1 ml of yogurt. The video fluoroscopic swallowing study showed profoundly limited epiglottic folding and CP muscle non-relaxation, despite several unsuccessful swallow attempts. INTERVENTIONS: To manage insufficient relaxation opening of the CP muscle, BTX injection was performed using ultrasound, electromyography, and balloon catheter guidance. The narrow CP muscle situated above the balloon was identified as the target of injection by ultrasound. OUTCOMES: The patient was able to eat a soft diet. The follow-up fibrotic endoscopic swallowing study demonstrated a reduction in the amount of pharyngeal residue. The video fluoroscopic swallowing study showed that CP muscle relaxation was significantly enhanced and no penetration was shown. CONCLUSION: The unique administration technique with triple guidance holds several advantages, suggesting that it may be a promising treatment for CP muscle achalasia.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Cateterismo/métodos , Sistemas de Liberação de Medicamentos/métodos , Eletromiografia/métodos , Acalasia Esofágica/tratamento farmacológico , Ultrassonografia/métodos , Idoso , Deglutição , Acalasia Esofágica/fisiopatologia , Esfíncter Esofágico Superior/fisiopatologia , Humanos , Injeções , Masculino , Resultado do Tratamento
9.
Sheng Wu Gong Cheng Xue Bao ; 37(3): 1017-1031, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33783165

RESUMO

Cyanobacteria is one of the promising microbial chassis in synthetic biology, which serves as a typical host for light-driven production. With the gradual depletion of fossil resources and intensification of global warming, the research on cyanobacterial cell factory using CO2 as carbon resource is ushering in a new wave. For a long time, research focus on cyanobacterial cell factory has mainly been the production of energy products, such as liquid fuels and hydrogen. One of the critical bottlenecks occurring in cyanobacterial cell factory is the poor economic performance, which is mainly caused by the inherent inefficiency of cyanobacteria. The problem is particularly prominent for these extremely cost-sensitive energy products. As an indispensable basis for modern industry, polymer monomers belong to the bulk chemicals with high added value. Therefore, increasing attention has been focused on polymer monomers which are superior in overcoming the economic barrier in commercialization of cyanobacterial cell factories. Here, we systematically review the progress on the production of polymer monomers using cyanobacteria, including the strategies for improving production, and the related technologies for the application of this important microbial cell factory. Finally, we summarize several issues in cyanobacterial synthetic biology and proposed future developing trends in this field.


Assuntos
Cianobactérias , Polímeros , Substâncias Macromoleculares , Biologia Sintética
10.
Thorac Cancer ; 12(9): 1469-1488, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33787090

RESUMO

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

11.
Thorac Cancer ; 12(8): 1244-1247, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33655632

RESUMO

Tyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2) have been extensively reported in non-small cell lung cancer (NSCLC). Nevertheless, the clinical significance of non-TKD mutations remains unknown. To date, no clinical trials have revealed that tyrosine kinase inhibitors are effective in NSCLC patients with non-TKD ERBB2 mutations. Here we report a patient with advanced lung adenocarcinoma harboring non-TKD mutation of ERBB2, S335C, without other actionable alterations benefited from pyrotinib. After first-line treatment of pyrotinib monotherapy, a pan-HER inhibitor, the patient achieved a durable partial response with good tolerance. This case powerfully illustrates that pyrotinib might be a promising first-line treatment strategy for NSCLC patients with non-TKD mutation of ERBB2.

12.
Cancer Biol Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710811

RESUMO

OBJECTIVE: Death receptor 4 (DR4; TRAIL-R1) critically mediates extrinsic apoptosis cascades via binding to TNF-related apoptosis-inducing ligand (TRAIL). However, intrinsic and/or acquired resistance are observed in the clinical application of TRAIL. The aim of this study was to investigate the function and molecular mechanism of CD13 in the TRAIL/DR4 pathway against tumor cells, and provide a new strategy for improving therapeutic efficacy or overcoming TRAIL-resistance. METHODS: TRAIL protein was expressed as a secretory protein in a Pichia pastoris expression system and was isolated and purified by affinity chromatography. The cell viability and apoptosis were evaluated with MTT (thiazolyl blue tetrazolium bromide) assays and annexin V-FITC/PI staining with flow cytometry analysis, respectively. Western blot analysis was used to detect the levels of the indicated proteins in tumor cells. DR4 degradation or stability was examined with cycloheximide chase assays, and cell surface DR4 was assessed with flow cytometric analysis after staining with a FITC-conjugated antibody. The effects of cell migration were determined with Transwell and gelatin zymography assays. A xenograft nude mouse model was used to detect the anti-tumor effect in vivo, and the proliferation in tumor tissues was examined with immunohistochemical staining. RESULTS: CD13 inhibition potently sensitized tumor cells to TRAIL-induced killing, including proliferation inhibition, increased apoptosis, and migration suppression. In addition, the inhibition of CD13 elevated both total cellular expression and cell surface DR4 through stabilizing DR4 by suppressing its degradation. DR4 siRNA attenuated the enhanced anti-tumor effects of TRAIL plus CD13 inhibition. Interestingly, these phenomena were p-ERK1/2 independent, although p-ERK1/2 down-regulation was tightly correlated with the cooperation of TRAIL and CD13 inhibition. Moreover, a synergistic decrease in tumor growth was surprisingly achieved in the xenograft model by treatment of TRAIL with a CD13 inhibitor (**P < 0.01, CDI = 0.47). CONCLUSIONS: CD13 inhibition cooperates with TRAIL in enhancing DR4-mediated cell death, through the up-regulation and stabilization of DR4 in a p-ERK1/2-independent manner. Thus CD13 inhibition has emerged as an effective strategy for TRAIL/DR4-based therapy.

13.
Chin Med J (Engl) ; 134(6): 646-654, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33625036

RESUMO

ABSTRACT: Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a rare but increasingly recognized subtype of CAA. CAA-RI consists of two subtypes: inflammatory cerebral amyloid angiopathy and amyloid ß (Aß)-related angiitis. Acute or subacute onset of cognitive decline or behavioral changes is the most common symptom of CAA-RI. Rapid progressive dementia, headache, seizures, or focal neurological deficits, with patchy or confluent hyperintensity on T2 or fluid-attenuated inversion recovery sequences and evidence of strictly lobar microbleeds or cortical superficial siderosis on susceptibility-weighted imaging imply CAA-RI. The gold standard for diagnosis is autopsy or brain biopsy. However, biopsy is invasive; consequently, most clinically diagnosed cases have been based on clinical and radiological data. Other diagnostic indexes include the apolipoprotein E ε4 allele, Aß and anti-Aß antibodies in cerebral spinal fluid and amyloid positron emission tomography. Many diseases with similar clinical manifestations should be carefully ruled out. Immunosuppressive therapy is effective both during initial presentation and in relapses. The use of glucocorticoids and immunosuppressants improves prognosis. This article reviews the pathology and pathogenesis, clinical and imaging manifestations, diagnostic criteria, treatment, and prognosis of CAA-RI, and highlights unsolved problems in the existing research.

14.
J Alzheimers Dis ; 80(2): 567-576, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33579854

RESUMO

BACKGROUND: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. OBJECTIVE: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. METHODS: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. RESULTS: Increased baPWV was significantly associated with lower mean global fractional anisotropy (ß= -0.118, p < 0.001), higher mean diffusivity (ß= 0.161, p < 0.001), axial diffusivity (ß= 0.160, p < 0.001), and radial diffusivity (ß= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (ß= -0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. CONCLUSION: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

15.
Clin Respir J ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565707

RESUMO

INTRODUCTION: Albumin-to-Alkaline Phosphatase Ratio (AAPR), a novel developed prognostic index for cancers. Chemotherapy was the only method for driver mutation-negative advanced non-small cell lung cancer (DANSCLC). OBJECTIVES: To evaluate the clinical significance of AAPR in these patients. METHODS: We retrospectively reviewed 167 DANSCLCs and 58 healthy controls. Associations of clinicopathological characteristics and survival analysis were conducted. RESULTS: Significantly decreased AAPR level was uncovered in DANSCLC patients compared to healthy controls. The correlation analysis revealed that the low AAPR level in DANSCLCs was correlated with poor differentiation (P = .024). Cox regression analysis showed that N stage, M stage, and different levels of AAPR were the independent risk factors of PFS and OS. The median PFS and OS survival ratio in patients with high and low AAPR level was, respectively, 17 months and 8 months, and 23 months and 13 months. The AUC of AAPR for both PFS and OS were higher than that of albumin and alkaline phosphatase (p < 0.05). The low AAPR was associated with much shorter PFS and OS than the high AAPR (mPFS: 8 vs. 25 months; mOS: 12 vs. 36 months). In the AP cohort, the low AAPR group experienced significantly shorter PFS and OS than the high AAPR (mPFS: 7 vs. 25 months; mOS: 12 vs. 36 months). Meanwhile, there was no significance in lung squamous cell carcinoma (LUSC) patients and GP regimens cohort. CONCLUSION: AAPR significantly decreased in patients with DANSCLC, and it affects the prognosis of patients with DANSCLC and is a biomarker for DANSCLCs prognosis and treatment choice.

16.
Inorg Chem ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615779

RESUMO

Although many strategies have been used to help design effective near-infrared (NIR) luminescent materials, it is still a huge challenge to realize long-wavelength NIR luminescence of diimineplatinum(II) complexes in the solid state. Herein, we have successfully achieved long-wavelength NIR luminescence of a family of diimineplatinum(II) complexes based on a new strategy that combines a one-dimensional (1D) "Pt wire" structure with the electronic effect of the substituent. The structures of six solvated diimineplatinum(II) complexes based on 4,4-dichloro-2,2'-bipyridine or 4,4-dibromo-2,2'-bipyridine and 4-substituted phenylacetylene ligands have been determined, namely, 1·1/2toluene, 2·1/2THF, 3·1/8toluene, 4·1/2THF, 5·1/8CH2Cl2, and 6·1/4toluene. All of them crystallize in the monoclinic space group C2/c or C2/m and stack in the 1D "Pt wire" structure. In the solid state, six complexes exhibited unusual long-wavelength metal-metal-to-ligand charge-transfer luminescence that peaked at 984, 1044, 972, 990, 1022, and 935 nm, respectively. Interestingly, 2·1/2THF has the shortest Pt···Pt distance and the longest emission wavelength among the six complexes. As far as we know, the luminescence of 2·1/2THF at 1044 nm is the longest emission wavelength among known diimineplatinum(II) complexes. Systematic studies revealed that good molecular planarity, suitable substituent position, weak hydrogen-bond-forming ability of the substituents, appropriate molecular bending, and weakening of the interaction between solvated molecules and platinum molecules are conducive to the construction of a 1D "Pt wire" structure of the diimineplatinum(II) complex. Furthermore, the emission energy of the complex is mainly determined by the strength of the Pt-Pt interaction and electronic effect of the substituent.

17.
Clin Cardiol ; 44(3): 357-363, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33410147

RESUMO

BACKGROUND: Myeloperoxidase (MPO) secreted by neutrophils is the enzyme that kills bacteria and other pathogens. Acute myocardial infarction (AMI) is usually caused by thrombosis in response to vulnerable plaque rupture. Circulating MPO was found to be associated with increased mortality in AMI patients. However, the relationship between MPO in thrombi and the prognosis of AMI patients remains unknown. HYPOTHESIS: MPO expression in thrombi is associated with the prognosis of patients who underwent primary percutaneous coronary intervention (PCI) after AMI. METHODS: This study included 41 consecutive patients with acute ST-elevation myocardial infarction, who successfully underwent primary PCI, during which we collected thrombi remaining in the culprit artery using aspiration catheters. These thrombus samples were fixed, and immunohistochemical staining against MPO and heme oxygenase-1 (HO-1) was conducted. Enrolled patients were divided into two groups based on the induction of thrombotic MPO, which was quantified using Image J software. METHODS: We observed that increased MPO was associated with lower left ventricular ejection fraction (LVEF) and worse LV remodeling in AMI patients. Instead, patients with decreased thrombotic MPO induction had a considerable improvement in LVEF 1 month after discharge (54.4 ± 2.0% vs. 61.1 ± 2.3%, p < 0.01). In the MPO group, a reduction in the thrombotic HO-1 level contributed to the development of adverse LV remodeling. Logistic regression showed that MPO was a considerable risk factor for adverse LV remodeling (adjusted OR 3.70, p < 0.05). CONCLUSION: MPO expression in thrombi is associated with reduced LVEF and deteriorated LV remodeling in AMI patients, which may be due to HO-1 suppression in thrombi.

18.
J Stroke Cerebrovasc Dis ; 30(4): 105612, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33493876

RESUMO

BACKGROUND: Following stroke, individuals commonly experience persisting loss of function. Whilst long-term care should involve continued support for ongoing stroke sequelae, this is often not routinely practiced globally. The Post Stroke Checklist was designed to standardise the process of detecting persisting treatable problems following stroke. AIMS: This cross-sectional study aimed to identify the long-term problems reported in Australian and Chinese participants at six months post stroke using the Post Stroke Checklist. It also aimed to provide global insight into poststroke sequelae by comparing the study results to previously published studies which administered the Post Stroke Checklist in other countries. METHODS: Participants were recruited from two hospitals in Australia and one hospital in China. The Post Stroke Checklist consists of 11 problem areas commonly experienced after stroke. This study follows a sequence of studies which have applied the checklist to monitor long-term outcomes after stroke in Germany, Italy, Singapore, Sweden and the United Kingdom. RESULTS: Comparisons between Australia (n = 112) and China (n = 97) demonstrated statistically significant differences on the Post Stroke Checklist items. Across all seven countries, collectively the most common persisting difficulties post-stroke related to: cognition, life after stroke, mood, mobility and activities of daily living. An analysis of means procedure compared individual countries for each checklist item against the overall group mean (all countries combined). CONCLUSIONS: Globally, individuals report persisting functional difficulties following stroke. There appear to be differences in the proportions affected across the various countries, and healthcare systems may benefit from geographically tailoring post-stroke care.


Assuntos
Atividades Cotidianas , Lista de Checagem , Acidente Vascular Cerebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Austrália , China , Estudos Transversais , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Valor Preditivo dos Testes , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Reabilitação do Acidente Vascular Cerebral , Fatores de Tempo , Resultado do Tratamento
19.
Sci China Life Sci ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33439457

RESUMO

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

20.
BMC Neurol ; 21(1): 37, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504323

RESUMO

BACKGROUND: Manifestations of intractable hyponatremia and hypokalemia in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy have been rarely reported. CASE PRESENTATION: A 75-year-old male patient presented as the case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and intractable hypokalemia, showed fever, fatigue, and mental disorders. Signs and symptoms of meningoencephalitis, ataxia, and cognitive abnormalities. Magnetic resonance imaging (MRI) revealed multiple white matter lesions of the central nervous system. He had GFAP-IgG in the cerebrospinal fluid (CSF). After treatment with corticosteroids, his symptoms were alleviated gradually, and the level of electrolytes was normal. However, head contrast-enhanced MRI + susceptibility-weighted imaging (SWI) showed a wide afflicted region, and the serum GFAP-IgG turned positive. Considering the relapse of the disease, ha was treated with immunoglobulin and mycophenolate mofetil (MMF) to stabilize his condition. CONCLUSION: This case showed a rare disease with uncommon manifestations, suggesting that careful examination and timely diagnosis are essential for disease management and satisfactory prognosis.


Assuntos
Corticosteroides/uso terapêutico , Astrócitos/patologia , Proteína Glial Fibrilar Ácida/imunologia , Doenças do Sistema Nervoso/tratamento farmacológico , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/líquido cefalorraquidiano , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imagem por Ressonância Magnética , Masculino , Meningoencefalite/imunologia , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/patologia , Doenças Raras
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