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1.
J Genomics ; 10: 8-15, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976226

RESUMO

Wheat (Triticum aestivum L.) flour mixing properties are essential quality parameters in the dough development process. Limited research on superior alleles for mixing properties has restricted their molecular improvement, and other factors related to the complex traits have been ignored. A molecular map of 9576 polymorphic markers in the RIL population (F8:9) (Shannong01-35/Gaocheng9411) was constructed to evaluate mixing property effects in three environments. The parents were selected with markedly distinct high-molecular-weight glutenin subunits (HMW-GS). This study not only evaluated mixing properties using conventional unconditional QTL mapping but also evaluated the relationships between protein-related traits using conditional QTL mapping. The analyses identified most additive QTLs for major mixing properties on chromosomes 1A, 1B, and 1D. Two major loci (1A.1-15 and 1D-1) associated with mixing properties have confirmed the important contributions of Glu-A1 and Glu-D1 to wheat quality at the QTL level, which were mainly affected by the gluten index. Another important locus, 1B.1-24 (associated with midline peak value and midline peak width, with high phenotypic variations explained), might represent a new variation distinct from Glu-B1. The favored alleles came from Gaocheng9411. Several mixing properties shared the same QTLs (1B.1-6 and 1A.1-15), indicating tight linkage or pleiotropism. Genotype-by-environment (G×E) interactions were also investigated in the present study. The QTL results in our study may improve our understanding of the genetic interrelationships between mixing properties and protein-related traits.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34986101

RESUMO

Robust and efficient vehicle detection is an important task of environment perception of intelligent vehicles, which directly affects the behavior decision-making and motion planning of intelligent vehicles. Due to the rapid development of sensor and computer technology, the algorithm and technology of vehicle detection have been updated rapidly. But, there are few reviews on vehicle detection of intelligent vehicles, especially covering all kinds of sensors and algorithms in recent years. This article presents a comprehensive review of vehicle detection approaches and their applications in intelligent vehicle systems to analyze the development of vehicle detection, with a specific focus on sensor types and algorithm classification. First, more than 300 research contributions are summarized in this review, including all kinds of vehicle detection sensors (machine vision, millimeter-wave radar, lidar, and multisensor fusion), and the performance of the classic and latest algorithms was compared in detail. Then, the application scenarios of vehicle detection with different sensors and algorithms were analyzed according to their performance and applicability. Moreover, we also systematically summarized the methods of vehicle detection in adverse weather. Finally, the remaining challenges and future research trends were analyzed according to the development of intelligent vehicle sensors and algorithms.

3.
J Hazard Mater ; 423(Pt B): 127137, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34560486

RESUMO

Most natural polymers exhibit limited functional groups, which is not favourable for the adsorption of various ions and their utilisation. To overcome this drawback, a novel in-situ-doped nano-calcium carbonate (CaCO3) chitin hydrogel was synthesised as an efficient adsorbent for Cu (II) and Cd (II) ions. Scanning electron microscopy and Brunauer-Emmett-Teller results revealed that the synthesised CaCO3/chitin hydrogel exhibited loose macropores and mesopores. Subsequently, Fourier transform infrared, Raman, and X-ray diffraction characterisation characterisation proved that chitin was successfully doped with nano-CaCO3. The mechanical properties of CaCO3/chitin hydrogel were superior to those of the unmodified chitin hydrogel and could efficiently adsorb Cu (II) and Cd (II) ions in water. The effect of pH, initial concentration, adsorbent dosage, and temperature was assessed to determine the adsorption properties of the hydrogel. Under suitable experimental conditions, the maximum adsorption rate of the CaCO3/chitin hydrogel was approximately 96%. The time-dependent adsorption kinetics followed a quasi-second order model, and the adsorption process followed the Langmuir model. The maximum adsorption capacities of Cu (II) and Cd (II) according to the Langmuir curve were 194.61 and 191.58 mg/g, respectively. Compared with the binary competitive system, the material exhibited a specific selectivity to the adsorption of Cu (II). X-ray photoelectron spectroscopy (XPS) revealed that nitrogen and oxygen atoms were involved in chelation with the metal ions. The successful compounding of calcium carbonate nanoparticles provided more active adsorption sites for the gel. The novel material exhibited excellent adsorption effects on Cu (II) and Cd (II) ions when applied to a water sample. Thus, the novel material exhibits excellent potential for application. The Cu (II) and Cd (II)ion removal efficiencies after five successive adsorption cycles were higher than 90%, which indicated that the composite material exhibited excellent stability and reproducibility.


Assuntos
Cádmio , Poluentes Químicos da Água , Adsorção , Carbonato de Cálcio , Quitina , Cobre , Hidrogéis , Concentração de Íons de Hidrogênio , Íons , Cinética , Reprodutibilidade dos Testes , Poluentes Químicos da Água/análise
4.
J Colloid Interface Sci ; 607(Pt 2): 1491-1499, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34587529

RESUMO

HYPOTHESIS: Synergistic stabilization of high internal phase Pickering emulsions (HIPPEs) by food-grade colloidal particles are necessary for food, pharmaceuticals or cosmetics owing to their biocompatibility and multi-functionality. By tuning the interfacial structure of adsorbed binary particles, the HIPPE may exhibit extraordinary characteristics compared to conventional all-natural HIPPEs solely stabilized by single-component particle or composite particle, which should have potential applications in varies fields. EXPERIMENTS: HIPPEs were prepared by using zein protein nanoparticles (ZNPs) and starch nanocrystals (SNCs) as stabilizers. We systematically investigated the effect of particle concentration and internal phase fraction on HIPPEs morphology, stability and rheological behaviors. Further, the stabilization mechanism as well as potential applications were demonstrated. FINDINGS: HIPPEs were prepared with excellent stability against centrifugation and high temperature (50 °C). Our result indicates the successful construction of unique bilayer interfacial structures consisting of inner ZNPs layer and outer SNCs layer. Since SNCs could gelatinize at 50 °C, dense shells can form around droplets afterwards. Such thermally responsive interfacial structures can be used to protect hydrophobic bioactive substances at higher temperatures while still allowing controlled release at certain conditions. Furthermore, with high internal phase fraction, HIPPEs can possibly replace mayonnaise and salad dressing on the market due to comparable appearance and properties. Following the removal of inner oil, porous materials can be further fabricated, which have potential applications in environmental protection or tissue engineering.


Assuntos
Nanopartículas , Zeína , Emulsões , Tamanho da Partícula , Água
5.
Stem Cells Dev ; 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34913751

RESUMO

Mesenchymal stem cells (MSCs) have recently emerged as an important candidate for cell therapy and tissue regeneration. However, some limitations in translational research and therapies still exist, such as insufficient cell supply, inadequate differentiation potential, and decreased immune capacity, all of which result from replicative senescence during long-term in vitro culture. In vitro, stem cells lack a protective microenvironment owing to the absence of physical and biochemical cues compared with the in vivo niche, which provides dynamic physicochemical and biological cues. This difference results in accelerated aging after long-term in vitro culture. Therefore, it remains a great challenge to delay replicative senescence in culture. Constructing a microenvironment to delay replicative senescence of MSCs by maintaining their phenotypes, properties, and functions is a feasible strategy to solve this problem, and has made measurable progress both in preclinical studies and in clinical trials. Here, we review the current knowledge on the characteristics of senescent MSCs, explore the molecular mechanisms of MSCs senescence, describe the niche of MSCs, and discuss some current microenvironment strategies to delay MSCs replicative senescence that can broaden their range of therapeutic applications.

6.
Phytomedicine ; 96: 153887, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34936968

RESUMO

BACKGROUND: Collective evidences have indicated that intracellular accumulation of hyperphosphorylated tau forms neurofibrillary tangles in the brain, which impairs memory, cognition and affects social activities in Alzheimer's disease (AD). PURPOSE: To investigate the tau-reducing, and memory-enhancing properties of protopine (PRO), a natural alkaloid isolated from Chinese herbal medicine Corydalis yanhusuo (Yanhusuo in Chinese). STUDY DESIGN: By using Histone deacetylase 6 (HDAC6) profiling and immunoprecipitation assays, we assessed that PRO mediated the heat shock protein 90 (HSP90) chaperonic activities for the degradation of pathological tau in AD cell culture models. To study the efficacy of PRO in vivo, we employed 3xTg-AD and P301S tau mice models. METHODS: Liquid chromatography/quadrupole time-of-flight mass spectrometry was used to analyze the pharmacokinetic profile of PRO. Seven-month-old 3xTg-AD mice and 1.5-month-old P301S mice were administered PRO (1 and 2.5 mg/kg) orally every day. Morris water maze, contextual fear conditioning and rotarod assays were applied for studying memory functions. Sarkosyl differential centrifugation was used to analyze soluble and insoluble tau. Immunohistochemical analysis were performed to determine tau deposits in AD mice's brain sections. Molecular docking, binding affinity studies and primary cell culture studies were performed to demonstrate the mechanism of action of PRO in silico and in vitro. RESULTS: Our pharmacokinetic profiling demonstrated that PRO significantly entered the brain at a concentration of 289.47 ng/g, and specifically attenuated tau pathology, improved learning and memory functions in both 3xTg-AD and P301S mice. Docking, binding affinity studies, and fluorometric assays demonstrated that PRO directly bound to the catalytic domain 1 (CD1) of HDAC6 and down-regulated its activity. In primary cortical neurons, PRO enhanced acetylation of α-tubulin, indicating HDAC6 inhibition. Meanwhile, PRO promoted the ubiquitination of tau and recruited heat shock protein 70 (HSP70) and heat shock cognate complex 71 (HSC70) for the degradation of pathological tau via the ubiquitin-proteasomal system (UPS). CONCLUSION: We identified PRO as a natural HDAC6 inhibitor that attenuated tau pathology and improved memory dysfunctions in AD mice. The findings from this study provides a strong justification for future clinical development of plant-derived protopine as a novel agent for the treatment of tau-related neurodegenerative diseases.

7.
Dermatology ; : 1-9, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875648

RESUMO

BACKGROUND: The newly described ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area [BSA]) is a 5-item mortality prediction model for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). It was developed in the United States, has at present been externally tested only in the United States, Spain, and Singapore, and remains to be validated in resource-restricted settings. We sought to compare the accuracy of ABCD-10 and Score of Toxic Epidermal Necrolysis (SCORTEN) in predicting in-hospital mortality in a cohort from central China. Due to disease progression affecting the accuracy of the prediction model during hospitalization, for example, higher predictive accuracy of SCORTEN based on parameters collected on day 3 of hospitalization, we also assessed the overall predictive value of ABCD-10 on days 1 and 3, respectively. METHODS: A retrospective study was performed over a 10-year period (2010-2020) from 3 medical institutions in Wuhan. The performance of predictive models was assessed by both discrimination and calibration. Receiver-operating characteristic (ROC) curves, Hosmer-Lemeshow goodness-of-fit tests and calibration plots were used to evaluate the model discrimination and calibration. RESULTS: Of 84 included patients, 11 (13.1%) did not survive. The discrimination power of ABCD-10 was not significantly different from that of SCORTEN (area under the curve: day 1, p > 0.05; day 3, p > 0.05). Although the calibration of ABCD-10 was good, it was inferior to SCORTEN as it underestimated total mortality (Hosmer-Lemeshow goodness-of-fit test: day 1, p = 0.17 vs. p = 0.63; day 3, p = 0.35 vs. p = 0.93). Besides, the performance of ABCD-10 was slightly better on day 3 relative to day 1. During hospitalization, bacteremia developed in 21 (25.0%) patients, which was associated with a higher risk of death in our cohort (odds ratio, 22.88; 95% CI, 4.38-119.40; p < 0.001). CONCLUSION: ABCD-10 showed acceptable overall performance, but revealed mortality underestimation and was inferior to the performance of SCORTEN. In consistence with SCORTEN, ABCD-10 was a better model when using values collected at day 3 of hospitalization relative to day 1.

8.
Adv Healthc Mater ; : e2101496, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34878725

RESUMO

The major obstacles of anti-PD therapy in metastatic tumors are limited drug delivery in primary tumors and metastatic foci, and the lack of tumor-infiltrating lymphocytes (TILs). Here, we constructed a novel cellular membrane nanovesicles platform (M/IR NPs) based on homologous targeting and near-infrared (NIR) responsive release strategy to potentiate PD-1/PD-L1 blockade therapy against metastatic tumors. In tumor-bearing mice, biomimetic M/IR NPs targeted to both primary tumors and their lung metastases. Upon laser irradiation, M/IR NPs reduced cancer-associated fibroblasts (CAFs) in tumor microenvironment, thus increasing the penetration of TILs. When shed from homologous tumor cell membranes, positively charged nanoparticles (IR NPs) core could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. When the photothermal conversion temperature under NIR-laser was higher than 42°C, M/IR NPs initiated the rupture of cell membranes and the responsive release of PD-1/PD-L1 inhibitor BMS, which significantly attenuated tumor-associated immunosuppression and synergistically induced T cellular immunity to inhibit the tumor growth and metastasis. Overall, biomimetic M/IR NPs can improve the targeting and therapeutic efficacy of anti-PD therapy in primary tumors and metastases, opening up a new avenue for the diagnosis and treatment of metastatic tumors in the future. This article is protected by copyright. All rights reserved.

10.
Nat Commun ; 12(1): 7142, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880251

RESUMO

Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be closely associated with poor tumour differentiation. Overexpression of GDF1 suppresses cell proliferation but strongly enhances tumour dissemination and metastasis. Ectopic expression of GDF1 can induce the dedifferentiation of hepatocellular carcinoma (HCC) cells into their ancestral lineages and reactivate a broad panel of cancer testis antigens (CTAs), which further stimulate the immunogenicity of HCC cells to immune-based therapies. Mechanistic studies reveal that GDF1 functions through the Activin receptor-like kinase 7 (ALK7)-Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signalling cascade and suppresses the epigenetic regulator Lysine specific demethylase 1 (LSD1) to boost CTA expression. GDF1-induced tumour lineage plasticity might be an Achilles heel for HCC immunotherapy. Inhibition of LSD1 based on GDF1 biomarker prescreening might widen the therapeutic window for immune checkpoint inhibitors in the clinic.

11.
ACS Nano ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34881574

RESUMO

Microwave ablation has attracted the most attention as a locoregional therapeutic method for solid neoplasms. However, the high incidence of incomplete ablation that could promote the rapid cancer progression still remains a challenge in clinic. Herein, we found that the high invasiveness of residual tumor following incomplete microwave ablation (iMWA) is mainly due to the myeloid cell-mediated immunosuppression. Accordingly, we develop a biohydrogel scaffold-enabled chemoimmunotherapeutic strategy by targeting myeloid cells with a phosphoinositide 3-kinase γ (PI3Kγ) inhibitor (IPI549) to synergize with immunostimulatory chemotherapy (Oxaliplatin, OX) for post-ablative cancer therapy. With several tumor mouse models, we reveal that OX&IPI549@Gel-based localized chemoimmunotherapy can substantially suppress the growth of tumor post-iMWA, simultaneously evoke robust systemic anticancer immunity to inhibit metastatic spread, and offer strong long-term immunological memory functions against tumor rechallenge. Besides, this work proposes a potential opportunity for precision medicine by utilizing a mechanism-based rationale to the adoption of our pre-existing arsenal of anticancer immunotherapeutic schedule.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34865740

RESUMO

HYPOTHESIS: Waterborne polyurethane (WPU) is a common colloidal dispersion that can aggregate in the aqueous phase to form nanoparticles with hydrophobic polyurethane chains as the core and hydrophilic ionic groups as the shell. Considering their structure and pH-responsive functional groups, WPU nanoparticles could be ideal particulate emulsifiers for preparing pH-responsive Pickering high internal phase emulsions (HIPEs). EXPERIMENTS: A series of anionic WPU with different content of 2,2-bis(hydroxymethyl)propionic acid (DMPA) side chains were synthesized via a polyaddition reaction. The DMPA content, size, ζ-potential, and interfacial behaviors of WPU were then investigated. Furthermore, the effects of particle concentration, internal phase fraction (ϕ), oil type, and pH values on the Pickering HIPEs' morphology, stability, and rheological behaviors were systematically studied. Finally, we demonstrated the emulsification-demulsification process of WPU-stabilized Pickering HIPEs and discussed its mechanism. FINDINGS: Oil-in-water (O/W) Pickering HIPEs with tailored morphology and excellent pH-responsiveness were prepared from anionic WPU nanoparticles. The WPU concentration, ϕ, and oil type had a large impact on the formation and mean droplet size of the WPU-stabilized emulsions. Rheology analysis demonstrated that the strictly limited movement of droplets endowed the WPU-stabilized HIPEs with high stability, shear sensitivity, and excellent thixotropic recovery. By simply changing the aqueous-phase pH value, the WPU-stabilized HIPEs could undergo more than ten emulsification-demulsification cycles, as the physical and interfacial properties of WPU nanoparticles were pH-dependent. The excellent performance of the WPU-stabilized pH-responsive Pickering HIPEs exhibited their potential practical applications, such as for oil transportation and recovery, emulsion polymerization, and heterogeneous catalysis.

13.
ACS Omega ; 6(47): 32133-32141, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34870034

RESUMO

Curcumin (CUR) possesses neuroprotective effects. However, its clinical therapeutic efficacy is limited because of its low systemic bioavailability due to poor water solubility and fast metabolism. Herein, we designed biomimetic therapeutic nanovesicles (NVs) with enhanced performance and biocompatibility for the intracellular delivery of hydrophobic CUR. Cell membrane NVs were constructed to function as drug carriers by the serial extrusion of macrophages using filters with decreasing pore sizes. Various CUR loading strategies were also evaluated. Furthermore, the neuroprotective effects of the CUR-loaded NVs (NVs-CUR) against 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal degeneration were studied thoroughly. CUR-loaded NVs were readily taken up by neurons in vitro, and the survival rate of MPP+-induced primary neurons increased from 65.37 ± 6.37 to 90.91 ± 3.18% after pretreatment with NVs-CUR. Compared with traditional Parkinson's disease chemotherapeutic treatment, NV formulations can improve the bioavailability of this drug. NVs are expected to become a new and effective drug-delivery platform for further applications in the field of central nervous system therapy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34886456

RESUMO

In view of the research gap whereby few studies have investigated the inner psychological situations underlying continuous drug use, this study used the Soulmate Scale to investigate the relationship between soulmate experience and drug-taking behaviour. Overall, 276 participants took part in this study. Results showed that soulmate experience was negatively related to drug-taking behaviour, which means that being psychologically attached to drugs and receiving comfort from them encourages dependency and a higher level of difficulty in quitting drugs. In addition, soulmate experience significantly mediated the effect of meaning of life and social isolation on drugs, suggesting that when such psychological bonding and sustenance can be developed in interpersonal relationships instead of drugs, drug users are likely to develop the meaning of life and a lower sense of social isolation, and are more likely to quit drugs. The corresponding implications were discussed.

15.
Trends Biotechnol ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34887105

RESUMO

Muscle stem cells (MuSCs) are essential for the growth, maintenance, and repair of skeletal muscle. In the emerging area of cultured meat, meat products are manufactured with MuSCs using theory and technology from the fields of cell culture, tissue engineering, and food processing. Recently, considerable progress has been made in bioprocessing technologies for MuSCs, including isolation, expansion, differentiation, and tissue building. Here we summarize cutting-edge operational strategies and recently characterized regulatory mechanisms for MuSCs. Furthermore, we discuss their applicability to refining the production process for cultured meat and accelerating its industrialization.

16.
Front Oncol ; 11: 752504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956877

RESUMO

Background: This retrospective cohort study aimed to evaluate the clinical outcomes of H101 combined with chemotherapy for advanced gastric carcinoma (GC) patients. Methods: The advanced GC patients, who were treated with H101 and/or chemotherapy, were enrolled and divided into three groups according to treatment method. The clinical characteristics of patients, clinical short-term and long-term outcomes, followed up, and complication were analyzed. Results: A total of 95 patients (30 patients in group A were treated with H101, 33 in group B patients were treated with chemotherapy, 32 patients in group C were treated with H101 combined with chemotherapy) were retrospectively reviewed. The disease control rate (DCR) and overall response rate (ORR) were significantly greater in group C (81.3% and 50.0%) than in groups A (63.3% and 30.0%) and B (66.7% and 33.3%, all p < 0.05). The 1- and 2-year survival rates and progression-free survival were significantly greater in group C than in groups A and B (all p < 0.05). There was no significant difference in complication among the three groups. At dose levels of 0.5 × 1012 vp/day, 1.0 × 1012 vp/day, and 1.5 × 1012 vp/day, complications were not increased as increased of dose. Conclusions: H101 combined with chemotherapy may be a potential therapeutic option for patients with advanced GC, and prospective studies with proper assessment of toxicity will be needed in the future.

17.
BMC Gastroenterol ; 21(1): 461, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895151

RESUMO

BACKGROUND: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma. CASE PRESENTATION: A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory. CONCLUSION: Our report supports the hypothesis that PIL is associated with lymphoma development.


Assuntos
Linfangiectasia Intestinal , Linfoma não Hodgkin , Enteropatias Perdedoras de Proteínas , Biópsia , Humanos , Linfangiectasia Intestinal/complicações , Linfócitos , Linfoma não Hodgkin/complicações , Masculino , Pessoa de Meia-Idade
18.
Front Immunol ; 12: 748585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925324

RESUMO

Adult patients with hematological malignancies are frequently accompanied by bacterial infections in the lungs when they are first diagnosed. Sputum culture, procalcitonin (PCT), C-reactive protein (CRP), body temperature, and other routinely used assays are not always reliable. Cytokines are frequently abnormally produced in adult hematological malignancies associated with a lung infection, it is uncertain if cytokines can predict lung bacterial infections in individuals with hematological malignancies. Therefore, we reviewed 541 adult patients newly diagnosed with hematological malignancies, of which 254 patients had lung bacterial infections and 287 patients had no other clearly diagnosed infections. To explore the predictive value of cytokines for pulmonary bacterial infection in adult patients with hematological malignancies. Our results show that IL-4, IL-6, IL-8, IL-10, IL-12P70, IL-1ß, IL-2, IFN-γ, TNF-α, TNF-ß and IL-17A are in the lungs The expression level of bacterially infected individuals was higher than that of patients without any infections (P<0.05). Furthermore, we found that 88.89% (200/225) of patients with IL-6 ≥34.12 pg/ml had a bacterial infection in their lungs. With the level of IL-8 ≥16.35 pg/ml, 71.67% (210/293) of patients were infected. While 66.10% (193/292) of patients had lung bacterial infections with the level of IL-10 ≥5.62 pg/ml. When IL-6, IL-8, and IL-10 were both greater than or equal to their Cutoff-value, 98.52% (133/135) of patients had lung bacterial infection. Significantly better than PCT ≥0.11 ng/ml [63.83% (150/235)], body temperature ≥38.5°C [71.24% (62/87)], CRP ≥9.3 mg/L [53.59% (112/209)] the proportion of lung infection. In general. IL-6, IL-8 and IL-10 are abnormally elevated in patients with lung bacterial infections in adult hematological malignancies. Then, the abnormal increase of IL-6, IL-8 and IL-10 should pay close attention to the possible lung bacterial infection in patients.

19.
Front Immunol ; 12: 742358, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938284

RESUMO

Background: Colorectal cancer is a lethal cancer worldwide. Due to the low tumor mutation burden and low proportion of tumor-infiltrating lymphocytes in the microenvironment of most patients, innovative immunotherapeutic approaches need to be identified. Methods: Using the TCGA-COAD dataset (n = 514), we identified TNFRSF11B as a prognostic factor of colon cancer. An immunohistochemistry (IHC) dataset (n = 86), 290 single colorectal cancer cells (GSE81861), and 31 paired colon cancer transcriptional datasets were further applied to validate the function of TNFRSF11B, which was confirmed via fluorescence-activated cell sorting (FACS) analysis. Results: A risk score system consisting of eight immune-related genes (IRGs) (FGFR2, ZC3HAV1L, TNFRSF11B, CD79A, IGHV3-11, IGHV3-21, IGKV2D-30, and IGKV6D-21) was constructed to predict the prognosis of colon cancer patients. Only TNFRSF11B was closely correlated with late-stage lymph node metastasis and worse survival outcomes (p = 0.010, p = 0.014, and p = 0.0061). In our IHC dataset, 72.09% (62/86) of the colon cancer patients had TNFRSF11B overexpression with significantly shorter overall survival times (p = 0.072). High TNFRSF11B expression typically had a later TNM stage (p = 0.067), a higher frequency of lymph node (p = 0.029) and lymphovascular (p = 0.007) invasion, and a higher incidence of pneumonia (p = 0.056) than their counterparts. The expression of six genes (KRT18, ARPC5L, ACTG1, ARPC2, EZR, and YWHAZ) related to pathogenic E. coli infection was simultaneously increased with TNFRSF11B overexpression via gene set enrichment analysis (GSEA). These genes are involved in the regulation of the actin cytoskeleton, shigellosis, bacterial invasion of epithelial cells, and Salmonella infection. Finally, only activated memory CD4+ T cells (p = 0.017) were significantly decreased in the high TNFRSF11B expression group via CIBERSORT comparison, which was confirmed by TIMER2.0 analysis of the TCGA-COAD dataset. We also performed FACS analysis to show that TNFRSF11B decreased the infiltration of central memory CD4+ T cells and effector memory CD4+ T cells in the colorectal cancer microenvironment (all p <0.001). Conclusion: TNFRSF11B acts as a prognostic factor for colon cancer patients and could affect the colon cancer immune response. TNFRSF11B was closely related to lymph node invasion and pathogenic E. coli. infection, which may negatively affect memory-activated CD4+ T cell infiltration in colon cancer.

20.
Front Public Health ; 9: 689123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746073

RESUMO

Background: Schizophrenia is a severe and complex disease with substantial economic and social burdens. Despite multiple treatment choices, adverse events, and impaired social functions are still challenges in clinical therapy. Pharmacoeconomic evaluations could provide evidence to help decision makers improve the utilization of scarce resources. However, there remains some challenges especially in modeling due to uncertainties in progression of schizophrenia. There are limited summaries about the overall methodologies of schizophrenia economic evaluations. Objective: The aim of this study is to review the existing economic evaluations of antipsychotics for the treatment of schizophrenia and summarize the evidence and methods applied. Methods: An electronic literature search was performed in PubMed, Web of Science, EBSCO host, The Cochrane Library and ScienceDirect from January 2014 to December 2020. Search terms included "schizophrenia," "schizophrenic," "pharmacoeconomic," "economic evaluation," "cost-effectiveness," and "cost-utility." The Literature was screened and extracted by two researchers independently and assessed with the Quality of Health Economic Studies (QHES) List and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Statement. Results: A total of 25 studies were included in the review. The regions included Europe, North America, Asia and Africa. Most of the studies chose second-generation antipsychotics as comparators and integrated treatment sequences. Time horizons varied from 1 year to lifetime. The healthcare sector was the most common perspective, accordingly, most of the evaluations considered only direct medical costs. The Markov model and decision tree model were the most common choices. Adverse events, compliance and persistence were considered important parameters. Quality-adjusted life-years were the major outcomes applied to the economic evaluations. All utilities for health states and adverse events were collected from published literature. All of the studies applied uncertainty analysis to explore the robustness of the results. The quality of the studies was generally satisfactory. However, improvements were needed in the choice of time horizons, the measurements of outcomes and the descriptions of assumptions. Conclusions: This study highlights the methodology of economic evaluation of schizophrenia. Recommendations for modeling method and future study are provided.


Assuntos
Antipsicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Análise Custo-Benefício , Farmacoeconomia , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Esquizofrenia/tratamento farmacológico
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