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1.
Value Health Reg Issues ; 24: 33-37, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33486460

RESUMO

OBJECTIVE: The HeartQoL is an ischemic heart disease (IHD) core questionnaire. This study aimed to map the HeartQoL to the EQ-5D to provide the specific patients' health status and utility using one instrument. METHODS: We conducted a cross-sectional study investigating IHD patients in China using the Chinese HeartQoL and EQ-5D. Data based on the total group were fitted by 2 linear regression models with the utility score derived from the EQ-5D as a dependent variable and the HeartQoL total and subscale (physical and emotional) scores as independent variables, respectively. The 2 models were compared via modeling fitting statistics. RESULTS: In total, 406 IHD patients were enrolled in China. The mean HeartQoL global score for the total group was 1.75 (standard deviation [SD] = 0.85), whereas the mean physical and emotional scores were 1.65 (SD = 0.91) and 1.99 (SD = 0.93), respectively. The mean utility calculated by the EQ-5D for IHD patients was 0.66 (SD = 0.38), as compared with 0.95 (SD = 0.06) for healthy people. From the linear regression model with total score, the total score was a significant predictor for the EQ-5D utility, with the equation as EQ-5D = 0.085 - 0.3294 × total. In the linear regression model with physical and mental scores, both scores were significant predictors for the EQ-5D utility, with an equation as EQ-5D = 0.0671- 0.2091 × physical - 0.1248 × mental. The fitting statistics suggest that the model using the HeartQoL total score is preferred. CONCLUSION: As the first effort to map the HeartQoL to EQ-5D, the linear relationship between these 2 instruments was explored, and this could potentially be useful in future health technology assessment decision making and clinical practice.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33471184

RESUMO

PURPOSE: Recent clinical trials with agents targeting immune checkpoint pathway have emerged as an important therapeutic approach for a broad range of cancer types. Resveratrol has been shown to possess cancer preventive and therapeutic effects and has potential to be chemotherapeutic agent/adjuvant. Here, we assessed the effect of resveratrol on immune checkpoint pathways. METHODS: The expression patterns of Wnt components and PD-L1 were examined by Western blot, Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction, the promoter activity was determined by luciferase reporter assay, apoptosis was analyzed by flow cytometry and the ability of the resveratrol to modulate T cell function was assessed in a co-culture system. RESULTS: Although the dose-, and cell-type dependent effects of resveratrol on PD-L1 expression have been reported, we show here that resveratrol dose-dependently upregulates PD-L1 expression at the range of pharmacologic-achievable concentrations in lung cancer cells and that is essential for suppression of T-cell-mediated immune response. We also found that Wnt pathway is critical for mediating resveratrol-induced PD-L1 upregulation. Mechanistically, resveratrol activates SirT1 deacetylase to deacetylate and stabilize transcriptional factor Snail. Snail in turn inhibits transcription of Axin2, which leads in disassembly of destruction complex and enhanced binding of ß-catenin/TCF to PD-L1 promoter. CONCLUSION: We conclude that resveratrol is capable to suppress anti-tumor immunity by controlling mainly PD-L1 expression. This finding will extend the understanding of resveratrol in regulation of tumor immunity and is relevant to the debate on resveratrol supplements for lung cancer patients.

3.
Aging (Albany NY) ; 122021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33428604

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) results in increased myocardial infarct size and leads to poor clinical outcomes. Hypoxia-inducible factor 2-alpha (HIF2α) exerts myocardial protective effects during MIRI through as yet unclear mechanisms. Here, we show that knockdown of HIF2α with cardiotropic recombinant adeno-associated virus serotype 9 (rAAV9) in mouse hearts significantly increased the infarct sizes during myocardial ischemia/reperfusion (MI/R). In addition, HIF2α transcriptionally regulated the expression of interleukin 6 (IL-6) in cardiomyocytes to elicit cardioprotection. Likewise, IL-6 deficiency aggravated MIRI, while treatment with recombinant IL-6 had cardioprotective effects and rescued the mice with HIF2α knockdown. Furthermore, IL-6 treatment significantly activated the PI3K/Akt and STAT3 signaling pathways in the myocardium during MI/R, and the specific inhibitors wortmannin (specific phosphoinositide 3-kinase inhibitor) and Stattic (specific STAT3 inhibitor) substantially abolished HIF2α/IL-6-induced cardioprotection. These studies suggest that HIF2α transcription regulates the expression of IL-6 in cardiomyocytes and plays a protective role during MI/R.

4.
J Synchrotron Radiat ; 28(Pt 1): 169-175, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399565

RESUMO

According to the estimated data rates, it is predicted that 24 PB raw experimental data will be produced per month from 14 beamlines at the first stage of the High-Energy Photon Source (HEPS) in China, and the volume of experimental data will be even greater with the completion of over 90 beamlines at the second stage in the future. To make sure that the huge amount of data collected at HEPS is accurate, available and accessible, an effective data management system (DMS) is crucial for deploying the IT systems. In this article, a DMS is designed for HEPS which is responsible for automating the organization, transfer, storage, distribution and sharing of the data produced from experiments. First, the general situation of HEPS is introduced. Second, the architecture and data flow of the HEPS DMS are described from the perspective of facility users and IT, and the key techniques implemented in this system are introduced. Finally, the progress and the effect of the DMS deployed as a testbed at beamline 1W1A of the Beijing Synchrotron Radiation Facility are shown.

5.
Vaccine ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33422379

RESUMO

BACKGROUND: Pakistan introduced Ten-valent pneumococcal-conjugate-vaccine PCV10 in 2012 as a 3 + 0 schedule without catch-up. METHODS: Children <2 years old in Matiari, Sindh provided nasopharyngeal swabs between 2014 and 2018, which were cultured for pneumococcus and serotyped through multiplex PCR at the Aga Khan University Hospital. Carriage rates over time for Vaccine-Type (VT) and Non-VT (NVT) serotypes were used to estimate direct, indirect, total and overall effects of vaccination. Regression analysis was used to determine factors associated with VT carriage. RESULTS: Pneumococcus was detected in 2370/3140 (75%). VT carriage decreased overall, 16.1-9.6% (p-trend <0.001); vaccinated (all 3 doses of PCV10 received) 11.3-8.1% (p-trend 0.031) and unvaccinated (no PCV10 dose received) 17.4-10.3% (p-trend 0.003) with a decline in serotypes 6B, 9V/9A and 19F. Immunization increased from 41.0% to 68.4% (p-trend 0.001). Direct effect of vaccine was 32.8% (95% CI 14.7-47.0%) and indirect effect 44.6%(95% CI 40.6-48.6%). Factors associated with decreased VT colonization were education 1-5 years (aOR 0.7, 95%CI 0.6-1.0), history of difficulty breathing (aOR 0.7, 95%CI 0.5-1.0), exposure to smoke (aOR 0.8, 95% CI 0.6-1.0), child fully immunized (aOR 0.7, 95%CI 0.5-1.0) and enrolled in 3rd (aOR 0.6, 95%CI 0.4-0.8) and 4th (aOR 0.6, 95%CI 0.5-0.9) year of the study whereas history of runny nose (aOR 1.5, 95% CI 1.2-1.9) was positively associated. CONCLUSIONS: Decrease in VT pneumococcal carriage in vaccinated and unvaccinated children indicates herd immunity. Sustained increase in vaccine coverage and close long-term surveillance is warranted.

6.
Br J Radiol ; 94(1118): 20200884, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33353397

RESUMO

OBJECTIVE: To compare the two-point Dixon T2 weighted imaging (T2WI) with conventional fat-sat T2WI in fat suppression (FS) quality and staging performance for patients with TAO. METHODS: We enrolled 37 thyroid-associated ophthalmopathy (TAO) patients and 15 healthy controls who underwent both coronal two-point Dixon and fat-sat T2WI. Qualitative (overall imaging quality, FS uniformity) and quantitative [signal intensity ratio of extraocular muscle (EOM-SIR)] parameters were assessed between the two-point Dixon T2WI and fat-sat T2WI. Additionally, water fraction of intraorbital fat (IF-WF) was measured on Dixon image. Dixon-EOM-SIR, Fat-sat-EOM-SIR and Dixon-IF-WF values were compared between active and inactive TAO groups, and the diagnostic efficiency for the active phase were evaluated. RESULTS: Two-point Dixon T2WI showed significantly higher overall image quality score, FS uniformity score as well as EOM-SIR value than fat-sat T2WI in both TAO and control groups (all p < 0.05). Active TAOs had significantly higher Dixon-EOM-SIR (p < 0.001), Fat-sat-EOM-SIR (p < 0.001) and Dixon-IF-WF (p = 0.001) than inactive TAOs. ROC curves analyses indicated that Dixon-EOM-SIR ≥3.32 alone demonstrated the highest staging sensitivity (75.0%). When integrating Dixon-EOM-SIR ≥3.32 and Dixon-IF-WF ≥0.09, improved staging efficiency and specificity could be achieved (area under the curve, 0.872; specificity, 97.1%). CONCLUSION: Compared with conventional fat-sat technique, two-point Dixon T2WI offers better image quality, as well as improved staging sensitivity and specificity for TAO. Dixon T2WI is suggested to be used to evaluate the patients with TAO in clinical practice. ADVANCES IN KNOWLEDGE: Two-point Dixon T2WI offers better image quality than fat-sat T2WI. Dixon-EOM-SIR alone demonstrated the highest staging sensitivity. Combining with Dixon-IF-WF showed improved staging efficiency and specificity. Dixon T2WI is suggested to be used to evaluate TAO patients in clinical practice.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33317348

RESUMO

Introduction: As a novel glucagon-like peptide-1receptor agonist (GLP-1 RA) for type 2 diabetes (T2D) treatment, the economic value of once-weekly semaglutide had been assessed in several country settings. The authors' objective was to systematically review the existing pharmacoeconomic literature evaluating the cost-effectiveness associated with once-weekly semaglutide compared with other GLP-1 RAs and provide implications for further researches. Areas covered: We conducted a systematic literature review of cost-effectiveness analysis (CEA) published up to 25 July 2020 in PubMed, web of science, and the ISPOR presentation database, compared once-weekly semaglutide with other GLP-1 RAs in T2D. Nineteen studies were identified, including 8 short-term and 11 long-term studies. General characteristics and main results of the included studies were summarized. Expert opinion: This review provided references for other countries to overview the value of once-weekly semaglutide compared with other GLP-1 RAs in T2D in the healthcare decision-making process and to conduct their CEA studies associated with once-weekly semaglutide. The authors found that the cardiovascular (CV) benefit of once-weekly semaglutide was under-estimated in current studies and suggested that the methods of economic evaluations for novel anti-diabetic drugs with CV benefit should be improved in future researches.

8.
J Inflamm (Lond) ; 17(1): 36, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33292270

RESUMO

BACKGROUND: Obesity, a risk factor for many chronic diseases, is a potential independent risk factor for iron deficiency. Evidence has shown that chronic intermittent hypobaric hypoxia (CIHH) has protective or improved effects on cardiovascular, nervous, metabolic and immune systems. We hypothesized that CIHH may ameliorate the abnormal iron metabolism in obesity. This study was aimed to investigate the effect and the underlying mechanisms of CIHH on iron metabolism in high-fat-high-fructose-induced obese rats. METHODS: Six to seven weeks old male Sprague-Dawley rats were fed with different diet for 16 weeks, and according to body weight divided into four groups: control (CON), CIHH (28-day, 6-h daily hypobaric hypoxia treatment simulating an altitude of 5000 m), dietary-induced obesity (DIO; induced by high fat diet and 10% fructose water feeding), and DIO + CIHH groups. The body weight, systolic arterial pressure (SAP), Lee index, fat coefficient, blood lipids, blood routine, iron metabolism parameters, interleukin6 (IL-6) and erythropoietin (Epo) were measured. The morphological changes of the liver, kidney and spleen were examined. Additionally, hepcidin mRNA expression in liver was analyzed. RESULTS: The DIO rats displayed obesity, increased SAP, lipids metabolism disorders, damaged morphology of liver, kidney and spleen, disturbed iron metabolism, increased IL-6 level and hepcidin mRNA expression, and decreased Epo compared to CON rats. But all the aforementioned abnormalities in DIO rats were improved in DIO + CIHH rats. CONCLUSIONS: CIHH improves iron metabolism disorder in obese rats possibly through the down-regulation of hepcidin by decreasing IL-6 and increasing Epo.

9.
Int J Chron Obstruct Pulmon Dis ; 15: 3171-3181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293806

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD) has become a significant risk factor that threatens public health. Many studies have confirmed that the professional services for COPD patients by community pharmacists can improve comprehensive benefits. However, there's less research investigating the factors affecting community pharmacists' knowledge about COPD management. Therefore, this study aimed to investigate the knowledge of COPD among community pharmacists in China and analyze the factors affecting community pharmacist's knowledge about COPD management. Methods: This study employed a face-to-face, self-administered questionnaire survey targeting community pharmacists from three cities (Nanjing, Zhuhai, Qingyang) in China. Descriptive statistics, t-test and one-way ANOVA were used for data analysis. Results: Out of the 794 pharmacists surveyed, 177 (22.3%) were completed and valid. The majority (91.0%) of participants had a positive attitude they were responsible for assisting patients to control the disease progression. Among 12 knowledge-related survey questions, only 34 (19.2%) pharmacists answered more than half of them correctly, showing that overall knowledge level of participants was generally low. The overall knowledge level was significantly (P < 0.05) associated with higher academic education, on-the-job training, and pharmacies selling drugs for treating COPD. Regarding medical knowledge, participants got higher accuracy rates at some questions as the symptoms of COPD and identifying the main causative factors but were weak in disease characteristics and guidelines for disease diagnosis. As for medication, participants had a certain understanding of different drugs for COPD and their adverse reactions. For non-drug treatment, participants could not entirely choose the best non-drug treatment for patients, while most of them recognize the importance of pulmonary rehabilitation. Conclusion: This research indicated that community pharmacists in China lacked sufficient knowledge about COPD management. It is necessary to improve university education, strengthen on-the-job training, adjust the social insurance system, and develop service guidelines for licensed pharmacists to support their professional services for COPD patients.

10.
Int J Mol Sci ; 21(23)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271967

RESUMO

Chemotherapy is still the most direct and effective means of cancer therapy nowadays. The proposal of drug delivery systems (DDSs) has effectively improved many shortcomings of traditional chemotherapy drugs. The technical support of DDSs lies in their excellent material properties. Polysaccharides include a series of natural polymers, such as chitosan, hyaluronic acid, and alginic acid. These polysaccharides have good biocompatibility and degradability, and they are easily chemical modified. Therefore, polysaccharides are ideal candidate materials to construct DDSs, and their clinical application prospects have been favored by researchers. On the basis of versatile types of polysaccharides, this review elaborates their applications from strategic design to cancer therapy. The construction and modification methods of polysaccharide-based DDSs are specifically explained, and the latest research progress of polysaccharide-based DDSs in cancer therapy are also summarized. The purpose of this review is to provide a reference for the design and preparation of polysaccharide-based DDSs with excellent performance.

11.
Food Funct ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295905

RESUMO

Long-term high-fat-diet (HFD)-induced obesity is associated with many comorbidities, such as cognitive impairment and anxiety, which are increasing public health burdens that have gained prevalence in adolescents. Although low-dose alcohol could attenuate the risk of cardiovascular disease, its mechanism on HFD-induced anxiety-related behavior remains not clear. The mice were divided into 4 groups, Control (Con), Alcohol (Alc), HFD and HFD + Alc groups. To verify the effects of low-dose alcohol on HFD-induced anxiety-related behavior, the mice were fed with HFD for 16 weeks. At the beginning of week 13, the HFD-fed mice were administered intragastrically with low-dose alcohol (0.8 g kg-1) for 4 weeks. After 4 weeks of oral administration, low-dose alcohol decreased body weight and Lee's index in HFD-induced obese mice. Moreover, low-dose alcohol alleviated the anxiety-related behaviors of obese mice in the open field test and the elevated plus maze test. The HFD-induced damage to the hippocampus was improved in hematoxylin-eosin staining assay in mice. In addition, low-dose alcohol also suppressed HFD-induced oxidative stress and increased HFD-suppressed adiponectin (APN) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the hippocampus. Taken together, low-dose alcohol significantly ameliorates HFD-induced obesity, oxidative stress and anxiety-related behavior in mice, which might be related to APN upregulation, Nrf2 activation and related antioxidase expression including SOD1, HO-1, and catalase.

12.
J Genet Genomics ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33358777

RESUMO

Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase ß (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33382122

RESUMO

BACKGROUND AND AIM: Traditionally, surgery is the only choice for esophageal foreign bodies (FBs) penetrating into the mediastinum or cervical para-esophageal space. Recent progress in endoscopic techniques and devices has made it possible to perform endoscopic procedures in the mediastinum. Here, we describe a novel method to remove the entirely embedded esophagus-penetrating FBs through an endoscopic approach. METHODS: Patients who underwent endoscopic removal of entirely embedded esophagus-penetrating FBs were prospectively enrolled between December 2018 and June 2020. All procedures were performed by using five major steps: localization of the FB; mucosal incision; wound debridement, myotomy, and FB exposure; FB extraction; and closure of the esophageal wound. RESULTS: A total of five cases of entirely embedded esophagus-penetrating FBs were evaluated, two in children and three in adults. All FBs were successfully removed and extracted using a therapeutic endoscope and a hook knife or a hybrid knife and a grasping forceps as accessories. The average procedure time was 19.0 ± 12.4 min (range 10-40 min). The major surgical procedure was avoided in all patients. The average length of hospital stay was 3.8 ± 2.5 days (range 2-8 days). There were no severe short-term adverse events after all procedures. During the 1 month and 3 months follow-up, no patient developed long-term adverse events including stenosis of the esophagus and fistula formation. CONCLUSIONS: Endoscopic approach was a safe and effective way to remove entirely embedded esophagus-penetrating FBs.

14.
PeerJ ; 8: e10281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194434

RESUMO

Background: Previous studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC. Methods: The RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC. Results: Transcriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-ß signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT. Conclusions: POLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.

15.
Opt Express ; 28(23): 34054-34068, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182883

RESUMO

Ultra-smooth surfaces with low contamination and little damage are a great challenge for aluminum optical fabrication. Ion beam sputtering (IBS) has obvious advantages of low contamination and non-contact that make it a perfect method for processing aluminum optics. However, the evolution laws of aluminum surface morphology are quite different from conventional amorphous materials, which affects the roughness change and needs systematic research. Thus, in this paper, the roughness evolution of an aluminum optical surface (i.e., aluminum mirror) subjected to IBS has been studied with experimental and theoretical methods. The surface morphology evolution mechanisms of turning marks and second phase during IBS are revealed. The newly emerging relief morphology and its evolution mechanism are studied in depth. The experimental results find that IBS causes the coarsening of optical surfaces and the appearance of microstructures, leading to the surface quality deterioration. Turning marks have been through the process of deepening and vanish, while second phase generates microstructures on the original surface. The corresponding mechanism is discussed exhaustively. Preferential sputtering, curvature-dependent sputtering and material properties play important roles on surface quality deterioration. A modified roughness evolution mechanism and an improved binary sputtering theory are proposed to describe the polycrystalline sputtering phenomena. The current research can provide a guidance for the application of IBS in aluminum optics manufacture fields.

16.
Int J Endocrinol ; 2020: 2575710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144856

RESUMO

Background: Accurate staging of patients with thyroid-associated ophthalmopathy (TAO) is crucial for clinical decision. Full cognition of pathologic changes and staging TAO using conventional T2-weighted imaging is still limited. Purpose: To investigate the feasibility of using T1 mapping to evaluate changes of extraocular muscles (EOMs) in TAO patients, as well as to compare T1 mapping and conventional T2-weighted imaging in staging TAO. Materials and Methods: Forty TAO patients were retrospectively enrolled. "Hot spot" and "cold spot" T1 relaxation times (T1RTHS and T1RTCS) of EOMs, as well as conventionally applied highest signal intensity ratio (SIR) of EOMs, were measured and compared between active and inactive groups. Results: T1RTCS and SIR were significantly higher in active TAOs than in the inactive ones (P < 0.001), while T1RTHS was not (P=0.093). Meanwhile, T1RTCS and SIR were positively correlated with clinical activity score (r = 0.489, 0.540; P < 0.001). TIRTCS and SIR showed no significant area under curve for staging TAO (0.830 vs. 0.852; P=0.748). T1RTCS ≥ 1000 alone showed optimal staging specificity (90.0%), while integration of T1RTCS ≥ 1000 and SIR ≥ 2.9 demonstrated optimal staging efficiency and sensitivity (area under curve, 0.900; sensitivity, 86.0%). Conclusions: Our findings suggest that the T1-mapping technique holds the potency to be utilized in TAO. The derived T1RTCS of EOMs, which may be associated with fat infiltration, could be a useful biomarker to stage the disease, serving added efficiency, sensitivity, and specificity to single usage of conventional SIR.

17.
PLoS Biol ; 18(11): e3000897, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33180773

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19) disease, has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used-appropriately and less appropriately-to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, often dominated by a small number of individuals, and heavily influenced by superspreading events (SSEs). The distinct transmission features of SARS-CoV-2, e.g., high stochasticity under low prevalence (as compared to other pathogens, such as influenza), and the central role played by SSEs on transmission dynamics cannot be overlooked. Many explosive SSEs have occurred in indoor settings, stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, produce processing facilities, fish factories, cruise ships, family gatherings, parties, and nightclubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity to effectively contain outbreaks with targeted interventions to eliminate SSEs. Here, we describe the different types of SSEs, how they influence transmission, empirical evidence for their role in the COVID-19 pandemic, and give recommendations for control of SARS-CoV-2.

18.
Proc Natl Acad Sci U S A ; 117(49): 31319-31330, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33229539

RESUMO

Autoimmune diabetes is one of the complications resulting from checkpoint blockade immunotherapy in cancer patients, yet the underlying mechanisms for such an adverse effect are not well understood. Leveraging the diabetes-susceptible nonobese diabetic (NOD) mouse model, we phenocopy the diabetes progression induced by programmed death 1 (PD-1)/PD-L1 blockade and identify a cascade of highly interdependent cellular interactions involving diabetogenic CD4 and CD8 T cells and macrophages. We demonstrate that exhausted CD8 T cells are the major cells that respond to PD-1 blockade producing high levels of IFN-γ. Most importantly, the activated T cells lead to the recruitment of monocyte-derived macrophages that become highly activated when responding to IFN-γ. These macrophages acquire cytocidal activity against ß-cells via nitric oxide and induce autoimmune diabetes. Collectively, the data in this study reveal a critical role of macrophages in the PD-1 blockade-induced diabetogenesis, providing new insights for the understanding of checkpoint blockade immunotherapy in cancer and infectious diseases.

19.
Int Immunopharmacol ; 89(Pt A): 107139, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33191179

RESUMO

Accumulating evidence has indicated that inflammation is required for the initiation and progression of hepatocellular carcinoma (HCC). The annexin family protein, which has a highly similar structure, has been demonstrated to participate in pro- or anti-inflammatory regulation in the developing of tumours. However, the potential effects of ANXA3 in the immune microenvironment of HCC remain unknown. In present study, we found that increased ANXA3 expression is associated with a higher infiltrated neutrophil-lymphocyte ratio (iNLR) in HCC. Moreover, HCC patients with a high iNLR and high ANXA3 expression confer the highest risk of death. ANXA3 can be detected in both cell lysates and culture supernatants. However, the secretory ANXA3 did not directly regulate the iNLR. Further study demonstrated that ANXA3 upregulated the iNLR by inducing chemokine CXCL8 and CCL25 release from HCC cells. We further confirmed that ANXA3 promotes tumourigenesis and detected the same associations between ANXA3 and the iNLR or chemokines in vivo. Our findings indicate that ANXA3 regulates the chemokine to remodel the iNLR and promotes tumourigenicity in HCC. These results further expanded our understanding of ANXA3 in the microenvironment of HCC and might provide novel targets for the investigation of molecular treatments for HCC patients.

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