To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC).
In all, ...185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).
EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio HR 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020).
Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.
To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of ...nasopharyngeal carcinoma (NPC).
Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared.
Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging.
Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.
Status of Cardiovascular Health in Chinese Adults Bi, Yufang, MD, PhD; Jiang, Yong, PhD; He, Jiang, MD, PhD ...
Journal of the American College of Cardiology,
03/2015, Letnik:
65, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Abstract Background Cardiovascular disease has become the leading cause of death in China. Objectives The goal of this study was to evaluate the current status of cardiovascular health in Chinese ...adults. Methods Cardiovascular health data were collected from a nationally representative sample of 96,121 Chinese adults age ≥20 years in 2010. Ideal cardiovascular health was defined according to the American Heart Association’s 2020 Strategic Impact Goals as follows: the simultaneous presence of 4 favorable health behaviors (ideal smoking status, ideal body mass index, physical activity at goal, and healthy dietary habits) and 4 favorable health factors (ideal smoking status, untreated total cholesterol <200 mg/dl, untreated blood pressure <120/<80 mm Hg, and untreated fasting plasma glucose <100 mg/dl) in the absence of a history of cardiovascular disease. Results The estimated percentage of ideal cardiovascular health was 0.2% in the general adult population in China (0.1% in men and 0.4% in women). An estimated 0.7% (0.4% in men and 1.0% in women) of Chinese adults had all 4 ideal health behaviors, and 13.5% (5.0% in men and 22.3% in women) had all 4 ideal health factors. Men most frequently had 3 to 4 ideal components, and women most commonly had 4 to 5 ideal components of the 7 cardiovascular health metrics. Ideal diet (1.6%) was the least common among all cardiovascular health metrics. Female sex and younger age were the 2 most common protective factors for cardiovascular health in Chinese adults. Conclusions The percentage of ideal cardiovascular health in Chinese adults is extremely low. Both population-wide and high-risk strategies should be implemented with great effort to promote cardiovascular health in China.
Highlights • The aim of this study is to determine the molecular mechanisms behind stereotactic body radiation therapy (SBRT) stimulating mesenchymal stem cell (MSC) migration and differentiation. • ...Bone-marrow derived MSCs migrate to the tumor parenchyma and differentiate into pericytes, inducing tumor vasculogenesis after SBRT, and promoting tumor recurrence. • MSC migration and maturation may be abrogated with AMD3100 and imatinib. • This novel treatment strategy warrants clinical investigation.
Objectives Surgical lung biopsy plays an important role in providing pathologic results, thus complementing the diagnostic rationale for suspected interstitial lung diseases. We performed a ...systematic review and meta-analysis regarding the diagnostic yield and postoperative mortality rate of surgical lung biopsy in patients with suspected interstitial lung diseases because of the wide variation in previously reported effectiveness and safety concerns. Methods We systematically searched for published studies between 2000 and 2014 evaluating surgical lung biopsy in the diagnosis of interstitial lung diseases. Subgroup analysis was performed to identify the possible source of study heterogeneity. Results Twenty-three studies contributed 2148 patients for the analysis. The median diagnostic yield was 95% (range, 42%-100%), with idiopathic pulmonary fibrosis as the most frequent diagnosis (618, 33.5%). Surgical lung biopsy was mainly guided by high-resolution computed tomography manifestations. Biopsy site, biopsy number, and the surgical lung biopsy method may not be associated with the diagnostic accuracy. The pooled postoperative mortality rate for included studies was 3.6% (95% confidence interval, 2.1-5.5), with significant heterogeneity observed. Subgroup analysis revealed that exclusion criteria based on immunocompromised status, mechanical ventilation, and severe respiratory dysfunction (diffusing capacity of lung for carbon monoxide <35% or forced vital capacity <55% predicted), but not surgical lung biopsy technique or underlying interstitial lung disease subtype, may be possible sources of heterogeneity. Conclusions We demonstrated a satisfactory diagnostic performance with a favorable safety profile of surgical lung biopsy in the diagnosis of suspected interstitial lung diseases. Surgical lung biopsy is especially recommended in patients with clinical information indicative but atypical of idiopathic pulmonary fibrosis, whereas the benefit of surgical lung biopsy should be carefully balanced against the risk for patients with immunocompromised status, mechanical ventilation dependence, or severe respiratory dysfunction.
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•DVDMS-SDT reduces neovascularization in late-stage atherosclerotic lesions in both rabbit and mouse models.•DVDMS-SDT enhances macrophage foam cell apoptosis, which in turn induces ...neovessel endothelial cell apoptosis and inhibits its proliferation, migration, and tubulogenesis, termed apoptosis-induced apoptosis.•Mechanistically, DVDMS-SDT induces macrophage foam cell apoptosis via mitochondrial-caspase pathway, which activates caspase 3 to cleave SP-1, leading to the reduction of HIF-1α and VEGF-A.•In the pilot translational study, DVDMS-SDT reduces plaque angiogenesis and inhibits vessel inflammation.
During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture. Briefly, DVDMS is injected to animals, and then the plaque was locally exposed to pulse ultrasound for a few minutes. Furthermore, a small size clinical trial was conducted on patients with atherosclerosis. Notably, a significant reduction of arterial inflammation and angiogenesis was recorded following a short period of DVDMS-mediated sonodynamic therapy treatment. This beneficial outcome was almost equivalent to the therapeutic outcome after 3-month intensive statin treatment.
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SCFAs alleviate the progression of AAA in both Ca
3
(PO
4
)
2
- and elastase-induced mouse AAA models.
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Propionate expands the pool of Tregs in the cLP and enhances the cell-intrinsic ability of ...cLP-Tregs to recirculate by downregulating CD69 expression on the surface of cLP-Tregs.
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Propionate facilitates the recirculation of cLP-Tregs from the cLP through colonic dLNs and circulating blood to the inflamed aneurysm to mitigate AAA.
Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.
Type 2 CRSwNP is characterized by severe symptoms, multiple comorbidities, longer recovery course and high recurrence rate. A simple and cost-effective diagnostic model for CRSwNP endotype ...integrating clinical characteristics and histopathological features is urgently needed.
To establish a clinical diagnostic model of inflammatory endotype in CRSwNP based on the clinical characteristics, pathological characteristics, and cytokines profile in the polyp tissue of patients.
A total of 244 participants with CRSwNP were enrolled at 2 different centers in China and Belgium from 2018 to 2020. IL-5 level of nasal polyp tissue was used as gold standard. Clinical characteristics were used to establish diagnostic models. The area under the receiver operating curve (AUC) was used to evaluate the diagnostic performance. The study was approved by the ethics board of the First Affiliated Hospital of Sun Yat-sen University (2020 302), and written informed consent was obtained from all subjects before inclusion.
In total, 134 patients from China (training set) and 110 patients from Belgium (validation set) were included. The logistic regression (LR) model in predicting inflammatory endotype of CRSwNP showed the AUC of 83%, which was better than the diagnostic performance of machine learning models (AUC of 61.14%–82.42%), and single clinical variables. We developed a simplified scoring system based on LR model which shows similar diagnostic performance to the LR model (P = 0.6633).
The LR model in this diagnostic study provided greater accuracy in prediction of inflammatory endotype of CRSwNP than those obtained from the machine learning model and single clinical variable. This indicates great potential for the use of diagnostic model to facilitate inflammatory endotype evaluation when tissue cytokines are unable to be measured.
Abstract Background The interaction between Siglec-10 and its ligand, CD24, selectively represses tissue damage-caused immune responses. However, the nature of Siglec-10 and CD24 in human ...hepatocellular carcinoma (HCC) is still poorly defined. Hereon, the expression, function, and regulation of CD24 and Siglec-10 in HCC were investigated in the present study. Methods Flow cytometry was performed to examine the expression of Siglec-10 in HCC tissues and adjacent non-tumor tissues of HCC patients. To further determine whether Siglec-10 expression is associated with the clinical characteristics and survival, conventional immunohistochemistry was performed in 96 HCC patients. Additionally, the role of Siglec-10 in the regulation of natural killer (NK) cell dysfunction was evaluated. Finally, CD24 expression in HCC was also assessed. Results Siglec-10 was expressed most on NK cells in HCC (40.7 ± 4.5%). Compared with surrounding non-tumor tissues, tumor tissues had higher Siglec-10 expression (31.0 ± 1.7% versus 40.7 ± 4.5%, n = 10, P < 0.05), and the expression was negatively associated with patient survival. Siglec-10+ CD56+ NK cells exhibited reduced effector function, as shown by decreased granules and cytokine expressions compared with Siglec-10− CD56+ NK cells. Moreover, the number of CD24+ CD45− cells in HCC tissues was higher than that in adjacent non-tumor tissues (9.4 ± 0.9% versus 3.1 ± 0.9%, n = 15, P < 0.05). Conclusions These findings suggest that Siglec-10 is associated with decreased survival and impaired NK cell function in human HCC. This process may function via the CD24-Siglec-10 interaction, which may represent a therapeutic target in HCC patients.
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