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Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology-based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches.

Introduction Hemorrhagic transformation (HT) is a complex and multifactorial complication among patients with acute ischemic stroke (AIS), and the inflammatory response has been considered as a risk factor for HT. We aimed to evaluate the stratification of FAR (fibrinogen‐to‐albumin ratio), an inflammatory biomarker, in HT patients. Methods A total of 256 consecutive stroke patients with HT and 256 age‐ and gender‐matched stroke patients without HT were included in this study. HT during hospitalization was diagnosed by follow‐up imaging assessment and was classified into hemorrhagic infarction (HI) and parenchymal hematoma (PH) according to the recommendations of European Cooperative Acute Stroke Study II classification. Blood samples were obtained at admission. Results Higher levels of FAR were observed in patients with HT compared with the non‐HT group [10.29 (8.39–12.95) vs. 8.60 (7.25–10.8), p < .001], but no significant difference was found between the PH and HI [10.88 (8.72–13.40) vs. 10.13 (8.14–12.60), p > .05]. Patients were assigned to groups of high FAR (≥9.51) and low FAR (<9.51) based on the optimal cut‐off value. After adjustment for potential confounders, the high FAR remained independently associated with the increased risk of HT (OR = 5.027, 95% CI = 5.027 (2.309–10.942), p < .001). Conclusions High FAR was independently associated with the increased risk of HT after AIS. This study is the first to explore the association between fibrinogen‐to‐albumin ratio (FAR) and hemorrhagic transformation (HT) in acute ischemic stroke patients. We observed that FAR was associated with HT. The calculation of FAR may assist clinicians identify patients at elevated risk of HT and make better‐informed individualized treatment.

The presence of alveolar epithelial type II cells (AECIIs) is one of the most important causes of bronchopulmonary dysplasia (BPD). Exosomes from bone mesenchymal stem cells (BMSCs) can reduce hyperoxia-induced damage and provide better results in terms of alveolar and pulmonary vascularization parameters than BMSCs. Currently, intervention studies using BMSC-derived exosomes on the signaling pathways regulating proliferation and apoptosis of alveolar epithelial cells under the condition of BPD have not been reported. This study investigated the effects of rat BMSC-derived exosomes on the proliferation and apoptosis of hyperoxia-induced primary AECIIs . The isolated AECIIs were grouped as follows: normal control (21% oxygen), hyperoxia (85% oxygen), hyperoxia+exosome (20 µg/mL), hyperoxia+exosome+LY294002 (PI3K/Akt inhibitor, 20 µM), and hyperoxia+exosome+rapamycin (mTOR inhibitor, 5 nM). We used the PI3K/Akt inhibitor LY294002 and the mTOR inhibitor rapamycin to determine the roles of the PI3K/Akt and mTOR signaling pathways. The effects of BMSC-derived exosomes on AECII proliferation and apoptosis were assessed, respectively. Decreased levels of the antiapoptotic protein Bcl-2, the cell proliferation protein Ki67, p-PI3K, p-Akt, and p-mTOR, as well as increased levels of AECII apoptosis and the proapoptotic protein Bax in the hyperoxia group were observed. Notably, Sprague Dawley rat BMSC-derived exosomes could reverse the effect of hyperoxia on AECII proliferation. However, the application of LY294002 and rapamycin inhibited the protective effects of BMSC-derived exosomes. Our findings revealed that BMSC-derived exosomes could regulate the expression of apoptosis-related proteins likely via the PI3K/Akt/mTOR signaling pathway, thereby preventing hyperoxia-induced AECII apoptosis.

Many studies have sought to construct a substitute to partially replace irreparably damaged meniscus. Only the meniscus allograft has been used in clinical practice as a useful substitute, and there are concerns about its longevity and inherent limitations, including availability of donor tissue and possibility of disease transmission. To overcome these limitations, we developed an acellular xenograft from whole porcine meniscus. Samples were treated with 2% Triton X-100 for 10 days and 2% sodium dodecyl sulfate for 6 days. The DNA content of extracellular matrix (ECM) scaffolds was significantly decreased compared with that of normal porcine menisci ( p < 0.001). Histological analysis confirmed the maintenance of ECM integrity and anisotropic architecture in the absence of nuclei. Biochemical and biomechanical assays of the scaffolds indicated the preservation of collagen ( p = 0.806), glycosaminoglycan ( p = 0.188), and biomechanical properties (elastic modulus and transition stress). The scaffolds possessed good biocompatibility and supported bone marrow mesenchymal stem cells (BMSCs) proliferation for 2 weeks in vitro , with excellent region-specific recellularization in vivo . The novel scaffold has potential value for application in recellularization and transplantation strategies.

Background Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses. Results We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group. Conclusions Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.

Nasopharyngeal carcinoma (NPC) is one of the common cancers in South China. It can easily invade into cranial nerves, especially in patients with local advanced disease. Despite the fact that the magnetic resonance imaging (MRI) findings are not always consistent with the symptoms of CN palsy, MRI is recommended for the detection of CN involvement (CNI). However, the prognostic impact of MRI-detected CNI in NPC patients is still controversial. To investigate the prognostic value of MRI detected CNI, we performed a retrospective analysis on the clinical data of 375 patients with NPC who were initially diagnosed by MRI. All patients had T3-4 disease and received radical intensity modulated radiation therapy (IMRT) as their primary treatment. The incidence of MRI-detected CNI was 60.8%. A higher incidence of MRI-detected CNI was observed in T4 disease compared with T3 disease (96.8% vs. 42.8%, P<0.001), and a higher incidence was also found in patients with Stage IV disease compared with those with Stage III disease (91.5% vs. 42.3%; P<0.001). The local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of patients with T3 disease, with or without MRI-detected CNI, was superior to that of patients with T4 disease (P<0.05). No significant differences in LRFS, DMFS or OS were observed between T3 patients with or without MRI-detected CNI. The survival of Stage III patients with or without MRI-detected CNI was significantly superior to that of Stage IV patients (P<0.01), but there was no significant difference between Stage III patients with or without MRI-detected CNI for all endpoints. Therefore, when treated with IMRT, MRI-detected CNI in patients with NPC does not appear to affect the prognosis. In patients with clinical T3 disease, the presence of MRI-detected CNI is not sufficient evidence for defining T4 disease.

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and meniscus allografts represent the treatment of choice; however, they have several limitations, including availability and compatibility. Another approach is the use of artificial implants but their chondroprotective activities are still not proved clinically. In this situation, tissue engineering offers alternative natural decellularized extracellular matrix (ECM) scaffolds, which have shown biomechanical properties comparable to those of native menisci and are characterized by low immunogenicity and promising regenerative potential. In this article, we present an overview of meniscus decellularization methods and discuss their relative merits. In addition, we comparatively evaluate cell types used to repopulate decellularized scaffolds and analyze the biocompatibility of the existing experimental models. At present, acellular ECM hydrogels, as well as slices and powders, have been explored, which seems to be promising for partial meniscus regeneration. However, their inferior biomechanical properties (compressive and tensile stiffness) compared to natural menisci should be improved. Although an optimal decellularized meniscus scaffold still needs to be developed and thoroughly validated for its regenerative potential in vivo, we believe that decellularized ECM scaffolds are the future biomaterials for successful structural and functional replacement of menisci.

Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. Stress hyperglycemia is frequent in patients with acute illness such as stroke. We aimed to explore the association between stress hyperglycemia and HT in AIS patients. A total of 287 consecutive participants with HT and 285 age- and sex-matched stroke patients without HT were enrolled in this study. Baseline glucose and glycated hemoglobin (HbA1c) levels were collected to measure stress hyperglycemia. The stress hyperglycemia ratio (SHR) was calculated by dividing the fasting plasma glucose at admission with HbA1c. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction type (HI) 1 or 2 or parenchymal hematoma type (PH) 1 or 2. Univariate analysis showed that SHR is significantly higher among patients with HT than those without HT. Compared to the patients in the lower three quartiles of SHR, the incidence of HT was significantly higher among patients with the highest quartile of SHR in total population, diabetic and non-diabetic population. We also observed that patients with the highest SHR quartile were associated with an increased risk of hemorrhagic transformation after adjusted for potential covariates (68.4% versus 39.1%; adjusted odds ratio, 2.320; 95% confidence interval, 1.207-4.459; =0.012). The stress hyperglycemia ratio, representing the state of stress hyperglycemia, was significantly associated with an increased risk of hemorrhagic transformation in patients with acute ischemic stroke.

Neonatal hypoxic-ischemic brain damage (HIBD) is a common clinical syndrome in newborns. Hypothermia is the only approved therapy for the clinical treatment; however, the therapeutic window of hypothermia is confined to 6 h after birth and even then, >40% of the infants either die or survive with various impairments, including cerebral palsy, seizure disorder and intellectual disability following hypothermic treatment. The aim of the present study was to determine whether nasal transplantation of Cytoglobin (CYGB) genetically modified human umbilical cord-derived mesenchymal stem cells (CYGB-HuMSCs) exhibited protective effects in neonatal rats with HIBD compared with those treated without genetically modified CYGB. A total of 120 neonatal Sprague-Dawley rats (postnatal day 7) were assigned to either a Sham, HIBD, HuMSCs or CYGB-HuMSCs group (n = 30 rats/group). For HIBD modeling, rats underwent left carotid artery ligation and were exposed to 8% oxygen for 2.5 h. A total of 30 min after HI, HuMSCs (or CYGB-HuMSCs) labeled with enhanced-green fluorescent protein (eGFP) were intranasally administered. After modeling for 3, 14 and 29 days, five randomly selected rats were sacrificed in each group, and the expression levels of CYGB, ERK, JNK and p38 in brain tissues were determined. Nissl staining of the cortex and hippocampal Cornu Ammonis 1 area of rats in each group were compared after 3 days of modeling. TUNEL assay and immunofluorescence were performed 3 days after modeling. Long term memory in rats was assessed using a Morris-water maze 29 days after modeling. The HIBD group demonstrated significant deficiencies compared with the Sham group based on Nissl staining, TUNEL assay and the Morris-water maze test. HuMSC treated rats exhibited improvement on in all the tests, and CYGB-HuMSCs treatment resulted in further improvements. PCR and western blotting results indicated that the CYGB mRNA and protein levels were increased from day 3 to day 29 after transplantation of CYGB-HuMSCs. Furthermore, it was identified that CYGB-HuMSC transplantation suppressed p38 signaling at all experimental time points. Immunofluorescence indicated the scattered presence of HuMSCs or CYGB-HuMSCs in damaged brain tissue. No eGFP and glial fibrillary acidic protein or eGFP and neuron-specific enolase double-stained positive cells were found in the brain tissues. Therefore, CYGB-HuMSCs may serve as a gene transporter, as well as exert a neuroprotective and antiapoptotic effect in HIBD, potentially via the p38 mitogen-activated protein kinase signaling pathway.