Epstein-Barr virus (EBV) is a human herpesvirus that latently infects approximately 95% of adults and is associated with a spectrum of human diseases including Infectious Mononucleosis and a variety ...of malignancies. However, understanding the pathogenesis, vaccines and antiviral drugs for EBV-associated disease has been hampered by the lack of suitable animal models. Tree shrew is a novel laboratory animal with a close phylogenetic relationship to primates, which is a critical advantage for many animal models for human disease, especially viral infections. Herein, we first identified the key residues in the CR2 receptor that bind the gp350 protein and facilitate viral entry. We found that tree shrew shares 100% sequence identity with humans in these residues, which is much higher than rabbits (50%) and rats (25%).
analysis showed that B lymphocytes of tree shrews are susceptible to EBV infection and replication, as well as EBV-enhanced cell proliferation. Moreover, results of
experiments show that EBV infection in tree shrews resembles EBV infection in humans. The infected animals exhibited transient fever and loss of weight accompanied by neutropenia and high viremia levels during the acute phase of the viral infection. Thereafter, tree shrews acted as asymptomatic carriers of the virus in most cases that EBV-related protein could be detected in blood and tissues. However, a resurgence of EBV infection occurred at 49 dpi. Nanopore transcriptomic sequencing of peripheral blood in EBV-infected animals revealed the dynamic changes in biological processes occurring during EBV primary infection. Importantly, we find that neutrophil function was impaired in tree shrew model as well as human Infectious Mononucleosis datasets (GSE85599 and GSE45918). In addition, retrospective case reviews suggested that neutropenia may play an important role in EBV escaping host innate immune response, leading to long-term latent infection. Our findings demonstrated that tree shrew is a suitable animal model to evaluate the mechanisms of EBV infection, and for developing vaccines and therapeutic drugs against EBV.
Objective: To retrospectively analyze the risk factors for death in patients with nasal or nasopharyngeal bleeding after radiotherapy for nasopharyngeal carcinoma, and to explore clinical management ...strategies for the disease.
Methods: This was a retrospective case-control study. The clinical data from patients diagnosed with nasopharyngeal or nasopharyngeal hemorrhage after radiotherapy for nasopharyngeal carcinoma at the First Affiliated Hospital of Guangxi Medical University between January 2006 and October 2021 were retrospectively analyzed. Chi-square analysis and odds ratio (OR) calculation were performed to evaluate the death risk factors associated with the disease. And binary logistic regression analysis was used to detect some independent factors in this study.
Results: Of the 85 patients, 71 (83.5%) were male and 14 (14.5%) were female; 11 patients died (mortality rate: 12.9%), of which 9 died of asphyxia (7 with hemorrhagic shock), 1 died of multiorgan failure and acute respiratory distress syndrome, and 1 died of left cerebellar infarction. Nine potential mortality factors were evaluated; age, sex, nasal tamponade, and open mouth restriction were not significantly associated with death (P > 0.5); absence of immediate airway protection (in the major bleeding group) , absence of angiography, skull base destruction, major bleeding, and re-irradiation were significantly associated with death (P < 0.05). Among these factors, binary logistic regression model showed increased risk of death in patients without immediate airway protection (OR=18.14,95%CI:1.48–221.64), in patients without angiography (OR=14.65, 95%CI:2.37–90.73), and in those with re-irradiation (OR=13.23,95%CI:1.004–174.23).
Conclusion: Binary logistic regression model shows that absence of immediate airway protection, absence of angiography, and re-irradiation are independent risk factors for death. The mortality rate due to bleeding after radiotherapy for nasopharyngeal carcinoma is high, and active management and intervention to address the risk factors for death is key to treat the disease and save patients' lives. At the same time, we need to consider the patient's causative state of bleeding.
Radiotherapy is an effective treatment for local solid tumors, but the mechanism of damage to human body caused by radiation therapy needs further study. In this study, gene expression profiles of ...human peripheral blood samples exposed to different doses and rates of ionizing radiation (IR) were used for bioinformatics analysis to investigate the mechanism of IR damage and radiation-induced bystander effect (RIBE). Differentially expressed genes analysis, weighted gene correlation network analysis, functional enrichment analysis, hypergeometric test, gene set enrichment analysis, and gene set variation analysis were applied to analyze the data. Moreover, receiver operating characteristic curve analysis was performed to identify core genes of IR damage. Weighted gene correlation network analysis identified 3 modules associated with IR damage, 2 were positively correlated and 1 was negatively correlated. The analysis showed that the positively correlated modules were significantly involved in apoptosis and p53 signaling pathway, and ESR1, ATM, and MYC were potential transcription factors regulating these modules. Thus, the study suggested that apoptosis and p53 signaling pathway may be the potential molecular mechanisms of IR damage and RIBE, which could be driven by ESR1, ATM, and MYC.
Systematic classification and determination of various cells in normal peripheral blood of artificially feeding Tupaia belangeri chinensis of different ages and genders and evaluation of the ...effectiveness of an automatic blood cell classification counter for measuring tree shrew blood cells. Child, young and adult tree shrews (forty for each group) were randomly selected, half male and half female. After the animals were stable, the peripheral blood of each group was collected through the femoral vein, and the morphology of various blood cells of the tree shrew was observed and classified by the manual microscopic counting method and by an automatic blood cell classification counter. The Reference intervals of the normal peripheral blood cell absolute count, cell diameter and white blood cell percentage in tree shrews of different ages and genders has been calculated. White blood cell count and neutrophil relative count increased with age, while lymphocyte relative count decreased. The white blood cell count, neutrophil relative count, and lymphocyte relative count in the child group, as well as lymphocyte relative count in the young group, significantly differed according to gender (P<0.05), and the differences in other indicators were not significant. The Bland-Altman plot and the Passing-Bablok scattergram showed that the change trend of each indicator was consistent but exhibited large systematic differences between methods. Differences in peripheral blood cells exist among different age groups and different genders. An automatic blood cell classification counter is not suitable for the absolute count of blood cells in the tree shrew.
The aim of the present study was to collect published studies and compare the diagnostic accuracy of different markers for nasopharyngeal carcinoma (NPC). We systematically searched PubMed/MEDLINE, ...EMBASE, Cochrane Library, CNKI, and Wanfang for relevant studies until April 29, 2020. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the methodological quality of the studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) values of the diagnostic markers were combined by a bivariate mixed effect model to compare their diagnostic accuracy. We explored heterogeneity through meta-regression. In total, 244 records from 101 articles were included, with 49,432 total study subjects (13,109 cases and 36,323 controls). EA-IgG, Zta-IgG, and Epstein-Barr virus (EBV) DNA load in non-invasive nasopharyngeal brushings (EBV-DNA brushings) have both high sensitivity and specificity, EBNA1-IgG and VCA-IgG have only high sensitivity, and EBNA1-IgA, VCA-IgA, Rta-IgG, Zta-IgA, HSP70, and serum sialic acid (SA) have only high specificity. The bivariate mixed effect model of EA-IgA had a significant threshold effect. Meta-regression analysis showed that ethnicity affected EBNA1-IgA, EBNA1-IgG, VCA-IgA, and EBV DNA load in plasma, test methods affected EBNA1-IgG, publication year affected VCA-IgA, and sample size affected Rta-IgG. There was significant publication bias for VCA-IgA and Rta-IgG (P < 0.05). EA-IgG, Zta-IgG, and EBV-DNA brushings are good diagnostic markers for NPC. The diagnostic accuracy was influenced by publication year, sample size, test methods, and ethnicity.
Objective
The anatomic structure of the cochlear aqueduct (CA) in human temporal bone specimens was observed using micro-computed tomography (CT).
Materials and methods
Micro-CT scanning of ...18-µm-thick slices was performed on 30 slides of human temporal bone specimens to observe the CA structure and its relationship with its surroundings. The length, internal and external apertures, and the narrowest width of the CA were measured. The differences in CAs were compared between high jugular bulb (HJB) specimens and normal specimens.
Results
A large number of CA images were acquired using Micro-CT scanning, which clearly displayed the basic anatomic structures, stereotactic localizations, and adjacent relationships of the CAs. The whole course of a CA was 12.31 ± 3.60 mm, the diameter of the internal aperture was 465 ± 242 µm, the diameter of the external aperture was 2.88 ± 1.06 mm, the narrowest diameter was 601 ± 335 µm, the diameter of the opening of inferior cochlear vein (ICV) was 151 ± 50 µm, the distance between the internal aperture and ICV was 270 ± 197 µm, and the distance between the inferior margin of the internal acoustic meatus (IAM) and the top most part of the external aperture of the CA was 6.783 ± 2.15 mm. No bony obstruction of the CA or CA enlargement was observed in the specimens. A total of 28 CAs had one accompanying bony canal in the surroundings. The length and travelling of the CA were not affected by the level of the jugular bulb (JB). The variation of the travelling of the ICV was larger than that of the CA.
Conclusion
Micro-CT adequately displayed the bony CA canal and provided a new method for anatomical studies of the CA and a basis for functional studies.
Reliable predictors for rehabilitation outcomes in patients with congenital sensorineural hearing loss (CSNHL) after cochlear implantation (CI) are lacking. The purchase of this study was to develop ...a nomogram based on clinical characteristics and neuroimaging features to predict the outcome in children with CSNHL after CI.
Children with CSNHL prior to CI surgery and children with normal hearing were enrolled into the study. Clinical data, high resolution computed tomography (HRCT) for ototemporal bone, conventional brain MRI for structural analysis and brain resting-state fMRI (rs-fMRI) for the power spectrum assessment were assessed. A nomogram combining both clinical and imaging data was constructed using multivariate logistic regression analysis. Model performance was evaluated and validated using bootstrap resampling.
The final cohort consisted of 72 children with CSNHL (41 children with poor outcome and 31 children with good outcome) and 32 healthy controls. The white matter lesion from structural assessment and six power spectrum parameters from rs-fMRI, including Power4, Power13, Power14, Power19, Power23 and Power25 were used to build the nomogram. The area under the receiver operating characteristic (ROC) curve of the nomogram obtained using the bootstrapping method was 0.812 (95 % CI = 0.772–0.836). The calibration curve showed no statistical difference between the predicted value and the actual value, indicating a robust performance of the nomogram. The clinical decision analysis curve showed a high clinical value of this model.
The nomogram constructed with clinical data, and neuroimaging features encompassing ototemporal bone measurements, white matter lesion values from structural brain MRI and power spectrum data from rs-fMRI showed a robust performance in predicting outcome of hearing rehabilitation in children with CSNHL after CI.
Epstein-Barr virus (EBV) is closely associated with many human diseases, including a variety of deadly human malignant tumours. However, due to the lack of ideal animal models,the biological ...characteristics of EBV, particularly its function in tumourigenesis, have not been determined. Chinese tree shrews (Tupaia belangeri chinensis), which are similar to primates, have been used to establish a variety of animal models and have recently received much attention. Here, we established tree shrews as a model for EBV infection by intravenous injection.
Ten tree shrews were inoculated with EBV by intravenous injection,and blood was collected at regular intervals thereafter from the femoral artery or vein to detect EBV markers.
Eight of 10 tree shrews showed evidence of EBV infection. In the 8 EBV-infected tree shrews, EBV copy number increased intermittently or transiently, EBV-related gene expression was detected, and anti-EBV antibodies increased to varying degrees. Macroscopic hepatomegaly was observed in 1 tree shrew, splenomegaly was observed in 4 tree shrews, and enlarged mesenteric lymph nodes were observed in 3 tree shrews. Haematoxylin and eosin (HE) staining showed splenic corpuscle hyperplasia in the spleens of 4 tree shrews and inflammatory cell infiltration of the liver of 1 tree shrew and of the mesenteric lymph nodes of 3 tree shrews. EBER in situ hybridization(ISH) and immunohistochemical (IHC) staining showed that EBER-, LMP1- and EBNA2- positive cells were present in the spleens and mesenteric lymph nodes of some tree shrews. Western blotting (WB) revealed EBNA1-positive cells in the spleens of 4 tree shrews. EBV markers were not detected by HE, EBER-ISH or IHC in the lung or nasopharynx.
These findings suggest that EBV can infect tree shrews via intravenous injection. The presented model offers some advantages for exploring the pathophysiology of EBV infection in humans.
Background
Osteogenesis imperfecta type I (OI‐I) is a rare genetic disorder characterized by skeletal deformity, bone fragility, blue sclerae, dentinogenesis imperfecta, and hearing loss. The current ...study aimed to confirm the clinical diagnosis and genetic cause of OI‐I in a four‐generation Chinese family.
Methods
Clinical investigation and pedigree analysis were conducted to characterize the phenotypic manifestations of a Chinese family with OI‐I. Follow‐up audiometry and imaging tests were used to evaluate the postoperative outcomes of stapes surgery in the proband with otosclerosis. Whole‐exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variants and for cosegregating analysis.
Results
We described in detail the clinical features of the collected family with autosomal dominant OI‐I, and firstly identified a pathogenic splicing variant (c.2344‐1G>T) in intron 33 of COL1A1 in a Chinese family. The molecular analysis suggested that the mutation might cause splice site changes that result in a loss of gene function. The proband, who suffered from otosclerosis and presented two‐side middle‐severe conductive hearing loss, benefitted significantly from successive bilateral middle ear surgery.
Conclusions
The diagnosis of OI‐I in a Chinese family was established by clinical and genetic investigation. A heterozygous pathogenic splicing variant in COL1A1 was directly responsible for the bone fragility and hearing loss of this family. Otosclerosis surgery should be suggested to rehabilitate conductive hearing impairment in OI patients.
1. A heterozygous pathogenic splicing variant (c.2344‐1 G > A) was firstly identified in a four‐generation Chinese family with osteogenesis imperfecta type I. 2. The c.2344‐1 G > A COL1A1 mutation might cause splice site changes that result in a loss of gene function. 3. Otosclerosis surgery should be suggested to rehabilitate conductive hearing impairment in OI‐I patients.
To understand the morphology and anatomical data of the temporal bone of tree shrews through micro-computed tomography (micro-CT) and microdissection.
Skull specimens from 10 tree shrews were scanned ...using micro-CT examination. The acquired images were used for three-dimensional reconstruction and measurement using the Mimics 10.01 software. Twenty tree shrews were subjected to microdissection and the data were measured.
Micro-CT and three-dimensional reconstruction could clearly define the three-dimensional spatial position of the ear structure. Micro-CT and microdissection showed that the otic vesicles of the tree shrews were located on both sides of posterior-inferior skull bone. The location of the otic vesicles was superficial, and the bone was thin. All of the structures of the middle and inner ear of the tree shrews were well developed. The ossicular chain was differentiated into the malleus, incus and stapes. The location of the three semi-circular canals of the tree shrews was superficial and easy to dissect. In vivo, the three semi-circular canals were easy to localize and the surface bone was thin. The contour and structure of the cochlea and number of cochlear turns were similar to those in humans.
This study could provide anatomical data to allow tree shrews to be used as animal models for studying ear diseases.
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