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Background: Epstein-Barr virus DNA (EBV-DNA) is closely related to the pathogenesis and prognosis of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The quantitative measurement of blood EBV-DNA is widely used in EBV-HLH, but there remains a lack of evidence to guide clinicians. Methods: A retrospective analysis was conducted on clinical manifestations, laboratory tests, 310 blood EBV-DNA loads, and prognosis of 51 pediatric patients diagnosed with EBV-HLH. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff values of EBV-DNA for predicting mortality and evaluating the active status of EBV-HLH. Results: EBV-positive- lymphoma-HLH had higher initial plasma EBV-DNA load(1.10 × 106copies/ml) compared to the EBV-HLH group (1.98 × 104 copies/ml) (P = 0.006), and experienced recurrently elevated plasma EBV-DNA levels during treatment. The optimal cut-off value of initial plasma EBV-DNA load in predicting mortality was 2.68 × 105 copies/ml, with a sensitivity of 88.57% and a specificity of 56.25%. For determining the active status of HLH, the optimal cutoff value of PBMC EBV-DNA load during treatment was 2.95 × 105 copies/ml, with a sensitivity of 69.14% and a specificity of 64.71%. The cut-off value of plasma EBV-DNA for determining active status was 1.32 × 103 copies/ml, with a sensitivity of 84.34%, and a specificity of 87.67%. Patients with higher PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses (P < 0.05). Conclusion: Dynamic monitoring of EBV-DNA is a valuable tool for assessing disease status and predicting the prognosis of EBV-HLH, with plasma EBV-DNA being more effective than PBMC EBV-DNA. Patients with high levels of PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management. Methods: This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children's hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests. Results: The study described 153 children aged 0–18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6–12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3–42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38–16 531.18), which was the heaviest among EBV-LPDs. Conclusions: Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) infection is likely to co-occur in pediatric respiratory tract infections (RTIs). Liver injury is the common complication of EBV infection. The detailed risk factors for liver injury in EBV infection remain elusive. We aimed to investigate the incidence, characteristics and potential risk factors for liver injury in EBV infection for early risk prediction. Methods: We retrospectively recruited the pediatric RTIs cases with EBV infection according to a predefined criteria from our hospital between January 2015 and December 2017. We extracted the clinical and laboratory data from the electronical medical records. The impact of age, gender, and various parameters on the liver injury risk was investigated. Univariate logistic regression analysis was performed to analyse the association between clinical/laboratory parameters and liver injury. The related indexes were enrolled in the multivariate logistic regression analysis. Decision curve analysis was used to yield the value of related parameters in predicting liver injury. Receiver operating curve (ROC) analysis was applied to produce the C-index of white blood cell (WBC) count for liver injury. We also tested the non-linear association between WBC count and alanine aminotransferase (ALT). Results: A total of 216 pediatric RTIs with EBV infection were enrolled. EBV infection is more likely to occur during the winter season. Cytomegalovirus infection was independently associated with liver injury in EBV infection (OR = 6.972, 95% CI = 1.648–29.490, p = 0.008). WBC count was independently associated with liver injury in EBV infection (OR = 1.169, 95% CI = 1.051–1.301, p = 0.004). The P interaction value between WBC count and cytomegalovirus was 0.149. The decision curve analysis showed that WBC count had larger area under curve compared with platelet (PLT) and birthweight (BW). ROC analysis yielded the c-index of WBC count: 0.75 and cut-point of 8.3. The turning point of WBC count in its association with ALT was 16.8. The p value before and after the turning point was < 0.001 and 0.123, respectively. Conclusions: Cytomegalovirus co-infection demonstrated 5.972 more times of liver injury risk in EBV infection. WBC count was an independent biomarker for liver injury before the turning point of 16.8 in EBV infection. More attention should be paid to the risk of EBV infection in the winter. Cytomegalovirus infection and WBC count merit attention in the monitoring of possible liver injury in EBV infection among pediatric RTIs. [ABSTRACT FROM AUTHOR]

Background: The incidence and clinical features of primary cutaneous lymphoma (PCL) tend to differ by age, gender, geographical, and racial variation. All-aged and adult groups of PCL in various regions have been well demonstrated and compared, while the research concentrating on pediatric PCL is rare, especially in Asian countries. Objective: The aim of this study was to investigate the clinical characteristics of PCL in pediatric population at a single center in China. Methods: We conducted a retrospective study of 101 pediatric cases with PCL, diagnosed at the Institute of Dermatology, Chinese Academy of Medical Sciences, from January 2010 to December 2021. Results: Mycosis fungoides (MF), accounting for 41.6% of the total cases, was the most common subtype in pediatric PCL, and the hypopigmented MF accounted for 47.6% of all the MF cases. Lymphomatoid papulosis and chronic active Epstein-Barr virus infection tied for second place with a proportion of 22.8%. Primary cutaneous anaplastic large cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, primary cutaneous peripheral T-cell lymphoma, rare subtypes and primary cutaneous B-cell lymphoma, respectively, accounted for 2.0%, 4.0%, 4.0%, and 3.0%. Most patients had favorable prognosis during the follow-up. Conclusion: The study suggested that MF was the most common subtype in pediatric PCL in China, and most types of pediatric PCL had favorable prognosis. [ABSTRACT FROM AUTHOR]

Background. Infectious mononucleosis (IM) is a common viral infection that typically presents with fever, pharyngitis and cervical lymphadenopathy. Our aim was to identify the different pathogens causing IM in children admitted to our hospital and to analyze the differences in features of infection with different organisms. Methods. We retrospectively analyzed the data of children aged 0-17 years admitted to Wuhan Children's Hospital during 2013-2022 with IM. We compared symptoms, physical findings, blood counts, and serum biomarkers between patients with IM due to Epstein-Barr virus (EBV) and IM due to other pathogens. Results. Among 1480 enrolled children, 1253 (84.66%) had EBV infection, 806 (54.46%) had M. pneumoniae infection, 796 (53.78%) had cytomegalovirus infection, 159 (10.74%) had parvovirus infection, 38 (2.57%) had influenza virus infection, and 25 (1.69%) had adenovirus infection. Receiver operating characteristic curves were used to determine the area under the curve for alanine transaminase (ALT), aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin (TBil), indirect bilirubin (IBil) levels to assess liver damage, and for creatine kinase (CK), CK-MB, and lactate dehydrogenase (LDH) levels to assess myocardial damage. The optimal cutoff values of these biomarkers were then determined. In multivariate analysis, elevated ALT, AST, ALP, TBil, and IBil were independently associated with liver damage, and age <3 years, CK, CK-MB, and LDH with myocardial damage. Conclusion. Evaluation of biomarkers and pathogen detection may help physicians to take preventive actions to avoid serious complications in children with infectious mononucleosis. [ABSTRACT FROM AUTHOR]

Previous studies reported the association between Epstein‐Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV‐encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high‐risk (HR)‐HPV was detected in all of EBV‐positive CSCC, and the difference of detection rate of HR‐HPV was significant when compared with EBV‐negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor‐positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+‐tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4)+‐TILs (p = 0.017) and higher expression of programmed cell death‐1 (PD‐1) (p = 0.002) and programmed cell death‐1 ligand 1 (PD‐L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV‐positive CSCC, similar significant differences were still found. In conclusions, EBV‐positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the epidemiology and infectious characteristics of Epstein-Barr virus (EBV) infection among children in Shanghai, China from 2017 to 2022. Methods: We conducted a retrospective analysis of 10,260 inpatient patients who were subjected EBV nucleic acid testing from July 2017 to December 2022. Demographic information, clinical diagnosis, laboratory findings, etc. were collected and analyzed. EBV nucleic acid testing were performed by realtime PCR. Results: A total of 2192 (21.4%) inpatient children were EBV-positive, with the average age of 7.3 ± 0.1 y. EBV detection was stable from 2017 to 2020 (26.9~30.1%), but showed essential decreases in 2021 (16.0%) and 2022 (9.0%). EBV was highest (>30%) detected from three quarters (Q) including 2018-Q4, 2019-Q4 and 2020-Q3. There were 24.5% of EBV coinfection with other pathogens, including bacteria (16.8%), other viruses (7.1%) and fungi (0.7%). EBV viral loads increased when coinfecting with bacteria ((142.2 ± 40.1) ×104/mL) or other viruses ((165.7 ± 37.4) ×104/mL). CRP significantly increased in EBV/fungi coinfection, while procalcitonin (PCT) and IL-6 showed remarkable increases in EBV/bacteria coinfection. Most (58.9%) of EBV-associated diseases belonged to immune disorders. The primary EBV-related diseases were systemic lupus erythematosus (SLE, 16.1%), immunodeficiency (12.4%), infectious mononucleosis (IM, 10.7%), pneumonia (10.4%) and Henoch-schonlein purpura (HSP, 10.2%). EBV viral loads were highest ((233.7 ± 27.4) × 104/mL) in patients with IM. Conclusion: EBV was prevalent among children in China, the viral loads increased when coinfecting with bacteria or other viruses. SLE, immunodeficiency and IM were the primary EBV-related diseases. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most prevalent cancer worldwide and accounts for approximately 20% of cancer-related death in China every year. High-grade lung cancer poses a significant threat to patients, and developing a novel treatment for these patients requires an understanding of its underlying mechanism. Methods: Chinese patients with lung cancer were enrolled. The tumor samples were collected by surgery or puncture and applied for next-generation sequencing. A panel of pan-cancer genes was targeted, and the sequencing depth was set to over 1,000 to improve the sensitivity of detecting mutations. Short-length mutations (substitution, insertion, and deletion), copy number variation, and gene fusion were called. Gene mutations were compared between low-grade, middle-grade, and high-grade tumors using Fisher's exact test. The enriched pathways in each grade of tumors were also inferred. Results: The study included 173 Chinese patients with non-small cell lung cancer, of whom 98 (56.6%) patients were female and 75 (43.4%) were male, with a mean age of 56.8 years. All patients were microsatellite stable; 66.4% were at the early stages (Stages 0, I, and II) with a tumor mutational burden of approximately 2.5 (confidence interval = [0, 48.3]). Compared to low-grade tumors, high-grade tumors had a significantly higher percentage of mutations in TP53 (75.9% vs 34.4%, p = 1.86e-3) and PIK3CA (24.1% vs. 0%, p = 3.58e-3). Pathway analysis found that high-grade tumors were enriched with mutations in bacterial invasion of epithelial cells (31% vs. 0%, p = 5.8e-4), Epstein-Barr virus infection (79.3% vs. 37.5%, p = 1.72e-3), and the Wnt signaling pathway (75.9% vs. 34.4%, p = 1.91e-3). High-grade tumors had a significantly higher tumor mutational burden than low-grade tumors (p-value = 0.0017). However, actionable mutations with high-level evidence were lower in high-grade tumors. Conclusion: Patients with high-grade tumors from lung cancer may be more affected by bacteria and Epstein-Barr virus than low-grade tumors. High-grade tumors were specially mutated in TP53 and PIK3CA and may benefit more from immunotherapy. Further research on the underlying mechanism of high-grade lung cancer is necessary to develop new therapeutic options. Lung cancer, tumor grade, genomic mutations, Epstein-Barr virus, pathway analysis. [ABSTRACT FROM AUTHOR]

Background: Use of kinase inhibitors such as dasatinib and imatinib might increase the risk of opportunistic infections, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. However, the effect of sorafenib on EBV and CMV infections remains unclear. The aim of this study was to investigate the effect of sorafenib maintenance post-transplantation on the incidence and mortality of EBV and CMV infections in patients with FLT3-ITD acute myeloid leukemia.Methods: This was a follow-up of our randomized controlled trial undertaken at seven hospitals in China. The primary endpoint was EBV and CMV infections within 3 years post-transplantation. Secondary endpoints included the cumulative incidences of relapse, non-relapse mortality (NRM), overall survival (OS), leukemia-free survival (LFS), and graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) at 3 years.Results: Two hundred two patients were assigned to sorafenib maintenance (n=100) or non-maintenance (control, n=102). Median extended follow-up post-transplantation was 36.8 (range, 2.5-67.1) months. The 3-year cumulative incidences of EBV-DNAemia and EBV-associated diseases were 24.0% (95% CI: 16.1-32.8%) and 5.0% (1.8-10.6%) in the sorafenib group, and 24.5% (16.6-33.2%) and 5.9% (2.4-11.6%) in the control group (P=0.937; P=0.771). The 3-year cumulative incidences of CMV-DNAemia and CMV-associated diseases were 56.0% (45.6-65.1%) and 8.0% (3.7-14.4%) in the sorafenib group, and 52.9% (42.7-62.1%) and 8.8% (4.3-15.3%) in the control group (P=0.997; P=0.826). The 3-year cumulative mortality of EBV- and CMV-associated diseases was 0.0% (0.0-0.0%) and 2.0% (0.4-6.4%) in the sorafenib group, and 1.0% (0.1-4.8%) and 2.0% (0.4-6.3%) in the control group (P=0.322, P=0.980). The 3-year cumulative incidences of relapse, NRM, OS, LFS, and GRFS were 13.0%, 11.1%, 79.0%, 75.9%, and 65.8% in the sorafenib group and 34.8%, 12.7%, 61.4%, 52.5%, and 46.6% in the control group, respectively (P<0.001, P=0.656, P=0.005, P<0.001, P=0.003). The reconstitution of T lymphocyte subsets, B lymphocytes, and natural killer cells was similar between the two groups (all P>0.05).Conclusions: Sorafenib maintenance post-transplantation does not increase the incidence and mortality of EBV and CMV infections, demonstrating a favorable safety profile.Trial Registration: ClinicalTrials.gov Identifier: NCT02474290 . Registered on June 14, 2015. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is often associated with the infection of Epstein-Barr virus in nasopharynx and is mainly happened in South China and Southeast Asia. Recently, noncoding RNAs have been reported to regulate NPC carcinogenesis. LncRNA OIP5-AS1 participates in tumorigenesis and progression; however, the inherent mechanism of OIP5-AS1-mediated progression of NPC is unclear. In the current study, we aimed to explore the role of OIP5-AS1 in NPC progression. We measured the cell viability, apoptosis, migration, and invasion in NPC cells after OIP5-AS1 modulation. Moreover, we determined whether OIP5-AS1 exerts its oncogenic functions via sponging miR-183-5p in NPC. Furthermore, we determined whether glutamate ammonia ligase (GLUL) was a downstream target of miR-183-5p. We found that OIP5-AS1 downregulation inhibited the viability, migration and invasion of NPC via targeting miR-183-5p. We also identified that GLUL might be a potential downstream target of miR-183-5p in NPC cells. Mechanistically, OIP5-AS1 promotes cell motility via regulating miR-183-5p and GLUL in NPC cells. We concluded that OIP5-AS1 performed its biological functions via targeting miR-183-5p and GLUL in NPC cells. [ABSTRACT FROM AUTHOR]