Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.
Humans ; Male ; Middle Aged ; Atrial Fibrillation ; Epstein-Barr Virus Infections ; Fibrin/genetics* ; Herpesvirus 4, Human/genetics* ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Myxoma ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Proto-Oncogene Proteins c-bcl-6/genetics*

Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

Humans ; Lymphohistiocytosis, Hemophagocytic ; Herpesvirus 4, Human ; Interleukin-2 ; Epstein-Barr Virus Infections/complications* ; T-Lymphocytes

The study investigated the inhibitory effect and mechanism of tectorigenin derivative(SGY) against herpes simplex virus type Ⅰ(HSV-1) by in vitro experiments. The cytotoxicity of SGY and positive drug acyclovir(ACV) on African green monkey kidney(Vero) cells and mouse microglia(BV-2) cells was detected by cell counting kit-8(CCK-8) method, and the maximum non-toxic concentration and median toxic concentration(TC_(50)) of the drugs were calculated. After Vero cells were infected with HSV-1, the virulence was determined by cytopathologic effects(CPE) to calculate viral titers. The inhibitory effect of the tested drugs on HSV-1-induced cytopathy in Vero cells was measured, and their modes of action were initially explored by virus adsorption, replication and inactivation. The effects of the drugs on viral load of BV-2 cells 24 h after HSV-1 infection and the Toll-like receptor(TLR) mRNA expression were detected by real-time fluorescence quantitative PCR(RT-qPCR). The maximum non-toxic concentrations of SGY against Vero and BV-2 cells were 382.804 μg·mL~(-1) and 251.78 μg·mL~(-1), respectively, and TC_(50) was 1 749.98 μg·mL~(-1) and 2 977.50 μg·mL~(-1), respectively. In Vero cell model, the half maximal inhibitory concentration(IC_(50)) of SGY against HSV-1 was 54.49 μg·mL~(-1), and the selection index(SI) was 32.12, with the mode of action of significantly inhibiting replication and directly inactivating HSV-1. RT-qPCR results showed that SGY markedly reduced the viral load in cells. The virus model group had significantly increased relative expression of TLR2, TLR3 and tumor necrosis factor receptor-associated factor 3(TRAF3) and reduced relative expression of TLR9 as compared with normal group, and after SGY intervention, the expression of TLR2, TLR3 and TRAF3 was decreased to different degrees and that of TLR9 was enhanced. The expression of inflammatory factors inducible nitric oxide synthase(iNOS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) was remarkably increased in virus model group as compared with that in normal group, and the levels of these inflammatory factors dropped after SGY intervention. In conclusion, SGY significantly inhibited and directly inactivated HSV-1 in vitro. In addition, it modulated the expression of TLR2, TLR3 and TLR9 related pathways, and suppressed the increase of inflammatory factor levels.
Animals ; Antiviral Agents/therapeutic use* ; Chlorocebus aethiops ; Herpes Simplex/pathology* ; Herpesvirus 1, Human/metabolism* ; Isoflavones ; Mice ; TNF Receptor-Associated Factor 3/pharmacology* ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 3/metabolism* ; Toll-Like Receptor 9/metabolism* ; Toll-Like Receptors/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Vero Cells ; Virus Replication

OBJECTIVE: To investigative the detection value of EB virus DNA (EBV-DNA), interleukin-2 (IL-2), and interleukin-6 (IL-6) level in peripheral blood of children with infectious mononucleosis (IM). METHODS: A total of 59 children clinically confirmed with IM in Anhui Provincial Children's Hospital from January 2018 to September 2020 were enrolled as IM group, while other 30 healthy children undergoing physical examination during the same period were enrolled as healthy group. The level of EBV-DNA load, IL-2, and IL-6 were compared between the two groups, and their diagnostic values for IM children were explored. According to the median level of EBV-DNA load, positive children were divided into high viral load group and low viral load group. The hepatomegaly and splenomegaly, and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-2, and IL-6 were compared between the two groups. The relationship between EBV-DNA load and IL-2, IL-6 levels were explored. RESULTS: The positive rate of EBV-DNA was 67.80% in IM group, which was significantly higher than 10.00% in healthy group (P<0.001), and the levels of serum IL-2 and IL-6 were also significantly higher than healthy group (P<0.001). The results of ROC curve analysis showed that AUC of IL-2 combined with IL-6 and EBV-DNA load was 0.948, which was significantly greater than that of IL-2, IL-6, and EBV-DNA load alone (0.847, 0.728, 0.789) (P<0.001). The cut-off value of IL-2 and IL-6 was 15.545 pg/ml and 56.560 pg/ml, respectively. Both the proportions of cases with moderate to severe hepatomegaly and splenomegaly in high viral load group were significantly higher than those in low viral load group (P<0.01, P<0.05). The levels of ALT, AST, and IL-2 in high viral load group were significantly higher than those in low viral load group (P<0.001), as well as IL-6 (P<0.01). In high and low viral load groups, EBV-DNA load was positively correlated with IL-2 and IL-6 (in high viral load group, r_IL-2=0.598, r_IL-6=0.416; in low viral load group, r_IL-2=0.621, r_IL-6=0.527, P<0.001). CONCLUSION The detection of EBV-DNA load combined with IL-2 and IL-6 can improve the diagnostic accuracy of IM, and EBV-DNA load, IL-2 and IL-6 levels are related to the disease progression.
Child ; DNA, Viral ; Epstein-Barr Virus Infections ; Hepatomegaly ; Herpesvirus 4, Human ; Humans ; Infectious Mononucleosis/diagnosis* ; Interleukin-2/blood* ; Interleukin-6/blood* ; Splenomegaly

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.
Adenocarcinoma ; Case-Control Studies ; DNA Mismatch Repair ; Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; Humans ; Male ; Middle Aged ; Mismatch Repair Endonuclease PMS2/metabolism* ; MutL Protein Homolog 1/genetics* ; MutS Homolog 2 Protein/metabolism* ; Retrospective Studies ; Stomach Neoplasms

Herpes simplex virus (HSV) is a common pathogen, that causes a broad spectrum of diseases, ranging from minor skin infections to severe encephalitis and widespread infections. Acute retinal necrosis (ARN), one of the most serious manifestations of HSV infection, is defined as a rapidly progressing necrotizing retinopathy that presents discrete areas of circumferential retinal necrosis, along with signs of uveitis, vitreitis, and retinal vasculitis. We encountered a case of a female infant, born at 33 weeks of gestation with a body weight at birth of 2,080 g, who had ARN and encephalomalacia due to HSV infection. ARN associated with HSV infection should be suspected when nonspecific retinal exudates are observed in neonates, especially preterm infants.
Body Weight ; Encephalitis ; Encephalomalacia ; Exudates and Transudates ; Female ; Herpes Simplex ; Herpesvirus 2, Human ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Necrosis ; Parturition ; Pregnancy ; Retinal Necrosis Syndrome, Acute ; Retinal Vasculitis ; Retinaldehyde ; Simplexvirus ; Skin ; Uveitis

To explore the antiviral activity of nano-realgar against herpes simplex virus Type II (HSV-2) in vitro.
 Methods: Acyclovir (ACV) as a positive control, the cytotoxicity of nano-realgar at different concentrations (including 200.00, 150.00, 100.00, 50.00, 25.00, 12.50, 6.25, 3.13, 1.54, 0.78, 0.39 and 0 mg/L) on normal Vero cells were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. HSV-2 virus titer was determined by plaque assay, and the Vero cells model of HSV-2 infection was established. Subsequently, the antiviral effects of nano-realgar at different concentrations (including 20.00, 10.00, 5.00, 2.50, 1.25, 0.63, 0.31, 0.15, 0.08, 0.04 and 0 mg/L) on infected cells model were evaluated by the observation of cytopathic effect (CPE) and MTT method under the 3 modes including pre-treatment, treatment and direct inactivation.
 Results: The 50% cytotoxic concentration (CC50) of nano-realgar on Vero cells was 37.15 mg/L. The titer of HSV-2 was 7.30 log PFUs/mL. In the 3 modes, the half-maximal effective concentration (EC50) of nano-realgar on HSV-2 infected Vero cells were 0.13, 1.80 and 0.52 mg/L, and the corresponding therapeutic index (TI) were 285.77, 20.64, 71.44, respectively. The TI value of nano-realgar on pre-treatment mode was higher than that of nano-realgar on treatment and direct inactivation modes.
 Conclusion: Nano-realgar can play a good anti-HSV-2 activity in the 3 modes (pre-treatment, treatment and direct inactivation), and the anti-HSV-2 efficacy of nano-realgar on pre-treatment mode is better than that of nano-realagr on other 2 modes.
Animals ; Antiviral Agents ; Arsenicals ; Chlorocebus aethiops ; Herpesvirus 1, Human ; Herpesvirus 2, Human ; Sulfides ; Vero Cells

BACKGROUND: Human papillomavirus (HPV) genotypes that infect the genital tract play a main etiologic role in cervical cancer progression. Other environmental factors, such as sexually transmitted diseases and the host genetic pattern, contribute to infection persistence of the uterus and cervical epithelium in sustaining their malignancy. The Janus kinase 2 is a non-receptor tyrosine kinase in cell signaling process of tumor genesis. In the present study, JAK2 V167F mutation was distinguished in women with sexually transmitted infections, such as Herpes simplex virus 2, Chlamydia trachomatis and Mycoplasma genitalium and cervical cancer. METHODS: This case-control survey was performed on 195 liquid based cytology of women specimens. Fifty, 98, and 47 samples were from women with known cervical cancer, HPV positive and HPV negative, respectively. Single nucleotide polymorphism analysis, sexually transmitted infections detection and HPV genotyping were carried out using approved PCR- RFLP, in-house multiplex TaqMan Real Time PCR and the reverse dot blot hybridization assay. RESULTS: HPVs 6, 16, 18, 11, 31, and 51 were the most common genotypes. The prevalence rate of multiple HPV genotypes was 46.0% to 10.1%. Analysis of JAK2 V617F (1849 G > T) showed that prevalence of mutation was GG (65.1%), GA (34.9%), and TT (0%), respectively. There were no statistically significant differences between this mutation and variables of population survey (P ≥ 0.05). CONCLUSIONS: The molecular epidemiology study on the genetic polymorphisms, i.e., JAK2 V617F and other single nucleotide polymorphisms as a diagnostic tool is necessary for cancer screening and prophylactic programs.
Case-Control Studies ; Chlamydia trachomatis ; Early Detection of Cancer ; Epithelium ; Female ; Genotype ; Herpesvirus 2, Human ; Humans ; Iran ; Janus Kinase 2 ; Molecular Epidemiology ; Mycoplasma genitalium ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Prevalence ; Protein-Tyrosine Kinases ; Real-Time Polymerase Chain Reaction ; Sexually Transmitted Diseases ; Uterine Cervical Neoplasms ; Uterus

BACKGROUND: Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for a plethora of human diseases, of which cutaneous and mucocutaneous infections are the most prevalent. In its most severe form, HSV infection can cause meningitis/encephalitis. We compared the Luminex ARIES HSV 1&2 assay (Luminex Corp., Austin, TX, USA), an automated sample-to-result molecular solution, to two non-automated HSV DNA assays. METHODS: A total of 116 artificial controls were used to determine the analytical performance of the ARIES assay. Controls were prepared by spiking universal transport medium (UTM) and cerebrospinal fluid (CSF) samples from patients who tested negative for HSV by an in-house HSV-1 and -2 DNA assay with reference materials (SeraCare Life Sciences, MA, USA; ZeptoMetrix Corp., MA, USA). Another 117 clinical samples were then used to compare the clinical performance of the ARIES assay with those of an in-house assay and the FTD Neuro 9 assay (Fast Track Diagnostics, Junglinster, Luxembourg). RESULTS: The analytical sensitivity (95% limit of detection) of the ARIES assay was 318 copies/mL (UTM samples) and 935 copies/mL (CSF samples) for HSV-1 strain 96 and 253 copies/mL (UTM samples) and 821 copies/mL (CSF samples) for HSV-2 strain 09. No cross-reactivity was observed in samples spiked with 14 non-HSV microorganisms. Compared with the reference result (agreement between the in-house and FTD Neuro 9 results), the ARIES assay had overall concordance rates of 98.2% (111/113) and 100% (113/113) for HSV-1 and HSV-2, respectively. CONCLUSIONS: The ARIES assay appears to be an excellent alternative for rapid detection and differentiation of HSV in skin and genital infections, meningitis, and encephalitis.
Biological Science Disciplines ; Cerebrospinal Fluid ; DNA ; Encephalitis ; Herpes Simplex* ; Herpesvirus 1, Human ; Herpesvirus 2, Human ; Humans ; Meningitis ; Real-Time Polymerase Chain Reaction* ; Simplexvirus* ; Skin