Características de recién nacidos hijos de madre con IgM positiva para el Virus Herpes Simplex

Introducción: El herpes connatal es una entidad infrecuente asociada a elevada morbimortalidad. La probabilidad de transmisión al recién nacido va de 5% al 85%. El diagnóstico se dificulta por falta de clínica, serología no confiable y por la no disponibilidad de PCR en los servicios públicos de países en vías de desarrollo. La IgM en gestantes podría ser utilizada como un marcador de sospecha para evaluar al neonato. Objetivo: Caracterizar a los recién nacidos, hijos de gestantes con IgM positiva para HVS 1-2 y la frecuencia de encefalitis en los infantes. Materiales y métodos : Estudio observacional, descriptivo, prospectivo, realizado de mayo de 2020 a octubre de 2021. Se incluyeron recién nacidos (RN) de madres con IgM positiva para Herpes Virus Simplex (HVS) a partir de la segunda mitad del embarazo. En el RN se realizó serología IgG e IgM, y además, PCR- RT para HVS 1-2 en sangre y/o LCR, excluyéndose los nacidos en otras maternidades y/o sin datos de serología materna. Resultados: 36 pacientes. Edad materna 28 años (DS + 4), 5% con antecedentes de HVS, 61% cesárea. 36% prematuros, 13% RCIU. Síntomas agudos en el RN 22%. De ellos, 19% plaquetopenia, 44% alteración de GOT. 63% PCR HVS en sangre y 44% en LCR. Se encontró hemorragia, hidrocefalia, leucomalacia en 27%. No se encontró diferencias en la expresión clínica por tipo de parto. Conclusiones: Los RN hijos de gestantes con IgM positiva para VHS desde la segunda mitad del embarazo o periparto, presentaron infección por VHS determinada por PCR en sangre o LCR, independiente de la vía del parto. El diagnóstico serológico en embarazadas permite la pesquisa, diagnóstico y tratamiento temprano del RN.

Introduction: neonatal herpes is a rare entity associated with high morbidity and mortality. The probability of transmission to the newborn ranges from 5% to 85%. The diagnosis is difficult due to the lack of clinical signs, unreliable serology and the non-availability of PCR in public services in developing countries. IgM in pregnant women could be used as a suspected marker to evaluate the neonate. Objective: To characterize newborn children of pregnant women with positive IgM for HSV 1-2 and the prevalence of encephalitis in infants. Materials and methods: Observational, descriptive, prospective study, carried out from May 2020 to October 2021. Newborns (NB) of mothers with positive IgM for Herpes Virus Simplex (HSV) from the second half of pregnancy were included. In newborns, IgG and IgM were performed, and in addition, PCR-RT for HSV 1-2 in blood and/or CSF, excluding those born in other hospitales and/or without maternal serology data. Results: We included 36 patients. Maternal age was 28 years (DS + 4), 5% with a history of HSV. 61% were delivered via cesarean section, 36% were premature, 13% had IUGR. 22% of the newborns had acute symptoms. 19% had thrombocytopenia, 44% had GOT alteration. 63% were PCR positive for HSV in serum and 44% were CSF-positive. Hemorrhage, hydrocephalus and leukomalacia were found in 27%. No differences were found in clinical expression by type of delivery. Conclusions: Newborns born to pregnant women with positive IgM for HSV from the second half of pregnancy or peripartum, presented HSV infection as determined by PCR in blood or CSF, regardless of the route of delivery. Serological diagnosis in pregnant women allows early screening, diagnosis and treatment of the NB.

Guías Latinoamericanas de Infecciones Congénitas y Perinatales de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE). Parte II / Latin American Guidelines on Congenital and Perinatal Infections from the Latin-American Society of Pediatric Infectious Diseases (SLIPE). Part II

Las infecciones perinatales son una causa de morbilidad, tanto fetal como neonatal, y que compromete la salud de la mujer embarazada, por lo que su diagnóstico, tratamiento, e intento de eliminación son una prioridad en América Latina y el Caribe. Este documento representa la segunda entrega realizada por expertos en la región dentro de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE), brindando una mirada actualizada en el manejo de las infecciones congénitas y entrega herramientas para detectar posibles momentos estratégicos de intervención y cambio en el manejo de las infecciones congénitas.

Perinatal infections are a major cause of morbidity and mortality in the fetus, neonate, and the health of the pregnant woman. Diagnosis, treatment, and the search for elimination of these diseases are a priority in Latin America and the Caribbean. This document represents the second delivery by a group of experts in the region inside the Latin-American Society of Pediatric Infectious Diseases (SLIPE), presenting a up-to-date look into the management of congenital infectious diseases and give a tool to detect possible strategic sceneries and a change in the management of congenital infections in our region.

Oncolytic spore eruption virus encoding IL-7 enhances killing activity of liver cancer by activating CD8+T cells / 中国免疫学杂志

Objective:To investigate whether IL-7-secreting oncolytic herpes simplex virus(HSV)could activate CD8+T cells and inhibit the growth of hepatocellular carcinoma.Methods:The expression of IL-7 was detected by Western blot.The in vitro cleavage of tumor cells by tumor oncolytic virus HSV and HSV-IL-7 were detected by crystal violet staining.The tumor inhibition ability of HSV-IL-7 and HSV were detected in subcutaneous transplanted tumor model.Levels of IL-7,IFN-γ and TNF-α in serum and tumor tissues were determined by ELISA.The infiltration of CD8+T cells in tumor tissues was detected by immunohistochemistry.Flow cytometry was used to detect Granzyme B secretion in CD8+T cells infiltrated by tumor.Results:Tumor cells infected with HSV-IL-7 expressed high level of IL-7.Both HSV and HSV-IL-7 can effectively lyse B16-F10,CT-26 and H22 tumor cell lines in a dose-dependent manner in vitro.HSV-IL-7 could significantly inhibit the growth of H22 hepatoma cells in vivo(P<0.01)and prolong the survival time of tumor-bearing mice(P<0.001).HSV-IL-7 could significantly increase the IL-7 content in tumor sites(P<0.000 1),and effectively increase the number of tumor infiltrating CD8+T cells(P<0.001).HSV-IL-7 significantly enhanced Granzyme B secretion of tumor-infiltrating CD8+T cells and IFN-γ and TNF-α in tumor tissues(P<0.000 1).Conclusion:HSV-IL-7 has well tumor inhibition activity in vivo and in vitro.It also can activate the anti-tumor activity of CD8+T cells in vivo by secreting IL-7,inhibit tumor growth and prolong the survival time of tumor-bearing mice.

Autoimmune encephalitis with double positive anti-NMDAR and anti-GABABR secondary to herpes simplex virus encephalitis:A case report and literature review / 吉林大学学报(医学版)

Objective:To analyze the clinical presentations and diagnostic and treatment process of one patient with autoimmune encephalitis(AE)with double positive anti-N-methyl-D-aspartate receptor(NMDAR)and anti-γ-aminobutyric acid B receptor(GABABR)secondary to herpes simplex virus encephalitis(HSVE),and to improve the clinicians'awareness of this disease.Methods:The clinical data of one AE patient with double positive anti-NMDAR and anti-GABABR secondary to HSVE were collected,the diagnostic and therapeutic processes were summarized,and the relevant literatures were reviewed.Results:The patient,a 36-year-old male,developed a headache followed by limb convulsions,and progressed to disturbed consciousness.After admission,the routine biochemistry of the cerebrospinal fluid(CSF)was abnormal,and the herpes simplex virus-1(HSV-1)IgG antibody showed positive in the CSF;both CSF and serum tests for NMDAR antibodies were positive;the head magnetic resonance imaging(MRI)results showed abnormal signals in the right occipital white matter,leading to the diagnosis of HSVE secondary to anti-NMDAR encephalitis.Several months later,the patient experienced psychiatric behavior abnormalities,cognitive dysfunction,and sleep disorders,and both the serum NMDAR and GABABR antibodies showed positive results,prompting the diagnosis of HSVE secondary anti-NMDAR encephalitis and anti-GABABR encephalitis.After treatment with steroid pulse therapy and intravenous immunoglobulin(IVIG),the patient's condition was improved and the patient was discharged.At one-year follow-up,the patient's psychiatric symptoms had completely resolved,leaving mild cognitive impairment.Conclusion:If the clinical symptoms of the patients recovering from antiviral treatment for HSVE is worsened,secondary AE should be highly suspected;it is important to complete autoimmunity antibody testing as soon as possible for the early diagnosis and treatment to improve the prognosis of the patient.

Research progress on herpes simplex virus type 1 respiratory tract infection / 军事医学

Human herpes simplex virus type 1(HSV-1)infection of the upper respiratory tract is a common,mostly self-limiting disease.Reactivation of HSV-1 can sometimes cause lower respiratory tract infections.Coinfection of HSV-1 and other pathogens in the respiratory tract may cause severe diseases,resulting in HSV pneumonia and acute respiratory distress syndrome.This article reviews the symptoms and pathogenesis of HSV-1 infection or co-infections with other pathogens in the respiratory tract,as well as recent advances on drugs and vaccines for HSV-1.

Advances in Epigenetic Regulatory Mechanisms in HSV1 Infection / 昆明医科大学学报

Herpes simplex viruses type 1(HSV1)is among the most ubiquitous human pathogens that cause a wide variety of disease states.The latent infection of the central nervous system and sporadically reactivation is the central part of HSV1 pathogenesis,which also brings challenges to antiviral therapies.At present,the mechanism of establishing,maintaining and reactivation of HSV1 has not been fully clarified,whereas it has been generally accepted that the epigenetic regulation may play an important role.Accumulating researches have also indicated that the lytic and latent viral genomes exhibit the different chromatin structures,and the accumulation of diverse post-translational modifies the histones endow viral genes with transcriptional activation or repression features.In addition,the latency-associate transcripts of virus may also participate in the genome epigenetic modification.In this review,we summarize the research progress of epigenetic regulation of HSV1 and highlight the critical role of chromatin remodeling in HSV1 lytic proliferation and establishment of latent infection.

eEF1A1 regulates virus replication of vesicular stomatitis virus and herpes simplex virus:a preliminary study / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of eukaryotic translation elongation factor 1A1(eEF1A1)on the replication of vesicular stomatitis virus(VSV)and Herpes simplex virus 1(HSV-1)to identify a potential target for broad-spectrum regulation of viruses.METHODS Small interfering RNA(si-eEF1A)was transfected into human skin fibroblasts(BJ-5ta)to inhibit the expression of eEF1A1,and the negative control group was set up.The transfection efficiency was detected by real-time fluo-rescence quantitative PCR(RT-qPCR)and Western blotting,the cell model of eEF1A1 gene silencing was constructed.The cell model was infected with VSV,the gene copy number and protein expression of VSV in the cells were detected.The cell model was infected with HSV-1,the mRNA and protein expres-sion of HSV-1 in the cells were detected.The cell models were transfected with polyinosinic acid[Poly(I:C)]or sodium deoxyribonucleic acid(HT-DNA),respectively.The mRNA expression of interferon-β(IFN-β),C-X-C Motif Chemokine 10(CXCL10)and interferon-stimulated gene 56(ISG56)were detected by RT-qPCR.The phosphorylation expression of interferon regulatory factor 3(IRF3)and TANK binding kinase 1(TBK1)were detected by Western blotting.RESULT Compared with the negative control group,the mRNA and protein expression of eEF1A1 in the eEF1A1 gene silencing group were signifi-cantly decreased(P<0.01),the cell model of eEF1A1 gene silencing was successfully constructed.Compared with the negative control group,the VSV gene copy number of the eEF1A1 gene silencing group decreased by 70%-80%.The VSV protein expression decreased significantly(P<0.01).The mRNA expression of HSV-1 was decreased by 50%-60%,and the protein expression of HSV-1 was significantly decreased(P<0.01).After stimulation with Poly(I:C)or HT-DNA,compared with the negative control group.there was no significant difference in the mRNA expressions of IFN-β,ISG56 and CXCL10 and the protein phosphorylation expression of IRF3 and TBK1 in the eEF1A1 gene silencing group.CONCLUSION eEF1A1 silencing can inhibit VSV and HSV-1 virus replication,suggesting that eEF1A1 has a potential broad-spectrum regulatory effect on RNA viruses and DNA viruses,and may not recog-nize activated immune pathways through intracellular nucleic acid recognition.

Clinical and Imaging Features of Neonatal Herpes Simplex Encephalitis / 中国医学影像学杂志

Purpose To summarize the clinical and imaging features of neonatal herpes simplex encephalitis(NHSE).Materials and Methods Clinical and imaging data of 5 NHSE from January 2016 to June 2023 in Beijing Children's Hospital,Capital Medical University were retrospectively collected.All five children underwent MRI examinations,with three of them undergoing enhanced scanning simultaneously.Two children had previously undergone CT scans.The location,density/signal,enhancement characteristics as well as follow-up imaging changes of the lesions were reviewed.Results The main clinical manifestations of NHSE were fever(5 cases)and seizure(4 cases),sometimes accompanied by herpes(2 cases).Imaging examinations in NHSE typically presented with symmetric(1 case)or diffuse/multifocal(4 cases)lesions in bilateral cerebral hemispheres,along with involvement of the bilateral thalamus(5 cases).Early CT scans showed either no abnormalities(1 case)or extensive areas of low density(1 case).MRI examinations usually demonstrated restricted diffusion of acute phase lesions(3 cases)and significant leptomeningeal enhancement in affected areas(3 cases).Intracranial lesions often led to the diffuse atrophy of brain parenchyma and polycystic encephalomalacia(3 cases),indicating a poor prognosis.Conclusion The clinical manifestations of NHSE are nonspecific.Early MRI examinations are of great value for accurate diagnosis and disease evaluation.

Tetrandrine enhances the host antiviral response through cGAMP-mediated cGAS-STING signaling pathway / 中华微生物学和免疫学杂志

Objective:To investigate whether tetrandrine could be used as an agonist of cGAMP to enhance the activation of cGAS-STING signaling pathway and analyze the antiviral function of tetrandrine.Methods:THP1-Lucia-ISRE and RAW-Lucia-ISRE cells were incubated with different doses of tetrandrine in combination with cGAMP, respectively. IRF3 reporter activity was analyzed by luciferase reporter assay. Western blot was used to detect the activation of cGAS-STING signaling pathway. The expression of IFN-β, CXCL10 and CCL5 at mRNA level was quantified by real-time quantitative PCR. The expression of IFN-β at protein level was assessed by ELISA. HeLa cells stably expressing STING-GFP gene (HeLa-STNG-GFP cells) were constructed and stimulated with tetrandrine and cGAMP, then puncta-like structures were imaged by ZEISS LSM780. THP1-Lucia-ISRE cells were infected with herpes simplex virus type 1 (HSV-1) in the presence or absence of tetrandrine or cGAMP. The antiviral function of tetrandrine was analyzed by Western blot and fluorescence intensity assay.Results:Tetrandrine enhanced cGAMP-mediated IRF3 responses and activated cGAS-STING signaling pathway in combination with cGAMP. Tetrandrine combined with cGAMP triggered STING translocation and the formation of puncta-like structures in HeLa-STNG-GFP cells. The titer of HSV-1, the expression of HSV-glycoprotein D/UL30 and the fluorescence intensity of HSV-GFP were all decline after treating HSV-1-infected THP1-Lucia-ISRE cells with tetrandrine and cGAMP.Conclusions:Tetrandrine combined with cGAMP activates cGAS-STING signaling pathway, thus enhancing the host antiviral response.

Progress in research on action mechanism of macrophages against herpes simplex virus type 1 infection / 中国生物制品学杂志

@#Herpes simplex virus type 1(HSV-1)is a DNA virus renowned for its ability to evade the immune response,establish latency,and reinfect.Despite extensive research into its biological characteristics,there are no specific therapeutics or preventative vaccines currently available for HSV-1.Infection with HSV-1 triggers innate and adaptive immune responses in the host,with macrophages playing a crucial role in antiviral immune responses through processes such as pathogen engulfment,processing,and presentation.This review aims to elucidate the latest research developments on the role of macrophages in combating HSV-1 infection,in hopes of providing insights for future vaccine design and drug development.

Research progress on herpes simplex virus membrane fusion protein interactions / 中国生物制品学杂志

@#Herpes simplex virus(HSV)is a ubiquitous enveloped virus containing double-stranded DNA. HSV-1 infection can cause inflammation of the lips,conjunctivitis and encephalitis,HSV-2 infection can cause genital herpes at many ages,and both viruses can establish lifelong latent infection in the body. Membrane fusion triggered by the interaction of various HSV membrane proteins is an important way for viruses to enter host cells. This review introduced the conserved core fusion mechanism of HSV composed of four viral glycoproteins gD,gH,gL and gB by analyzing the structure of glycoproteins and their interaction modes. Since there is currently no HSV vaccine approved for marketing in the world,it is of great significance to study the mode of action of HSV and host cells for the development of vaccines

Catarata congênita nas infecções intrauterinas mais comuns (STORCH): revisão de literatura / Congenital cataract in the most common intrauterine infections (STORCH): a review of the literature

RESUMO Objetivo: O objetivo deste estudo foi revisar os aspectos clínicos e patológicos da catarata congênita secundária às infecções por sífilis, toxoplasmose, rubéola, citomegalovírus e herpes simples. Métodos: Trata-se de uma revisão de literatura, na qual foram incluídos artigos de periódicos indexados às bases de dados PubMed®, Cochrane, Lilacs, Embase e SciELO de 2010 a 2023. Resultados: Foram encontrados 45 artigos, e, após seleção, restaram 9 artigos. Além disso, foram adicionados artigos para enriquecer a discussão. A infecção por sífilis está relacionada a alterações corneanas. O citomegalovírus e a toxoplasmose estão relacionados com a coriorretinite e/ou microftalmia. A rubéola é responsável por causar catarata, glaucoma, microftalmia e retinite em sal e pimenta. Conclusão: Foram abordadas as principais etiologias infecciosas e seu quadro clínico na CC. O melhor tratamento para CC é cirúrgico associado a acompanhamento clínico, mas a prevenção é a maneira mais eficaz de combater a CC de etiologia infecciosa. O diagnóstico precoce e o tratamento efetivo previnem alterações e sequelas visuais irreversíveis. Nesse contexto, mostram-se importantes as ações de políticas públicas para o melhor desfecho clínico e melhor qualidade de vida.

ABSTRACT Objective: To review the clinical and pathological aspects of CC secondary to infections by syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex. Methods: This is a literature review. Articles from journals indexed to PubMed, COCHRANE, LILACS, EMBASE and SCIELO from 2010 to 2023 were included. Results: A total of 45 articles were found, which, after selection, remained in 9 articles. Some articles were included to enrich the discussion in this topic. The infection caused by syphilis is related to corneal changes. Cytomegalovirus and Toxoplasmosis due to chorioretinitis and/or microphthalmia. Rubella is responsible for causing cataracts, glaucoma, microphthalmia, and salt and pepper retinitis. Conclusion: The main infectious etiologies and their clinical status in CC were addressed. The best treatment for CC is surgery associated with clinical follow-up, but prevention is the most effective way to combat CC of infectious etiology. Early diagnosis and effective treatment prevent irreversible visual changes and sequelae. In this context, public policy actions are important for the best clinical outcome and better quality of life.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

Estudio de seroprevalencia de HVS 1-2 en gestantes y recién nacidos de 2017 a 2021

El virus herpes simple (VHS) pertenece a la subfamilia alfa virus, miembro de la familia Herpes viridae. Existen dos tipos de VHS íntimamente relacionados, el VHS tipo 1 (VHS1) y el VHS tipo 2 (VHS2), que causan enfermedades de diversa gravedad. El VHS1 se transmite principalmente por contacto de boca a boca y el VHS2 se transmite por vía sexual; ambos pueden causar herpes genital. La carga de morbimortalidad a nivel mundial derivada de patógenos de transmisión sexual compromete la vida, así como la salud sexual y reproductiva, y la salud del recién nacido. Objetivos: Determinar la seroprevalencia IgG e IgM por VHS1 y VHS2 de los recién nacidos y madres en el periodo de enero 2017 a julio 2021 en un hospital de tercer nivel. Materiales y Métodos: Estudio observacional, retrospectivo de corte transversal de enero 2017 a julio 2021. Se midió anticuerpos IgG e IgM en recién nacidos y gestantes de ultimo trimestre, utilizando el método de ELISA. Resultados: De un total de 4712 serologías IgG e IgM de madres y RN analizados la seroprevalencia de IgG en gestantes fue cercana al 100% con valor similar en los RN (87%), la seroprevalencia de IgM en las madres fue 0,23% y de los RN 0,36% con tendencia ascendente. Conclusión: la seroprevalencia de IgG para VHS es elevada, en cambio la seroprevalencia de IgM en gestantes y recién nacidos en el periodo de estudio es significativamente baja.

The herpes simplex virus (HSV) belongs to the alpha virus subfamily, a member of the family Herpes viridae. There are two closely related types of HSV, HSV type 1 and HSV-2, which cause diseases of varying severity. HSV-1 is transmitted mainly by mouth-to-mouth contact and HSV-2 is transmitted sexually, both of which can cause genital herpes. The global burden of morbidity and mortality from sexually transmitted pathogens compromises life, as well as sexual and reproductive health, and the health of the newborn. Objective: To determine the IgG and IgM seroprevalence for HSV 1 - 2 of newborns and mothers in the period from January 2017 to July 2021 in a third level hospital. Materials and Methods: Observational, retrospective, cross-sectional study of January 2017 to July 2021. IgG and IgM antibodies were measured in newborns and pregnant women in the last trimester, using the ELISA method. Results: Of a total of 4712 IgG and IgM serologies of mothers and newborns analyzed the seroprevalence of IgG in pregnant women was close to 100% with similar value in newborns (87%), IgM seroprevalence in mothers was 0.23% and the RN 0.36% with an upward trend. Conclusion: The IgG seroprevalence for HSV is high, while the IgM seroprevalence in pregnant women and newborns during the study period is significantly low.

Enfermedad de castleman multicéntrica y tuberculosis diseminada en paciente HIV positivo / Multicentric Castleman disease and tuberculosis in HIV positive patient

Resumen Presentamos el caso de un hombre de 40 años, HIV positivo con regular adherencia al tratamiento, que consultó por episodios febriles intermitentes de dos años de evolución, agregando en los últimos dos meses dolor abdominal difuso progresivo y adenomegalias ge neralizadas indoloras. En el laboratorio presentó panci topenia, coagulopatía, hipoalbuminemia y reactantes de fase aguda aumentados. La tomografía computarizada (TC) de tórax, abdomen y pelvis únicamente evidenció hepato-esplenomegalia y adenomegalias generalizadas. Se realizaron múltiples exámenes microbiológicos, in cluyendo cultivos para Mycobacterium sp. de distintas muestras, todos con resultados negativos, a excepción de la RT-PCR para VHH-8. Se tomó biopsia escisional de ganglio iliaco izquierdo con hallazgos compatibles con enfermedad de Castleman. A pesar de reiniciar terapia antirretroviral, la sintomatología progresó, iniciando tratamiento con corticoides y ganciclovir. Luego de una semana, desarrolló falla mulitorgánica y anasarca, que contraindicaron los fármacos iniciados. Se realizó nueva TC de tórax que mostró infiltrados con patrón en árbol en brote en lóbulo superior derecho asociado a derra me pleural bilateral, y a nivel abdominal, progresión de hepato-esplenomegalia y ascitis. Pasó a unidad de cui dados intensivos 48 horas después por falla hepática ful minante. El paciente falleció en pocas horas. Se recibió postmortem el cultivo del aspirado traqueal positivo para Mycobacterium tuberculosis y la punción-biopsia hepática con granulomas no necrotizantes. Nuestro objetivo es remarcar la importancia de pesquisar tuberculosis activa en nuestro país frente a la sospecha de enfermedad de Castleman antes de iniciar tratamiento, y resaltar que la TBC también puede presentarse como complicación infecciosa elevando la morbimortalidad.

Abstract We present the case of a 40-year-old man, HIV posi tive with regular adherence to treatment, who consulted for intermittent febrile episodes during a two-years period, progressive diffuse abdominal pain and painless generalized lymphadenopathy in the last two months. Laboratory analysis showed pancytopenia, altered co agulation tests, hypoalbuminemia, and increased acute phase reactants. Computed tomography (CT) of the chest, abdomen and pelvis revealed hepato-splenomegaly and generalized lymphadenopathy. Multiple microbiological tests were performed, including cultures for Mycobacte rium sp. from different samples, with negative results, except for the RT-PCR for HHV-8. An excisional biopsy of the left iliac lymph node was taken with findings compatible with Castleman's disease. Despite restarting antiretroviral therapy, the symptoms progressed, starting treatment with steroids and ganciclovir. After a week, he developed multiple organ failure and anasarca, which contraindicated the drugs previously started. A new CT of the chest showed infiltrates with a tree-in-bud pattern in the right upper lobe with bilateral pleural effusion, and at the abdominal level, progression of hepatospleno megaly and ascites. He was transferred to the intensive care unit 48 hours later due to fulminant hepatic fail ure. The patient died within a few hours. Postmortem recieved culture results of the tracheal aspirate were positive for tuberculosis (TB) and the histopathology of the liver biopsy showed non-necrotizing granulomas. Our objective is to highlight the importance of screening for active TB, in our country, when Castleman's disease is suspected, before starting treatment, and to stand out that TB can also present as an infectious complication, increasing morbidity and mortality.

Research progress on the mechanisms of the latency and recurrence of herpes simplex virus type Ⅰ in trigeminal ganglion / 国际眼科杂志(Guoji Yanke Zazhi)

Herpes simplex keratitis(HSK), caused by the infection of herpes simplex virus type Ⅰ(HSV-1)in cornea, is a global blinding corneal disease. After the primary infection in ocular surface, HSV-1 is transported into trigeminal ganglion and establishes the life-lasting latency, and it results in recurrent keratopathy. In the process of studying the latent mechanism of HSV, it has been gradually recognized that both the virus itself and the host response regulate the latent process of HSV. In recent years, a large number of research results have been obtained on the molecular mechanisms of invasion, immunity, latency and recurrence of neurotropic viruses, which provide new ideas for the prevention and treatment of HSK. In the present review, the recent progress of HSV latency mechanism in trigeminal ganglion after the primary infection in corneal surface was introduced, and the unsolved basic and clinical problems in HSK were discussed.

Research progress on corneal nerves and substance P in viral keratitis / 国际眼科杂志(Guoji Yanke Zazhi)

Diseases like viral keratitis can harm corneal nerves, which are necessary for maintaining the health and functionality of the cornea. Recent research has shown that corneal nerve pathology affects the infected eye as well as the contralateral one, and that aberrant changes in sympathetic nerves can be seen, with the exception of sensory nerves that correspond to corneal sensation. However, apart from in vivo confocal microscopy and corneal sensation, there have been no additional prognostic indicators that allow clinicians to assess the severity of corneal nerve damage. While multiple functions of corneal nerves are mediated by neuropeptides, substance P, the first topical neuropeptide used in ocular clinical practice, was proved to regulate the process of viral infections, and it is involved in bilateral corneal pathologies through pro-inflammatory and neurotrophic functions in viral keratitis, so it may be used as a diagnostic biomarker or a therapeutic target. Therefore, this review summarized the changes and roles of corneal nerves as well as substance P in viral keratitis, which may serve as a reference for further study into associated mechanisms and clinical applications.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Research progress of oncolytic herpes simplex virus in the treatment of glioma / 中国中西医结合急救杂志

Glioma is a highly aggressive malignant tumor of the central nervous system that necessitates active treatment through surgery,radiotherapy,and chemotherapy.However,the prognosis of high-grade gliomas[World Health Organization(WHO)classification of central nervous system tumorsgrade Ⅲ-Ⅳ]remains poor,thus new treatment strategies are urgently needed.Oncolytic virus(OV)therapy is a kind of immunotherapy that can specifically infect and effectively kill tumor cells while activating anti-tumor immunity.The oncolytic herpes simplex virus(oHSV)is expected to emerge as a new adjuvant treatment for glioma due to its unique advantages.This article reviews the current understanding of oHSV,the anti-tumor mechanism of OV,the current clinical research status of oHSV targeted therapy for glioma,the research progress of oHSV collaborative anti-tumor strategy,and the existing problems in oHSV anti-glioma research,aiming to provide valuable insights for the treatment of glioma.

Manifestações clínicas de ceratite ulcerativa periférica com ceratite neurotrófica: desafio terapêutico / Clinical manifestations of peripheral ulcerative keratitis together with neurotrophic keratitis: therapeutic challenge

RESUMO A ceratite ulcerativa periférica é uma infiltração corneana imunomediana associada a doenças autoimunes e inflamatórias sistêmicas. Comumente associada à artrite reumatoide, ela também pode estar associada a outras doenças reumatológicas, inflamatórias e doenças infecciosas. A ceratite ulcerativa periférica é geralmente unilateral e periférica, devido à proximidade com a vasculatura conjuntival. Há tipicamente um defeito epitelial sobrejacente ao infiltrado e afinamento do estromal associado. O objetivo deste relato de caso foi abordar uma das possíveis etiologias de ceratite ulcerativa periférica associada a quadro de ceratite neurotrófica por herpes simplex, apresentar sua apresentação clínica aguda e alertar sobre as implicações do tratamento.

ABSTRACT Peripheral ulcerative keratitis (PUK) is an immune-mediated corneal infiltration associated with autoimmune diseases and systemic inflammation. Commonly associated with rheumatoid arthritis, it may also be associated with other rheumatologic, inflammatory, and infectious diseases. PUK is usually unilateral and peripheral, due to its proximity to the conjunctival vasculature. There is usually an epithelial defect overlying the infiltrate and the associated stromal thinning. The objective of this case report is to address one of the possible etiologies of PUK associated with a picture of neurotrophic keratitis due to Herpes Simplex and its acute clinical presentation, and to warn about possible suggestions for treatment.