Comparative analysis of the incidence of enteroparasitosis andthe COVID-19 pandemic profile in the city of Bananeiras - PB / Análise comparativa da incidência de enteroparasitoses e doperfil pandêmico da COVID-19 na cidade de Bananeiras - PB

Enteroparasitosis are diseases caused by parasitic agents present in the environment and in the gastrointestinal tract of living beings. In addition, they are still considered neglected diseases, but of great importance for public health, especially when they are related to secondary infections and currently their co-infection profile with COVID-19. The interaction of protozoa and/or helminths with the SARS-CoV-2 virus is timely and its signs and symptoms are confused with other pathogen relationships. In this way, this study aims to correlate the incidence of enteroparasitosis and COVID-19, in the pandemic period from 2020 to April 2022. This is a documentary and exploratory study of secondary data from laboratory tests of patients who were treated and diagnosed with COVID-19 and enteroparasitosis at Hospital Doutor Cloves Bezerra Cavalcante, Municipal Hospital of Bananeiras, Paraíba, Brazil. In the analysis of the database, a significant increase of approximately 48.85% in the incidence of COVID-19 cases from 2020 to 2021 stands out, remaining high until 2022. In contrast, cases of enteroparasites peaked at 48.74% in 2021, followed by an average reduction of 23.12%, with a deviation of 1.49%, in relation to the years 2020 and 2022. It was concluded that COVID-19 is predominantly associated with an increase in secondary infections, highlighting the crucial need to promote health education, improve basic sanitation and guarantee access to health services as essential components in combating the increase in parasitic infections, especially those related to viral pathologies.

As enteroparasitoses são enfermidades originadas por agentes parasitários presentes no meio ambiente e no trato gastrointestinal dos seres vivos. Ademais, ainda são consideradas doenças negligenciadas, porém de grande importância para a saúde pública, em especial, quando estão relacionadas com infecções secundárias e atualmente seu perfil de coinfecção com a COVID-19. A interação de protozoários e/ou helmintos com o vírus SARS-CoV-2 é oportuna e seus sinais e sintomas são confundidos com outras relações de patógenos. Desta maneira, este estudo visa correlacionar a incidência de enteroparasitoses e COVID-19, no período pandêmico de 2020 a abril de 2022. Trata--se de uma pesquisa documental e exploratória, de dados secundários dos exames laboratoriais de pacientes que foram atendidos e diagnosticados com COVID-19 e enteroparasitoses no Hospital Doutor Cloves Bezerra Cavalcante, Hospital Municipal de Bananeiras, Paraíba, Brasil. Na análise da base de dados, destaca-se um aumento significativo de aproximadamente 48,85% na incidência de casos de COVID-19 de 2020 a 2021, mantendo-se elevado até 2022. Em contraste, os casos de enteroparasitas atingiram um pico de 48,74% em 2021, seguido por uma redução média de 23,12%, com um desvio de 1,49%, em relação aos anos de 2020 e 2022. Conclui-se que a COVID-19 está predominantemente associada ao aumento de infecções secundárias, destacando a necessidade crucial de promover a educação em saúde, melhorar o saneamento básico e garantir o acesso aos serviços de saúde como componentes essenciais no combate ao aumento de infecções parasitárias, especialmente aquelas relacionadas a patologias virais.

Caracterización de pacientes con enfermedades asociadas a inmunosupresión con infecciones por Cryptosporidium spp. atendidos en un hospital pediátrico referencial de Argentina, 2018-2023 / Description of the characteristics of patients with diseases associated with immunosuppression and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina, 2018­2023

Cryptosporidium spp. es un protozoario productor de diarrea. Los pacientes inmunocomprometidos pueden desarrollar formas clínicas graves y persistentes. Se describen las características de pacientes con enfermedad de base asociada a inmunosupresión (EAI) con infección por Cryptosporidium spp. (IC) atendidos en un hospital pediátrico referencial de Argentina entre los años 2018 y 2023. Se analizaron datos demográficos, EAI, características de la diarrea y coinfecciones. Se incluyeron 30 pacientes con EAI e IC. La mayoría registró trasplante de órgano sólido, neoplasia hematológica e inmunodeficiencia primaria. Dieciocho presentaron diarrea persistente al momento del diagnóstico. Seis pacientes registraron coinfecciones. Se debe considerar la criptosporidiosis en el diagnóstico diferencial de enfermedad diarreica aguda o persistente en niños con distintos tipos de EAI, como el trasplante de órgano sólido, neoplasias hematológicas e inmunodeficiencias primarias.

Cryptosporidium spp. is a diarrhea-causing protozoan. Immunocompromised patients may develop severe and persistent clinical forms. Here we describe the characteristics of patients with an underlying disease associated with immunosuppression (DAI) and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina between 2018 and 2023. Demographic data, DAI, diarrhea characteristics, and co-infections were analyzed. A total of 30 patients with DAI and cryptosporidiosis were included. Most of them had undergone a solid organ transplant, had a hematologic neoplasm, or primary immunodeficiency. Persistent diarrhea was observed in 18 patients at the time of diagnosis. Co-infections were recorded in 6 patients. Cryptosporidiosis should be considered in the differential diagnosis of acute or persistent diarrhea in children with different types of DAI, such as solid organ transplant, hematologic neoplasms, and primary immunodeficiencies.

Could the acute Strongyloides venezuelensis infection cause non-reversible host morphological changes? / A infecção aguda por Strongyloides venezuelensis pode causar alterações morfológicas irreversíveis no hospedeiro? / ¿Puede la infección aguda por Strongyloides venezuelensis provocar cambios morfológicos irreversibles en el huésped?

Although research has investigated the host-parasite relationship in Strongyloides venezuelensis infection in the scope of its immunological implications, the morphological consequences of this response for the host organism are yet to be explored. Our objective was to perform an organ morphometric analysis in Wistar rats infected with the intestinal parasite Strongyloides venezuelensis compared with infected rats treated with ivermectin. Twenty-six animals composed three groups: control (non-infected), infected (infected with 2,000 Strongyloides venezuelensis larvae), and infected treated (infected with 2,000 Strongyloides venezuelensis larvae and treated with ivermectin). All rodents were killed 21 days after infection and morphometric analysis of different organs was performed. The results showed significantly higher body and fecal weight in the infected-treated group. The weight of the small intestine increased considerably in the infected group and decreased in the infected-treated group. Pancreas, right kidney, and heart volume increased in the infected group compared with the control group. Despite treatment, the volumes of the stomach, brain, and left kidney increased in both the infected groups compared with the control group indicating the possibility of non-reversible host morphological adaptations. S. venezuelensis infection can augment both, volume and weight of organs ­ not necessarily related to the Strongyloides expulsion process ­ even if the acute infection had been in remission. A potential explanation for these host adaptations, including the occurrence of organ plasticity, are briefly discussed. The following steps encompass a histological analysis to verify the occurrence of hypertrophy/hyperplasia and observe if such morphological alterations remain after infection.

Embora pesquisas tenham investigado a relação parasita-hospedeiro na infecção por Strongyloides venezuelensis no âmbito de suas implicações imunológicas, as consequências morfológicas dessa resposta para o organismo hospedeiro ainda precisam ser exploradas. Nosso objetivo foi realizar uma análise morfométrica de órgãos em ratos Wistar infectados com o parasito intestinal Strongyloides venezuelensis em comparação com ratos infectados tratados com ivermectina. Vinte e seis animais compuseram três grupos: controle (não infectados), infectados (infectados com 2.000 larvas de Strongyloides venezuelensis) e tratados infectados (infectados com 2.000 larvas de Strongyloides venezuelensis e tratados com ivermectina). Todos os roedores foram sacrificados 21 dias após a infecção e a análise morfométrica de diferentes órgãos foi realizada. Os resultados mostraram peso corporal e fecal significativamente maior no grupo tratado infectado. O peso do intestino delgado aumentou consideravelmente no grupo infectado e diminuiu no grupo infectado tratado. O volume do pâncreas, rim direito e coração aumentou no grupo infectado em comparação com o grupo controle. Apesar do tratamento, os volumes do estômago, cérebro e rim esquerdo aumentaram em ambos os grupos infectados em comparação com o grupo controle, indicando a possibilidade de adaptações morfológicas não reversíveis do hospedeiro. A infecção por S. venezuelensis pode aumentar tanto o volume quanto o peso dos órgãos ­ não necessariamente relacionado ao processo de expulsão de Strongyloides ­ mesmo que a infecção aguda estivesse em remissão. Uma possível explicação para essas adaptações do hospedeiro, incluindo a ocorrência de plasticidade de órgãos, é brevemente discutida. As etapas a seguir compreendem uma análise histológica para verificar a ocorrência de hipertrofia/hiperplasia e observar se tais alterações morfológicas permanecem após a infecção.

Aunque se ha investigado la relación parásito-hospedador en la infección por Strongyloides venezuelensis en el contexto de sus implicaciones inmunológicas, aún no se han explorado las consecuencias morfológicas de esta respuesta para el organismo hospedador. Nuestro objetivo fue realizar un análisis morfométrico de los órganos de ratas Wistar infectadas con el parásito intestinal Strongyloides venezuelensis en comparación con ratas infectadas tratadas con ivermectina. Veintiséis animales se distribuyeron en tres grupos: control (no infectados), infectados (infectados con 2000 larvas de Strongyloides venezuelensis) e infectados tratados (infectados con 2000 larvas de Strongyloides venezuelensis y tratados con ivermectina). Todos los roedores fueron sacrificados 21 días después de la infección y se realizaron análisis morfométricos de diferentes órganos. Los resultados mostraron pesos corporales y fecales significativamente superiores en el grupo infectado-tratado. El peso del intestino delgado aumentó considerablemente en el grupo derecho y el corazón aumentó en el grupo infectado en comparación con el grupo de control. A pesar del tratamiento, los volúmenes del estómago, el cerebro y el riñón izquierdo aumentaron en ambos grupos infectados en comparación con el grupo de control, lo que indica la posibilidad de adaptaciones morfológicas no reversibles del hospedador. La infección por S. venezuelensis puede aumentar tanto el volumen como el peso de los órganos, que no están necesariamente relacionados con el proceso de expulsión de Strongyloides, incluso si la infección aguda estaba en remisión. Se debate brevemente una posible explicación de estas adaptaciones del hospedador, incluida la ocurrencia de plasticidad de los órganos. Los pasos siguientes comprenden un análisis histológico para verificar la aparición de hipertrofia o hiperplasia y observar si estas alteraciones morfológicas persisten tras la infección.

Manifestaciones clínicas y radiológicas de la Aspergilosis Pulmonar: Informe de tres casos / Pulmonary aspergillosis, an approach to clinical and radiological manifestations. Report of three cases

RESUMEN La aspergilosis pulmonar, causada por el hongo oportunista Aspergillus, afecta principalmente a individuos inmunocomprometidos. Este reporte presenta tres casos: Una mujer de 18 años con leucemia aguda desarrolló dificultad respiratoria y patrones bilaterales de "árbol en brote" en la tomografía computarizada (TC). A pesar del tratamiento con voriconazol, falleció debido a insuficiencia respiratoria. Una mujer de 58 años con diabetes y EPOC presentó disnea y hemoptisis. Las imágenes revelaron una lesión cavitada, confirmando un aspergiloma. Se consideró la cirugía debido a la hemoptisis activa. Una mujer de 41 años con antecedentes de tuberculosis presentó fiebre y síntomas respiratorios. La TC mostró lesiones cavitadas y bronquiectasias, confirmando aspergilosis crónica. Respondió bien al voriconazol. Estos casos destacan la variabilidad en la aspergilosis pulmonar y subrayan la importancia de un diagnóstico y tratamiento oportunos para mejorar los resultados en los pacientes.

ABSTRACT Pulmonary aspergillosis, caused by the opportunistic fungus Aspergillus, primarily affects immunocompromised individuals. This report presents three cases: An 18-year-old female with acute leukemia developed respiratory distress and bilateral "tree-in-bud" patterns on CT. Despite voriconazole treatment, she succumbed to respiratory failure. A 58-year-old female with diabetes and COPD had dyspnea and hemoptysis. Imaging revealed a cavitated lesion, confirming aspergilloma. Surgery was considered due to active hemoptysis. A 41-year-old female with a history of tuberculosis presented with fever and respiratory symptoms. CT showed cavitated lesions and bronchiectasis, confirming chronic aspergillosis. She responded well to voriconazole. These cases highlight the variability in pulmonary aspergillosis and underscore the importance of timely diagnosis and treatment to improve patient outcomes.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later

ABSTRACT Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6)

Fiebre en pacientes inmunodeprimidos / Fever in immunocompromised patients

Introducción: La fiebre es un marcador de enfermedades infecciosas e inflamatorias que se da por una respuesta inmune innata y por diferentes mediaciones entre marcadores moleculares. En el paciente inmunodeprimido, uno o varios mecanismos inmunológicos pueden estar alterados, debido a que la respuesta inmune puede estar deprimida y la fiebre puede denotar un estado patológico grave subyacente. Se realizó una búsqueda exploratoria en las bases de datos PubMed/Medline, Scopus y Scielo entre septiembre y octubre de 2022. Se incluyeron los términos fiebre, pacientes inmunodeprimidos, tratamiento y sistema inmune. Se seleccionaron 41 artículos científicos con diferentes diseños epidemiológicos. Objetivo: Describir aspectos relacionados con la fisiopatología de la fiebre, el tratamiento de la presencia de fiebre en pacientes con virus de inmunodeficiencia humana y síndrome de inmunodeficiencia adquirida, así como también en pacientes receptores de trasplantes de órgano sólido y de trasplantes hematopoyéticos, pacientes neutropénicos y pacientes tratados con corticosteroides y terapia biológica. Desarrollo: El tratamiento del paciente inmunodeprimido con fiebre incluye aspectos fundamentales como una adecuada anamnesis y examen físico, además de pruebas diagnósticas orientadas para establecer la causa de la fiebre. En estos pacientes, las infecciones juegan un papel protagónico y su intervención temprana es fundamental para impactar en la morbimortalidad. Conclusiones: El paciente inmunodeprimido con presencia de fiebre presenta un panorama desafiante para su manejo médico integral. Entre otros aspectos es relevante considerar el tipo y tiempo de inmunosupresión, así como los factores de riesgo, con el fin de orientar los diagnósticos y tratamientos(AU)

Introduction: Fever is a marker of infectious and inflammatory diseases that is caused by an innate immune response and by different mediations between molecular markers. In the immunocompromised patient, one or more immunological mechanisms may be altered because the immune response may be compromised, and fever may denote a serious underlying disease state. An exploratory search was conducted in the PubMed/Medline, Scopus, and Scielo databases between September and October 2022. The terms fever immunocompromised patients, treatment, and immune system. A total of 41 scientific articles with different epidemiological designs were selected. Objective: To describe aspects related to the pathophysiology of fever, management of the presence of fever in patients with Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome, as well as in patients who have received solid organ transplants and hematopoietic transplants, neutropenic patients and patients treated with corticosteroids and biological therapy. Developing: The approach to the immunocompromised patient with fever includes fundamental aspects such as an adequate history and physical examination, as well as diagnostic tests aimed at establishing the cause of the fever. In these patients, infections play a leading role and early intervention is essential to impact morbidity and mortality. Conclusions: The immunocompromised patient with the presence of fever presents a challenging panorama for his/her comprehensive medical approach. Among other aspects, it is relevant to consider the type and duration of immunosuppression, as well as the risk factors, to guide diagnoses and treatments(AU)

Effect of LncRNA SNHG1 on homocysteine-induced podocytespyrophosis / 实用医学杂志

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte.Methods Cbs+/-mice were randomly divided into two groups:a normal diet group(ND)and a high me-thionine diet group(HMD).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocytes were cultured in vitro,and then assigned into a control group(Control,0 μmol/L Hcy)and a homocysteine intervention group(Hcy,80 μmol/L Hcy).Western blotting was used to detect the protein expression levels of Caspase-1,Cleaved Caspase-1,and NLRP3.Mouse renal glomerular podocyion group(OE-NC + Hcy)and the lncSNHG1 overexpression + homocysteine intervention group(OE-SNHG1 + Hcy)were also established.After 48 hours of intervention,Real-time fluorescence quantita-tive PCR was used to detect the expression of lncSNHG1 in podocytes after Hcy intervention.Western blot was used to detect the expressions of Caspase-1,Cleaved Caspase-3 and NLRP3.Immunofluorescence was used to de-tect the expression levels of GSDMD and GSDMD-N.ELISA was used to detect the contents of IL-1β and IL-18.Results(1)In the animal experiments,the expression levels of pyroptosis-related proteins Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the HMD group compared with the ND group.(2)In the cellular experiments,the expression levels of Caspase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were all increased in the Hcy group compared with the Control group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased as well.(3)In the cellular experiments,the expres-sion of lncSNHG1 was increased in the Hcy group compared with the control group.After transduction with lnc-SNHG1 lentivirus,the expression of lncSNHG1 was increased in the OE-SNHG1 group,compared with the control group and the OE-NC group.(4)In the cellular experiments,the expressions of pyroptosis-related proteins Cas-pase-1,Cleaved Caspase-1,NLRP3,GSDMD,and GSDMD-N were increased compared with the OE-NC+Hcy group,and the contents of pyroptosis-mediated inflammatory factors IL-1β and IL-18 were increased in the OE-SNHG1+Hcy group.Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis.

LncRNA SNHG4 regulates miR-152-3p during osteoblastic differentiation of periodontal ligament stem cells / 中国组织工程研究

BACKGROUND:Studies have shown that long non-coding RNA small nucleolar RNA host gene 4(lncRNA SNHG4)is involved in the progress of many inflammatory diseases,but the effect of lncRNA SNHG4 on the osteogenic differentiation of human periodontal ligament stem cells during the treatment of periodontitis is still unclear. OBJECTIVE:To investigate the effect of lncRNA SNHG4 on the osteogenic differentiation of human periodontal ligament stem cells by regulating miR-152-3p. METHODS:Human periodontal ligament stem cells were isolated from periodontal membranes of premolars extracted for orthodontic purposes.After human periodontal ligament stem cells were induced to differentiate into osteoblasts for 0,7,and 14 days,the expression levels of RUNX family transcription factor 2,osteocalcin mRNA,lncRNA SNHG4 and miR-152-3p in human periodontal ligament stem cells were detected by qRT-PCR.The third-generation human periodontal ligament stem cells were divided into the NC group,pcDNA group,pcDNA-SNHG4 group,inhibitor NC group,miR-152-3p inhibitor group,pcDNA-SNHG4+mimic NC group,and pcDNA-SNHG4+miR-152-3p mimic group.The expression of lncRNA SNHG4 and miR-152-3p in human periodontal ligament stem cells was detected by qRT-PCR.The proliferation of human periodontal ligament stem cells was detected by CCK-8 assay.Alkaline phosphatase activity was detected by colorimetry.The formation of mineralized nodules was detected by alizarin red staining.Western blot assay was used to detect the expression of RUNX family transcription factor 2,osteocalcin and alkaline phosphatase proteins.A double luciferase reporter gene experiment was applied to verify the relationship between lncRNA SNHG4 and miR-152-3p. RESULTS AND CONCLUSION:(1)The expression of RUNX family transcription factor 2,osteocalcin mRNA and lncRNA SNHG4 in human periodontal ligament stem cells after 7 and 14 days of osteogenic induction was higher than that after 0 days of osteogenic induction,while the expression of miR-152-3p was lower(P<0.05).(2)Overexpression of lncRNA SNHG4 or inhibition of miR-152-3p was able to enhance the proliferation of human periodontal ligament stem cells,the alkaline phosphatase activity,mineralized nodule formation,the expression of RUNX family transcription factor 2,osteocalcin,and alkaline phosphatase proteins(P<0.05).miR-152-3p mimic attenuated the promoting effect of overexpression of lncRNA SNHG4 on osteogenic differentiation of human periodontal ligament stem cells.LncRNA SNHG4 had a targeting relationship with miR-152-3p.(3)These findings indicate that overexpression of lncRNA SNHG4 may promote the osteogenic differentiation of human periodontal ligament stem cells by inhibiting miR-152-3p.

Analysis of risk factors for short-term death after allogeneic hematopoietic stem cell transplantation / 中国组织工程研究

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an effective and even the only way to cure various hematological diseases,but the short-term mortality rate is relatively high after transplantation. OBJECTIVE:To investigate the risk factors affecting the overall survival of patients with hematological diseases in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation,so as to reduce mortality and effectively prevent related risks in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation. METHODS:Clinical data of 585 patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation at the Hematopoietic Stem Cell Transplantation Center of First Affiliated Hospital of Zhengzhou University from January 1,2018 to June 30,2021 were retrospectively analyzed.The risk factors that affected overall survival within 100 days after allogeneic hematopoietic stem cell transplantation were explored. RESULTS AND CONCLUSION:A total of 585 patients with hematologic diseases underwent allogeneic hematopoietic stem cell transplantation.92 patients died within 100 days after transplantation,with a mortality rate of 15.7%(92/585).The median age of death cases was 26.5 years old(1-56 years),and the median survival time of death cases was 48 days(0-97 days).Univariate analysis exhibited that age≥14 years old,acute graft-versus-host disease,grade IV acute graft-versus-host disease,bacterial bloodstream infection,as well as carbapenem-resistant organism bloodstream infection,were risk factors for overall survival within 100 days after allogeneic hematopoietic stem cell transplantation(P<0.05).Multivariate regression analysis showed that age≥14 years old,grades Ⅲ-Ⅳ acute graft-versus-host disease,bacterial bloodstream infection,and carbapenem-resistant organism bloodstream infections were independent risk factors for overall survival(within 100 days)in patients after allogeneic hematopoietic stem cell transplantation.Hazard ratios were 1.77(95%CI 1.047-2.991),7.926(95%CI 3.763-16.695),2.039(95%CI 1.117-3.722),and 3.389(95%CI 1.563-7.347),respectively.In conclusion,all-cause mortality rate after allogeneic hematopoietic stem cell transplantation is relatively high in the short term.A timely diagnosis and effective treatment of bacterial bloodstream infection and acute graft-versus-host disease are essential to improving allogeneic hematopoietic stem cell transplantation outcomes.

Efficacy of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical hematopoietic stem cell transplantation / 中国组织工程研究

BACKGROUND:HLA haploid allogeneic hematopoietic stem cell transplantation provides a chance of survival for patients with high-risk hematologic malignancies.In recent years,the research on the transplantation mode and graft selection of haploidentical transplantation is still ongoing.At present,the mixed transplantation model of non-extracorporeal T-cell removal bone marrow and peripheral blood stem cells established by the Hematology Research Center of Peking University is gradually becoming popular in China,but this model requires the collection of donor bone marrow fluid,which increases the pain and risk of the donor. OBJECTIVE:To explore the curative effect of infusion of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical peripheral blood hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:Fifty hematological malignancies patients who underwent haploidentical hematopoietic stem cell transplantation from January 2019 to May 2022 were selected and randomly assigned to two study groups at a ratio of 2:3.Among them,19 patients received umbilical cord mesenchymal stem cell combined with peripheral blood stem cell transplantation,and 31 patients were treated with bone marrow cells combined with peripheral blood stem cells.The study was approved by the Ethics Committee of Henan Provincial People's Hospital.The recipients of umbilical cord mesenchymal stem cells were first transfused with third-party umbilical cord mesenchymal stem cells(1×106/kg)on the day of transplantation,followed by peripheral blood hematopoietic stem cells 6 hours later.In the bone marrow group,donor bone marrow cells were transfused +1 day after transplantation and peripheral blood stem cells were transfused +2 days after transplantation.After transplantation,rabbit anti-human thymocyte immunoglobulin,cyclosporine A,mycophenolate mofetil,and a short-course methotrexate were used for graft-versus-host disease prophylaxis for all recipients. RESULTS AND CONCLUSION:No adverse events occurred during the reinfusion of umbilical cord mesenchymal stem cells.There were no significant differences between the mesenchymal stem cell group and the bone marrow group in the engraftment rate[100%(19/19)vs.96.8%(30/31),P>0.05],median duration for neutrophil engraftment(14 days vs.15 days,P>0.05)and median duration for platelet engraftment(20 days vs.19 days,P>0.05).The incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease in the mesenchymal stem cell group was significantly lower than in the bone marrow group[21.1%(4/19)vs.58.1%(18/31),P = 0.01].There were no significant differences between the two groups in the incidence of chronic graft-versus-host disease[21.1%(4/19)vs.25.8%(8/31),P>0.05],the relapse rates[15.8%(3/19)vs.16.1%(5/31),P>0.05]and the incidence of early cytomegalovirus viremia[42.1%(8/19)vs.35.5%(11/31),P>0.05],and the 2-year overall survival rate[68.4%(10/19)vs.70.9%(16/31),P>0.05].It is indicated that umbilical cord mesenchymal stem cells replace donor bone marrow cells in haploidentical peripheral blood stem cell transplantation for malignant hematological diseases,which reduced the incidence of acute graft-versus-host disease after transplantation,did not increase the incidence of chronic graft-versus-host disease,recurrence rate and early cytomegalovirus viremia,and reduced the pain and risk of donor pulp extraction.

Characteristics of acute graft-versus-host disease of the intestine after unrelated cord blood transplantation / 中国组织工程研究

BACKGROUND:Despite unrelated cord blood transplantation is expected to become an important method for treating malignant hematological diseases,the manifestation and clinical characteristics of acute graft-versus-host disease in the gastrointestinal tract still require further in-depth investigation. OBJECTIVE:To analyze the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation. METHODS:A retrospective analysis was conducted on 668 malignant hematological disease patients after unrelated cord blood transplantation who underwent hematopoietic stem cell transplantation subspecialty in the Department of Hematology,First Affiliated Hospital of University of Science and Technology of China from December 2016 to December 2020.Among them,clinical data of 138 patients with intestinal acute graft-versus-host disease were analyzed,including 76 males and 62 females,with a median age of 13(1-62)years.All patients were treated with a myeloablative regimen(without antihuman thymocyte globulin)and cyclosporin A combined with mycophenolate mofetil to prevent graft-versus-host disease. RESULTS AND CONCLUSION:(1)The patients with intestinal acute graft-versus-host disease had diarrhea of varying degrees,most of which were yellow-green,yellow-brown watery stools or mucous stools.53 patients(38.4%)had blood stools,82 patients(57.9%)had skin involvement,18 patients(13.0%)had a secondary intestinal bacterial infection,and 90 patients(65.2%)had cytomegaloviremia.(2)The clinical characteristics of patients(70 cases,50.7%)with grade 1-2 intestinal acute graft-versus-host disease were compared with those(68 cases,49.3%)with grade 3-4 intestinal acute graft-versus-host disease.It was found that the age of grade 3-4 intestinal acute graft-versus-host disease patients was higher than that of grade 1-2 intestinal acute graft-versus-host disease patients(P<0.001),and they were complicated with cytomegaloviremia probably(P=0.035).Diarrhea lasted longer(P=0.00)and the length of hospital stay increased substantially(P<0.001).However,there were no significant differences in recipient gender,pre-transplant disease status,HLA matching,diagnosis,combined skin graft-versus-host disease,and secondary intestinal infection rate in patients of the two groups.(3)These findings conclude that the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation are complex,which affects the prognosis and quality of life of patients seriously and requires early identification and precise treatment.

Research progress on nutritional support for gastrointestinal graft-versus-host disease / 中华临床营养杂志

Gastrointestinal graft versus host disease is one of the most severe complications after hematopoietic stem cell transplantation, which can occur in patients of any age groups. Its clinical manifestations include nausea, vomit, abdominal pain, diarrhea and the like. Severe gastrointestinal graft versus host disease could directly influence the patients' clinical prognosis and therapeutic efficacy of transplantation. Here we had a review of the research progress on nutritional support and diet management strategies for gastrointestinal graft versus host disease. It is of great clinical significance to form a step-wise nutritional support model to reduce the risk of malnutrition in patients with gastrointestinal graft versus host disease, which would contribute to improving patients' general condition, relieving digestive tract symptoms, and reducing the risk of complications.

Application of the OmniLogTM microbial identification system in the detection of the host spectrum for wild-type plague phage in Qinghai Plateau / 中国人兽共患病学报

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.

qPCR在重组腺相关病毒产品大片段宿主细胞残留DNA检测中的应用 / 中国生物制品学杂志

@#Objective To investigate the feasibility of using quantitative PCR(qPCR)technology to detect large fragments of host cell residual DNA(HCD)in recombinant adeno-associated virus(rAAV)gene therapy products.Methods Four different serotypes of rAAV were extracted for the nucleic acids,two fragment sequences of 244 bp and 562 bp within the long terminal repeat sequence(LTR)in the genome of host cells HEK293 were specifically quantified by qPCR,and the proportion of HCD in the total nucleic acids was calculated.Results Large fragments of HCD in qPCR quantifiable range were detected in four different serotype rAAV products,with the abundance ranging from 0. 3% to 5. 4%. As the length of the detected fragment increased,the abundance of HCD fragments showed a decreasing trend.Conclusion qPCR technology can be used to determine the presence of large fragments of HCD in rAAV products.

Bioinformatics Analysis of Modified Lugen Formula in the Treatment of Influenza:Perspectives from the Virus-Host Interaction Network / 中药新药与临床药理

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Research progress on pathology and pathogenesis of chronic ocular graft-versus-host disease / 国际眼科杂志(Guoji Yanke Zazhi)

Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is a treatment for many malignant tumors of blood system and severe immunodeficiency, and chronic graft-versus-host disease(cGVHD)is one of the major complications after transplantation, which seriously affects the life quality of patients. The cGVHD can attack all the target tissues of the eye. The more common ones are lacrimal gland, eyelid, conjunctiva, cornea and limbus, meibomian gland, etc. The pathophysiological process is inflammation and fibrosis. Although many researchers at home and abroad have gradually begun to explore the disease and obtained many new findings, its pathology and pathogenesis are still not fully understood, and there is no unified and effective treatment. Clinically, the treatment of the disease is usually when symptoms have appeared. At this time, the target tissue is likely to have irreversible and permanent damage, resulting in a protracted and refractory situation. Therefore, this thesis mainly clarifies the research progress of the pathology and pathogenesis of ocular cGVHD in recent years, in order to provide new guidance for the treatment of the disease.

Comparison of two pretreatment methods for detection of free and mispackaged host cell DNA in recombinant adeno-associated virus / 中国生物制品学杂志

@#Objective To compare the application of two pretreatment methods,deoxyribonuclease(DNase)treatment and ligand affinity,in detecting the residual amount of free and mispackaged host cell DNA(HCDNA)in recombinant adenoassociated virus(rAAV).Methods Free and mispackaged HCDNA were isolated by DNase treatment and ligand affinity respectively,and then the nucleic acid was extracted and detected by qPCR. The accuracy and reproducibility of two pretreatment methods for detecting HCDNA residues were compared.Results Using DNase treatment,the result of nucleic acid quantitative detection in non-DNase-treated group was the total residual amount of HCDNA,that in DNase-treated group was the amount of mispackaged HCDNA,and the difference between them was the residual amount of free HCDNA. The recovery rates of both the untreated and treated groups were more than 75%,and the RSD of reproducibility was less than 30%. Using affinity extraction method,with the affinity ligand combined with rAAV,the result of recovery rate of mispackaged HCDNA was over 75%,and that of free HCDNA was only 36%.Conclusion DNase treatment method can effectively detect free and mispackaged HCDNA,laying a foundation for further research.

Clinical analysis of lung transplantation for lung chronic graft-versus-host disease after hematopoietic stem cell transplantation / 器官移植

<b>Objective</b> To evaluate clinical efficacy of lung transplantation for lung chronic graft-versus-host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT). <b>Methods</b> Clinical data of 12 patients undergoing lung transplantation for lung cGVHD were retrospectively analyzed. Preoperative clinical manifestations and involved organs of patients were analyzed. The lung function before and after lung transplantation was compared, and the survival of patients after lung transplantation was analyzed. <b>Results</b> Eleven patients underwent HSCT due to primary hematological malignancies, including 9 cases of leukemia, 1 case of myelodysplastic syndrome, 1 case of lymphoma. And 1 case underwent HSCT for systemic lupus erythematosus. Among 12 cGVHD patients, skin involvement was found in 8 cases, oral cavity involvement in 5 cases, gastrointestinal tract involvement in 4 cases and liver involvement in 3 cases. All 12 patients developed severe respiratory failure caused by cGVHD before lung transplantation, including 9 cases of typeⅡ respiratory failure and 3 cases of type Ⅰ respiratory failure. Two patients underwent right lung transplantation, 2 cases of left lung transplantation and 8 cases of bilateral lung transplantation. The interval from HSCT to lung transplantation was 75 (19-187) months. Upon the date of submission, postoperative follow-up time was 18 (7-74) months. Ten patients survived, 1 died from severe hepatitis at postoperative 22 months, and 1 died from gastrointestinal bleeding at postoperative 6 months. No recurrence of primary diseases was reported in surviving patients. <b>Conclusions</b> Lung transplantation is an efficacious treatment for lung cGVHD after HSCT, which may prolong the survival time and improve the quality of life of the recipients.

Preparation of the first national reference standard for determination of HEK293 cell DNA content / 中国生物制品学杂志

@#Objective To prepare a national reference standard for the quantification of HEK293 cell DNA content,so as to provide a support for the determination of residual DNA in HEK293 cells in the industry.Methods HEK293 cell DNA prepared using Genomic-tip 500/G and genomic DNA purification reagents was used as source materials,and the purity and content were assessed using ultraviolet spectrophotometry and agarose gel electrophoresis.After dilution to approximately 100 ng/μL,the DNA was aliquoted at 160 μL/tube.Five different laboratories were organized for collaborative calibration by using ultraviolet spectrophotometry, and the stability and applicability were evaluated.Results The HEK293 cell DNA national reference standard exhibited A_(260)/A_(280) ratios between 1.8 and 2.0 and displayed a single band on electrophoresis,meeting the specified criteria.Collaborative calibration across five laboratories yielded 78 valid data points with an average content of 104.8 ng/μL,a relative standard deviation(RSD) of 4.2%.The 95% confidence interval for the mean was 103.8—105.8 ng/μL,and the 95% reference range for single measurements was 96.0—113.6 ng/μL.The average confidence limit rate was 1.0%,and the recommended storage condition was-80 ℃.Applicability studies were conducted using two different models of fluorescence quantitative PCR instruments.The reference standard exhibited good applicability within the range of 0.3—3 000 pg/reaction,with amplification efficiencies of 101% and 95%,and R~2 values of 0.999 2 and 0.999 5 for the standard curves,respectively.Conclusion This batch of HEK293 cell DNA national reference standard meets all required specifications and can be utilized as a national reference standard for fluorescence quantitative PCR detection,with a certified content of 104.8 ng/μL,assigned batch number 270039-202301.

Efficacy and safety of ruxolitinib for refractory graft-versus-host disease in Chinese population: a Meta-analysis / 白血病·淋巴瘤

Objective:To systematically evaluate the efficacy and safety of ruxolitinib in the treatment of Chinese patients with refractory graft-versus-host disease(SR-GVHD) by using meta-analysis.Methods:China National Knowledge Infrastructure(CNKI), WanFang database, VIP database, China Biology Medicine disc, PubMed, Ebscore Medline, EMBASE, Web of Science Core Collection and Cochrane Library were searched by using "ruxolitinib" "Graft vs Host Disease" "graft versus host disease" "Graft-Versus-Host Disease" as key words. The retrieve time was from the establishment of the database to December 7th, 2021. The related literatures of ruxolitinib for Chinese patients with SR-GVHD were screened according to inclusion and exclusion criteria, and the characteristics of the literatures were extracted. Outcomes indexes included overall objective response rate (ORR), proportion of hormone reduction and discontinuation, survival indexes and incidence of adverse events. Meta-analysis of ORR, remission rate of affected organs, 12-month overall survival rate, overall mortality and mortality due to graft-versus-host disease (GVHD) were performed by using Stata 16.0 software or R3.6.3 software. The statistics analysis was performed on the hormone usage and adverse events.Results:A total of 19 literatures involving 775 Chinese patients with SR-GVHD treated by ruxolitinib were included. Meta analysis showed that the ORR of ruxolitinib for treatment of acute GVHD (aGVHD) was 84% (285/339), with moderate heterogeneity among studies ( I2 = 62.04%, P<0.01), and the complete remission (CR) rate, partial remission (PR) rate and non-remission (NR) rate was 56% (190/339), 28% (95/339), and 14%(47/339), respectively. The ORR of ruxolitinib for treatment of chronic GVHD (cGVHD) was 77% (332/431), with moderate heterogeneity among studies ( I2 = 50.17%, P = 0.02), and the CR rate, PR rate and NR rate was 36% (155/431), 41% (177/431) and 21% (91/431), respectively. As for hormone usage, 46.51% of aGVHD patients had steroid reduction and 34.88% patients had steroid discontinuation. Similarly, 28.2% of patients with cGVHD had steroid reduction and 36.9% had steroid discontinuation. The overall 12-month survival rate of patients with SR-GVHD after the treatment of ruxolitinib was 71% (95% CI: 63%-79%, I2 = 72.70%, P<0.01). Adverse events occurred for 760 times in total, among which 287 times (36.0%) of viral infection and 269 times (34.7%) of hemocytopenia were the most common adverse events. Conclusions:Ruxolitinib is effective in the treatment of Chinese patients with SR-GVHD, and it helps reduce hormone-dependency and prolong the survival time.