Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos

Introducción: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. Objetivo: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. Métodos: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. Resultados: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). Conclusiones: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

Background: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. Aim: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. Methods: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. Results: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). Conclusions: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

Vaccination in children with immune-mediated disorders

Abstract Objective: To present an updated review of recommendations for the vaccination of children with immune-mediated diseases, with an emphasis on rheumatic and inflammatory diseases. Source of data: Studies published in the PubMed and Scielo databases between 2002 and 2022, Guidelines of Brazilian Scientific Societies, Manuals and Technical Notes of the Ministry of Health of Brazil, on current immunization schedules for special populations. Data synthesis: Immunosuppressive drugs and biological agents reduce the immunogenicity of vaccines and favor susceptibility to infections. The safety and efficacy of immunogens are important points for vaccination in children with immune-mediated diseases. The safety threshold of a vaccine applied to immunocompromised individuals can be reduced when compared to healthy individuals. Very often, the recommendations for the immunization of children with immunemediated diseases follow the recommendations for immunocompromised patients. Vaccination against COVID-19, on the other hand, should ideally occur when the disease is stabilized and in the absence of a low degree of immunosuppression. The patients should be informed about the possibility that the immunization may fail during treatment with immunosuppressants. Specific vaccination schedules should be considered to ensure better protection. Conclusions: Recent studies have allowed updating the recommendations on the safety and immunogenicity of vaccination in children with immune-mediated diseases, especially for live attenuated vaccines. There is a scarcity of data on the safety and efficacy of COVID-19 vaccines in patients, particularly pediatric patients, with rheumatic diseases. The completion of ongoing studies is expected to help guide recommendations on COVID-19 vaccines in this group of patients.

Roles of P2X7 receptor and NLRP3 inflammasome in inflammatory diseases / 中华微生物学和免疫学杂志

Purinergic 2X7 receptor (P2X7R) is an ionotropic receptor that is involved in various inflammatory diseases through affecting the release of inflammatory cytokines such as IL-1β and IL-18 after inducing the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). In recent years, the P2X7R/NLRP3 signaling pathway has become one of the more studied pathways in inflammatory diseases, and some inhibitors of P2X7R and NLRP3 have already been used in early clinical treatment. In this paper, the progress in P2X7R and NLRP3 was summarized, aiming to provide reference for further investigation on the roles of P2X7R/NLRP3 in the pathogenesis of tumors and inflammatory diseases and the potential of P2X7R/NLRP3 as therapeutic targets.

Nuevo panorama para las enfermedades reumáticas pediátricas / New landscape for pediatric rheumatic diseases

Introducción: Las enfermedades reumáticas no se limitan a la edad adulta. Afectan a personas de todas las edades, incluidos los niños, y a menudo afectan a adultos jóvenes. En consecuencia, las enfermedades reumáticas pediátricas necesitan una evaluación y un seguimiento minuciosos y cuidadoso. Pueden ser debilitantes y, si no se tratan adecuadamente, pueden poner en peligro la vida. Objetivos: En este artículo se comentará sobre avances en el diagnóstico y tratamiento de las enfermedades reumáticas pediátricas, destacando las ventajas del empleo de determinados medios diagnósticos. Desarrollo: Para ello se ha realizado una revisión bibliográfica que permite aportar elementos importantes a considerar. Conclusiones: Se ha avanzado mucho en las últimas décadas en el campo de la reumatología pediátrica, que incluyen, entre otros, la patogenia, los criterios de clasificación y las terapias. Los reumatólogos pediátricos deben mantenerse al día con el progreso para aumentar la precisión del diagnóstico y mejorar el pronóstico de los pacientes(AU)

ABSTRACT Introduction: The effective treatment of postoperative pain is today a challenge for anesthetists, rheumatologists, orthopedic surgeons, surgeons and researchers of various specialties, who constantly propose protocols based on scientific evidence. Objective: Reflect and open the debate regarding the role of anesthesia in the relief of pain of rheumatological origin. Development: In Rheumatology, it is recommended, in all patients with chronic rheumatic pain, to calculate the intensity of the pain, both for the first choice of the analgesic treatment and for the measurement of the response. And, for this, several methods of quantification have been proposed. Conclusions: Diagnostic management and multidisciplinary treatment preside when this type of case is examined, since it is the only way to identify the origin of pain and provide prudent relief. In general, patients respond to conservative treatment and only a small group will need invasive anesthetic techniques(AU)

Advances in small molecular inhibitors of IL-6/STAT3 signaling pathway / 药学学报

As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.

The function and regulation of TET2 in innate immunity and inflammation

TET2, a member of ten-eleven translocation (TET) family as α-ketoglutarate- and Fe

Advances of using microfluidic chips for research and diagnosis of pulmonary inflammatory diseases / 生物工程学报

Microfluidic chip technology integrates the sample preparation, reaction, separation and detection on a chip. It consists a network of microchannels, which controls the whole system through fluid. With the advantages of portability, high throughput, and the ability to simulate the microenvironment in vivo, it has a broad application prospect in the research of disease diagnosis, pathogenesis and drug screening. Pulmonary inflammatory disease is a common disease usually caused by bacterial, viral and fungal infections. Early pneumonia is often difficult to diagnose due to lack of obvious respiratory symptoms or the symptoms are mostly atypical, but the disease progresses rapidly. Recently, microfluidic chip technology has been increasingly used to the study of pulmonary inflammatory diseases. In particular, it has been used to develop a "lung-on-a-chip" model, which can reproduce the key structure, function and mechanical properties of human alveolar capillary interface (i.e., the basic functional unit of a living lung), and well simulate the alveoli in vitro. Compared with the cell and animal models, this multifunctional micro experimental platform has great advantages. This article summarizes the advances of using microfluidic chips for the research and diagnosis of pulmonary inflammatory diseases, with the aim to provide new ideas for researchers in this area.

COVID-19 and patients with immune-mediated inflammatory diseases undergoing pharmacological treatments: a rapid living systematic review

ABSTRACT BACKGROUND: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of infection. OBJECTIVE: To assess whether patients undergoing pharmacological treatment for IMID present higher risk of worse outcomes when diagnosed with COVID-19. DESIGN AND SETTING: Rapid systematic review conducted in the medical school of the Federal University of São Paulo (SP), Brazil. METHODS: We searched CENTRAL, MEDLINE, EMBASE, LILACS, SCOPUS, Web of Science, L·OVE, ClinicalTrials.gov and WHO-ICTRP for studies evaluating patients diagnosed with COVID-19 who were undergoing pharmacological treatment for IMID. Two authors selected studies, extracted data and assessed risk of bias and certainty of evidence, following the Cochrane recommendations. RESULTS: We identified 1,498 references, from which one cohort study was included. This compared patients with and without rheumatic diseases (RD) who all had been diagnosed with COVID-19. Those with RD seemed to have higher chances of hospitalization and mortality, but no statistical difference was detected between the groups: hospitalization: odds ratio (OR) 1.17; 95% confidence interval (CI) 0.6 to 2.29; mortality rate: OR 1.53; 95% CI 0.33 to 7.11 (very low certainty of evidence). Patients with RD were three times more likely to require admission to intensive care units (ICUs), with invasive mechanical ventilation (IMV), than those without RD: OR 3.72; 95% CI 1.35 to 10.26 (for both outcomes; very low certainty of evidence). CONCLUSION: Patients undergoing pharmacological treatment for IMID seem to present higher chances of requiring admission to ICUs, with IMV. Additional high-quality studies are needed to analyze the effects of different treatments for IMID.

Doença de Coronavírus-19 e o Miocárdio / Coronavirus Disease 2019 and the Myocardium

Resumo A infecção pelo coronavírus denominada COVID-19 promoveu crescente interesse de cardiologistas, emergencistas, intensivistas e pesquisadores, pelo estudo do acometimento miocárdico partindo de diferentes formas clínicas decorrentes de desmodulação imunoinflamatória e neuro-humoral.O acometimento miocárdico pode ser mínimo e apenas identificado a partir de alterações eletrocardiográficas, principalmente por aumento de troponinas cardíacas, ou no outro lado do espectro pelas formas de miocardite fulminante e síndrome de takotsubo.A descrição de provável miocardite aguda tem sido comumente apoiada pela observação da troponina elevada em associação com disfunção. A clássica definição de miocardite, respaldada pela biópsia endomiocárdica de infiltrado inflamatório é rara, e foi observada em um único relato de caso até o momento, não se identificando o vírus no interior dos cardiomiócitos.Assim, o fenômeno que se tem documentado é de injúria miocárdica aguda, sendo obrigatório afastar doença coronária obstrutiva a partir da elevação de marcadores de necrose miocárdica, associada ou não à disfunção ventricular, provavelmente associada à tempestade de citoquinas e outros fatores que podem sinergicamente promover lesão miocárdica, tais como hiperativação simpática, hipoxemia, hipotensão arterial e fenômenos trombóticos microvasculares.Fenômenos inflamatórios sistêmicos e miocárdicos após infecção viral estão bem documentados, podendo evoluir para remodelamento cardíaco e disfunção miocárdica. Portanto, será importante a cardiovigilância desses indivíduos para monitorar o desenvolvimento do fenótipo de miocardiopatia dilatada.A presente revisão apresenta os principais achados etiofisiopatológicos, descrição da taxonomia desses tipos de acometimento cardíaco e sua correlação com as principais formas clínicas do componente miocárdico presente nos pacientes na fase aguda de COVID-19.

Abstract Infection with the coronavirus known as COVID-19 has promoted growing interest on the part of cardiologists, emergency care specialists, intensive care specialists, and researchers, due to the study of myocardial involvement based on different clinical forms resulting from immunoinflammatory and neurohumoral demodulation.Myocardial involvement may be minimal and identifiable only by electrocardiographic changes, mainly increased cardiac troponins, or, on the other side of the spectrum, by forms of fulminant myocarditis and takotsubo syndrome.The description of probable acute myocarditis has been widely supported by the observation of increased troponin in association with dysfunction. Classical definition of myocarditis, supported by endomyocardial biopsy of inflammatory infiltrate, is rare; it has been observed in only one case report to date, and the virus has not been identified inside cardiomyocytes.Thus, the phenomenon that has been documented is acute myocardial injury, making it necessary to rule our obstructive coronary disease based on increased markers of myocardial necrosis, whether or not they are associated with ventricular dysfunction, likely associated with cytokine storms and other factors that may synergistically promote myocardial injury, such as sympathetic hyperactivation, hypoxemia, arterial hypotension, and microvascular thrombotic phenomena.Systemic inflammatory and myocardial phenomena following viral infection have been well documented, and they may progress to cardiac remodeling and myocardial dysfunction. Cardiac monitoring of these patients is, therefore, important in order to monitor the development of the phenotype of dilated myocardiopathy.This review presents the main etiological and physiopathological findings, a description of the taxonomy of these types of cardiac involvement, and their correlation with the main clinical forms of the myocardial component present in patients in the acute phase of COVID-19.

Depresión e inflamación: ¿Una relación más allá del azar? / Depression and inflammation: a relationship beyond random?

El tratamiento actual de la depresión mayor, una condición de alta prevalencia a nivel mundial, aún no resulta satisfactorio por las significativas tasas de falta de respuesta o de síntomas residuales. Esto, entre otras razones, ha motivado a la búsqueda de nuevos modelos de comprensión de los procesos biológicos que están a la base de esta enfermedad, con el propósito de encontrar mejores estrategias terapéuticas, al menos desde el punto de vista farmacológico. Se examinan algunas correspondencias entre los fenómenos clínicos y la articulación de los sistemas inmune, nervioso y endocrino, y se revisa algunas relaciones entre depresión y enfermedades inflamatorias sistémicas.

The current treatment of major depression, a condition of high prevalence worldwide, is still unsatisfactory due to the elevated rates of non-response or residual symptoms. This, among other reasons, has motivated the search for new models of understanding the biological processes that could better explain this disease, with the purpose of finding better therapeutic strategies, at least from the pharmacological point of view. Some correspondences between clinical phenomena and the interplay of the immune, nervous and endocrine systems are examined. Also, some relationships between depression and systemic inflammatory diseases are reviewed.

Factores de riesgo asociados a la enfermedad inflamatoria intestinal en ancianos / Risk factors associated with the intestinal inflammatory disease in elderly

Introducción: Las enfermedades inflamatorias intestinales representan un importante problema de salud pública por el aumento en su prevalencia e incidencia a nivel mundial. Objetivo: Identificar los principales factores de riesgo asociados a la enfermedad inflamatoria intestinal en ancianos. Métodos: Se realizó una investigación analítica, de casos y controles, de pacientes de 60 y más años, con diagnóstico y confirmación histológica de alguna enfermedad inflamatoria intestinal, ingresados en el Servicio de Medicina del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba, durante el 2015. El grupo de estudio estuvo conformado por 61 pacientes y el de control por 122 integrantes (2 por cada caso), seleccionados de los consultorios de procedencia de los afectados. En el análisis estadístico se calculó el porcentaje para las variables cualitativas y, a fin de comprobar la existencia de asociación, se aplicó la prueba de independencia de la Χ2, con 95 % de confiabilidad. Cada variable se analizó calculando la oportunidad relativa, con intervalos límite de confianza superior e inferior. Resultados: Se obtuvo una asociación causal de 5,4 veces más posibilidades de padecer alguna enfermedad inflamatoria intestinal si estaba presente el antecedente familiar de colitis. Asimismo, existió una asociación significativa (p<0,05) entre el antecedente familiar de enfermedad de Crohn y la enfermedad inflamatoria intestinal (9,8 %), y fue 9,7 veces más posible que apareciera algún trastorno inflamatorio de los intestinos si se consumían alimentos inadecuados. Conclusiones: Los factores de riesgo mayormente relacionados con la enfermedad inflamatoria intestinal fueron los antecedentes familiares de colitis y de enfermedad de Crohn, así como el consumo inadecuado de alimentos, el uso prolongado de antibióticos y el tabaquismo.

Introduction: The intestinal inflammatory diseases represent an important problem of public health due to the increase in their prevalence and incidence worldwide. Objective: To identify the main risk factors associated with the intestinal inflammatory disease in elderly. Methods: An analytic cases and controls investigation of 60 years and over patients, with diagnosis and histological confirmation of some intestinal inflammatory disease was carried out. They were admitted to the Medicine Service of Saturnino Lora Torres Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba, during 2015. The study group was conformed by 61 patients and the control group by 122 members (2 for each case), belonging to the family doctor´s office of the affected patients. In the statistical analysis the percentage for the qualitative variables was calculated and, in order to check the existence of any association, the chi-square test was implemented, with 95 % of confidence. Each variable was analyzed calculating the relative opportunity, with upper and lower limit intervals of confidence. Results: There was a causal association of 5.4 times more possibilities of suffering some intestinal inflammatory disease if the family history of colitis was present. Also, a significant association existed (p <0.05) between the family history of Crohn disease and the intestinal inflammatory disease (9.8 %), and it was 9.7 times more possible that some inflammatory disorder of the bowels appeared if inadequate foods were eaten. Conclusions: The risk factors mostly related to the intestinal inflammatory disease were the family history of colitis and Crohn disease, as well as the inadequate consumption of foods, the long use of antibiotics and nicotine addiction.

Advances in autophagy-related genes in inflammatory diseases / 解放军医学杂志

Autophagy is a highly conserved physiological and biochemical process in which organisms maintain homeostasis of the cellular environment. Autophagy is widely involved in the occurrence and development of many diseases, especially in inflammatory diseases, which is a hot topic in recent years. Autophagy-related genes (ATGs) play important roles in regulating autophagy in many aspects, thus affecting the process and prognosis of inflammatory diseases. This article reviews the regulatory roles and mechanisms of autophagy in inflammatory diseases, as well as the functions and roles of several important ATGs in inflammatory diseases.

Expression of procalcitonin in polygenic auto-inflammatory diseases / 中华风湿病学杂志

Objective To detect the levels of procalcitonin in multiple genes autoinflammatory disease (adult Still disease,systemic juvenile idiopathic arthritis,crohn's Crohn's disease),and to explore the relationship between erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),ESR/CRP and disease or complicated infection combined disease.Methods One hundred and fifty-three patients were en-rolled,88 patients with multiple genes autoinflammatory disease,including 32 cases of adult Still disease,27 cases of systemic juvenile idiopathic arthritis,29 cases of Crohn's disease.In addition,30 cases of healthy controls,35 patients with systemic lupus erythematosus (SLE) were included into this study.Electroche-miluminescence was used to test the value of serum PCT,erythrocyte sedimentation rate was tested by blood sedimentation instrument method,the CRP level was tested by lmmunoturbidimetry,and the data was handed managed and analysised by matlab software and One-way analysis of variance (ANOVA) was used to compare the differences of PCTs between groups.Results ① In the non-infection condition,the PCT value of the autoimmune inflammatory diseases [(0.36±0.74) μg/L,95％confidence interval (CI) (0.174 9,0.550 9) μg/L)] was signifieantly higher than that of the healthy control group [(0.06±0.06) μg/L,95％CI (0.035 1,0.081 7 μg/L)],the difference was statistically significant (F=5.03,P=0.027 4),but there was no statistically significant (F=1.03,P=0.475 5) when comparing with SLE group.② The PCT level of the non-infected inflammatory enteric arthritis [(0.20±0.32),95％CI(0.042 7,0.364 3) μg/L] was different compared with the healthy group,the difference was statistically significant (F=5.77,P=0.020 4),at the same time,the difference was not statistically significant when comparing with the SLE group (F=0.22,P=0.647 6).When the PCT value in non-infected adults Still disease [(0.60±1.02) 95％CI(0.048 4,1.153 6) μg/L] compared with the healthy group,the difference was statistically significant (F=7.22,P=0.01) but the difference was not statistically different when compared with the SLE group (F=2.65,P=0.114 3).The PCT level difference was statistically significant (F=2.23,P＜0.01)when comparing infection-free juvenile idiopathic arthritis [(1.52±2.02) μg/L,95％CI(0.054 8,4.591 9) μg/L] and the healthy group,the difference was statistically significantly different (F=8.34,P=0.004 7) when compared with the PCT of the non-infected SLE group.③ In the case of autoinflammatory diseases without infection,the 95％CI of ESR/CRP ratio was between 1.121 2 and 3.589 4.In the case of co-infection,the 95％ CI of ESR/CRP ratio was between 1.502 2 and 8.718 8,so we considered autoimmune inflammatory diseases might had a high possibility of co-infection when the ESR/CRP ratio was higher than 3.5.Conclusion ① The multiple genes autoinflammatory disease group has a higher value of PCT level than healthy controls even without infection.② The mean and 95％CI range of PCT of the inflammatory bowel disease arthritis,adult Still disease and the juvenile id-iopathic arthritis is significantly higher than the healthy controls,partially higher than SLE group.In addition,the PCT level in the juvenile idiopathic arthritis is the highest.③ In clinical,to estimate whether the multiple genes autoinflammatory disease has bacterial infection,we can't just simply rely on PCT to estimate whether the multiple genes autoinflammatory disease has bacterial infection,we may consider the ratio of the ESR/CRP,when the value is higher than 3.5,we may consider patients has strong probability with infection.

Mastitis granulomatosa idiopática: Reporte de caso / Idiopathic granulomatous mastitis: Case report

Idiopathic granulomatous mastitis is a rare, benign chronic disease. Its etiology is not clear; however, the disease has been associated with breastfeeding, use of oral contraceptives, and an autoimmune component. The characteristic presentation is an inflammatory reaction with non-caseating granulomas. Histological features include signs of chronic granulomatous inflammation with giant cells, leukocytes, epithelioid cells, and macrophages, as well as microabscesses. In the differential diagnosis, all causes of granulomatous changes should be excluded. Due to its low frequency, the treatment is difficult to standardize and optimize. We present the case of a 36-year-old woman with a painful nodule in the right breast. Clinical presentation and imaging raised suspicion of carcinoma. Histopathology revealed acute and chronic inflammation, infiltration of macrophages and giant perivascular histiocytes with granulomatous giant cell reaction, with no signs of malignancy and suggestive of a granulomatous process. Stains were negative for fungi and mycobacteria.

La mastitis granulomatosa idiopática es una enfermedad benigna, rara y crónica. Su etiología no está clara; sin embargo, se ha demostrado que la enfermedad se correlaciona con la lactancia, uso de anticonceptivos orales y hasta un componente autoinmune. La presentación característica es la reacción inflamatoria con granulomas no caseificantes. Las características histológicas incluyen signos de inflamación granulomatosa crónica con células gigantes, leucocitos, células epitelioides y macrófagos, así como microabscesos. En el diagnóstico diferencial, todas las causas de cambios granulomatosos deben excluirse antes de realizar el diagnóstico. Debido a su baja frecuencia, es difícil estandarizar y optimizar el tratamiento. Se presenta un caso de mujer de 36 años con nódulos dolorosos en mama derecha. La clínica y los hallazgos del estudio de imágenes llevaron a sospecha de carcinoma. El examen histopatológico reveló inflamación aguda y crónica con infiltración de macrófagos e histiocitos gigantes perivasculares con reacción granulomatosa gigantocelular, sin signos histológicos sugerentes de malignidad y sugestivos de proceso granulomatoso. Las coloraciones para hongos y micobacterias fueron negativas. La paciente fue diagnosticada como mastitis granulomatosa idiopática. El tratamiento consistió en corticosteroides más metotrexato. La paciente se encuentra libre de recurrencia 18 meses después del tratamiento.

Regulatory Roles of the Caspase-11 Non-Canonical Inflammasome in Inflammatory Diseases

Inflammation is an immune response mediated by innate immune cells of tissues, against invading microbes and cellular stress. The hallmark of inflammatory responses is the activation of inflammasomes — multiprotein oligomers comprising intracellular pattern recognition receptors and inflammatory effectors — such as ASC and pro-cysteine-aspartic protease (pro-caspase)-1. Inflammasomes can be classified as canonical or non-canonical, and their activation in response to various ligands commonly induces caspase-1 activation and gasdermin D (GSDMD) processing, leading to caspase-1-mediated maturation and secretion of the pro-inflammatory cytokines IL-1β and IL-18, and GSDMD-mediated pyroptosis through pore generation in cell membranes. Although inflammation protects the host from harmful stimuli, chronic inflammation is a critical risk factor for inflammatory diseases, and several studies have investigated the role of canonical inflammasomes in inflammatory responses and diseases, with emerging studies focusing on the role of non-canonical inflammasomes. This review discusses recent studies on the regulatory roles of the caspase-11 non-canonical inflammasome in the pathogenesis of inflammatory diseases. Additionally, it provides an insight into the development of novel therapeutics based on targeting caspase-11 non-canonical inflammasome and its downstream effectors to prevent and treat human inflammatory conditions.

IL-36 in inflammatory diseases / 中国免疫学杂志

The IL-36,which is a member of IL-1 family,consists of three ligands IL-36α,IL-36β and IL-36γ. The cytokines exert their proinflammatory effects through a specific IL-36 receptor(IL-36R),IL-36Ra is an antagonist of IL-36R.IL-36 acts as a helper,involved in dendritic cell and T cell activation, maturation, polarization, antigen presentation and stimulating inflammatory factor production,and so on.IL-36,as a new proinflammatory factor,plays a very important role in many inflammation diseases, including psoriasis,inflammatory bowel disease,arthritis,SLE,lung diseases and so on.

High lights of advances in immunology research in 2017 / 中国免疫学杂志

During the past year,there has been remarkable advances in the field of immunological research at home and abroad.In the field of basic immunology,scientists have identified new roles of variable regulatory mechanisms,such as epigenetic modifications,RNA modifications,protein post-translational modifications,energy metabolisms in the development and functions of immune system.In the field of translational medicine and tumor immunotherapy,scientists have identified novel mechanisms of tumor initiation and progression,providing new target for the diagnosis and treatment of tumor.Notably,immunological researchers in China have made a number of innovative achievements in many areas of immunological researches in 2017.In this paper,we summarized the representative advances in the field of immunological research in 2017,and discussed the leading edge and challenging directions in this field.

Damage-Associated Molecular Patterns in Inflammatory Diseases

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). Although DAMPs contribute to the host's defense, they promote pathological inflammatory responses. Recent studies have suggested that various DAMPs, such as high-mobility group box 1 (HMGB1), S100 proteins, and heat shock proteins (HSPs), are increased and considered to have a pathogenic role in inflammatory diseases. Here, we review current research on the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. We also discuss the possibility of DAMPs as biomarkers and therapeutic targets for these diseases.

KAP Investigation of the Cognition to Tengyao Used in Treatment of Pelvic Inflammatory Disease among Medical Workers / 中国药师

Objective: To provide reference for promoting the use of Tengyao in the treatment of pelvic inflammatory diseases (PID). Methods: From January to March 2017, 111 health workers in department of gynaecology were investigated. The quantitative research of KAP questionnaire was used, and the content of questionnaire included personal information, knowledge, attitudes and practices. Results: A total of 111 copies of questionnaire were distributed and 95. 5% of them were effective. Interviewees' overall knowledge was at low level while the attitude was at high level; the main way to obtain knowledge was coming from colleagues (76. 42% ); working lifetime and speciality classification had significant impacts on the level of knowledge (P<0. 05); the majority of interviewees were willing to learn the relevant knowledge through training sessions (54. 72% ) and new media (27. 36% ); 48 inter-viewees would like to continue to use Tengyao for treating PID. The main problem of Tengyao in the treatment of PID was inconvenient operation (63. 64% ). Totally 83. 96% of interviewees considered that the dosage forms of Tengyao should be improved, and 50. 94% of interviewees considered that the clinical efficiency evaluation should be studied. Conclusion: Interviewees'overall knowledge is still at low level, especially in the junior medical staff. Pharmacists should improve the knowledge level of medical staff by meeting train-ing, and study how to improve the dosage forms and evaluate the clinical efficiency of Tengyao.

Prospective study of ocular and periocular diseases in animals: 188 cases / Estudo prospectivo de doenças oculares e perioculares em animais: 188 casos

istopathology of the ocular and periocular tissues submitted for diagnosis and research is still incipient in Brazil, in contrast to veterinary clinical ophthalmology. In this study, ocular and periocular tissues from domestic and wild animal species, mainly from the state of Minas Gerais, Brazil, were evaluated between February 2012 and September 2015. The samples were analyzed grossly and microscopically. Histochemistry and immunohistochemistry were performed on some of the samples. The frequency, type of ocular alteration, affected animal species, and affected ocular or periocular tissues were recorded. One hundred eighty-eight ocular and periocular tissues from domestic and, occasionally, wild animals were examined. Nine animals presented two concurrent alterations, adding up to 197 alterations. Proliferative lesions were the most frequent (92), followed by traumatic (43), inflammatory (37), degenerative (18), developmental (4) and vascular/hemorrhagic diseases (3). The globe was the most affected structure (112), followed by eyelids (52), third eyelid (17), bulbar conjunctiva (14) and retrobulbar region (2). Neoplasms arising from periocular tissues were the most frequent alteration (60), possibly related to a more active surgical service and histopathologic evaluation request. Many animals presented ocular lesions that reflected systemic diseases, which were diagnosed by necropsy and examination of other organs. Particularly in cases of neoplasia, early detection and surgical treatment can prevent systemic involvement. Ocular histopathologic evaluation can provide better characterization and prognosis of the clinical-pathological condition of the patient as well.(AU)

O envio de bulbos oculares e tecidos perioculares para histopatologia na rotina diagnóstica e pesquisa ainda é incipiente no Brasil, diferentemente da área de oftalmologia clínica veterinária. Neste estudo, olhos e tecidos perioculares de animais domésticos e silvestres, especialmente provenientes do estado de Minas Gerais, Brasil, foram avaliados entre fevereiro de 2012 e setembro de 2015. As amostras foram analisadas macro e microscopicamente. Em algumas amostras, histoquímica e imuno-histoquímica também foram realizadas. Frequência, tipo de alteração ocular, espécie animal e estrutura ocular e/ou periocular acometidas foram registrados. Foram examinados 188 bulbos oculares e tecidos perioculares de animais domésticos e, ocasionalmente, silvestres. Nove animais apresentaram duas alterações concomitantes, totalizando 197 alterações. Doenças neoplásicas foram as mais frequentes (92), seguidas pelas traumáticas (43), inflamatórias (37), degenerativas (18), de desenvolvimento (4) e vasculares/hemorrágicas (3). O bulbo ocular foi a estrutura mais acometida (112), seguida pelas pálpebras (52), terceira pálpebra (17), conjuntiva bulbar (14) e região retrobulbar (2). Neoplasmas com origem em tecido periocular foram a alteração mais frequente (60), possivelmente relacionado a uma rotina cirúrgica mais ativa e consequente solicitação de avaliação histopatológica. Muitos animais apresentaram lesões oculares como reflexo de doença sistêmica, as quais foram diagnosticadas por necropsia e análise de outros órgãos. Particularmente em casos de neoplasia, detecção precoce e tratamento cirúrgico podem evitar envolvimento sistêmico. Ademais, a avaliação histopatológica ocular é capaz de oferecer melhor caracterização e prognóstico de condições clínico-patológicas do paciente animal.(AU)