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This guideline aims to provide comprehensive and practical guidance for clinical management of tuberculosis in kidney transplant recipients. First, it summarizes the particularity of tuberculosis in kidney transplant recipients, and highlights the high incidence and diverse clinical manifestations. To better understand the patients' conditions, relevant assessment of tuberculosis is recommended before kidney transplantation. Extensive attention should be paid to the monitoring of tuberculosis after kidney transplantation. Regarding the diagnosis, the guideline explicitly introduces common diagnostic approaches for tuberculosis, and evaluates the applicability in kidney transplant recipients. After the diagnosis is confirmed, it discusses how to balance the treatment and rejection of tuberculosis under the background of immunosuppressants, and focuses upon the potential drug interaction. In terms of prevention, it emphasizes the screening of tuberculosis prior to kidney transplantation. This guideline is designed to deepen the understanding of medical staff for tuberculosis management in kidney transplant recipients, promote more effective clinical practice and improve the quality of life of the recipients.
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Objective:To investigate the level change of cytokines in patients with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:A retrospective case control study was conducted. The clinical data of 65 patients with EBV-HLH, 30 patients with infectious mononucleosis (IM) (IM group) and 40 patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis (non-EBV-HLH group) who admitted to Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from February 2022 to February 2023 were retrospectively analyzed. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of the interleukin (IL)-6, IL-2, IL-10, IL-8, IL-1β, tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in serum samples of patients in the above 3 groups. The cytokines levels in EBV-HLH group were compared with those in IM group and non-EBV-HLH group, respectively.Results:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α and IFN-γ in EBV-HLH group were higher than those in the non-EBV-HLH group, and the differences were statistically significant (all P < 0.05). The cytokines levels of IL-2, IL-10 and IFN-γ in EBV-HLH group were higher than those in IM group, and the differences were statistically significant (all P < 0.05). Conclusions:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α, IFN-γ are increased in EBV-HLH patients, which may play an important role in the development and progression of EBV-HLH.
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Objective:To investigate the mechanism of interferon γ(IFN-γ)combined with ferroptosis inducer Erastin in the inhibi-tion of the growth of oral tongue squamous cell carcinoma(OTSCC).Methods:The expression of SLC7A11 in OTSCC was studied by bioinformatics analysis and immunohistochemical staining.SLC7A11 gene in OTSCC CAL-27 cells was knocked out by CRISPR-CAS9,and the survival rate of WT and SLC7A11 KO cells treated with Erastin was measured by MTT assay.Glutathione kit,lipid oxidation kit and flow cytometry were used to detect the changes of lipid peroxides in the cells treated with Erastin.After 24 h pretreatment with IFN-γ,MTT assay was used to detect the changes of cell sensitivity to Erastin,and the changes in lipid peroxides were detected by glu-tathione kits,lipid oxidation kits and flow cytometry.Results:Bioinformatics analysis and immunohistochemical staining showed that SLC7A11 was highly expressed in OTSCC.SLC7A11 KO CAL-27 cells were more sensitive to Erastin than WT cells.The GSH content of SLC7A11 KO cells was lower than that of WT cells,and the lipid peroxide content was higher than that of WT cells after treatment with Erastin.IFN-γ increased cell sensitivity to Erastin,decreased GSH content and increased lipid peroxides content in the cells.Conclusion:IFN-γ can reduce GSH and increase MDA and Lipid ROS levels by degrading SLC7A11,this increases the sensitivity of OTSCC to Erastin.
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Objective@#To evaluate the effectiveness of recombinant Mycobacterium tuberculosis fusion protein skin test (EC-ST) in screening for latent tuberculosis infection (LTBI) among HIV/AIDS patients, so as to provide insights into the applicability of EC-ST in LTBI screening among HIV/AIDS patients.@*Methods@#From April to June 2023, HIV/AIDS patients under management and treatment in Yangzhou City, Jiangsu Province, were selected as study subjects. Basic information was collected through questionnaire surveys. LTBI was screened by EC-ST and interferon-gamma release assay (IGRA). Taking IGRA results as the diagnostic standard, the positive rate, sensitivity, specificity and consistency rate of EC-ST, and the impact of CD4+T lymphocyte (CD4) counts on the screening effect of EC-ST were analyzed.@*Results@#A total of 523 HIV/AIDS patients were screened, including 458 males (87.57%) and 65 females (12.43%). The median age was 48.00 (interquartile range, 21.00) years. The positive rate of EC-ST was 7.27% and the positive rate of IGRA was 7.46%, with no statistically significant difference (P>0.05). The consistency rate of the two methods was 94.84%, and the Kappa value of 0.621 (95%CI: 0.489-0.752, P<0.05). The sensitivity of EC-ST was 64.10% and the specificity was 97.31%. Comparing the groups with CD4 counts <500 and ≥500 cells/μL, the consistency rates of the two methods were 95.32% and 94.44%, and the Kappa values were 0.568 and 0.650, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05). Comparing the groups with CD4 counts <200 and ≥200 cells/μL, the consistency rates of the two methods were 96.55% and 94.62%, and the Kappa values were 0.648 and 0.619, respectively (both P<0.05). There were no statistically significant differences in the positive rates, sensitivity, and specificity of EC-ST (all P>0.05).@*Conclusion@#The effectiveness of EC-ST in screening for LTBI among HIV/AIDS patients is consistent with that of IGRA and is not affected by CD4 counts.
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Objective:To explore the correlation between serum levels of interleukin-9 (IL-9), platelet activating factor (PAF), total immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin-4 (IL-4) in patients with chronic spontaneous urticaria (CSU).Methods:Sixty CSU active phase patients admitted to the First Affiliated Hospital of Hebei North University from March 2018 to March 2019 were selected and included in the CSU active phase group. Based on the 7-day Urticaria Activity Score (UAS7), they were divided into three groups: 15 mild group, 25 moderate group, and 20 severe group; And 19 patients who entered the quiescent phase of the disease after 28 days of standardized antihistamine treatment were included in the CSU quiescent phase group. Another 30 healthy subjects who participated in the physical examination at the same time at our hospital′s physical examination center were selected to be included in the healthy control group. 5 ml of fasting elbow vein blood was collected from CSU active and stationary patients, as well as healthy subjects. The serum levels of IL-9, PAF, total IgE, IFN-γ, and IL-4 were detected using enzyme-linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between serum IL-9, PAF levels and total IgE, IFN-γ, and IL-4 levels in CSU active patients.Results:The serum levels of IL-9, PAF, total IgE, and IL-4 in the CSU active phase group were higher than those in the CSU stationary phase group and healthy control group (all P<0.05), and the serum IFN-γ levels were lower than those in the CSU stationary phase group and healthy control group (all P<0.05). There was no statistically significant difference in the levels of the above indicators between the healthy control group and the CSU stationary group (all P>0.05). The serum levels of IL-9, PAF, total IgE, and IL-4 in the severe group were significantly higher than those in the mild and moderate groups (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild and moderate groups (all P<0.05); The serum levels of IL-9, PAF, total IgE, and IL-4 in the moderate group were significantly higher than those in the mild group (all P<0.05), and the serum IFN-γ levels were significantly lower than those in the mild group ( P<0.05). Pearson correlation analysis showed that serum IL-9 and PAF levels were positively correlated with serum total IgE and IL-4 levels in CSU active phase patients (IL-9: r=0.726, 0.870, PAF: r=0.788, 0.795, all P<0.01), and negatively correlated with serum IFN-γ levels (IL-9: r=-0.831, PAF: r=-0.816, all P<0.01). Conclusions:The serum levels of IL-9 and PAF in patients with active CSU are elevated and correlated with total IgE, IFN-γ, and IL-4 levels, suggesting that IL-9 and PAF may be related to the occurrence and development of CSU.
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Abstract Background Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. Objective To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. Methods Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. Results The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). Study limitations The mechanism of the IFNGR1 gene has not been further investigated in this study. Conclusions The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.
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Background & objectives: Toll-like receptors (TLRs) are transmembrane proteins that recognize specific molecular patterns and activate downstream cytokine production usually for the eradication of invading pathogens. The objective of this study was to evaluate the genetic polymorphism of TLR2 Arg753Gln (rs 5743708) and soluble cytokines and TLR2 expression levels in malaria disease cases. Methods: The study included prospectively collected 2 ml blood samples from 153 individuals clinically suspected for malaria and confirmed by microscopy and RDT from Assam. Stratification of the study groups was done as healthy control (HC, n=150), uncomplicated malaria (UC-M, n=128) and severe malaria (SM, n=25). The PCR-restriction fragment length polymorphism (RFLP) method was applied for the analysis of TLR2 Arg753Gln polymorphism and following the ELISA for soluble serum TLR2 (sTLR2) and its associated downstream cytokines, viz. tumour necrosis factor (TNF)-? and interferon (IFN)-? levels. Results: Variation in TLR2 Arg753Gln gene showed no association with the susceptibility and the severity of malarial infection. Soluble TLR2 expression was significantly higher in uncomplicated malaria (UC-M) cases compared to healthy controls (P=0.045) and in terms of SM cases, the expression was also found to be higher in UC-M cases (P=0.078). The TNF-? expression was significantly higher in SM cases compared to both UC-M and control (P=0.003 and P=0.004). Similarly, significantly elevated expression of IFN-? was noted in SM cases compared to both UC-M (P=0.001) and healthy controls (P<0.001). Interpretation & conclusions: The present study suggests the association of deregulated TLR2 pathway that leads to the deleterious downstream immune response in the development of malarial pathogenicity.
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@#Abstract: Objective To explore the early diagnostic value of peripheral blood peroxisome proliferator-activated receptor γ (PPARγ) combined with γ-interferon (IFN-γ) release assay (IGRA) in the diagnosis of pulmonary tuberculosis in patients with end-stage renal disease (ESRD), and to provide reference for clinical diagnosis and treatment. Methods From January 2019 to December 2021, 70 ESRD patients with suspicious symptoms of pulmonary tuberculosis were treated at Hebei Chest Hospital were selected as the research objects. According to the examination results, they were divided into ESRD group (40 cases) and ESRD complicated by pulmonary tuberculosis (40 cases, comorbidity group). In addition, 40 cases with pulmonary tuberculosis were used as the PTB group. All three groups of patients underwent IGRA test, and the peripheral blood PPARγ level was detected by enzyme-linked immunosorbent assay, and the diagnostic value of PPARγ combined with IGRA test for ESRD patients with pulmonary tuberculosis was explored. Results The expression level of PPARγ and IFN-γ content in the PTB group and the comorbidity group were obviously higher than those in the ESRD group (P<0.05), while the differences in PPARγ expression level and IFN-γ content between the PTB and comorbidity groups were not statistically significant (P>0.05). The ROC curve showed that the areas under the curve (AUC) of PPARγ and IGRA in the diagnosis of end-stage renal disease combined with tuberculosis were 0.823 (95%CI: 0.722-0.925) and 0.773 (95%CI: 0.662-0.883), respectively, and the AUC of combined detection was 0.928 (95%CI: 0.871-0.984), which was better than that of PPARγ and IGRA alone (Z/P=2.057/0.039, 2.843/0.005). The Kappa values of serum PPARγ and IGRA test compared with the clinical gold standard results in the diagnosis of ESRD complicated with pulmonary tuberculosis were 0.557 and 0.444 (P<0.05). The combined screening of ESRD with pulmonary tuberculosis was consistent with the clinical gold standard (Kappa=0.661, P<0.05). Among the 30 ESRD patients complicated with pulmonary tuberculosis, the sensitivity of PPARγ combined with IGRA test in diagnosis of ESRD complicated with pulmonary tuberculosis was 93.33% (28/30), which was higher than 70.00% (21/30) of PPARγ and 66.67% (20/30) of IGRA test alone (P<0.05). Conclusions Peripheral blood PPARγ and IGRA tests have certain diagnostic value for ESRD complicated with tuberculosis, and the combined detection of the two can improve the sensitivity and reduce the rate of missed diagnosis, which is worthy of clinical promotion.
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La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.
Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.
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Humanos , Tuberculosis Latente/tratamiento farmacológico , Rifamicinas/uso terapéutico , Tuberculosis/prevención & control , Prueba de Tuberculina , Tuberculosis Latente/diagnóstico , Ensayos de Liberación de Interferón gamma , Isoniazida/uso terapéutico , Antituberculosos/uso terapéuticoRESUMEN
ABSTRACT Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.
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Cancer is the second leading cause of mortality worldwide preceded by cardiovascular diseases. The therapeutic approaches for drug developmentinclude the use of small molecules, antibodies, peptidesor short nucleic acid sequences. The peptide-based drugs have been developed to treat many diseases like cardiovascular diseases, cancer, metabolic disorders, immunological diseases and viral infections. More than 80 peptide drugs are already in the market. These therapeutic peptides have several important benefits over antibodies and proteins due to their small size, ease for chemical synthesis and further the ability to penetrate cell membrane. Furthermore, peptide drugs have high specificity, activity, and affinity. The plant defensins BcDef1, TPP3, NaD1, 2N2R and 2LR3 have been studied for their role in wide range of diseases. This study focussed on the conformation of plant defensins rich in disulfide bonds. The structure for BcDef1 has been predicted from the conformational ensemble. Then, we designed anticancer peptides from these defensins with computational methods. The designed anticancer peptides have been studied for their immunogenicity as well as homology with human proteome. The role of designed peptides has been suggested for interferon-gamma induction, the later has been shown to possess a very important role in cancer.
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Cancer is the second leading cause of mortality worldwide preceded by cardiovascular diseases. The therapeutic approaches for drug developmentinclude the use of small molecules, antibodies, peptidesor short nucleic acid sequences. The peptide-based drugs have been developed to treat many diseases like cardiovascular diseases, cancer, metabolic disorders, immunological diseases and viral infections. More than 80 peptide drugs are already in the market. These therapeutic peptides have several important benefits over antibodies and proteins due to their small size, ease for chemical synthesis and further the ability to penetrate cell membrane. Furthermore, peptide drugs have high specificity, activity, and affinity. The plant defensins BcDef1, TPP3, NaD1, 2N2R and 2LR3 have been studied for their role in wide range of diseases. This study focussed on the conformation of plant defensins rich in disulfide bonds. The structure for BcDef1 has been predicted from the conformational ensemble. Then, we designed anticancer peptides from these defensins with computational methods. The designed anticancer peptides have been studied for their immunogenicity as well as homology with human proteome. The role of designed peptides has been suggested for interferon-gamma induction, the later has been shown to possess a very important role in cancer.
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Cancer is the second leading cause of mortality worldwide preceded by cardiovascular diseases. The therapeutic approaches for drug developmentinclude the use of small molecules, antibodies, peptidesor short nucleic acid sequences. The peptide-based drugs have been developed to treat many diseases like cardiovascular diseases, cancer, metabolic disorders, immunological diseases and viral infections. More than 80 peptide drugs are already in the market. These therapeutic peptides have several important benefits over antibodies and proteins due to their small size, ease for chemical synthesis and further the ability to penetrate cell membrane. Furthermore, peptide drugs have high specificity, activity, and affinity. The plant defensins BcDef1, TPP3, NaD1, 2N2R and 2LR3 have been studied for their role in wide range of diseases. This study focussed on the conformation of plant defensins rich in disulfide bonds. The structure for BcDef1 has been predicted from the conformational ensemble. Then, we designed anticancer peptides from these defensins with computational methods. The designed anticancer peptides have been studied for their immunogenicity as well as homology with human proteome. The role of designed peptides has been suggested for interferon-gamma induction, the later has been shown to possess a very important role in cancer.
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Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.
Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.
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ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.
RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.
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RESUMEN Introducción: en la literatura biomédica son escasos los reportes sobre el uso de los interferones como tratamiento en el carcinoma epidermoide. En una unidad de atención primaria, en Colón, Matanzas, se implementó el HeberFERON® en este tipo de tumor, con experiencias favorables. Objetivo: describir la efectividad del HeberFERON® en el carcinoma epidermoide. Materiales y métodos: se realizó un estudio observacional, descriptivo en 33 lesiones de carcinoma epidermoide en 29 pacientes. La dosis fue de 7,0 y 10,5 MUI de actividad antiviral, infiltrada de forma perilesional tres veces por semana durante tres semanas. Se realizó el seguimiento clínico de los pacientes antes del tratamiento y a las 16 semanas del inicio del mismo. Las variables fueron: edad, sexo, fototipo de piel, procedencia, localización, tipo clínico, estadio y respuesta clínica al tratamiento. Se consideraron cuatro categorías de respuesta: completa, parcial, enfermedad estable y progresiva. Se incluyó la respuesta objetiva (completa más parcial). Se recogieron los datos en una historia clínica. Se utilizaron los programas Microsoft Excel y SPSS para el procesamiento estadístico. Resultados: el 65,5 % de los pacientes correspondió al sexo masculino. Un 58,6 % son fototipo II y de procedencia urbana. Predominaron las edades entre 61 y 80 años (55,2 %). Hubo respuesta objetiva en 57,6 % (cinco completas y 14 parciales). Las mejores respuestas la mostraron el carcinoma epidermoide queratósico superficial y el noduloulceroso. Conclusiones: la mezcla de interferones fue efectiva en el carcinoma epidermoide en todos los subtipos clínicos, aunque los autores sugieren un segundo ciclo de HeberFERON® o asociarlo con quimioterapia cuando la respuesta no sea completa.
ABSTRACT Introduction: there are few reports in the literature on the use of interferon in the treatment of the squamous cell carcinoma. In a primary care unit in Colon, Matanzas, HeberFERON® was implemented in this type of tumor with favorable experiences. Objective: to describe the effectiveness of HeberFERON® in epidermoid carcinoma. Materials and methods: an observational, descriptive study was conducted in 33 epidermoid carcinoma lesions in 29 patients. The doses were 7.0 and 10.5 MUI of antiviral activity, perilesionally infiltrated three times a week for three weeks. Clinical follow-up of patients was performed before the treatment and at 16 weeks from the beginning of the treatment. The variables were: age, sex, skin phototype, origin; location, clinical type, stage and clinical response to treatment. Four categories of response were considered: complete, partial, stable and progressive disease. The objective response (complete plus partial) was included. Data were collected in a clinical record. The Microsoft Excel and SPSS programs were used for statistical processing. Results: 65.5 % of patients were male. 58.6 % are phototype II and of urban origin. Ages ranging from 61 to 80 years (55.2 %) predominated. There was objective response in 57.6 % (five complete and 14 partials). The superficial keratotic squamous cell carcinoma and the nodular ulcerative one showed the best responses. Conclusions: interferon mixing was effective in all clinical subtypes of epidermoid carcinoma, although the authors suggest a second cycle of HeberFERON® or to associate it with chemotherapy when the response is not complete.
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OBJECTIVE@#To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism.@*METHODS@#A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 μs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method.@*RESULTS@#After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 μs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05).@*CONCLUSION@#Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.
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Humanos , Terapia por Acupuntura , Músculos Faciales , Interferón gamma , Interleucina-4 , Miastenia Gravis/tratamiento farmacológicoRESUMEN
Objective:To evaluate the influencing factors of inconsistency between γ-interferon release test QFT-GIT and etiological results in tuberculosis patients.Methods:The clinical data of 1 398 patients with positive Mycobacterium tuberculosis infection confirmed by pathogen culture after QFT-GIT test who were admitted to Hangzhou Chest Hospital Affiliated to Zhejiang University School of Medicine from September 2017 to August 2021 were retrospectively analyzed. There were 1 242 cases in whom both the pathogenic culture and QFT-GIT results were positive(consistent result group) and 156 cases in whom the QFT-GIT test results were negative or indeterminate(inconsistent result group). Logistic regression was used to analyze the influencing factors of inconsistent results between QFT-GIT and tuberculosis pathogenic tests. SPSS 25.0 software was used to analyze the data. Results:The overall incidence of inconsistency between QFT-GIT and tuberculosis etiological results was 11.16% (156/1 398). The incidence of inconsistency was 0, 7.09% (63/889) and 19.58% (93/475) in patients aged <18, 18-<65 and ≥65 years old, respectively; the incidence of inconsistency in age group ≥65 was higher than that in age groups <18 and 18-<65 ( χ2=6.584 and 36.762, P<0.01). Multivariate Logistic regression analysis showed that age ( OR=1.026, 95% CI 1.016-1.037), smoking ( OR=1.649, 95% CI 1.159-2.347), chronic liver disease ( OR=1.868, 95% CI 1.213-2.876), cardiovascular disease ( OR=2.353, 95% CI 1.361-4.069) and blood albumin level ( OR=0.956, 95% CI 0.928-0.985) were independent influencing factors for the inconsistency between the results of QFT-GIT and tuberculosis etiology. Conclusion:Patients with advanced age, smoking, chronic liver disease, cardiovascular disease and low albumin level are more likely to have inconsistent results between QFT-GIT and tuberculosis etiological tests.
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Objective:To investigate clinical characteristics of acquired palmoplantar keratodermas (PPK) and the effect of metal implants (MIs) on plasma cytokines in patients with PPK.Methods:An observational study was conducted. Patients with acquired PPK were collected from Department of Dermatology, General Hospital of Eastern Theater Command from June 2020 to December 2021, and health checkup examinees during the same period served as controls. The PPK area and severity index was evaluated according to the eczema area and severity index, metal allergens were detected by metal patch test (MPT) , and plasma levels of cytokines, including tumor necrosis factor (TNF) -α, interferon (IFN) -γ, interleukin (IL) -4, IL-13, IL-17A and IL-8, were detected by enzyme-linked immunosorbent assay. Non-normally distributed measurement data were expressed as median (quartile 1, quartile 3) , and analyzed by rank sum test; intergroup comparisons of enumeration data were performed by chi-square test.Results:A total of 81 PPK patients were collected, including 42 males and 39 females, and their average age was 48 years (range, 21 - 65 years) . In vivo MIs were found in 37 (45.7%) patients, including dental implants in 34, orthopedic implants in 2, and cardiac implants in 1. During the same period, 36 healthy subjects were included in the control group, and there was no significant difference in the age and gender composition between the two groups ( P > 0.05) . No significant difference was observed in the PPK area and severity index between the MI group (37 cases, 0.40 [0.27, 0.75] points) and non-MI group (44 cases, 0.38 [0.19, 0.70] points; Z = 1.21, P = 0.225) . Forty-six patients in the PPK patient group and 30 in the control group were subjected to MPT, and the positive rate of MPT was significantly higher in the patient group (14/46) than in the control group (2/30, χ2 = 6.17, P = 0.013) , and was significantly higher in the patients with in vivo MIs (10/25) than in the patients without (4/21, adjusted P < 0.017) . Plasma cytokines were detected in 36 cases in the patient group and 36 in the control group. The plasma levels of TNF-α and IFN-γ were significantly lower in the patient group (66.2 [58.7, 69.3] pg/ml, 645.0 [571.5, 681.1] pg/ml, respectively) than in the control group (71.5 [64.5, 73.9] pg/ml, 716.5 [620.4, 785.0] pg/ml, respectively; both P < 0.05) , but there was no significant difference in the levels of plasma IL-4, IL-13, IL-17A and IL-8 between the two groups (all P > 0.05) . Conclusions:Positive MPT reaction is more common in acquired PPK patients, especially in patients with in vivo MIs. There may be a correlation between metal and acquired PPK, and changes in plasma TNF-α and IFN-γ levels may be related to the onset of some acquired PPK.