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BACKGROUND Leprosy is a highly neglected disease that is considered a serious public health problem in many countries. This illness is characterised by a variety of clinical and histopathological manifestations that are related to the patient immune response. OBJECTIVES This work aimed evaluate the profile of circulating immune mediators in the plasma from patients classified clinically as paucibacillary (PB), multibacillary (MB), households contacts (HHC), type1 leprosy reaction (T1R), type2 leprosy reaction (T2R) and control individuals without medical history of leprosy (CTL). METHODS To assessment of the plasma immune mediators was used multiplex microbeads immunoassay "Luminex". FINDINGS The results showed that patients (PB) had a regulatory-biased profile, while MB revealed a pro-inflammatory trend of highly expressed biomarkers. HHC display conspicuously increased levels in the plasma of the chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8), pro-inflammatory cytokines (IFN-γ,TNF and IL-1β), modulating cytokines (IL-9 and IL-1Ra) and growth factors (PDGF, G-CSF and IL-2). Interestingly, HHC displayed superior production of IFN-γ as compared to other leprosy groups, indicating a putative protective role for this cytokine during chronic Mycobacterium leprae exposure. MAIN CONCLUSION Further investigations are currently underway to elucidate the potential of these mediators as biomarkers applicable to the diagnosis/prognosis of leprosy and also T1R and T2R leprosy reactions.
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Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.
Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.
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Humans , Female , Ovarian Neoplasms , Cytokines , Chemokines , InflammationABSTRACT
Introduction: Oral Submucous Fibrosis (OSF) is a chronic fibrosis condition of oral cavity. It is a multifactorial condition, are- canut chewing being the prime etiologic factors. Objectives: Arecanut alkaloids stimulate the oral tissue initiating the inflammatory response. As an inflammatory response, cells release cytokines activating the cascade of different fibrinogenic pathways leading to fibrosis. Conclusion: This review briefs about the various cytokines studied in Oral Submucous Fibrosis.
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Resumen Introducción: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). Objetivo: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. Métodos: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. Resultados: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. Conclusiones: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.
Abstract Introduction: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). Objective: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. Methods: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. Results: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complement C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. Conclusions: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.
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Objective:To investigate the role of serum CX3CR1 in the diagnosis of coronary artery stenosis and in the evaluation of prognosis after percutaneous coronary intervention.Methods:A total of 101 patients with coronary artery stenosis (≥ 50% stenosis) confirmed with coronary angiography (CAG) in Haiyang People's Hospital from January 2018 to May 2019 who were followed up till May 2021 were included in the observation group. Thirty-four healthy individuals who underwent physical examination during the same period were included in the control group. Patients in the observation group were divided into an in-stent restenosis group (ISR group, n = 28) and a non-ISR group ( n = 73). The expression of CX3CR1 was detected. The incidence of adverse cardiac events was calculated. The sensitivity, specificity, and area under the curve (AUC) plotted for the use of CX3CR1 to diagnose coronary artery stenosis and predict adverse cardiac events were evaluated. Results:The expression of CX3CR1 in the observation group was (3.95 ± 1.05) μg/L, which was significantly higher than (2.30 ± 0.65) μg/L in the control group ( t = 2.87, P < 0.05). The receiver operating characteristic curve analysis showed that the AUC, sensitivity, and specificity of the use of CX3CR1 in diagnosing coronary artery stenosis were 0.892, 75.2%, and 88.2%. The incidence of non-fatal myocardial infarction, angina pectoris, heart failure, and cardiac death in the ISR group was significantly higher compared with the non-ISR group ( χ2 = 8.06, 7.17, 8.06, 7.17, all P < 0.05). The receiver operating characteristic curve analysis results showed that the AUC value of CX3CR1 in predicting non-fatal myocardial infarction, angina pectoris, heart failure, and cardiac death were 0.786, 0.895, 0.997, and 0.887, respectively. Conclusion:CX3CR1 is highly expressed in coronary artery stenosis, which can provide a reference for the diagnosis and prognostic evaluation of coronary artery stenosis.
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Objective:To investigate the clinical efficacy and mechanism of Ganoderma lucidum hypoglycemic formula in the treatment of insulin resistance in patients with type 2 diabetes mellitus (T2DM) with liver and kidney yin deficiency. Methods:A total of 86 patients with T2DM with liver and kidney yin deficiency who were diagnosed and treated at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine from January 2021 to February 2022 were included in this study. These patients were divided into a control group and a treatment group, with 43 patients in each group using a 1:1 ratio using the sealed envelope method. Both groups were treated with standardized Western medicine. The treatment group was also treated with the Ganoderma lucidum hypoglycemic formula. All patients were followed up for 12 weeks. The clinical symptoms, curative effect, glucose and lipid metabolism, inflammatory factors, oxidative stress change, and safety were compared between the two groups. Results:The total response rate in the treatment group was 88.4% (38/43), which was significantly higher than 53.5% (23/43) in the control group ( χ2 = 12.69, P < 0.001). After treatment, the traditional Chinese medicine syndrome score, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, insulin resistance index, total cholesterol, triglyceride, tumor necrosis factor α, and interleukin-6 decreased in each group. The amplitudes of decrease of the above indexes were greater in the treatment group compared with the control group (all P < 0.05). C-peptide in the fasting state, C-peptide at 2 hours after a diet, and superoxide dismutase increased in each group. The amplitudes of increase of the three indexes were greater in the treatment group compared with the control group (all P < 0.05). Conclusion:Ganoderma lucidum hypoglycemic formula can greatly improve insulin resistance and glucose and lipid metabolism in T2DM patients with liver and kidney yin deficiency. The underlying mechanism may be to further reduce the inflammatory response and anti-oxidative stress by down-regulating tumor necrosis factor α and interleukin-6 levels and up-regulating superoxide dismutase level, thereby effectively alleviating insulin resistance in T2DM.
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Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.
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La Artritis Reumatoide (AR) es una enfermedad autoinmune frecuente, caracterizada por inflamación crónica en las articulaciones que puede progresar a la destrucción ósea. Aunque la fisiopatología de la AR no es clara, se ha visto que las células T y las células B desempeñan un importante papel en la misma. Estudios con Rituximab (RTX), un fármaco que elimina las células B CD20+, han contribuido a esclarecer y destacar la participación de las células B en la AR. Las células B pueden contribuir a la autoinmunidad de manera dependiente de la producción de los anticuerpos e independiente de esta producción. Esta última función puede ser debida al papel de las células B como presentadoras de antígeno para las células T y productoras de citocinas y quimiocinas. Para contribuir a entender este último mecanismo, se revisaron los artículos donde se evidenciaron los efectos del tratamiento con RTX sobre la citocinas y quimiocinas circulantes en pacientes con AR. Se encontró que la mayoría de las citocinas estudiadas disminuyeron sus niveles en circulación luego del tratamiento con RTX. La IL-10 y la IL-6 se vieron consistentemente disminuidas en los pacientes que respondieron al tratamiento y podrían ser marcadores del tratamiento con Rituximab.
Summary Rheumatoid Arthritis (RA) is a common autoimmune disease characterized by chronic inflammation in the joints that can progress to bone destruction. Although the pathophysiology of RA is unclear, T cells and B cells are though to be involved. Rituximab (RTX), a drug that eliminates CD20 + B cells, has helped to clarify and highlight the role of B cells in RA. B cells can contribute to autoimmunity by mechanisms dependent on the production of antibodies and independent of this production. The latter may depend on the role of B cells as antigen-presenting cells for T cells and their capacity to produce cytokines and chemokines. To contribute to our understanding of this mechanism, studies that evaluated levels of circulating cytokines and chemokines in patients with RA after treatment with RTX were reviewed. Most cytokines studied decreased their levels in circulation after treatment with RTX. IL-10 and IL-6 consistently were decreased in patients responding to treatment and maybe markers of Rituximab treatment.
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Este estudo busca avaliar quantitativamente a expressão do RNA mensageiro (mRNA) das integrinas alfa1, alfa4, alfa 5, alfa L, citocinas e quimiocinas, a partir de células presentes no líquido intersticial periapical adjacente a dentes com infecção do canal radicular. Foram selecionados 22 indivíduos com necessidade de tratamento endodôntico e encaminhados à Faculdade de Odontologia da Universidade Federal de Minas Gerais (Belo Horizonte, MG, Brasil). As amostras foram coletadas em 11 dentes necróticos e portadores de infecções endodônticas e 11 dentes hígidos que necessitavam de tratamento endodôntico por motivos protéticos. Após a cirurgia de acesso e antes dos procedimentos de limpeza e modelagem do sistema de canais radiculares (T0), imediatamente após a limpeza e formatação do sistema de canais radiculares(T1), em 7 (T2) e 14 dias (T3), um cone de papel esterilizado endodôntico # 20 foi inserido no SCR, mantido por 2 min, e posteriormente armazenado a -70°C. Real-Time PCR analisou microbiologicamente essas amostras para ler a expressão gênica do rRNA microbiano 16S e fragmentos da região ITS do gDNA fúngico da espécie Candida. Após os procedimentos de limpeza e formatação do SCR, três cones de papel absorvente esterilizados foram inseridos. Passivamente, a ponta do papel ultrapassou o ápice radicular em 2 mm e permaneceu por 2 minutos. As amostras foram coletadas imediatamente após a limpeza e modelagem do RCS, 7 e 14 dias após a primeira sessão. As pontas de papel tiveram os 4 mm finais cortados, inseridos em Eppendorf e armazenados a - 70°C. Com este procedimento, o RNA foi extraído do líquido intersticial periapical para caracterizar as expressões dos genes ITGA1, ITGA4, ITGA5, ITGAL, IL-1ß, TNF-α, IL-17A, IL-10, IFN-γ, CCL2/MCP-1, CCL5, CXCR4, e 16S usando PCR em tempo real. O DNA genômico (gDNA) foi extraído para se avaliar a abundância de Candida utilizando-se sequências ITS, por PCR em tempo real. Os resultados demonstraram que os níveis de expressão de mRNA do 16S diminuíram após os procedimentos de limpeza e modelagem e que a abundância de Candida foi insipiente na amostra analisada. As citocinas pro- inflamatórias IL-1ß e IL-17 apresentaram níveis de expressão elevados frente a infecção, reduzindo significativamente após os procedimentos de limpeza e formatação. Os níveis de expressão gênica de TNF-α significantemente aumentaram, em ambos os grupos. Não se observou diferença significativa quanto a expressão gênica das citocinas IFN-γ, IL-10, CCL-2 e CCL-5 e das integrinas ITGAL e ITGA5 nos tempos avaliados. A expressão gênica de CXCR4 reduziu significativamente do tempo T1 para o T2, no grupo experimental. As expressões gênicas de ITGA1 e ITGA4, no grupo experimental, reduziram significativamente de maneira tempo dependente. Finalmente, não houve alteração significativa na expressão de marcadores de macrófagos (CD64), enquanto expressão de marcadores de fibroblastos (S100A4) aumentou significativamente no grupo controle. Concluiu-se que a carga microbiana e a abundância de leveduras correlacionam-se positivamente com a expressão de mediadores pró-inflamatórios e que a que terapia endodôntica negativamente impacta a expressão dos mediadores pró-inflamatórios e das integrinas nos tecidos perirradiculares.
This study seeks to quantitatively evaluate the expression of messenger RNA (mRNA) of integrins alpha1, alfa4, alpha 5, alpha L, cytokines, and chemokines, from cells present in the periapical interstitial fluid adjacent to teeth with root canal infection. Twenty-two individuals needing endodontic treatment and referred to the School of Dentistry of the Federal University of Minas Gerais (Belo Horizonte, MG, Brazil) were selected. The samples were collected in 11 necrotic teeth and carriers of endodontic infections and 11 healthy teeth needing endodontic treatment for prosthetic reasons. After access surgery and before root canal system (RCS) cleaning and shaping procedures (T0), immediately after cleaning and shaping the root canal system (T1), in 7 (T2) and 14 days (T3) an endodontic sterilized paper point #20 was inserted into the RCS, maintained for 2 min, and subsequently stored at -70°C. Real-Time PCR microbiologically analyzed these samples to read the gene expression of microbial rRNA 16S and fragments of the ITS region of the Fungus Candida species gDNA. After RCS cleaning and shaping procedures, three sterilized absorbent paper cones were inserted. Passively, the paper point exceeded the root apex by 2 mm and remained for 2 minutes. Samples were collected immediately after RCS cleaning and shaping, 7 and 14 days after the first session. The paper points have the 4 mm of their tip cut, inserted in Eppendorf, and stored at - 70°C. This procedure extracted RNA from the periapical interstitial fluid to characterize the expressions of the genes ITGA1, ITGA4, ITGA5, ITGAL, IL-1ß, TNF- α, IL-17A, IL-10, IFN-γ, CCL2/MCP-1, CCL5, CXCR4, ITS using Real-Time PCR. The results showed that 16S mRNA expression levels decreased after cleaning and modeling procedures and that Candida abundance was incipient in the analyzed sample. Pro-inflammatory cytokines IL-1ß and IL-17 showed high expression levels against infection, significantly reduced after cleaning and formatting procedures. TNF-α gene expression levels significantly increased in both experimental and control groups. No significant difference was observed regarding the gene expression of the cytokines IFN-γ, IL-10, CCL-2, and CCL-5 and the integrins ITGAL and ITGA5. The gene expressions of ITGA1 and ITGA4 in the experimental group were significantly reduced time-dependent. Finally, there was no significant change in their macrophage markers (CD64) expression, while fibroblast markers (S100A4) expression significantly increased in the control group. It was concluded that microbial load and yeast abundance are positively correlated with the expression of pro-inflammatory mediators and that endodontic therapy negatively impacts the expression of pro-inflammatory mediators and integrins in periradicular tissues.
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Periapical Periodontitis , Colony Count, Microbial , Integrins , Cytokines , ChemokinesABSTRACT
ABSTRACT Background: The inflammatory response plays a significant role in the outcome of coronavirus disease (COVID-19). Methods: We investigated plasma cytokine and chemokine concentrations in non-infected (NI), asymptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected blood donors (AS), and patients with severe COVID-19 (SC). Results: The SC group showed significantly higher levels of interleukin 6 (IL-6), IL-10, and CCL5 than the AS and NI groups. The SC and AS groups had considerably greater CXCL9 and CXCL10 concentrations than the NI group. Only NI and infected people showed separate clusters in the principal component analysis. Conclusions: SC, as well as AS was characterized by an inflammatory profile.
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Objective:To investigate the clinical efficacy of Qianjin Weijing Decoction in the treatment of severe pneumonia with the accumulation of phlegm and heat in the lung. Methods:Eighty patients with severe pneumonia with the accumulation of phlegm and heat in the lung received treatment in Wenzhou Hospital of Traditional Chinese Medicine from December 2018 to December 2020. They were randomly allocated to undergo routine treatments (control group, n = 40) or routine treatments combined with Qianjin Weijing Decoction (observation group, n = 40) for 7 days. Clinical efficacy, blood gas analysis, oxygenation index, inflammatory factors (C-reactive protein and procalcitonin), and sequential organ failure score were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [87.50% (35/40) vs. 65.00% (26/40), χ2 = 5.59, P < 0.05]. Partial pressure of carbon dioxide (PaCO 2) post-treatment was significantly lower in the observation group than that in the control group [(30.24 ± 2.68) mmHg vs. (39.95 ± 3.27) mmHg, t = 14.52, P < 0.05]. The partial pressure of blood oxygen (PaO 2) and oxygenation index (PaO 2/FiO 2) in the observation group were (76.85 ± 4.56) mmHg and (326.84 ± 8.49) mmHg, respectively, which were significantly higher than those in the control group [(68.39 ± 4.12) mmHg, (284.16 ± 15.56) mmHg, t = -8.70, -15.22, both P < 0.05). Serum levels of C-reactive protein and procalcitonin post-treatment in the observation group were (23.12 ± 6.56) mg/L and (0.31 ± 0.08) μg/L, respectively, which were significantly lower than those in the control group [(38.92 ± 5.62) mg/L, (0.78 ± 0.20) μg/L, t = 11.56, 13.80, both P < 0.05]. Sequential organ failure score was significantly lower in the observation group than in the control group [(2.31 ± 0.46) points vs. (5.12 ± 1.25) points, t = 13.34, P < 0.05)]. Conclusion:Qianjin Weijing Decoction has a good therapeutic effect on severe pneumonia with the accumulation of phlegm and heat in the lung. The treatment can improve blood gas analysis and decrease inflammatory factor levels with a good prognosis.
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Objective:To investigate the relationship between Helicobacter pylori(Hp)infections in Parkinson's disease(PD)patients at high altitude and peripheral inflammatory markers.Methods:In this prospective study, 120 PD patients in Qinghai Province(altitude: 2260 m)were enrolled and evaluated using PD motor symptom scales and a non-motor symptom scale.The 13C-Urea breath test was used to detect Hp, and patients were divided into an Hp infection group and a non-Hp infection group based on test results.The levels of high-sensitivity C-reactive protein(hs-CRP), white blood cell counts and ratios, serum interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)were measured. Results:The incidence of Hp infections in PD patients was 56.67%(68/120).The scores of Unified Parkinson's Disease Rating Scale(UPDRS)-Ⅲ, UPDRS-Ⅳ, total UPDRS, Hoehn-Yahr(H-Y)score, constipation scoring system(CSS)and Leeds dyspepsia questionnaire(LDQ)in the Hp infection group were higher than those in the non-Hp infection group, while the mini-mental state examination(MMSE)score was lower in the non-Hp infection group(all P<0.05).The neutrophil count, neutrophil-to-lymphocyte ratio(NLR), monocyte-to-lymphocyte ratio(MLR), serum IL-6 and TNF-α in the Hp-infection group were elevated compared with the non-Hp infection group(all P<0.05).Multivariate Logistic regression analysis showed that IL-6, TNF-α, NLR and H-Y score were independent risk factors for Hp infections in PD patients( OR=1.103, 1.188, 3.320, 4.593, respectively, all P<0.05).Correlation analysis showed that IL-6, TNF-α and NLR had positive correlations with UPDRS-Ⅲ( r=0.676, 0.644, 0.488, respectively), UPDRS-Ⅳ( r=0.679, 0.660, 0.430, respectively), UPDRS-total score( r=0.391, 0.448, 0.319, respectively), H-Y( r=0.610, 0.750, 0.460, respectively), CSS( r=0.529, 0.366, 0.212, respectively)and LDQ( r=0.581, 0.440, 0.263, respectively), but were negatively correlated with MMSE score( r=-0.617, -0.596, -0.321, respectively)(all P<0.05). Conclusions:Peripheral inflammation caused by Hp infections may be involved in the occurrence and development of Parkinson's disease at high altitude and serum IL-6, TNF-α and NLR could serve as indicators to evaluate PD patients with Hp infections.
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Objective:To investigate the significance of 12 inflammatory cytokines in early detection and treatment guidance of hematologic malignant patients with Cytokine release syndrome (CRS) after Chimeric antigen receptor (CAR)-T cell immunotherapy.Methods:A total of 12 patients, including 6 males and 6 females, aged 53.0 (49.8, 62.5) years old, were treated with CAR-T cell immunotherapy in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2020. Cytometric bead array was used to detect the serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IFN-α, IFN-γ, and TNF-α at different time points after cell infusion in all patients receiving CAR-T cell immunotherapy. C-reactive protein (CRP), D-dimer (D-D), serum ferritin (SF), and lactate dehydrogenase (LDH) were measured at the corresponding period. CRS was classified into four grades according to the diagnostic criteria, from 0 to 3. The differences of the above mentioned parameters between the four groups were compared. The Speedman correlation coefficient was used to analyze the correlation between inflammatory cytokine expression levels and CRS grades. Plot the subject′s receiver operating characterist (ROC) curve to determine the sensitivity and specificity of inflammatory cytokines to predict CRS.Results:CRS grading was performed on day 1, 4, 7, and 11 after CAR-T cell infusion in 12 patients. There are 48 cases in total, including 25 cases of CRS grade 0, 6 cases of CRS grade 1, 9 cases of CRS grade 2, and 8 cases of CRS grade 3. The correlation analysis of 48 cases showed that the expression levels of IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-1β, and IL-8 were positively correlated with CRS grade ( P<0.05). The correlation coefficients were 0.384, 0.730, 0.632, 0.341, 0.681, 0.319, and 0.622, respectively. 7 inflammatory cytokines (IL-6, IL-10, IFN-γ, IL-8, IL-2, TNF-α, and IFN-α) were elevated in 12 patients, and the average time to start the rise was 3.4, 5.3, 6.1, 2.9, 4.3, 6.0 and 5.8 days, respectively. The time for CRP, D-D, SF, and LDH to begin to rise were 6.6, 7.6, 8.3 and 7.6 days, which were higher than that of the 7 inflammatory cytokines. After effective treatment, except for IL-6, the remaining 6 inflammatory cytokines (IL-10, IFN-γ, IL-8, IL-2, TNF-α and IFN-α) had their recovery times as 7.8, 3.9, 5.1, 8.0, 6.0, and 2.5 day,respectively, which were lower than that of CRP, D-D, SF, and LDH(9.7, 9.2, 13.7, and 13.8 days, respectively). The ROC showed that IL-6, IL-10, IFN-γ, and IL-8 can serve as biomarkers for diagnosis of CRS with high sensitivity and specificity. Conclusion:The monitoring of 12 inflammatory cytokines play an important role in CRS grading after CAR-T cell immunotherapy, which contributes to the early diagnosis of CRS and the prediction of clinical outcome.
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Objective:To investigate changes in circadian gene cryptochrome 2 (CRY2) expression in mouse models of psoriasis and HaCaT cells, and to explore underlying mechanisms.Methods:Imiquimod-induced mouse model experiment: 12 C57BL/6 female mice were randomly and equally divided into imiquimod group receiving topical imiquimod treatment for 5 consecutive days and control group receiving no treatment; these mice were sacrificed on day 6, skin tissues were resected from the back of mice, and immunofluorescence staining was performed to determine the CRY2 expression in the epidermis. HaCaT cell transfection experiment: HaCaT cells with small interfering RNA (siRNA) -mediated knockdown of CRY2 served as siRNA-CRY2 group, and siRNA-NC group as control group; 5-ethynyl-2′-deoxyuridine (EdU) staining was performed to evaluate the proliferative activity of the HaCaT cells, real-time fluorescence-based quantitative PCR (qPCR) to determine the mRNA expression of chemokines in the HaCaT cells, and Western blot analysis to determine phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2) . Tumor necrosis factor-α (TNF-α) -stimulated animal and cell experiments: 12 C57BL/6 female mice were randomly and equally divided into TNF-α group subcutaneously injected with TNF-α solution in the ear for 6 days, and phosphate buffered saline (PBS) group subcutaneously injected with the same amount of PBS; the mice were sacrificed on day 7, skin tissues were resected from the ear of mice, and immunofluorescence staining was conducted to determine the CRY2 expression in the epidermis; CRY2-knockdown HaCaT cells stimulated with 50 ng/ml TNF-α for 12 hours served as siRNA-CRY2 + TNF-α group, and siRNA-NC + TNF-α group as control group; qPCR was performed to determine the mRNA expression of chemokines in HaCaT cells in the above groups. Statistical analysis was carried out by using two-independent-sample t test. Results:Immunofluorescence staining showed that the CRY2 protein expression was significantly lower in the mouse dorsal epidermis in the imiquimod group (0.94 ± 0.23) than in the control group (2.30 ± 0.25, t = 3.99, P = 0.016) . Compared with the siRNA-NC group, the siRNA-CRY2 group showed significantly increased proportions of EdU-positive cells (48.13% ± 10.97% vs. 38.23% ± 0.81%, t = 5.00, P = 0.007) , mRNA expression levels of chemokines CXCL1 and CXCL8, as well as significantly increased phosphorylated (p) -ERK1/2 protein expression levels (all P < 0.05) , while there were no significant differences in the CCL20 mRNA expression or ERK1/2 protein expression between the two groups (both P > 0.05) . Immunofluorescence staining showed significantly decreased CRY2 protein expression level in the mouse ear epidermis in the TNF-α group (0.37 ± 0.34) compared with the PBS group (2.04 ± 0.17, t = 4.38, P = 0.012) ; the relative mRNA expression levels of chemokines CXCL1, CXCL8, and CCL20 in HaCaT cells were significantly higher in the siRNA-CRY2 + TNF-α group than in the siRNA-NC + TNF-α group (all P < 0.05) . Conclusion:CRY2 was markedly underexpressed in psoriasis, which might promote the proliferation of keratinocytes and expression of chemokines CXCL1, CXCL8 and CCL20, and TNF-α might be an upstream cytokine that could downregulate CRY2 expression.
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Objective:To explore the association of inflammatory markers and thromboinflammatory factors before and after thrombolytic intervention with functional outcomes in elderly patients with acute cerebral infarction.Methods:392 patients with acute cerebral infarction admitted to our hospital were randomly selected as study subjects and divided into an observation group(196 cases)treated with arterial thrombolytic therapy and a control group(196 cases)treated with intravenous thrombolysis.Functional outcomes of patients were assessed 72 hours after thrombolysis using the activities of daily living(ADL)scale and, based on the results, patients were divided into a poor functional outcome group and a good functional outcome group.Inflammatory markers such as neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)and thromboinflammatory factors such as monocyte chemoattractant protein-1(MCP-1), tissue plasminogen activator(t-PA), soluble CD40 ligand(sCD40L)and P-selectin before and after thrombolysis were measured.The relationship of these inflammatory markers and thromboinflammatory factors before thrombolysis with functional outcomes 72 hours after thrombolysis was analyzed.Results:NLR and PLR levels in the two groups after thrombolysis were significantly lower than those before thrombolysis(all P<0.05); Their levels in the observation group were lower than those in the control group(all P<0.05). After thrombolysis, MCP-1 levels in both groups were significantly higher and t-PA, sCD40L, P-selectin levels were significantly lower than pre-thrombolysis levels(all P<0.05); After thrombolysis, the observation group had better results than the control group(all P<0.05). Correlation analysis showed that NLR, PLR, MCP-1 and t-PA were positively correlated with NIHSS score( r=0.336, 0.264, 0.483, 0.549, all P<0.05). NLR, PLR, MCP-1, t-PA and sCD40L levels were significantly lower and P-selectin levels were significantly higher in the good functional outcome group than in the poor functional outcome group both before and 72 hours after thrombolysis( t=13.850, 18.208, 23.636, 22.371, 59.868, 96.646, 378.112, 141.213, 131.160, 110.039, 10.716, 11.108, P<0.05 for all). Logistic regression analysis showed that abnormal levels of NLR, PLR, MCP-1 and t-PA before and after thrombolysis were risk factors for adverse outcomes with thrombolytic intervention( P<0.05). ROC curves showed that the levels of NLR, PLR, MCP-1, t-PA, sCD40L and P-selectin before thrombolysis had a certain predictive value for the risk of adverse functional outcomes with thrombolysis. Conclusions:The levels of these inflammatory markers and thromboinflammatory factors before and after thrombolytic intervention have varying degrees of correlation with functional outcomes in elderly patients with acute cerebral infarction.
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Objective:To investigate the effect and safety of Guanxinning tablets combined with antiplatelet therapy on acute coronary syndrome. Methods:A total of 120 patients with acute coronary syndrome who received treatment in Shulan (Hangzhou) Hospital from January 2021 to December 2021 were included in this study. They were randomly divided into a control group and a study group ( n = 60/group). The control group was treated with antiplatelet drugs clopidogrel and aspirin. The study group was treated with clopidogrel, aspirin and Guanxinning tablets in combination. All patients were treated for 3 months. The levels of blood lipids (high-density lipoprotein cholesterol, total cholesterol, triglyceride, low-density lipoprotein cholesterol), C-reactive protein, tumor necrosis factor-α, endothelin-1, and vascular endothelial growth factor measured before and after treatment as well as the incidence of adverse reactions were compared between the two groups. Results:After treatment, serum levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride in each group were significantly decreased compared with those measured before treatment (all P < 0.05). After treatment, serum level of high-density lipoprotein cholesterol in each group was significantly increased compared with that measured before treatment ( P < 0.05). After treatment, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglyceride in the control group were (4.36 ± 1.01) mmol/L, (3.02 ± 0.28) mmol/L, and (1.98 ± 0.12) mmol/L respectively which were significantly higher than (3.98 ± 1.05) mmol/L, (2.52 ± 0.42) mmol/L, (1.58 ± 0.23) mmol/L in the study group ( t = -2.02, -7.67, -11.94, all P <0.05). Serum level of high-density lipoprotein cholesterol in the control group was significantly lower than that in the study group [(1.26 ± 0.08) mmol/L vs. (2.36 ± 0.16) mmol/L, t = 47.63, P < 0.001). After treatment, serum levels of C-reactive protein and endothelin-1 in the control group were (5.62 ± 0.56) mg/L and (86.24 ± 12.68) pg/L, respectively, which were significantly higher than (4.32 ± 0.82) mg/L and (75.26 ± 12.46) pg/L in the study group, ( t = -10.14, -4.78, both P < 0.001). After treatment, serum levels of tumor necrosis factor-α and vascular endothelial growth factor in the control group were (5.62 ± 0.56) mg/L and (76.28 ± 13.52) pg/L, which were significantly lower than (8.76 ± 1.06) mg/L and (86.32 ± 13.46) pg/L in the study group ( t = 20.23, 4.08, both P < 0.05). The incidence of adverse reactions in the study group was significantly lower than that in the control group [5.00% (3/60) vs. 8.33% (5/60), χ2 = -0.54, P > 0.05). Conclusion:Guanxinning tablets combined with antiplatelet has a remarkable therapeutic effect on acute coronary syndrome. It is highly safe and has a clinical application value.
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Objective:To investigate the effect of monosialotetrahexosylganglioside sodium treatment on neurological function, inflammatory factor, and blood coagulation function in patients with traumatic brain injury.Methods:The clinical data of 90 patients with traumatic brain injury who received treatment in Taizhou Central Hospital from February 2018 to May 2020 were retrospectively analyzed. These patients were divided into a control group ( n = 46) and an observation group ( n = 44) according to different treatment methods. The control group was given routine symptomatic treatment and the observation group was given monosialotetrahexosylganglioside sodium treatment based on routine symptomatic treatment. Remission rate, inflammatory factor level, the National Institutes of Health Stroke Scale score, Glasgow Outcome Scale score, and coagulation function were compared between the two groups at each time point. Results:At 3 days and 2 weeks post-surgery, neuropeptide Y in the observation group was (121.13 ± 12.68) ng/L and (68.52 ± 10.21) ng/L, tumor necrosis factor α was (96.15 ± 8.16) ng/L and (46.68 ± 5.95) ng/L, interleukin-6 was (231.26 ± 9.41) ng/L and (126.74 ± 12.23) ng/L, C-reactive protein was (47.52 ± 4.32) μg/L and (18.65 ± 1.32) μg/L, the National Institutes of Health Stroke Scale score was (20.12 ± 2.22) points and (17.67 ± 1.31) points. They were significantly lower than those in the control group [neuropeptide Y: (135.69 ± 15.42) ng/L, (79.36 ± 11.15) ng/L; tumor necrosis factor-α: (108.56 ± 10.13) ng/L, (69.33 ± 6.42) ng/L; interleukin-6: (264.13 ± 10.24) ng/L and (157.89 ± 12.13) ng/L; C-reactive protein: (65.19 ± 5.17) μg/L and (24.39 ± 3.45) μg/L; the National Institutes of Health Stroke Scale score: (24.56 ± 2.54) points and (20.39 ± 2.55) points] ( t3 days post-surgery = 4.88, 6.38, 15.83, 17.55, 8.81; t2 weeks post-surgery= 4.80, 17.33, 12.12, 10.33, 6.32, all P < 0.001). At 3 days and 2 weeks post-surgery, the Glasgow Outcome Scale score in the observation group was (3.65 ± 0.35) points and (4.65 ± 0.26) points, respectively, which was significantly higher than (3.15 ± 0.10) points and (4.11 ± 0.11) points in the control group ( t = 9.30, 12.93, both P < 0.05). At 3 days and 2 weeks post-surgery, fibrinogen in the observation group was (4.52 ± 0.39) g/L and (3.12 ± 0.10) g/L, thrombin time was (18.46 ± 2.95) seconds and (21.79 ± 2.45) seconds, prothrombin time was (12.42 ± 1.33) seconds and (15.79 ± 2.36) seconds, activated partial thromboplastin time was (34.59 ± 2.64) seconds and (38.98 ± 2.78) seconds, which were significantly superior to those in the control group [fibrinogen: (5.02 ± 0.13) g/L and (4.29 ± 0.16) g/L; thrombin time: (17.36 ± 1.56) seconds and (19.63 ± 1.62) seconds; prothrombin time: (10.69 ± 1.21) seconds and (13.26 ± 1.78) seconds; activated partial thromboplastin time: (32.16 ± 2.59) seconds and (35.69 ± 2.91) seconds] ( t3 days post-surgery = 8.23, 2.22, 6.46, 4.40; t2 weeks post-surgery = 41.38, 4.95, 5.75, 5.48, all P < 0.001). At 1 and 2 weeks post-surgery, the remission rate in the observation group was significantly higher than that in the control group ( χ2 = 4.75, 4.44, both P < 0.05). Conclusion:Monosialotetrahexosylganglioside sodium treatment for a traumatic brain injury can inhibit inflammatory reactions, improve blood coagulation and protect brain tissue.
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Objective:To investigate the relationship between neutrophil chemotactic function and chemokine receptor in the early stage of deep second- and third-degree burns.Methods:Twenty patients with severe burns (burn group) who received treatment within 6 hours after burns in Yantai Yeda Hospital from January 2019 to June 2020 were included in this study. Twenty healthy controls (healthy group) who concurrently received physical examination in the same hospital were also included. The general data and laboratory examination indexes in each group were analyzed. The correlation between neutrophil chemotactic function and chemokine receptor was evaluated.Results:There were no significant differences in general data between the two groups (all P > 0.05). At 1, 3 and 5 days after admission, the number of neutrophils, the number of white blood cells, and procalcitonin, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor-α levels in the burn group were significantly higher than those in the healthy control groups ( F = 12.56, 13.45, 15.78, 17.83, 22.56, 13.39, 10.82, all P < 0.05). At 1, 3 and 5 days after admission, neutrophil migration distance in the burn group was (1 510.22 ± 108.45) μm, (1 380.90 ± 115.67) μm, (1 026.10 ± 95.48) μm, respectively, which were significantly shorter than (1 944.67 ± 139.20) μM in the healthy control group ( t = 23.44, 25.67, 27.52, all P < 0.05). At 5 days after admission, chemokine receptors 1 and 2 positive rates in the burn group were (47.40 ± 1.76)% and (75.33 ± 2.42)%, respectively, which were significantly lower than (95.24 ± 4.89)% and (97.78 ± 2.10)% in the healthy control groups ( t = 4.92, 5.67, both P < 0.05). Correlation analysis showed that neutrophil migration distance was positively correlated with chemokine receptor expression in patients with deep second- and third-degree burns ( r = 0.72, 0.61, both P < 0.05). Conclusion:Neutrophil chemotactic function and chemokine receptor expression decrease in the early stage of deep second- and third-degree burns.
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Objective:To investigate the clinical efficacy of Bacille Calmette-Guerin polysaccharide nucleic acid combined with montelukast in the treatment of bronchial asthma and its effect on lung function and serum inflammatory factor level.Methods:Eighty patients with bronchial asthma who met inclusion criteria and received treatment in The First People's Hospital of Huzhou from January 2019 to December 2020 were included in this study. They were randomly assigned to undergo either routine systematic treatment and oral montelukast (control group, n = 40) or routine systematic treatment, oral montelukast, and intramuscular injection of Bacille Calmette-Guerin polysaccharide nucleic acid in combination (combined group, n = 40). The changes in serum inflammatory factors and pulmonary function after treatment relative to before treatment, clinical efficacy and adverse reactions were compared between the two groups. Results:Total response rate in the control and combined groups was 80.00% (32/40) and 95.00% (38/40) respectively. Total response rate in the combined group was significantly higher than that in the control group ( χ2 = 4.11, P = 0.043). There were no significant differences in peak expiratory flow rate, forced expiratory volume in 1 second, maximum voluntary ventilation, forced vital capacity, airway resistance and forced expiratory volume in 1 second/forced vital capacity between the two groups before treatment (all P > 0.05). In the combined group, peak expiratory flow rate, forced expiratory volume in 1 second,forced expiratory volume in 1 second/forced vital capacity, maximum voluntary ventilation and forced vital capacity were significantly increased, and airway resistance was significantly decreased after treatment compared with before treatment ( t = -4.81, -5.09, -7.39, -4.12, -7.14, 5.17, all P < 0.001). After treatment, clinical efficacy in the combined group was superior to that in the control group. Before treatment, there were no significant differences in the St George's Respiratory Questionnaire score and Asthma Control Test score between the two groups (both P > 0.05). After treatment, St George's Respiratory Questionnaire score in the combined group was significantly decreased, while Asthma Control Test score was significantly increased compared with before treatment ( t = 9.19, -3.44, both P < 0.001). Before treatment, there were no significant differences in serum interleukin-4, interleukin-5, and interferon-γ levels between the two groups (all P > 0.05). After treatment, serum levels of interleukin-4, interleukin-5, and interferon-γ in the combined group were significantly lower than those in the control group ( t = 6.95, 4.72, -11.24, all P < 0.001). No drugs-related adverse reactions were found in each group during the treatment period. Conclusion:Bacille Calmette-Guerin polysaccharide nucleic acid combined with montelukast is highly effective on bronchial asthma. The combined therapy can improve quality of life and lung function, decrease serum inflammatory factor levels, and is safe.
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Objective:To investigate the effects of Xueshuan Xinmaining tablet combined with metoprolol on creatine kinase-MB and troponin in patients with coronary heart disease after percutaneous coronary intervention. Methods:A total of 104 patients with coronary heart disease who received percutaneous coronary intervention in Zhoushan Hospital from March 2020 to March 2021 were included in this study. They were randomly divided into observation and control groups ( n = 52/group). The control group was give metoprolol (oral, 25 mg once,3 times/day). The observation group was given Xueshuan Xinmaining tablet (2 tablets once, 3 times per day) based on medication given in the control group. Two groups were treated for 1 month. Clinical efficacy, changes in vascular endothelial function and serum inflammatory factors post-treatment relative to those before treatment, and the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [86.54% (45/52) vs. 67.31% (35/52), χ2 = 4.99, P < 0.05]. After treatment, nitric oxide in the observation group was significantly higher than that in the control group [(67.23 ± 9.52) μmol/L vs. (60.49 ± 9.71) μmol/L, t = 3.57, P < 0.001]. Endothelin in the observation group was significantly lower than that in the control group [(53.12 ± 7.28) ng/L vs. (61.25 ± 8.36) ng/L, t = 5.28, P < 0.001]. Tumor necrosis factor α, C-reactive protein and interleukin-6 in the observation group were (39.51 ± 6.37) μg/L, (4.13 ± 1.02) mg/L, and (19.43 ± 2.57) μg/L, respectively, which were significantly lower than (51.37 ± 7.28) μg/L, (5.62 ± 1.15) mg/L, (26.16 ± 3.19) μg/L in the control group ( t = 8.84, 6.99, 11.84, all P < 0.05). Creatine kinase-MB and troponin in the observation group were (30.18 ± 5.89) U/L and (7.32 ± 1.12) ng/L, respectively, which were significantly lower than (41.74 ± 6.76) U/L and (9.63 ± 1.45) ng/L in the control group, respectively ( t = 9.29, 9.09, both P < 0.05). No serious adverse reactions occurred during the treatment period in each group. Conclusion:Xueshuan Xinmaining tablet combined with metoprolol exhibit remarkable therapeutic effects on patients with coronary heart disease subjected to percutaneous coronary intervention. The combined therapy can greatly reduce inflammatory reaction and decrease creatine kinase-MB level and improve vascular endothelial function.