RESUMO
OBJECTIVES: Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) DM complicated by rapidly progressive interstitial lung disease (RP-ILD) has a high incidence and poor prognosis. The objective of this study was to establish a model for the prediction and early diagnosis of anti-MDA5+ DM-associated RP-ILD based on clinical manifestations and imaging features. METHODS: A total of 103 patients with anti-MDA5+ DM were included. The patients were randomly split into training and testing sets of 72 and 31 patients, respectively. After image analysis, we collected clinical, imaging and radiomics features from each patient. Feature selection was performed first with the minimum redundancy and maximum relevance algorithm and then with the best subset selection method. The final remaining features comprised the radscore. A clinical model and imaging model were then constructed with the selected independent risk factors for the prediction of non-RP-ILD and RP-ILD. We also combined these models in different ways and compared their predictive abilities. A nomogram was also established. The predictive performances of the models were assessed based on receiver operating characteristics curves, calibration curves, discriminability and clinical utility. RESULTS: The analyses showed that two clinical factors, dyspnoea (P = 0.000) and duration of illness in months (P = 0.001), and three radiomics features (P = 0.001, 0.044 and 0.008, separately) were independent predictors of non-RP-ILD and RP-ILD. However, no imaging features were significantly different between the two groups. The radiomics model built with the three radiomics features performed worse than the clinical model and showed areas under the curve (AUCs) of 0.805 and 0.754 in the training and test sets, respectively. The clinical model demonstrated a good predictive ability for RP-ILD in MDA5+ DM patients, with an AUC, sensitivity, specificity and accuracy of 0.954, 0.931, 0.837 and 0.847 in the training set and 0.890, 0.875, 0.800 and 0.774 in the testing set, respectively. The combination model built with clinical and radiomics features performed slightly better than the clinical model, with an AUC, sensitivity, specificity and accuracy of 0.994, 0.966, 0.977 and 0.931 in the training set and 0.890, 0.812, 1.000 and 0.839 in the testing set, respectively. The calibration curve and decision curve analyses showed satisfactory consistency and clinical utility of the nomogram. CONCLUSION: Our results suggest that the combination model built with clinical and radiomics features could reliably predict the occurrence of RP-ILD in MDA5+ DM patients.
Assuntos
Doenças Pulmonares Intersticiais , Radiômica , Humanos , Nomogramas , Algoritmos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Tomografia Computadorizada por Raios XRESUMO
Lathyrane-based diterpenoid is one of the critical bioactive elements of Euphorbia lathyris L., a widely used traditional Chinese medicine for the treatment of inflammation and infection. In this study, we introduced and evaluated seven synthetic or natural lathyrane-based diterpenoids with the same core structure but notable structural variations at specific positions, for their anti-inflammatory and gout-alleviating properties. There was no significant cytotoxicity below 10 µM among the initial test of the cell counting kit 8 of the seven candidate derivatives (compounds 13 to 19) in this work. Furthermore, maintaining the acyloxy group at 15-C position and the strongly hydrophobic aryl structure at 3-C and 5-C positions, compounds 15 (Euphorbia factor L3, EFL3) and 17 strikingly inhibited the production of IL-1ß related to the actuation of the inflammasome in our study. The ELISA assay indicated that the anti-inflammatory effects of EFL3 were better associated with MSU stimulation than other second-line pathways triggered by inflammasome. Further examinations on the acute paw gout model in C57BL/6 mice showed that EFL3 had a significantly inflammatory retarding effect by intraperitoneal injection. It decreased swelling volume as well as the cleavage and activation of local IL-1ß and casepas-1 in the paw. To conclude, our findings reveal several potential key structure-activity relationships that govern the anti-inflammatory effects of lathyrane-type diterpenoids, the dispensable acyl group at the 15-C position, the importance of maintaining the spatial structure of the B-ring, and the potential importance of hydrophobic substituents at the 3-C position. These insights may provide guidance for the structural design of lathyrane-type agents in the future; furthermore, we found that the lathyrane-based diterpenoid EFL3 is a potential agent for gout that is expected to provide a novel therapeutic strategy for inflammation intervention.
Assuntos
Artrite Gotosa , Diterpenos , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Relação Estrutura-Atividade , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/síntese química , Artrite Gotosa/tratamento farmacológico , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamação/tratamento farmacológico , Estrutura Molecular , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos Endogâmicos C57BL , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese químicaRESUMO
In the blood sample management pipeline environment, we have innovatively improved the traditional A-star algorithm to enhance the efficiency of mobile robots. This study employs a grid environmental modeling approach to accurately simulate medical testing laboratories. On the grid map, we utilize an 8-neighbor search method for path planning to accommodate the complex structure within the laboratory. By introducing an improved evaluation function and a bidirectional search strategy, we have successfully reduced the number of search nodes and significantly improved path search efficiency. Additionally, we eliminate redundant nodes in the path, smooth the path using cubic uniform B-spline curves, remove unnecessary inflection points, and further optimize the motion trajectory of the robot. The experimental results of the path planning simulation under different scenarios and specifications show that the improved A-star algorithm has higher search efficiency and traverses fewer nodes compared to the traditional A-star algorithm and the bidirectional A-star algorithm. Overall, the simulation experiments verify the feasibility of the improved A-star algorithm, which can better meet the needs of actual mobile robots in real medical testing laboratories.
RESUMO
BACKGROUND: To explore the diagnostic value of changes in serum C-X-C Motif Chemokine Ligand 16 (CXCL16), cystatin C (CysC), cyclooxygenase-2 (COX-2), and urinary microalbumin (mALB) in patients with gout complicated by early renal damage. METHODS: A retrospective analysis of 47 patients with gout without complications and 48 patients with gout complicated by early renal damage was conducted in our hospital. A retrospective analysis was performed with 50 healthy people as controls. Serum IL-8, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), CXCL16, CysC, COX-2, and urine mALB levels were detected and analyzed, and the diagnostic efficacy of single factor and multifactor combined detection for early renal damage in patients with gout was analyzed and compared. RESULTS: Serum interleukin-8 (IL-8), TNF-α, IL-1ß, CXCL16, CysC, COX-2, and urine mALB/Cr levels of patients with gout were significantly higher than those of healthy people (p < 0.01). Serum IL-8, TNF-α, IL-1ß, CXCL16, CysC, COX-2 and urinary mALB/Cr levels in patients with gout complicated by early renal damage were significantly higher than those in patients with gout but without complications (p < 0.01). The sensitivity of CXCL16, CysC, COX-2, and mALB in diagnosing gout patients with early renal damage can reach 91.7%. CXCL16 and COX-2 were positively correlated with CysC and mALB/Cr, respectively, p < 0.01. The area under the ROC curve of CXCL16, CysC, COX-2, and mALB in the diagnosis of gout patients with early renal damage was 0.763, 0.832, 0.518, and 0.895, respectively. CONCLUSIONS: CysC and mALB are sensitive indicators for the diagnosis of early renal damage. The combined diagnosis of CXCL16 and COX-2 can effectively improve the detection sensitivity of early renal damage in patients with gout.
Assuntos
Gota , Rim , Biomarcadores , Creatinina , Taxa de Filtração Glomerular , Gota/complicações , Gota/diagnóstico , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of this study was to evaluate the prognostic value of a novel scoring system, based on Ddimer, total cholesterol, high-sensitivity cardiac troponin T (hs-cTnT), and serum albumin levels, in patients with heart failure. METHODS: A total of 221 patients diagnosed with heart failure between May 2016 to January 2020 were enrolled in this retrospective study. The prognostic significance of the biomarkers Ddimer, total cholesterol, hs-cTnT, and serum albumin was determined with univariate and multivariate Cox proportional hazard models. A novel prognostic score based on these predictors was established. The Kaplan-Meier method and log-rank test were used to compare the adverse outcomes of patients in different risk groups. RESULT: Results from univariate and multivariate analyses showed that high Ddimer, low serum albumin, high hs-cTnT, and low total cholesterol levels were independent prognostic factors for adverse outcomes (D-dimer >0.63â¯mg/l, HRâ¯= 1.84, 95% CIâ¯= 1.16-2.94, pâ¯= 0.010; serum albumin >34â¯g/l, HRâ¯= 0.67, 95% CIâ¯= 0.45-0.99, pâ¯= 0.046; hs-cTnT >24.06â¯pg/ml, HRâ¯= 1.65, 95% CIâ¯= 1.08-2.53, pâ¯= 0.020; total cholesterol >3.68â¯mmol/l, HRâ¯= 0.63, 95% CIâ¯= 0.43-0.92, pâ¯= 0.017). Moreover, all the patients were stratified into low-risk or high-risk group according to a scoring system based on these four markers. Kaplan-Meier analyses demonstrated that patients in the high-risk group were more prone to having adverse outcomes compared with patients in the low-risk group. CONCLUSION: Ddimer, total cholesterol, hs-cTnT, and serum albumin levels were independent prognostic factors in the setting of heart failure. A novel and comprehensive scoring system based on these biomarkers is an easily available and effective tool for predicting the adverse outcomes of patients with heart failure.
Assuntos
Insuficiência Cardíaca , Troponina T , Biomarcadores , Ácido Edético/análogos & derivados , Insuficiência Cardíaca/diagnóstico , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND The aim of this study was to explore the correlation between HLA-B27 and the intracellular elimination, replication, and trafficking of Salmonella enteritidis (S. enteritidis) collected from patients with reactive arthritis. MATERIAL AND METHODS Confocal microscopy, flow cytometry, and sandwich enzyme-linked immunosorbent assay (ELISA) were employed in this study to evaluate the localization of proteins of interest, to assess the intracellular trafficking of S. enteritidis, and to measure the production of cytokines of interest. RESULTS HLA-B27 was negatively associated with intracellular S. enteritidis elimination in healthy human monocytes/macrophages. In S. enteritidis infected monocytes/macrophages, HLA-27B was also negatively correlated with bacteria elimination but positively related to bacteria replication. S. enteritidis did not co-localize with NRAMP1 and LAMP1/2 in HLA-B27 cells. S. enteritidis did not co-exist with transferrin or dextran within HLA-B27 and A2 cells. CONCLUSIONS HLA-B27 is closely associated with the intracellular elimination and replication of S. enteritidis. Replicated bacteria in HLA-B27 monocytic cells were located within unique vacuoles rather than disturbing host endocytosis.
Assuntos
Artrite Reativa/microbiologia , Antígeno HLA-B27/análise , Adulto , Artrite/microbiologia , Artrite Reativa/sangue , Biomarcadores/sangue , Linhagem Celular , Citocinas/metabolismo , Feminino , Antígeno HLA-B27/sangue , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/microbiologia , Salmonella enteritidis/metabolismo , Salmonella enteritidis/patogenicidade , Células U937RESUMO
Cat scratch disease may occur during etanercept therapy, but there has been no report on infliximab-associated cat scratch disease. We report a case of a 23-year-old woman who developed right inguinal lymph node enlargement following a cat scratch. The patient had received infliximab therapy for spondyloarthropathy. She was successfully managed by discontinuing infliximab and by treatment with moxifloxacin and amikacin.
Assuntos
Antirreumáticos/efeitos adversos , Doença da Arranhadura de Gato/etiologia , Hospedeiro Imunocomprometido , Infliximab/efeitos adversos , Linfonodos/patologia , Espondiloartropatias/tratamento farmacológico , Bartonella henselae/isolamento & purificação , Doença da Arranhadura de Gato/patologia , Feminino , Humanos , Adulto JovemRESUMO
OBJECTIVE: To explore the role of type I interferon (IFNalpha) on the function of CD4+ CD25+ regulatory T (Treg) cells in patients with systemic lupus erythematosus (SLE). METHODS: Twenty patients with newly-onset active SLE and 20 healthy controls were recruited in this study. The expressions of type I interferon a receptor (IFNAR) on Treg cells were analyzed using flow cytometry. CD4+ CD25+ Treg cells were purified by magnetic-activated cell sorter (MACS). The function of these cells was assessed in vitro with or without IFNalpha (500 U/mL). The effect of exogenous IFNalpha on the apoptosis of Treg cells and the expression level of FOXP3, CTLA-4, and pAKT in Treg cells were analyzed using flow cytometry. Results The expression levels of IFNAR1 on CD4+ CD25+ Treg cells were significantly higher in the SLE patients than in the healthy controls (P=0.0006). There was a positive correlation between the expression levels of IFNAR on Treg cells and the SLEDAI scores in the SLE patients. Exogenous IFNalpha impaired the suppressive capacity of Treg cells in the SLE patients. However, neither the apoptosis of Treg cells nor the expression levels of FOXP3 and CTLA-4 on Treg cells were influenced by IFNalpha stimulation. IFNalpha enhanced AKT phosphorylation in Treg cells in the SLE patients. CONCLUSION: Altered IFNAR expression may contribute to Treg cell dysfunction in SLE patients through enhancing AKT phosphorylation in Treg cells.
Assuntos
Lúpus Eritematoso Sistêmico/fisiopatologia , Receptores de Interferon/metabolismo , Linfócitos T Reguladores/patologia , Apoptose , Antígeno CTLA-4/metabolismo , Estudos de Casos e Controles , Separação Celular , Células Cultivadas , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica , Humanos , Interferon-alfa/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
INTRODUCTION: Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA. METHODS: Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16. RESULTS: In total, 147 patients were randomized to receive placebo (n = 73) or IXEQ4W (n = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n = 66; 40.9%) than the placebo group (n = 64, 7.8%; p < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest. CONCLUSIONS: IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04285229.
Assuntos
Antirreumáticos , Espondiloartrite Axial , Espondilartrite , Adulto , Humanos , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Espondilartrite/diagnóstico por imagem , Espondilartrite/tratamento farmacológico , Método Duplo-Cego , ChinaRESUMO
BACKGROUND: Routine use of immunosuppressive agents in systemic lupus erythematosus (SLE) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially increases the risk of adverse outcomes. belimumab, a monoclonal antibody for the treatment of SLE, remains untested for its specific impact on coronavirus disease 2019 (COVID-19) symptoms in these patients. Here, this research investigated the effect of belimumab on COVID-19 symptoms in SLE patients infected with SARS-CoV-2. METHODS: This study enrolled SLE patients who underwent treatment with belimumab. After thorough screening based on the inclusion and exclusion criteria, data pertaining to COVID-19 for both the participants and their cohabitants were obtained through telephone follow-up. The potential impact of belimumab on COVID-19 was evaluated by comparing COVID-19 symptoms and medication use across various groups to investigate the association between belimumab treatment and COVID-19 in SLE. RESULTS: This study involved 123 SLE patients, of whom 89.4% tested positive for SARS-CoV-2. Among cohabitants of SLE patients, the SARS-CoV-2 positive rate was 87.2% (p = 0.543). Patients treated with belimumab exhibited a lower incidence of multiple COVID-19 symptoms than their cohabitating counterparts (p < 0.001). This protective effect was found to be partially related to the time of last belimumab administration. Among those with COVID-19, 30 patients opted to discontinue their anti-SLE drugs, and among them, 53% chose to discontinue belimumab. Discontinuing drugs did not increase the risk of hospitalization due to SARS-CoV-2 infection. CONCLUSION: This study concluded that treatment with belimumab did not increase susceptibility to COVID-19 and beneficially alleviated the symptoms of COVID-19.
Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Imunossupressores , Lúpus Eritematoso Sistêmico , SARS-CoV-2 , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/epidemiologia , Feminino , Estudos Retrospectivos , Adulto , Masculino , Pessoa de Meia-Idade , Imunossupressores/uso terapêuticoRESUMO
INTRODUCTION: Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. METHODS: In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. RESULTS: Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. CONCLUSION: IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04285229.
RESUMO
The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366-1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.
Assuntos
Artrite Psoriásica , COVID-19 , Espondilartrite , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Estudos Retrospectivos , SARS-CoV-2 , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológicoRESUMO
PURPOSE: We report a rare case of Takayasu arteritis causing isolated complete obliteration of the aorta. A 24-year-old woman with night sweats, weight loss, and claudication was hospitalized because of refractory hypertension. Laboratory tests showed increased inflammatory indexes. Imaging studies revealed isolated complete occlusion of thoracic and abdominal aorta. Takayasu arteritis was diagnosed. Glucosteroids and revascularization surgery were given. Clinical symptoms were relieved immediately without relapse after operation. Revascularization surgery was the effective therapy for the patient.
Assuntos
Doenças da Aorta/etiologia , Arteriopatias Oclusivas/etiologia , Arterite de Takayasu/diagnóstico , Adulto , Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/cirurgia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Tontura/etiologia , Feminino , Glucocorticoides/uso terapêutico , Cefaleia/etiologia , Humanos , Hipertensão/etiologia , Claudicação Intermitente/etiologia , Prednisona/uso terapêutico , Sudorese , Arterite de Takayasu/tratamento farmacológico , Redução de PesoRESUMO
RATIONALE: Limited literatures are available on lower gastrointestinal bleeding in systemic lupus erythematosus (SLE) combined with intestinal tuberculosis. Sharing the treatment experiences of a 26-year-old female patient diagnosed with this complex condition in this report may contribute valuable insights. PATIENT CONCERNS: The patient initially presented with abdominal pain and active gastrointestinal bleeding, leading to admission to the hospital. Over a 2-week period, she experienced persistent bleeding, with daily volumes ranging from 300 mL to 800 mL. DIAGNOSES: Lower gastrointestinal bleeding was diagnosed in this patient with concurrent systemic lupus erythematosus and intestinal tuberculosis. INTERVENTIONS: As her symptoms rapidly progressed, food and water intake had to be completely restricted. The parenteral nutrition was implemented. OUTCOMES: The medical team effectively controlled the bleeding, leading to a notable improvement in the patient's condition. Consequently, she was able to resume oral intake and was discharged from the hospital. LESSONS: This case highlights the significance of using parenteral nutrition in the management of lower gastrointestinal bleeding in patients with concurrent systemic lupus erythematosus and intestinal tuberculosis. Close monitoring and collaborative efforts among healthcare professionals are crucial to achieve successful outcomes in similar cases.
Assuntos
Enterite , Lúpus Eritematoso Sistêmico , Peritonite Tuberculosa , Tuberculose Gastrointestinal , Tuberculose dos Linfonodos , Humanos , Feminino , Adulto , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Lúpus Eritematoso Sistêmico/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/terapia , Nutrição ParenteralRESUMO
Interstitial lung disease (ILD) is a highly fatal manifestation of idiopathic inflammatory myopathies (IIMs). Th cells play important roles in the initiation of ILD. Here, we investigated the clinical significance of peripheral blood Th cells in IIMs-ILD patients. Eleven healthy controls (HC) and 53 patients diagnosed with IIMs were included, including 30 with ILD (IIMs-ILD) and 23 without ILD (IIMs-non-ILD). Circulating Th1, Th2, Th17, and Treg cells were examined by flow cytometry, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation and logistic regression. The proportion of Th1 cells decreased and Th2 cells increased in IIMs-ILD compared with IIMs-non-ILD (median (quartile): 2.99 (1.59-5.39) vs. 6.91 (3.48-10.04), p < 0.001; 2.67 (1.79-4.67) vs. 1.62 (0.85-2.66), p = 0.006) and correlated with disease activity. The Th1-cell proportion decreased in anti-MDA5 antibody-positive patients, while the Th2 cell proportion increased in patients with nonspecific interstitial pneumonia compared with IIMs-non-ILD (2.66 (1.06-4.35) vs. 6.91 (3.48-10.04), p = 0.002; 3.09 (2.03-5.72) vs. 1.62 (0.85-2.66), p = 0.016). Univariate analysis showed that a lower Th1 proportion, higher Th2 proportion increased, lower CK level, positivity for ARS, or anti-Ro52 antibodies (OR = 0.7122; OR = 1.679; OR = 0.9993; OR = 9.188; and OR = 6.161, respectively) were associated with the occurrence of ILD in IIMs patients. Decreased Th1 cells and elevated Th2 cells in peripheral blood may be involved in the pathogenesis of ILD in IIMs patients and have different effects on different serological and imaging subtypes.
Assuntos
Pneumonias Intersticiais Idiopáticas , Doenças Pulmonares Intersticiais , Miosite , Humanos , Células Th2 , Células Th1 , Doenças Pulmonares Intersticiais/complicações , Miosite/complicações , AutoanticorposRESUMO
Patients with idiopathic inflammatory myopathies (IIMs), referred to as myositis, are prone to infectious complications, which hinder the treatment of the disease and worsen the outcome of patients. The purpose of this study was to explore the different types of infectious complications in patients with myositis and to determine the predisposing factors for clinical reference. A retrospective study was conducted on 66 patients with IIM who were divided into different subpopulations by an unsupervised analysis of their clinical manifestations, laboratory features, and autoantibody characteristics. Combined with the incidence of infectious complications, the types of infectious pathogens and the sites of infection, the characteristics of infection, and susceptibility factors were explored. Three clusters with significantly different clinical characteristics and coinfection rates were identified (76.2% vs. 41.6% vs. 36.4%, p = 0.0139). Cluster 1 (n = 12) had a moderate risk of infection, with an infection rate of 41.6%. The patients in cluster 1 had a high probability of positive mechanic's hands, periungual erythema, anti-Ro52 antibody, and anti-Jo1 antibody. CD3 and CD4 were the highest among the three groups. Cluster 2 (n = 21) had a high risk of infection, and the incidence of infection was 76.2%. Almost all patients in this cluster had a rash, prominent clinical symptoms, and decreased WBC, PMN, LYM, CD3, and CD4 counts. Cluster 3 (n = 33) had a low risk of infection, with an infection rate of 36.4%. Compared with the other two clusters, cluster 3 (n = 33) lacked a typical rash but had a high ANA-positive rate. The patients in cluster 1 and cluster 3 were mainly infected by viruses, followed by bacterial infections. In cluster 2 patients, bacterial infections were the most prevalent. Fungal and Pneumocystis carinii were common causes of cluster 2 and 3 infections. In addition, the patients within a cluster often have a single infection, and pulmonary infections are the most common. We clustered the patients with IIM complicated with infection into three different types by their clinical symptoms and found that there were differences in the infection risk and infection types among the different cluster groups.
Assuntos
Miosite , Humanos , Estudos Retrospectivos , Miosite/diagnóstico , Miosite/epidemiologia , Autoanticorpos , Biomarcadores , Análise por ConglomeradosRESUMO
Interstitial lung disease (ILD) is one of the most serious lung complications of connective tissue disease (CTD). The application of proteomics in the past decade has revealed that various proteins are involved in the pathogenesis of each subtype of CTD-ILD through different pathways, providing novel ideas to study pathological mechanisms and clinical biomarkers. On this basis, a multidimensional diagnosis or prediction model is established. This paper reviews the results of proteomic detection of different subtypes of CTD-ILD and discusses the role of some differentially expressed proteins in the development of pulmonary fibrosis and their potential clinical applications.
Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Humanos , Proteômica , Doenças Pulmonares Intersticiais/diagnóstico , Doenças do Tecido Conjuntivo/diagnóstico , Prognóstico , BiomarcadoresRESUMO
Aim: The gut microbiota plays an important role in human health. In this study, we aimed to investigate whether and how gut microbiota communities are altered in patients with immune-mediated necrotizing myopathy (IMNM) and provide new ideas to further explore the pathogenesis of IMNM or screen for its clinical therapeutic targets in the future. Methods: The gut microbiota collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta-diversity analyses were applied to examine the bacterial diversity and community structure. Welch's t test was performed to identify the significantly abundant taxa of bacteria between the two groups. Spearman correlation analysis was performed to analyze the correlation between gut microbiota and clinical indicators. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P < 0.05 was considered statistically significant. Results: Nineteen IMNM patients and 23 HCs were included in the analysis. Among IMNM patients, 94.74% (18/19) of them used glucocorticoids, while 57.89% (11/19) of them used disease-modifying antirheumatic drugs (DMARDs), and the disease was accessed by MITAX (18.26 ± 8.62) and MYOACT (20.68 ± 8.65) scores. Participants in the groups were matched for gender and age. The diversity of the gut microbiota of IMNM patients differed and decreased compared to that of HCs (Chao1, Shannon, and Simpson indexes: p < 0.05). In IMNM patients, the relative abundances of Bacteroides, Roseburia, and Coprococcus were decreased, while that of Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies, anti-Ro52 antibodies, and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP, and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, the prediction model was built using the top five differential genera, which was verified using a ROC curve (area under the curve (AUC): 87%, 95% confidence interval: 73%-100%). Conclusion: We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and is correlated with systemic autoimmune features.
Assuntos
Doenças Autoimunes , Disbiose , Microbioma Gastrointestinal , Lactobacillus , Miosite , Disbiose/complicações , Disbiose/microbiologia , Lactobacillus/classificação , Lactobacillus/isolamento & purificação , Humanos , Miosite/complicações , Doenças Autoimunes/complicações , Necrose , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with unclear pathogenesis. We performed single-cell RNA-seq and surface proteome analyses on 61,379 PBMCs from 9 treatment-naive IgG4-RD patients and 7 age- and sex-matched healthy controls. Integrative analyses were performed for altered gene expression in IgG4-RD, and flow cytometry and immunofluorescence were used for validation. We observed expansion of plasmablasts with enhanced protein processing and activation, which correlated with the number of involved organs in IgG4-RD. Increased proportions of CD4+ cytotoxic T lymphocytes (CTLs), CD8+ CTLs-GNLY (granulysin), and γδT cells with enhanced chemotaxis and cytotoxicity but with suppressed inhibitory receptors characterize IgG4-RD. Prominent infiltration of lymphocytes with distinct compositions were found in different organs of IgG4-RD patients. Transcription factors (TFs), including PRDM1/XBP1 and RUNX3, were upregulated in IgG4-RD, promoting the differentiation of plasmablasts and CTLs, respectively. Monocytes in IgG4-RD have stronger expression of genes related to cell adhesion and chemotaxis, which may give rise to profibrotic macrophages in lesions. The gene activation pattern in peripheral immune cells indicated activation of multiple interaction pathways between cell types, in part through chemokines or growth factors and their receptors. Specific upregulation of TFs and expansion of plasmablasts and CTLs may be involved in the pathogenesis of IgG4-RD, and each of these populations are candidate targets for therapeutic interventions in this disease.
Assuntos
Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/genética , Análise da Expressão Gênica de Célula Única , Linfócitos T CD4-Positivos , Plasmócitos , Linfócitos T CitotóxicosRESUMO
OBJECTIVE: In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis. METHODS: Fecal samples were collected from 38 healthy individuals and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA) positivity (Pre-RA), 12 of 53 Pre-RA individuals developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the healthy controls and Pre-RA individuals or among Pre-RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice that received GM from the healthy control or Pre-RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre-RA individuals on arthritis severity in mice. RESULTS: Stool microbial diversity was lower in Pre-RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre-RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre-RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre-RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre-RA group increased intestinal permeability in FMT mice and zonula occludens-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre-RA feces compared to healthy controls. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice. CONCLUSION: Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.