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OBJECTIVES: The objective of this study was to address the biological function of miR-7 in an animal model of systemic lupus erythematosus. METHODS: MRLlpr/lpr lupus mice were administrated antagomiR-7 or a scramble control by tail vein for 5weeks. Three groups of animals' tissues were assessed for lupus manifestations by immunofluorescence and immunohistochemistry, and serum was examined for levels of autoantibodies and inflammatory cytokines. Splenic B cell subsets were assessed for intracellular expression of PI3K signaling by FACS. Finally, the ability of the miR-7 antagomir to regulate the expansion of T follicular helper (Tfh) cells and B cell hyperresponsiveness was further explored. RESULTS: We found that miR-7 was up-regulated in MRLlpr/lpr lupus mice and directly targeted PTEN mRNA in B cells. Up-regulated miR-7 in MRLlpr/lpr lupus B cells was negatively correlated with PTEN expression. Notably, miR-7 antagomir treatment reduced lupus manifestations in MRLlpr/lpr lupus mice. miR-7-mediated down-regulation of PTEN/AKT signaling promoted B cell differentiation into plasmablasts/plasma cells and spontaneous germinal center (GC) formation, whereas miR-7 antagomir normalized splenic B cell subtypes. Besides suppressing the activation of B cells, miR-7 antagomir intervention also down-regulated STAT3 phosphorylation and production of IL-21 and reduced Tfh expansion. CONCLUSION: The above data have demonstrated the critical roles of miR-7 not only in regulating PTEN expression and also B cell and Tfh cell function in lupus-prone MRLlpr/lpr lupus mice. Furthermore, the disease manifestations in MRLlpr/lpr lupus mice are efficiently improved by miR-7 antagomir, indicating miR-7 as a potential treatment strategy in SLE.
Assuntos
Linfócitos B/imunologia , Linfócitos B/metabolismo , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/metabolismo , Ativação Linfocitária/genética , MicroRNAs/genética , Animais , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , PTEN Fosfo-Hidrolase/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
OBJECTIVE: Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS: We analyzed the fecal metagenome of 85 untreated AS patients and 62 healthy controls by metagenomic shotgun sequencing, and 23 post-treatment feces of those AS patients were collected for comparison. Comparative analyses among different cohorts including AS, rheumatoid arthritis and Behcet's disease were performed to uncover some common signatures related to inflammatory arthritis. Molecular mimicry of a microbial peptide was also demonstrated by ELISpot assay. RESULTS: We identified AS-enriched species including Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri. Pathway analysis revealed increased oxidative phosphorylation, lipopolysaccharide biosynthesis and glycosaminoglycan degradation in AS gut microbiota. Microbial signatures of AS gut selected by random forest model showed high distinguishing accuracy. Some common signatures related to autoimmunity, such as Bacteroides fragilis and type III secretion system (T3SS), were also found. Finally, in vitro experiments demonstrated an increased amount of IFN-γ producing cells triggered by a bacterial peptide of AS-enriched species, mimicking type II collagen. CONCLUSIONS: These findings collectively indicate that gut microbiota was perturbed in untreated AS patients with diagnostic potential, and some AS-enriched species might be triggers of autoimmunity by molecular mimicry. Additionally, different inflammatory arthritis shared some common microbial signatures.
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Microbioma Gastrointestinal , Mediadores da Inflamação/metabolismo , Metagenoma , Metagenômica , Espondilite Anquilosante/etiologia , Espondilite Anquilosante/metabolismo , Autoimunidade , Estudos de Casos e Controles , Suscetibilidade a Doenças , Disbiose , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metagenômica/métodos , Espondilite Anquilosante/patologiaRESUMO
OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5â mg once a week, or TwHF 20â mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS: 174/207 (84.1%) patients completed 24â weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Tripterygium , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do TratamentoRESUMO
OBJECTIVES: Our objective was to better understand the roles of single nucleotide polymorphisms (SNPs) in the CCL21, ERBB3, and TERT genes region in the development of idiopathic inflammatory myopathies (IIMs), we explored the associations between SNPs in the mentioned three genes and IIMs susceptibility in a Chinese Han population. METHODS: Chinese polymyositis (PM) patients (n =291), dermatomyositis (DM) patients (n=526) and ethnically-matched healthy controls (n =968) were genotyped for the CCL21 region SNPs (rs951005 and rs2492358), ERBB3 (rs2292239 and rs11171739), and TERT (rs2853676 and rs10069690), by using the Sequenom MassArray system. RESULTS: Our study indicated strong allele and genotype associations between rs951005 (OR: 1.65, 95%CI: 1.18-2.30, Pc=0.015; Pc=0.041, respectively) in CCL21 gene and PM patients. Additionally, rs951005 was associated with interstitial lung disease (ILD) in PM patients (Pc =0.01), and was associated with PM patients in additive model. However, the Chinese Han PM/DM patients and controls had statistically similar frequencies of alleles, genotypes and different genetic models (additive, dominant, and recessive) of ERBB3 and TERT polymorphisms. CONCLUSIONS: This was the first study to demonstrate that the CCL21 gene SNP (rs951005) might confer genetic predisposition to PM patients or such patients with ILD in a Chinese Han population.
Assuntos
Povo Asiático/genética , Quimiocina CCL21/genética , Doenças Pulmonares Intersticiais/genética , Polimorfismo de Nucleotídeo Único , Polimiosite/genética , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etnologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Polimiosite/diagnóstico , Polimiosite/etnologia , Receptor ErbB-3/genética , Fatores de Risco , Telomerase/genéticaRESUMO
Pathogen-mediated interactions between insect vectors and their host plants can affect herbivore fitness and the epidemiology of plant diseases. While the role of plant quality and defense in mediating these tripartite interactions has been recognized, there are many ecologically and economically important cases where the nature of the interaction has yet to be characterized. The Bemisia tabaci (Gennadius) cryptic species Mediterranean (MED) is an important vector of tomato yellow leaf curl virus (TYLCV), and performs better on virus-infected tomato than on uninfected controls. We assessed the impact of TYLCV infection on plant quality and defense, and the direct impact of TYLCV infection on MED feeding. We found that although TYLCV infection has a minimal direct impact on MED, the virus alters the nutritional content of leaf tissue and phloem sap in a manner beneficial to MED. TYLCV infection also suppresses herbivore-induced production of plant defensive enzymes and callose deposition. The strongly positive net effect on TYLCV on MED is consistent with previously reported patterns of whitefly behavior and performance, and provides a foundation for further exploration of the molecular mechanisms responsible for these effects and the evolutionary processes that shape them.
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Begomovirus/fisiologia , Hemípteros/fisiologia , Interações Hospedeiro-Patógeno , Insetos Vetores/fisiologia , Solanum lycopersicum/virologia , Animais , Feminino , Hemípteros/virologia , Insetos Vetores/virologiaRESUMO
The western flower thrips, Frankliniella occidentalis (Pergande), and the sweetpotato whitefly, Bemisia tabaci (Gennadius), are both invasive insect pests and are present in most of the same agricultural crops without a clear dominance of either species. Here, intra- and interspecific competition in B. tabaci and F. occidentalis was determined under controlled experiments. The results showed that intraspecific competition was distinct in F. occidentalis and that the co-occurrence of B. tabaci had a strong effect on F. occidentalis, resulting in a decrease in oviposition. Significant intraspecific competition was found in B. tabaci, and the coexistence of F. occidentalis had limited effect on the oviposition of B. tabaci. In a selective host plant preference experiment, both F. occidentalis and B. tabaci preferred eggplants most, followed by cucumbers and tomatoes. On cucumber plants, B. tabaci was predominant, whereas on eggplant and tomato plants, F. occidentalis and B. tabaci exhibited comparative competitive abilities during the initial stage. However, over time, higher numbers of B. tabaci than that of F. occidentalis were found on the two host plants. Our in vitro and potted plant experiments indicate that B. tabaci is competitively superior to F. occidentalis, which might help to explain their differential distribution patterns in China.
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Hemípteros/fisiologia , Tisanópteros/fisiologia , Animais , Comportamento Competitivo , Comportamento Alimentar , Feminino , Fertilidade , Cadeia Alimentar , Masculino , Oviposição , Densidade Demográfica , Especificidade da EspécieRESUMO
Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a destructive insect pest of many crops. Rickettsia infection in different cryptic species of B. tabaci has been observed worldwide. Understanding the interactions between these 2 organisms is critical to developing Rickettsia-based strategies to control B. tabaci and thereby reduce the transmission of related vector-borne viruses. In this study, we investigated the effects of Rickettsia infection on the biological characteristics of the Middle East Asia Minor 1 (MEAM1) strain of B. tabaci through biological analysis of infected and uninfected individuals. The results of this study suggest that Rickettsia may confer fitness benefits. These benefits include increased fertility, improved survival rates, accelerated development, and resulted in female bias. We also investigated the transcriptomics impact of Rickettsia infection on B. tabaci by performing a comparative RNA-seq analysis of nymphs and adult females, both with and without the infection. Our analysis revealed 218 significant differentially expressed genes (DEGs) in infected nymphs compared to uninfected ones and 748 significant DEGs in infected female adults compared to their uninfected whiteflies. Pathway analysis further revealed that Rickettsia can affect many important metabolic pathways in whiteflies. The results suggest that Rickettsia plays an essential role in energy metabolism, and nutrient synthesis in the B. tabaci MEAM1, and depends on metabolites obtained from the host to ensure its survival. Overall, our findings suggest that Rickettsia has beneficial effects on B. tabaci and offered insights into the potential molecular mechanisms governing the interactions between Rickettsia and B. tabaci MEAM1.
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Hemípteros , Ninfa , Rickettsia , Transcriptoma , Animais , Hemípteros/microbiologia , Feminino , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , MasculinoRESUMO
BACKGROUND: Patients of interstitial lung disease (ILD) combined with pulmonary lesions are increasingly common in clinical practice. Patients with ILD are at significantly higher risk for complications after pulmonary resection (including lobectomy and sublobar resection), especially acute exacerbations of ILD (AE-ILD). The purpose of this study is to summarize the short-term and long-term outcomes after pulmonary resection in ILD patients and to analyze the clinical factors affecting surgical safety. METHODS: From January 2004 to January 2022, a total of 78 patients who were diagnosed with ILD and underwent pulmonary resection at our center were enrolled in this study. Clinical data, pathological findings, surgical procedures, and intraoperative safety of these patients were collected retrospectively. Postoperative 90-day complications and mortality, long-term surgical outcomes from postoperative 90 days to 24 months, and changes in ILD condition were investigated. Logistic regression analysis was used to identify the risk factors associated with postoperative complications. RESULTS: The median age of patients was 66.5 (range 33-86) years, 82.1% (64/78) of patients were male, and 78.2% (61/78) of patients had comorbidities. Idiopathic ILD and secondary ILD accounted for 86% and 14%, thoracotomy and video-assisted thoracoscopic surgery accounted for 12.8% and 87.2%, and lobectomy and sublobar resection accounted for 37.2% and 62.8%, respectively. Postoperative 90-day complications occurred in 25.6% (20/78) of patients, with pulmonary complications and AE-ILD occurring in 15.4% and 9.0% of patients, respectively. The postoperative 90-day mortality rate was 5.1% (4/78), and the cause of death was AE-ILD. Exacerbation of ILD or other complications occurred in 12.8% (10/78) of patients from postoperative 90 days to 24 months. Univariate logistic regression analysis showed that comorbidity, extent of resection, systemic lymph node dissection, operation time, intraoperative blood loss, and pathology of pulmonary lesion were associated with postoperative 90-day complications. In multivariate logistic regression analysis, age-adjusted Charlson Comorbidity Index and intraoperative blood loss were identified as independent risk factors of postoperative 90-day complications. CONCLUSIONS: Patients with ILD have a significantly higher risk of postoperative 90-day complications and mortality after pulmonary resection, especially pulmonary complications and AE-ILD. After postoperative 90 days, the risk of deterioration of pulmonary status remains high, including exacerbation of ILD and complications associated with long-term use of glucocorticoids and immunosuppressant. Age, comorbidity and intraoperative blood loss are high risk factors for postoperative 90-day complications.
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Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Fatores de Risco , Complicações Pós-Operatórias/etiologia , Pneumonectomia/métodos , Resultado do Tratamento , PrognósticoRESUMO
Bacterial endosymbionts play important roles in the life histories of herbivorous insects by impacting their development, survival, reproduction, and stress tolerance. How endosymbionts may affect the interactions between plants and insect herbivores is still largely unclear. Here, we show that endosymbiotic Rickettsia belli can provide mutual benefits also outside of their hosts when the sap-sucking whitefly Bemisia tabaci transmits them to plants. This transmission facilitates the spread of Rickettsia but is shown to also enhance the performance of the whitefly and co-infesting caterpillars. In contrast, Rickettsia infection enhanced plant resistance to several pathogens. Inside the plants, Rickettsia triggers the expression of salicylic acid-related genes and the two pathogen-resistance genes TGA 2.1 and VRP, whereas they repressed genes of the jasmonic acid pathway. Performance experiments using wild type and mutant tomato plants confirmed that Rickettsia enhances the plants' suitability for insect herbivores but makes them more resistant to fungal and viral pathogens. Our results imply that endosymbiotic Rickettsia of phloem-feeding insects affects plant defenses in a manner that facilitates their spread and transmission. This novel insight into how insects can exploit endosymbionts to manipulate plant defenses also opens possibilities to interfere with their ability to do so as a crop protection strategy. IMPORTANCE: Most insects are associated with symbiotic bacteria in nature. These symbionts play important roles in the life histories of herbivorous insects by impacting their development, survival, reproduction as well as stress tolerance. Rickettsia is one important symbiont to the agricultural pest whitefly Bemisia tabaci. Here, for the first time, we revealed that the persistence of Rickettsia symbionts in tomato leaves significantly changed the defense pattern of tomato plants. These changes benefit both sap-feeding and leaf-chewing herbivore insects, such as increasing the fecundity of whitefly adults, enhancing the growth and development of the noctuid Spodoptera litura, but reducing the pathogenicity of Verticillium fungi and TYLCV virus to tomato plants distinctively. Our study unraveled a new horizon for the multiple interaction theories among plant-insect-bacterial symbionts.
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Hemípteros , Infecções por Rickettsia , Rickettsia , Animais , Hemípteros/microbiologia , Herbivoria , Simbiose , PlantasRESUMO
Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.
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The sweet potato whitefly, Bemisia tabaci (Gennadius) (Hemiptera:Aleyrodidae), is an invasive and damaging pest of field crops worldwide. The neonicotinoid insecticide imidacloprid has been widely used to control this pest. We assessed the species composition (B vs. Q), imidacloprid resistance, and association between imidacloprid resistance and the expression of five P450 genes for 14-17 B. tabaci populations in 12 provinces in China. Fifteen of 17 populations contained only B. tabaci Q, and two populations contained both B and Q. Seven of 17 populations exhibited moderate to high resistance to imidacloprid, and eight populations exhibited low resistance to imidacloprid, compared with the most susceptible field WHHB population. In a study of 14 of the populations, resistance level was correlated with the expression of the P450 genes CYP6CM1 and CYP4C64 but not with the expression of CYP6CX1, CYP6CX4, or CYP6DZ7. This study indicates that B. tabaci Q has a wider distribution in China than previously reported. Resistance to imidacloprid in field populations of B. tabaci is associated with the increased expression of two cytochrome P450 genes (CYP6CM1 and CYP4C64).
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hemípteros/efeitos dos fármacos , Hemípteros/metabolismo , Imidazóis/farmacologia , Proteínas de Insetos/metabolismo , Inseticidas/farmacologia , Nitrocompostos/farmacologia , Animais , China , Sistema Enzimático do Citocromo P-450/genética , Resistência a Medicamentos , Hemípteros/genética , Proteínas de Insetos/genética , NeonicotinoidesRESUMO
OBJECTIVE: To explore the clinical features of immunoglobin (IgG4)-related Mikulicz's disease (MD). METHODS: Since December 2010, a prospective cohort study of IgG4 related disease (IgG4RD) was performed our hospital. A total of 42 IgG4RD patients were recruited along with 18 MD patients. Their clinical, laboratory and histopathological features and response to treatment were analyzed. RESULTS: The 18 MD patients accounted for 42.9% of IgG4RD. There were 10 males and 8 females with a mean age of (48 ± 14) years. The mean follow-up period was 8.18 months. All of them had an involvement of salivary and lacrimal glands. Fifteen cases suffered other organs' damage, including autoimmune pancreatitis (n = 7), sclerosing cholangitis (n = 4) and lymph nodes (n = 6). And 10 patients complained of a history of allergies. All serum levels of IgG4 subclass significantly increased. Histological examinations in 16 patients revealed massive infiltration of lymphocytes and IgG4 positive plasma cells with obvious tissue fibrosis. Glucocorticoid and immunosuppressive therapies were effective for MD. CONCLUSION: As an IgG4-related systemic disease involving predominantly lacrimal and salivary glands without autoantibodies, MD is treated optimally with a combination therapy of glucocorticoid and immunosuppressive drugs.
Assuntos
Imunoglobulina G/sangue , Doença de Mikulicz/imunologia , Adulto , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Feminino , Humanos , Aparelho Lacrimal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença de Mikulicz/diagnóstico , Doença de Mikulicz/terapia , Estudos Prospectivos , Glândulas Salivares/fisiopatologiaRESUMO
BACKGROUND: To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation. METHODS: Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0. RESULTS: A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2-137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications. CONCLUSIONS: The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.
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Miastenia Gravis , Neoplasias Epiteliais e Glandulares , Timoma , Neoplasias do Timo , Masculino , Humanos , Feminino , Timoma/cirurgia , Seguimentos , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias do Timo/cirurgia , Neoplasias Epiteliais e Glandulares/complicações , Neoplasias Epiteliais e Glandulares/patologia , Miastenia Gravis/cirurgia , Timectomia/efeitos adversos , PrognósticoRESUMO
The sweet potato whitefly, Bemisia tabaci, (Gennadius) (Hemiptera:Aleyrodidae) is a global pest of crops. Neonicotinoids are efficient insecticides used for control of this pest. Insecticidal targets of neonicotinoids are insect nicotinic acetylcholine receptors (nAChRs). Here, we characterized and cloned the full length of the nAChR ß1 subunit (BTß1) in B. tabaci and confirmed the consistency of BTß1 in B. tabaci MEAM1 and MED. Expression levels of BTß1 in different developmental stages and body parts of adults were investigated and compared in B. tabaci MED. dsRNA was prepared to knock down BTß1 in adult B. tabaci and significantly decreases the susceptibility to five neonicotinoid insecticides, including imidacloprid, clothianidin, thiacloprid, nitenpyram, and dinotefuran. This study indicated BTß1 as a notable site influencing the susceptibility of B. tabaci to neonicotinoids.
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Hemípteros , Inseticidas , Receptores Nicotínicos , Animais , Inseticidas/toxicidade , Inseticidas/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Resistência a Inseticidas/genética , Neonicotinoides/metabolismo , Nitrocompostos/farmacologia , Nitrocompostos/metabolismoRESUMO
Thiamethoxam has been used as a major insecticide to control the B-biotype sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Due to its excessive use, a high level of resistance to thiamethoxam has developed worldwide over the past several years. To better understand the molecular mechanisms underlying this resistance in B. tabaci, gene profiles between the thiamethoxam-resistant and thiamethoxam-susceptible strains were investigated using the suppression subtractive hybridization (SSH) library approach. A total of 72 and 52 upand down-regulated genes were obtained from the forward and reverse SSH libraries, respectively. These expressed sequence tags (ESTs) belong to several functional categories based on their gene ontology annotation. Some categories such as cell communication, response to abiotic stimulus, lipid particle, and nuclear envelope were identified only in the forward library of thiamethoxam-resistant strains. In contrast, categories such as behavior, cell proliferation, nutrient reservoir activity, sequence-specific DNA binding transcription factor activity, and signal transducer activity were identified solely in the reverse library. To study the validity of the SSH method, 16 differentially expressed genes from both forward and reverse SSH libraries were selected randomly for further analyses using quantitative realtime PCR (qRT-PCR). The qRT-PCR results were fairly consistent with the SSH results; however, only 50% of the genes showed significantly different expression profiles between the thiamethoxam-resistant and thiamethoxam-susceptible whiteflies. Among these genes, a putative NAD-dependent methanol dehydrogenase was substantially over-expressed in the thiamethoxamresistant adults compared to their susceptible counterparts. The distributed profiles show that it was highly expressed during the egg stage, and was most abundant in the abdomen of adult females.
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Perfilação da Expressão Gênica/métodos , Genes de Insetos , Hemípteros/genética , Inseticidas/farmacologia , Nitrocompostos/farmacologia , Oxazinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Tiazóis/farmacologia , Animais , Etiquetas de Sequências Expressas , Hemípteros/efeitos dos fármacos , Resistência a Inseticidas , Larva/efeitos dos fármacos , Larva/genética , Masculino , Neonicotinoides , Óvulo/efeitos dos fármacos , TiametoxamRESUMO
HLA-C*03:597 differs from HLA-C*03:03:01:01 by a single non-synonymous nucleotide substitution in exon 5 (922 A>G).
Assuntos
Antígenos HLA-C , Nucleotídeos , Alelos , China , Antígenos HLA-C/genética , Humanos , Análise de Sequência de DNARESUMO
OBJECTIVE: To investigate the clinical features of multicentric reticulohistiocytosis (MRH). METHODS: The clinical manifestations, laboratory examination results and histologic characteristics of eleven patients with MRH were collected and compared with those of 33 patients with rheumatoid arthritis. RESULTS: In total, 72.7% of the MRH patients were women. The median age was 46 years (range 33-84 years). Diagnosed by specific pathologic features, all MRH patients exhibited cutaneous involvement. The dorsa of the hands, arms, face and auricle were the most commonly affected areas. Nodules were also located on the legs, scalp, trunk, neck, and even the hypoglossis and buccal mucosa. Ten MRH patients (90.9%) had symmetric polyarthritis. Compared with rheumatoid arthritis (RA) patients, MRH patients were more likely to have distal interphalangeal joint (DIP) involvement (63.6% vs 24.2%, P = 0.017) and less likely to have elbow (36.4% vs 72.7%, P = 0.003), ankle (45.5% vs 93.9%, P < 0.001) and metacarpophalangeal joint (MCP) (36.4% vs 78.8%, P = 0.009) involvement. Positivity for rheumatoid factor (RF) (36.4% vs 84.6%, P = 0.001) and anti-CCP antibody (9.1% vs 81.8%, P = 0.000), as well as the median RF titer [43.8 (31.7-61.0) vs 175.4 (21.3-940.3), P = 0.021], in MRH patients was lower than in RA patients. Elevation of the erythrocyte sedimentation rate (ESR) was also less common in MRH patients than in RA patients (36.4% vs 72.7%, P = 0.030). After treatment with median- to large-dose corticosteroids and disease-modifying antirheumatic drugs, 8 patients achieved complete remission and 2 patients partial remission (skin lesions ameliorated, joint lesions not ameliorated). CONCLUSION: Always pathologically diagnosed, MRH is a systemic disease involving RA-like erosive polyarthritis and a specific distribution of skin nodules characterized by "coral beads". More DIP involvement and less elbow, ankle and MCP involvement are seen in MRH than in RA. In addition, less positivity and lower-titer RF, uncommon presence of anti-CCP antibodies and ESR elevation may be helpful to distinguish MRH from RA.
Assuntos
Artrite Reumatoide , Histiocitose de Células não Langerhans , Dermatopatias , Corticosteroides/uso terapêutico , Anticorpos Antiproteína Citrulinada/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Histiocitose de Células não Langerhans/diagnóstico , Histiocitose de Células não Langerhans/tratamento farmacológico , Histiocitose de Células não Langerhans/patologia , HumanosRESUMO
Background: Thymic neuroendocrine neoplasms (Th-NENs) are extremely rare. Th-NENs are divided into four pathological subtypes: typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC). The latter three subtypes are highly aggressive with poor prognosis. There are limited reports on the optimal surgical strategies for Th-NENs. This study aims to report a case series of Th-NENs after surgical treatment and review the literatures. Methods: We report a case series of five patients diagnosed with Th-NENs and summarize their clinical characteristics. Literatures related to surgical treatment of Th-NENs were reviewed. Results: There were three males and two females, and mean age was 53.6 years. No myasthenia gravis or neuroendocrine symptoms were found. Three patients were diagnosed with AC and the other two were diagnosed with LCNEC. Two patients were stage II-b, one patient was stage III-a, and two patients were stage IV-b. One patient received preoperative chemotherapy, one patient received preoperative chemoradiotherapy, and three patients underwent surgery directly. Two patients underwent extended thymectomy via video-assisted thoracoscopic surgery (VATS), two patients underwent extended thymectomy via median sternotomy, and one patient underwent resection of anterior mediastinal tumor, sternal metastases, superior vena cava and partial right atrium via median sternotomy and cardiopulmonary bypass. R0 resection was achieved in 80% (4/5) of patients. There was no postoperative 90-day complication and death. One patient had no recurrence. One patient had lymph node metastases and was still alive after somatostatin analogue therapy. One patient had no recurrence of Th-NENs but died of other tumors. Two patients had distant metastases. Median overall survival (mOS) was 49 (range, 4-134) months. A total of 22 original studies related to surgical treatment of Th-NENs were retrieved. Conclusions: Th-NENs is a very rare and extremely aggressive malignancy. Early diagnosis and surgical resection are the most important methods to improve prognosis. Radical resection and lymph node dissection are recommended for accurate staging and better prognosis. Currently, there are few clinical data on Th-NENs and several important surgical issues remain unresolved. In the future, multi-center, large-sample database and clinical studies are urgently needed to explore better treatment modality.
RESUMO
Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). QingreHuoxue treatment (QingreHuoxue decoction [QRHXD]/QingreHuoxue external preparation [QRHXEP]) is a Chinese medicine treatment for RA. To date, very few studies have compared the long-term effects of QRHXD with those of conventional disease-modifying antirheumatic drugs on RA disease activity and radiological progression. QRHXD delayed the radiological progression and showed long-term clinical efficacy of RA. In clinical experiments, the clinical evidence of delaying the radiological progression of RA patients was obtained. A portion of the patients who participated in the "Traditional Chinese Medicine QingreHuoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis" study were followed up for 52 weeks, and intention-to-treat (ITT) and compliance protocol (PP) analyses were used to collect and compare the clinical indicators and imaging data between baseline and week 52. Two radiologists who were blind to treatment scored the images independently. Of the 468 subjects, 141 completed the 52-week follow-up. There were no significant differences among the three groups: the traditional Chinese medicine comprehensive treatment group, the Western medicine treatment group, and the integrated traditional Chinese and Western medicine treatment group. There were no differences in the total Sharp score, joint space stenosis score, and joint erosion score at baseline or 52 weeks. In the comparison of the estimated annual radiographic progression (EARP) and the actual annual Sharp total score changes among the three groups, the actual changes were much lower than the EARP at baseline. The radiological progress in all three groups was well controlled. Results of the ITT and PP data sets showed that the disease activity score 28 level of the three groups at 52 weeks was significantly lower than that at baseline. During the 52-week treatment period, the clearance of heat and promotion of blood circulation controlled disease activity and delayed the radiological progress of active RA.
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BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION: Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.