RESUMO
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by multilineage immune dysregulation, which subsequently causes inflammation, fibrosis, and even cirrhosis of liver. Due to the limitation of traditional assays, the local hepatic immunopathogenesis of PBC has not been fully characterized. Here, we utilize single-cell RNA sequencing technology to depict the immune cell landscape and decipher the molecular mechanisms of PBC patients. We reveal that cholangiocytes and hepatic stellate cells are involved in liver inflammation and fibrosis. Moreover, Kupffer cells show increased levels of inflammatory factors and decreased scavenger function related genes, while T cells exhibit enhanced levels of inflammatory factors and reduced cytotoxicity related genes. Interestingly, we identify a liver-resident Th1-like population with JAK-STAT activation in the livers of both PBC patients and murine PBC model. Finally, blocking the JAK-STAT pathway alleviates the liver inflammation and eliminates the liver-resident Th1-like cells in the murine PBC model. In conclusion, our comprehensive single-cell transcriptome profiling expands the understanding of pathological mechanisms of PBC and provides potential targets for the treatment of PBC in patients.
Assuntos
Janus Quinases , Cirrose Hepática Biliar , Fígado , Fatores de Transcrição STAT , Análise de Célula Única , Células Th1 , Animais , Análise de Célula Única/métodos , Células Th1/imunologia , Humanos , Fígado/patologia , Fígado/metabolismo , Fígado/imunologia , Camundongos , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/patologia , Cirrose Hepática Biliar/metabolismo , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/genética , Janus Quinases/metabolismo , Janus Quinases/genética , Modelos Animais de Doenças , Análise de Sequência de RNA/métodos , Camundongos Endogâmicos C57BL , Feminino , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/imunologia , Células Estreladas do Fígado/patologia , Células de Kupffer/metabolismo , Células de Kupffer/imunologia , Inflamação/genética , Inflamação/patologia , Inflamação/metabolismo , Transdução de Sinais , Transcriptoma , Perfilação da Expressão Gênica , MasculinoRESUMO
A type of colorectal cancer (CRC)ï¼Colitis-associated colorectal cancer (CAC)ï¼ is closely associated with chronic inflammation and gut microbiota dysbiosis. Berberine (BBR) has a long history in the treatment of intestinal diseases, which has been reported to inhibit colitis and CRC. However, the mechanism of its action is still unclear. Here, this study aimed to explore the potential protective effects of BBR on azoxymethane (AOM)/dextransulfate sodium (DSS)-induced colitis and tumor mice, and to elucidate its potential molecular mechanisms by microbiota, genes and metabolic alterations. The results showed that BBR inhibited the gut inflammation and improved the function of mucosal barrier to ameliorate AOM/DSS-induced colitis. And BBR treatment significantly reduced intestinal tumor development and ki-67 expression of intestinal tissue along with promoted apoptosis. Through microbiota analysis based on the 16â¯S rRNA gene, we found that BBR treatment improved intestinal microbiota imbalance in AOM/DSS-induced colitis and tumor mice, which were characterized by an increase of beneficial bacteria, for instance Akkermanisa, Lactobacillus, Bacteroides uniformis and Bacteroides acidifaciens. In addition, transcriptome analysis showed that BBR regulated colonic epithelial signaling pathway in CAC mice particularly by tryptophan metabolism and Wnt signaling pathway. Notably, BBR treatment resulted in the enrichment of amino acids metabolism and microbiota-derived SCFA metabolites. In summary, our research findings suggest that the gut microbiota-amino acid metabolism-Wnt signaling pathway axis plays critical role in maintaining intestinal homeostasis, which may provide new insights into the inhibitory effects of BBR on colitis and colon cancer.
Assuntos
Azoximetano , Berberina , Neoplasias Associadas a Colite , Colite , Sulfato de Dextrana , Microbioma Gastrointestinal , Metabolômica , Transcriptoma , Berberina/farmacologia , Berberina/uso terapêutico , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Camundongos , Azoximetano/toxicidade , Colite/microbiologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Neoplasias Associadas a Colite/microbiologia , Neoplasias Associadas a Colite/tratamento farmacológico , Neoplasias Associadas a Colite/patologia , Masculino , Camundongos Endogâmicos C57BL , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/tratamento farmacológico , Disbiose , Modelos Animais de DoençasRESUMO
PURPOSE: The evidence of apatinib plus immune checkpoint inhibitors (ICIs) and transarterial chemoembolization (TACE) for treating advanced hepatocellular carcinoma (HCC) is limited. This study aimed to compare the treatment efficacy and safety of apatinib plus ICIs and TACE with apatinib plus TACE in these patients. METHODS: This study retrospectively enrolled 90 patients with advanced HCC treated with apatinib plus TACE (A-TACE group, n = 52) or apatinib plus ICIs and TACE (IA-TACE group, n = 38). RESULTS: The objective response rate was numerically higher in IA-TACE group compared with A-TACE group without statistical significance (57.9% vs. 36.5%, P = 0.055). Disease control rate was not different between groups (86.8% vs. 76.9%, P = 0.248). Progression-free survival (PFS) was improved in IA-TACE group compared with A-TACE group (P = 0.018). The median PFS (95% confidence interval) was 12.5 (8.7-16.3) months in IA-TACE group and 8.5 (5.6-11.4) months in A-TACE group. Overall survival (OS) was also prolonged in IA-TACE group compared with A-TACE group (P = 0.007). The median OS (95% confidence interval) was 21.1 (15.8-26.4) months in IA-TACE group and 14.3 (11.5-17.1) months in A-TACE group. By multivariate Cox regression model, IA-TACE was independently associated with prolonged PFS (hazard ratio = 0.539, P = 0.038) and OS (hazard ratio = 0.447, P = 0.025). Most adverse events were not different between groups. Only the incidence of reactive cutaneous capillary endothelial proliferation was higher in IA-TACE group compared with A-TACE group (10.5% vs. 0.0%, P = 0.029). CONCLUSION: Apatinib plus ICIs and TACE may be an effective and safe treatment for patients with advanced HCC, but further large-scale studies are needed for verification.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Feminino , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Resultado do TratamentoRESUMO
Background: The causative relationship between chronic rhinosinusitis (CRS) and depression remains unclear. Herein we employed Mendelian randomization (MR) coupled with single-cell analysis to investigate the causality between CRS and depression. Methods: Data pertaining to CRS and depression were mined from the genome-wide association study database, and a single-cell dataset was sourced from the literature. To explore causality, we conducted bidirectional MR analysis using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW representing the most important method. Further, sensitivity analysis was performed to evaluate the robustness of MR analysis results. Candidate genes were analyzed via single-cell combined MR analysis. Results: Forward MR analysis indicated depression as a risk factor for CRS when depression was the exposure factor and CRS was the outcome (OR = 1.425, P < 0.001). Reverse MR analysis revealed the same positive relationship between CRS and depression when CRS was the exposure factor and depression was the outcome (OR = 1.012, P = 0.038). Sensitivity analysis validated the robustness of bidirectional MR analysis results. Ten cell types (endothelial, ciliated, basal, myeloid, mast, apical, plasma, glandular, fibroblast, and T cells) were identified in the single-cell dataset. The network of receptor-ligand pairs showed that in normal samples, cell-cell interactions were present among various cell types, such as epithelial, mast, myeloid, and endothelial cells. In contrast, CRS samples featured only one specific receptor-ligand pair, confined to myeloid cells. TCF4 and MEF2C emerged as potentially crucial for CRS-associated depression development. Conclusions: Our findings suggest a bidirectional causal relationship between CRS and depression, offering a new perspective on the association between CRS and depression.
RESUMO
Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease ï¼N-ERDï¼ is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis ï¼CRSï¼, asthma, and intolerance to cyclooxygenase 1 ï¼COX-1ï¼ inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.
Assuntos
Anti-Inflamatórios não Esteroides , Humanos , Anti-Inflamatórios não Esteroides/efeitos adversos , China , Rinite/diagnóstico , Rinite/terapia , Rinite/induzido quimicamente , Sinusite/diagnóstico , Sinusite/terapia , Sinusite/tratamento farmacológico , Consenso , Asma/diagnóstico , Asma/tratamento farmacológico , Doença CrônicaRESUMO
Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.
RESUMO
OBJECTIVES: To investigate the basic characteristics of patients with diffuse large B-cell lymphoma (DLBCL) and whether hepatitis B surface antigen positive (HBsAg [+]) affects the survival of patients with DLBCL. METHODS: The study was carried out at Affiliated Hospital of Hebei University, Baoding, China, including 602 DLBCL cases from January 2011 to December 2021. We analyzed patients' general clinical data and applied multivariate and univariate Cox analyses to assess the factors influencing their survival times. RESULTS: The HBsAg(+) and HBsAg(-) groups comprised 154 (25.6%) and 448 (74.4%) of the 602 cases, respectively. HBsAg(+) cases tended to be later-stage (III-IV) with higher international prognostic index (IPI) points (3-5) and a greater tendency toward B symptoms, impaired liver function, and recurrence than HBsAg(-) cases (all p<0.05). After follow-up, 194 (32.2%) patients died. The median overall survival (OS) and 5-year OS rates in the HBsAg(+) and HBsAg(-) groups were 16.5 months (42%) and 35 months (63%), respectively. Cox analyses indicated that HBsAg(+) affected the prognosis of DLBCL cases (HR=1.46, 95%CI=1.07-1.99, p=0.017). CONCLUSION: The HBsAg(+) seems to be an independent hazard factor for the worse prognosis of DLBCL patients; hence, a focus on these patients in clinic is required.
Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B/complicações , Hepatite B/epidemiologia , Adulto , Idoso , Prognóstico , Taxa de Sobrevida , China/epidemiologia , Adulto Jovem , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou mais , Estadiamento de NeoplasiasAssuntos
Bibliometria , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Neoplasias Nasofaríngeas/cirurgia , Neoplasias Nasofaríngeas/patologia , Carcinoma Nasofaríngeo/cirurgia , Carcinoma Nasofaríngeo/patologia , Recidiva Local de Neoplasia/epidemiologia , Fatores de TempoRESUMO
Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a notable role in the oncogenesis of digestive tract tumors. Typically activated by pro-inflammatory cytokines, it regulates important biological processes, such as cell growth, differentiation, apoptosis, immune responses, and inflammation. The aberrant activation of this pathway manifests in different forms, including mutations in JAKs, overexpression of cytokine receptors, and sustained STAT activation, and contributes to promoting the malignant characteristics of cancer cells, including uncontrolled proliferation, resistance to apoptosis, enhanced invasion and metastasis, angiogenesis, acquisition of stem-like properties, and drug resistance. Numerous studies have shown that aberrant activation of the JAK-STAT pathway is closely related to the development and progression of digestive tract tumors, contributing to tumor survival, angiogenesis, changes in the tumor microenvironment, and even immune escape processes. In addition, this signaling pathway also affects the sensitivity of digestive tract tumors to chemotherapy and targeted therapy. Therefore, it is crucial to comprehensively understand the oncogenic mechanisms underlying the JAK-STAT pathway in order to develop effective therapeutic strategies against digestive tract tumors. Currently, several JAK-STAT inhibitors are undergoing clinical and preclinical trials as potential treatments for various human diseases. However, further investigation is required to determine the role of this pathway, as well as the effectiveness and safety of its inhibitors, especially in the context of digestive tract tumors. In this review, we provide an overview of the structure, classic activation, and negative regulation of the JAK-STAT pathway. Furthermore, we discuss the pathogenic mechanisms of JAK-STAT signaling in different digestive tract tumors, with the aim of identifying potential novel therapeutic targets. Video Abstract.
Assuntos
Neoplasias Gastrointestinais , Janus Quinases , Humanos , Janus Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Microambiente TumoralRESUMO
BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1- NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.
Assuntos
Hepatite B Crônica , Humanos , Antivirais , Interferon-alfa , Transcriptoma , Análise de Sequência de RNA , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , DNA ViralRESUMO
Aspiration pneumonitis is an inflammatory lung disease caused by the inhalation of oropharyngeal secretions colonized by pathogenic bacteria. Accurate diagnosis of aspiration pneumonitis can be challenging, and cerebrospinal fluid (CSF) rhinorrhea is often overlooked as a rare cause of aspiration. In this case report, we present the case of a 48-year-old male patient who experienced right-sided nasal flow of clear watery secretions for 6 months, accompanied by a dry cough as the major symptom. Through comprehensive assessment of clinical symptoms, sinus imaging, nasal endoscopy, and relevant laboratory testing, a presumptive diagnosis of traumatic cribriform plate fracture with CSF rhinorrhea was made. Chest imaging revealed flocculent ground glass shadows in the bilateral lungs. After ruling out viral pneumonia, nasal endoscopic repair of the skull base defect was performed. The patient's dry cough and rhinorrhea symptoms resolved within 1 week after surgery, and the pneumonia showed significant improvement and complete resolution within 2 weeks postoperatively. Despite the absence of characteristic symptoms and evident inhalation factors, chronic CSF rhinorrhea caused by the cribriform plate fracture was ultimately identified as the primary etiology of the patient's aspiration pneumonitis. This rare case highlights the importance of considering traumatic CSF rhinorrhea as an uncommon cause of aspiration, which can enhance physicians' awareness and focus on the less-common etiologies of aspiration. Such awareness can contribute to more accurate diagnosis and early operative intervention, particularly in the context of the coronavirus disease 2019 pandemic.
RESUMO
Background: The impact of lymphocyte-C-reactive protein ratio (LCR) on clinical outcomes has been reported in liver cancer such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), but the results remain inconsistent. Methods: We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for relevant studies evaluating the association of LCR with survival outcomes and clinicopathological parameters. Results: Eight studies with 4316 patients were included in this meta-analysis. Low LCR was significantly associated with poor overall survival, disease-free survival/relapse-free survival and disease progression clinicopathological parameters in patients with HCC or ICC. Conclusion: Low pretreatment LCR was an adverse prognostic indicator in patients with HCC or ICC. In addition, it was correlated with clinicopathological parameters indicating a higher stage of malignancy.
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Prognóstico , Proteína C-Reativa , Colangiocarcinoma/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Linfócitos/patologiaRESUMO
Bell's palsy is an idiopathic, acute, unilateral peripheral facial nerve paralysis, where incomplete or failed recovery causes substantial social and psychological stress to the patient, seriously influencing their quality of life and social activities. We conducted a bibliometric investigation of the knowledge structure and frontier hotspots in Bell's palsy research. Bell's palsy publications between 2002 and 2021 were retrieved from Web of Science. CiteSpace, VOSviewer, and an online bibliometric platform were used for visual, burst, citation, and co-occurrence analyses, respectively. A total of 1,378 publications were included. The annual Bell's palsy publication output followed an upward trend from 2002 to 2021. The USA and Harvard University published the most Bell's palsy research articles. Yeo SG and Otology & Neurotology were the most prolific author and journal, respectively, on Bell's palsy. The results suggested that Bell's palsy research hotspots focused on rehabilitating facial nerve function and improving prognosis, and combining specific therapies (acupuncture) would be of future interest. The cited references timeline revealed that Bell's palsy following COVID-19 vaccination was an emerging research hotspot. The bibliometric analysis demonstrated that the USA dominates Bell's palsy research and that rehabilitating facial nerve function and prognosis were research hotspots. Emerging mechanistic studies mainly focused on Bell's palsy following COVID-19 vaccination. Our findings could be a reliable source for global scholars to rapidly identify research hotspots and potential research directions and frontiers.
RESUMO
Background and Aims: A functional cure, or hepatitis B virus (HBV) surface antigen (HBsAg) loss, is difficult to achieve in patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B. The HBV vaccine and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to help reduce HBsAg levels and promote HBsAg loss. In this prospective randomized trial, we evaluated HBsAg loss in patients receiving pegylated interferon-α2b (PEGIFN-α2b) and tenofovir disoproxil fumarate (TDF), with and without GM-CSF and HBV vaccination. Methods: A total of 287 patients with HBeAg positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment were assigned randomly to three treatment groups for 48 weeks, TDF alone (control), PEGIFN-α2b + TDF, and PEGIFN-α2b + TDF + GM-CSF + HBV vaccine. The primary endpoints were the proportions of patients with HBsAg loss and seroconversion at 48 and 72 weeks. Results: The cumulative HBsAg loss rates in the control, PEGIFN-α2b + TDF, and PEGIFN-α2b + TDF + GM-CSF + HBV vaccine groups at week 48 were 0.0%, 28.3%, and 41.1%, respectively. The cumulative HBsAg seroconversion rates in these groups at week 48 were 0.0%, 21.7%, and 33.9%, respectively. Multivariate regression analysis showed that GM-CSF use plus HBV vaccination was significantly associated with HBsAg loss (p=0.017) and seroconversion (p=0.030). Conclusions: In patients with HBeAg-positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment, immunomodulatory/antiviral treatment regimens effectively improved HBsAg loss, and the regimen including GM-CSF and HBV vaccination was most effective.
RESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
Assuntos
Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
BACKGROUND: Vestibular schwannoma is the most common benign tumor in the pontocerebellar horn region. As the tumor grows, it often causes severe hearing loss due to compression of nearby nerves, resulting in a lower quality of life. This study examined vestibular schwannoma-related research through a bibliometric and visualization analysis, and it explored current trends and research hot spots. METHODS: Research related to vestibular schwannoma published from 2002 to 2021 was searched using the Web of Science Core Collection. The processing and visualization analysis of the data were conducted using R software, VOSviewer, and CiteSpace. RESULTS: A total of 3,909 publications were included in this study, and an overall increasing trend in the annual output of publications was found. The United States, Germany, and the United Kingdom were the most prolific countries, publishing the most articles. Germany had the most frequent international cooperation and the highest centrality score. The Mayo Clinic, University of California, and Harvard University were the three most productive institutions. Otology & Neurotology was the most prolific journal, and MJ Link was the most productive and highest scoring author for centrality. Current frontier topics mainly focused on "hearing preservation" and "radiosurgery". A map of trends in topics and a thematic graph revealed that "hearing loss", "vertigo", "magnetic resonance imaging", "radiosurgery", "stereotactic radiosurgery", and "gamma knife" were the topics of focus of current discussions. CONCLUSION: Hearing preservation is a current frontier topic in this area. Radiosurgery has a promising future in the field of vestibular schwannoma, and stereotactic radiosurgery is a focus of global attention. Bibliometric and visualization analysis offer a unique and objective perspective of the field of vestibular schwannoma and may assist scholars in the identification of new research directions.
RESUMO
OBJECTIVES: To investigate the clinicopathological features, insulin resistance (IR) status, and the outcomes of populations with diffuse large B-cell lymphoma (DLBCL) of the breast. METHODS: This study was carried out at Department of Haematology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, that included 32 patients treated form January 2009 to June 2020. The primary endpoints of the study were their survival time. RESULTS: There were 32 patients in the study. A total of 18 (56.2%) patients had IR. In terms of treatment, 31.2% were treated with surgery, most (93.8%) received chemotherapy, and 25% received radiotherapy and intrathecal therapy. Univariate analysis indicated the patients with stages III-IV, B symptoms, tumour recurrence, PAX5 positivity, and c-MYC positivity showed a shorter survival time (p<0.05). The overall survival and progression-free survival (PFS) rates in IR group were shorter than those without IR, but there was no statistical difference (p>0.05). Multivariate analysis indicated that tumour recurrence shortened the 5-year PFS of the patients (p=0.037). CONCLUSION: Primary DLBCL of the breast was very rare; more than half of the cases had IR, but IR did not affect their survival.
Assuntos
Resistência à Insulina , Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Prognóstico , Recidiva Local de Neoplasia/epidemiologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , RituximabRESUMO
Background: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with a very high mortality rate, and a large number of studies have confirmed the correlation between inflammation and malignant tumors and the involvement of inflammation-related regulators in the progression of HNSCC. However, a prognostic model for HNSCC based on genes involved in inflammatory factors has not been established. Methods: First, we downloaded transcriptome data and clinical information from patients with head and neck squamous cell carcinoma from TCGA and GEO (GSE41613) for data analysis, model construction, and differential gene expression analysis, respectively. Genes associated with inflammatory factors were screened from published papers and intersected with differentially expressed genes to identify differentially expressed inflammatory factor-related genes. Subgroups were then typed according to differentially expressed inflammatory factor-related genes. Univariate, LASSO and multivariate Cox regression algorithms were subsequently applied to identify prognostic genes associated with inflammatory factors and to construct prognostic prediction models. The predictive performance of the model was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic curve (ROC). Subsequently, we analyzed differences in immune composition between patients in the high and low risk groups by immune infiltration. The correlation between model genes and drug sensitivity (GSDC and CTRP) was also analyzed based on the GSCALite database. Finally, we examined the expression of prognostic genes in pathological tissues, verifying that these genes can be used to predict prognosis. Results: Using univariate, LASSO, and multivariate cox regression analyses, we developed a prognostic risk model for HNSCC based on 13 genes associated with inflammatory factors (ITGA5, OLR1, CCL5, CXCL8, IL1A, SLC7A2, SCN1B, RGS16, TNFRSF9, PDE4B, NPFFR2, OSM, ROS1). Overall survival (OS) of HNSCC patients in the low-risk group was significantly better than that in the high-risk group in both the training and validation sets. By clustering, we identified three molecular subtypes of HNSCC carcinoma (C1, C2, and C3), with C1 subtype having significantly better OS than C2 and C3 subtypes. ROC analysis suggests that our model has precise predictive power for patients with HNSCC. Enrichment analysis showed that the high-risk and low-risk groups showed strong immune function differences. CIBERSORT immune infiltration score showed that 25 related and differentially expressed inflammatory factor genes were all associated with immune function. As the risk score increases, specific immune function activation decreases in tumor tissue, which is associated with poor prognosis. We also screened for susceptibility between the high-risk and low-risk groups and showed that patients in the high-risk group were more sensitive to talazoparib-1259, camptothecin-1003, vincristine-1818, Azd5991-1720, Teniposide-1809, and Nutlin-3a (-) -1047.Finally, we examined the expression of OLR1, SCN1B, and PDE4B genes in HNSCC pathological tissues and validated that these genes could be used to predict the prognosis of HNSCC. Conclusion: In this experiment, we propose a prognostic model for HNSCC based on inflammation-related factors. It is a non-invasive genomic characterization prediction method that has shown satisfactory and effective performance in predicting patient survival outcomes and treatment response. More interdisciplinary areas combining medicine and electronics will be explored in the future.
RESUMO
Background: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vestibular vertigo. Although BPPV is benign, its underlying mechanisms are complicated, and patients diagnosed with BPPV are significantly affected by it in their daily lives. Hence, this study's purpose was to investigate global trends and frontiers in the field of BPPV. Methods: We searched the research literature published from 2002 to 2021 on BPPV using two databases from the Web of Science Core Collection, and we conducted a bibliometric and visualization analysis. Bibliometric tools were used to perform co-authorship, co-citation, and co-occurrence analyses of countries or regions, institutions, authors, journals, keywords, and references. Results: In all, 1,419 publications from 4,594 authors, 1,542 institutions, and 65 countries or regions with 71 subject categories were included in the study. The number of articles increased gradually from 2002 to 2021. Seoul National University, the University of Munich, and Osaka University were among the leading institutions with the most publications, while United States of America, South Korea, and China were the leading countries. JS Kim was the most prolific author, Otology & Neurotology was the most prolific journal, and Otorhinolaryngology was the most published subject category. The five most frequently occurring keywords were BPPV, vertigo, dizziness, nystagmus, and management and the top research hot spots were osteoporosis and vitamin D. Conclusion: This study systematically analyzed trends in global scientific research on BPPV. The academic understanding of BPPV has improved significantly over the last two decades, with osteoporosis and vitamin D the two main research hot spots in the field of BPPV in recent years. These findings provide direction for current research to grasp the trends and research frontiers of current research.
RESUMO
OBJECTIVES: This study aimed to investigate the differences between elderly patients hospitalized with COVID-19 or influenza A H1N1 virus infections. METHODS: We contrasted two absolute groups of patients (age ≥60 years) infected with either COVID-19 (n = 222) or influenza A H1N1 virus infections (n = 96). Propensity score matching was used to reduce the imbalance between the two matched groups. The clinical features, imaging presentations, therapies, and prognosis data were compared between the two groups. RESULTS: The patients with influenza showed higher proportions of cough, expectoration, fatigue, and shortness of breath. Higher counts of lymphocytes, hemoglobin, and creatine kinase and lower counts of white blood cells, neutrophils, blood urea nitrogen, and C-reactive protein were found in the patients with COVID-19. Regarding the imaging characteristics, bilateral pneumonia was the most abnormal pattern in the two groups of patients. The incidence of acute respiratory distress syndrome or death was lower among the patients with COVID-19. CONCLUSION: The clinical manifestations of patients with COVID-19 are more concealed than those of patients with influenza. Fewer symptoms of sputum production, fatigue, and shortness of breath, combined with lower counts of white blood cells, neutrophils, and C-reactive protein are the possible predictive factors of COVID-19 among elderly patients.