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Treating Multiple sclerosis (MS), a well-known immune-mediated disease characterized by axonal demyelination, is challenging due to its complex causes. Naphthalenedione, present in numerous plants, is being explored as a potential medicine for MS due to its immunomodulatory properties. However, its effects on lymphocytes can vary depending on factors such as the specific compound, concentration, and experimental conditions. In this study, we aim to explore the therapeutic potential of 2-bromo-1,4-naphthalenedione (BrQ), a derivative of naphthalenedione, in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and to elucidate its underlying mechanisms. We observed that mice treated with BrQ exhibited reduced severity of EAE symptoms, including lower clinical scores, decreased leukocyte infiltration, and less extensive demyelination in central nervous system. Furthermore, it was noted that BrQ does not directly affect the remyelination process. Through cell-chat analysis based on bulk RNA-seq data, coupled with validation of flow analysis, we discovered that BrQ significantly promotes the expansion of CD8+ T cells and their interactions with other immune cells in peripheral immune system in EAE mice. Subsequent CD8+ T cell depletion experiments confirmed that BrQ alleviates EAE in a CD8+ T cell-dependent manner. Mechanistically, expanded CD8+ cells were found to selectively reduce antigen-specific CD4+ cells and subsequently inhibit Th1 and Th17 cell development in vivo, ultimately leading to relief from EAE. In summary, our findings highlight the crucial role of BrQ in modulating the pathogenesis of MS, suggesting its potential as a novel drug candidate for treating MS and other autoimmune diseases.
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Linfócitos T CD8-Positivos , Encefalomielite Autoimune Experimental , Camundongos Endogâmicos C57BL , Células Th1 , Células Th17 , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Camundongos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Feminino , Naftalenos/farmacologia , Naftalenos/uso terapêutico , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: As comprehensive surgical management for gastric cancer becomes increasingly specialized and standardized, the precise differentiation between ≤T1 and ≥T2 gastric cancer before endoscopic intervention holds paramount clinical significance. OBJECTIVE: To evaluate the diagnostic efficacy of contrast-enhanced gastric ultrasonography in differentiating ≤T1 and ≥T2 gastric cancer. METHODS: PubMed, Web of Science, and Medline were searched to collect studies published from January 1, 2000 to March 16, 2023 on the efficacy of either double contrast-enhanced gastric ultrasonography (D-CEGUS) or oral contrast-enhanced gastric ultrasonography (O-CEGUS) in determining T-stage in gastric cancer. The articles were selected according to specified inclusion and exclusion criteria, and the quality of the included literature was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale. Meta-analysis was performed using Stata 12 software with data from the 2 × 2 crosslinked tables in the included literature. RESULTS: In total, 11 papers with 1124 patients were included in the O-CEGUS analysis, which revealed a combined sensitivity of 0.822 (95% confidence interval [CI] = 0.753-0.875), combined specificity of 0.964 (95% CI = 0.925-0.983), and area under the summary receiver operating characteristic (sROC) curve (AUC) of 0.92 (95% CI = 0.89-0.94). In addition, five studies involving 536 patients were included in the D-CEGUS analysis, which gave a combined sensitivity of 0.733 (95% CI = 0.550-0.860), combined specificity of 0.982 (95% CI = 0.936-0.995), and AUC of 0.93 (95% CI = 0.91-0.95). According to the I2 and P values ââof the forest plot, there was obvious heterogeneity in the combined specificities of the included papers. Therefore, the two studies with the lowest specificities were excluded from the O-CEGUS and D-CEGUS analyses, which eliminated the heterogeneity among the remaining literature. Consequently, the combined sensitivity and specificity of the remaining studies were 0.794 (95% CI = 0.710-0.859) and 0.976 (95% CI = 0.962-0.985), respectively, for the O-CEDUS studies and 0.765 (95% CI = 0.543-0.899) and 0.986 (95% CI = 0.967-0.994), respectively, for the D-CEGUS studies. The AUCs were 0.98 and 0.99 for O-CEGUS and D-CEGUS studies, respectively. CONCLUSION: Both O-CEGUS and D-CEGUS can differentiate ≤T1 gastric cancer from ≥T2 gastric cancer, thus assisting the formulation of clinical treatment strategies for patients with very early gastric cancer. Given its simplicity and cost-effectiveness, O-CEGUS is often favored as a staging method for gastric cancer prior to endoscopic intervention.
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Meios de Contraste , Estadiamento de Neoplasias , Neoplasias Gástricas , Ultrassonografia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Humanos , Ultrassonografia/métodos , Sensibilidade e Especificidade , Curva ROC , Estômago/diagnóstico por imagem , Estômago/patologiaRESUMO
OBJECTIVE: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). METHODS: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. RESULTS: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74-27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27-18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. CONCLUSION: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.
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Carcinoma Papilar , Aprendizado Profundo , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Radiômica , Carcinoma Papilar/patologia , Fatores de Risco , Linfonodos/patologiaRESUMO
OBJECTIVES: The preoperative classification of pleomorphic adenomas (PMA) and Warthin tumors (WT) in the parotid gland plays an essential role in determining therapeutic strategies. This study aims to develop and validate an ultrasound-based ensemble machine learning (USEML) model, employing nonradiative and noninvasive features to differentiate PMA from WT. METHODS: A total of 203 patients with histologically confirmed PMA or WT who underwent parotidectomy from two centers were enrolled. Clinical factors, ultrasound (US) features, and radiomic features were extracted to develop three types of machine learning model: clinical models, US models, and USEML models. The diagnostic performance of the USEML model, as well as that of physicians based on experience, was evaluated and validated using receiver operating characteristic (ROC) curves in internal and external validation cohorts. DeLong's test was used for comparisons of AUCs. SHAP values were also utilized to explain the classification model. RESULTS: The USEML model achieved the highest AUC of 0.891 (95% CI, 0.774-0.961), surpassing the AUCs of both the US (0.847; 95% CI, 0.720-0.932) and clinical (0.814; 95% CI, 0.682-0.908) models. The USEML model also outperformed physicians in both internal and external validation datasets (both p < 0.05). The sensitivity, specificity, negative predictive value, and positive predictive value of the USEML model and physician experience were 89.3%/75.0%, 87.5%/54.2%, 87.5%/65.6%, and 89.3%/65.0%, respectively. CONCLUSIONS: The USEML model, incorporating clinical factors, ultrasound factors, and radiomic features, demonstrated efficient performance in distinguishing PMA from WT in the parotid gland. CLINICAL RELEVANCE STATEMENT: This study developed a machine learning model for preoperative diagnosis of pleomorphic adenoma and Warthin tumor in the parotid gland based on clinical, ultrasound, and radiomic features. Furthermore, it outperformed physicians in an external validation dataset, indicating its potential for clinical application. KEY POINTS: ⢠Differentiating pleomorphic adenoma (PMA) and Warthin tumor (WT) affects management decisions and is currently done by invasive biopsy. ⢠Integration of US-radiomic, clinical, and ultrasound findings in a machine learning model results in improved diagnostic accuracy. ⢠The ultrasound-based ensemble machine learning (USEML) model consistently outperforms physicians, suggesting its potential applicability in clinical settings.
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INTRODUCTION: Allergic rhinitis (AR) is one of the leading allergic diseases worldwide. Allergen immunotherapy (AIT) induces persistent specific allergen tolerance to achieve remission of the symptoms in AR patients. We creatively conducted the intra-cervical lymphatic immunotherapy (ICLIT) for AR patients. However, the underlying molecular mechanism of immune cell response of AIT in AR remains elusive. METHOD: To investigate the transcriptome profile in AR patients who underwent ICLIT, we comprehensively investigated the transcriptional changes in B cells from peripheral blood mononuclear cells of AR patient by single-cell RNA sequencing. Immunoglobulins and relative key gene, which influences the B cell differentiation, was demonstrated. The biomarkers' association with different types of tumors was investigated. RESULTS: Naive B cells, germinal center B cells, activated memory B cells, and memory B cells constituted the B cells subsets. The expression of IGHE, IGHGs, IGHA, IGHD, and IGHM from memory B cells was validated. Pseudotime analysis further indicated the dynamic change from the expression of the immunoglobulins in the memory B cells, suggesting that ITGB1 may contribute to the differentiation procedure of memory B cells. The cell-cell communication among these immune cells demonstrated the significantly enhanced CD23, BTLA signaling after ICLIT in AR patient. ITGB1 was upregulated in 13 tumors and downregulated in six others. High ITGB1 expression was linked to poor prognosis in eight types of tumors. ITGB1 expression showed correlations with tumor mutation burden, tissue purity, and microsatellite instability in different types of tumors. DISCUSSION: ITGB1 was demonstrated as a potential biomarker for AR patients after ICLIT and is significant in identifying immune infiltration in tumor tissue and predicting tumor prognosis.
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Neoplasias , Rinite Alérgica , Humanos , Leucócitos Mononucleares , Rinite Alérgica/genética , Rinite Alérgica/terapia , Rinite Alérgica/diagnóstico , Imunoglobulinas , Biomarcadores , Análise de Sequência de RNARESUMO
Renovascular hypertension (RVH) can induce cardiac damage that is reversible using adipose tissue-derived mesenchymal stromal/stem cells (A-MSCs). However, A-MSCs isolated from patients with obesity are less effective than lean-A-MSC in blunting hypertensive cardiomyopathy in mice with RVH. We tested the hypothesis that this impairment extends to their obese A-MSC-extracellular vesicles (EVs) progeny. MSCs were harvested from the subcutaneous fat of obese and lean human subjects, and their EVs were collected and injected into the aorta of mice 2 wk after renal artery stenosis or sham surgery. Cardiac left ventricular (LV) function was studied with MRI 2 wk later, and myocardial tissue ex vivo. Blood pressure, LV myocardial wall thickness, mass, and fibrosis that were elevated in RVH mice were suppressed only by lean EVs. Hence, human A-MSC-derived lean EVs are more effective than obese EVs in blunting hypertensive cardiac injury in RVH mice. These observations highlight impaired paracrine repair potency of endogenous MSCs in patients with obesity.NEW & NOTEWORTHY Injection of A-MSC-derived EVs harvested from patients who are lean can resolve myocardial injury in mice with experimental renovascular hypertension more effectively than A-MSC-derived EVs from patients with obesity. These observations underscore and might have important ramifications for the self-healing capacity of patients with obesity and for the use of autologous EVs as a regenerative tool.
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Vesículas Extracelulares , Hipertensão Renovascular , Humanos , Animais , Camundongos , Hipertensão Renovascular/terapia , Obesidade/complicações , Cardiomegalia , Fibrose , Células EstromaisRESUMO
To study risk factors for central lymph node metastasis (CLNM) in papillary thyroid cancer (PTC) using the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). We retrospectively analysed patients who underwent PTC surgery and central lymph node dissection at First People's Hospital of Foshan City. The clinical and ultrasonic data of the patients from 1150 cases were analysed by multivariate regression to evaluate the correlation between grayscale ultrasound (US) features, C-TIRADS score, and the classification of thyroid nodules and CLNM of PTCs. The C-TIRADS score was 3.0±1.0 in the CLNM group, which was higher than that in the non-CLNM group (p<0.001). Sex (male) (OR=1.586, 95% CI 1.232-2.042, p<0.001), age (≤45 years) (OR=1.508, 95% CI 1.184-1.919, p=0.001), location of nodes (lower pole) (OR=2.193, 95% CI 1.519-3.166, p<0.001), number (multifocal) (OR=2.204, 95% CI 1.227-2.378, p<0.001), microcalcification (OR=1.610, 95% CI 2.225-4.434, p=0.002), extrathyroidal extension (OR=2.204, 95% CI 1.941-3.843, p<0.001), maximum diameter of nodule (≥20 mm) (OR=3.211, 95% CI 2.337-4.411, p<0.001), and C-TIRADS score (OR=1.356, 95% CI 1.204-1.527, p<0.001) were PTC in independent risk factors for CLNM. The C-TIRADS score of PTC combined with the location, number, size, and ultrasound features of the lesion and the patient's sex and age are important in predicting whether they present with CLNM and provide a reference basis for the clinical formulation of a reasonable surgical treatment plan.
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Neoplasias da Glândula Tireoide , Humanos , Masculino , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/secundário , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Metástase Linfática , Fatores de RiscoRESUMO
In our large-scale study, the correlation between obstructive sleep apnea (OSA) related to rapid eye movement (REM) sleep and cardiac autonomic dysfunction was assessed by standard polysomnography (PSG). Cardiac autonomic dysfunction was evaluated by the measurement of heart rate variability (HRV). The cardiovascular disease (CVD) risk was determined using the cross-sectional prevalence of CVD and its overall 10 year risk according to the Framingham risk score (FRS). 4152 individuals were included in the study. A higher apnea-hypopnea index during REM sleep (AHIREM ) was correlated with increased CVD risk. The adjusted odds ratios (95% CIs) for CVD prevalence and its high 10 year risk in participants having severe OSA during REM sleep (AHIREM ≥30 events/h) were 1.452 (1.012-2.084) and 1.904 (1.470-2.466) in the demographic adjusted model and 1.175 (0.810-1.704) and 1.716 (1.213-2.427) in the multivariate adjusted model, respectively, compared with the group with a AHIREM of <5 events/h. Fully adjusted multivariate linear regression models showed the independent association between AHIREM and a more elevated ratio of low-frequency and high-frequency (LF/HF) and LF in normalised units [LF (n.u.)] (P = 0.042, P = 0.027 in all participants and P = 0.033, P = 0.029 in participants with AHI during non-REM sleep <5 events/h, respectively). Mediation analysis demonstrated that OSA during REM sleep and CVD risk was significantly mediated by LF/HF and LF (n.u.). OSA during REM sleep may be a marker behind CVD risk because it promotes cardiac autonomic dysfunction.
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Doenças Cardiovasculares , Apneia Obstrutiva do Sono , Humanos , Sono REM/fisiologia , Polissonografia , Estudos Transversais , China/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologiaRESUMO
Electrochemical oxidation has been demonstrated to be a useful method for removing biorefractory organic pollutants in mature landfill leachate but suffers from low efficiency in eliminating ammonium because of its resistance to being oxidized by HO⢠or free chlorine (FC) at decreased pH. Here, we propose a new bipolar membrane-electrochlorination (BPM-EC) process to address this issue. We found that the BPM-EC system was significantly superior to both the undivided and divided reactors with monopolar membranes in terms of elevated rate of ammonium removal, attenuated generation of byproducts (e.g., nitrate and chloramines), increased Faradaic efficiency, and decreased energy consumption. Mechanistic studies revealed that the integration of BPM was helpful in creating alkaline environments in the vicinity of the anode, which facilitated production of surface-bound HO⢠and FC and eventually promoted in situ generation of ClOâ¢, a crucial reactive species mainly responsible for accelerating ammonium oxidation and selective transformation to nitrogen. The efficacy of BPM-EC in treating landfill leachates with different ammonium concentrations was verified under batch and continuous-flow conditions. A kinetic model that incorporates the key parameters was developed, which can successfully predict the optimal number of BPM-EC reactors (e.g., 2 and 5 for leachates containing 589.4 ± 5.5 and 1258.1 ± 9.6 mg L-1 NH4+-N, respectively) necessary for complete removal of ammonium. These findings reveal that the BPM-EC process shows promise in treating ammonium-containing wastewater, with advantages that include effectiveness, adaptability, and flexibility.
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Compostos de Amônio , Poluentes Químicos da Água , Águas Residuárias , Compostos Orgânicos , Nitratos , Oxirredução , NitrogênioRESUMO
BACKGROUND: The use of cardiac implantable electronic devices has grown substantially over the past two decades, lead-related vascular issues are commonly encountered in clinical practice. Superior vena cava (SVC) syndrome due to pacemaker leads is an uncommon complication. Anticoagulation remains the mainstay of therapy to restore some degree of patency and relieve swelling. However, there are limited clinical trials on direct oral anticoagulants (DOACs). CASE PRESENTATION: We report a case of an 80-year-old man who developed SVC syndrome after transvenous pacemaker implantation with symptoms of obstruction that were significantly relieved after four months of DOACs. His symptoms had completely resolved nine months later. CONCLUSIONS: DOACs are effective in the treatment of SVC syndrome after pacemaker implantation, representing an important new approach. It is a very good choice for patients who do not want to undergo interventional therapy.
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Oxidative stress and a series of excessive inflammatory responses are major obstacles to neurological functional recovery after ischemic stroke. In this study, we synthesized several novel 9-phenanthranilamide derivatives and evaluated their anti-inflammatory and antioxidant activities. Among the initially screened compounds, most could strongly inhibi lipopolysaccharide (LPS)-stimulated production of IL-1ß, IL-6 and TNF-α in microglial cells. Additionally, compounds 8b, 8q, 8r and 8s significantly inhibited the production of NO, and they also had dose-dependent protective effects on PC12 neuronal cells induced by H2O2. The antineuroinflammatory effects of 8r and 8s were associated with the downregulation of LPS-induced inflammatory mediators of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and both compounds inhibited the NF-κB signaling pathway. Further examinations showed that 8s had a significant neuroprotective effect on rats with middle cerebral artery occlusion (MCAO). It decreased the infarct volume and the neurological deficit score. Overall, our results suggested that compound 8s might be a promising agent for stroke treatment.
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Antioxidantes , Fármacos Neuroprotetores , Ratos , Animais , Antioxidantes/farmacologia , Lipopolissacarídeos/farmacologia , Peróxido de Hidrogênio/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Transdução de Sinais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
PURPOSE: Mice can develop arterial damage and even atherosclerosis under intermittent hypoxia (IH); however, the specific mechanism of arterial damage induced by IH remains unclear. Hence, this research aimed to illustrate the underlying mechanism linking IH to arterial injury. MATERIALS AND METHODS: The differential gene expression of the thoracic aorta under normoxia or IH mice was analyzed utilizing RNA sequencing. Furthermore, GO, KEGG pathway, and CIBERSORT analyses were carried out. For verification of the expression of candidate genes affected by IH, quantitative RT-qPCR (qRT-PCR) was conducted. Immunohistochemical (IHC) staining revealed immune cell infiltration in the thoracic aorta. RESULTS: The thickness of the intima-media of the mouse aorta was increased, and the fiber structure was disordered under IH. Transcriptomics analysis showed that in the aorta, 1137 upregulated genes and 707 downregulated genes were affected by IH, significantly related to the activation of the immune system and cell adhesion. Furthermore, B cell infiltration around the aorta was observed under IH. CONCLUSIONS: IH might lead to structural changes in the aorta by activating the immune response and enhancing cell adhesion.
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Hipóxia , Transcriptoma , Camundongos , Animais , Transcriptoma/genética , Hipóxia/genética , Hipóxia/metabolismo , Aorta/metabolismo , Aorta Torácica , ImunidadeRESUMO
OBJECTIVES: We aimed to develop and validate a nomogram integrating clinical and sonographic characteristics for the individualized SUI risk evaluation in the early postpartum stage. METHODS: This was a prospective cross-sectional study. From June 2020 to September 2022, singleton primiparas who underwent TPUS examination at 6-8 weeks postpartum were recruited. They were divided into the training and validation cohorts at a ratio of 8:2 according to the temporal split. All subjects were interviewed before TPUS examination. Univariate and multivariate logistic analyses were performed to develop three models: the clinical, sonographic, and combined models. The ROC curve was plotted to evaluate model discrimination ability. Finally, the combined model was selected to establish the nomogram. The nomogram's discrimination, calibration, and clinical usefulness were evaluated in the training and validation cohorts. RESULTS: The performance of the combined model was better than that of the clinical and sonographic models. Six predictors (BMI, delivery mode, lateral episiotomy, SUI during pregnancy, cystocele, and bladder neck funneling) remained in the combined model. The nomogram based on the combined model had good discrimination with AUCs of 0.848 (95% CI: 0.796-0.900) and 0.872 (95% CI: 0.789-0.955) in the training and validation cohorts, respectively, and the calibration curve showed good efficiency in assessing postpartum SUI. Decision curve analysis showed that the nomogram was clinically useful. CONCLUSIONS: The nomogram based on clinical and sonographic characteristics showed good efficiency in assessing postpartum SUI risk and can be a convenient and reliable tool for individual SUI risk assessment.
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BACKGROUND: Porous cages are considered a promising alternative to high-density cages because their interconnectivity favours bony ingrowth and appropriate stiffness tuning reduces stress shielding and the risk of cage subsidence. METHODS: This study proposes three approaches that combine macroscopic topology optimization and micropore design to establish three new types of porous cages by integrating lattices (gyroid, Schwarz, body-centred cubic) with the optimized cage frame. Using these three porous cages along with traditional high-density cages, four ACDF surgical models were developed to compare the mechanical properties of facet articular cartilage, discs, cortical bone, and cages under specific loads. RESULTS: The facet joints in the porous cage groups had lower contact forces than those in the high-density cage group. The intervertebral discs in all models experienced maximum stress at the C5/6 segment. The stress distribution on the cortical bone surface was more uniform in the porous cage groups, leading to increased average stress values. The gyroid, Schwarz, and BCC cage groups showed higher average stress on the C5 cortical bone. The average stress on the surface of porous cages was higher than that on the surface of high-density cages, with the greatest difference observed under the lateral bending condition. The BCC cage demonstrated favourable mechanical stability. CONCLUSION: The new porous cervical cages satifies requirements of low rigidity and serve as a favourable biological scaffold for bone ingrowth. This study provides valuable insights for the development of next-generation orthopaedic medical devices.
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Disco Intervertebral , Doenças da Coluna Vertebral , Fusão Vertebral , Humanos , Porosidade , Análise de Elementos Finitos , Disco Intervertebral/cirurgia , Fenômenos Biomecânicos , Vértebras Cervicais/cirurgiaRESUMO
OBJECTIVE: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. METHODS: Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. CONCLUSIONS: In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Metanálise em Rede , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêuticoRESUMO
PURPOSE: To evaluate the prevalence, characteristics, and respiratory arousal threshold (ArTH) of Chinese patients with positional obstructive sleep apnea (POSA) according to the Cartwright Classification (CC) and Amsterdam Positional Obstructive Sleep Apnea Classification (APOC). METHODS: A large-scale cross-sectional study was conducted in our sleep center from 2007 to 2018 to analyze the clinical and polysomnography (PSG) data of Chinese POSA patients. Low ArTH was defined based on PSG indices. RESULTS: Of 5,748 OSA patients, 36.80% met the CC criteria, and 42.88% the APOC criteria, for POSA. The prevalence of POSA was significantly higher in women than men (40.21% and 46.52% vs. 36.13% and 42.18% for CC and APOC, respectively). Chinese POSA patients had a lower apnea hypopnea index (AHI) and lower oxygen desaturation index, shorter duration of oxygen saturation (SaO2) < 90%, and a higher mean SaO2 and higher lowest SaO2 value compared to subjects with non-positional OSA (NPOSA). More than 40% of the POSA patients had a low ArTH; the proportion was extremely high in the supine-isolated-POSA (si-POSA) group and APOC I group. In multivariate logistic regression analyses, higher mean SaO2 and lower AHI during sleep were positive predictors of POSA. CONCLUSIONS: According to the CC and APOC criteria, more than 1/3 of our Chinese subjects with OSA had POSA. Chinese POSA patients had less severe OSA and nocturnal hypoxia. Compared to NPOSA patients, significantly more patients with POSA had a low ArTH. A low ArTH may be an important endotype in the pathogenesis of POSA, especially in patients with si-POSA and APOC I. Further studies are necessary to develop personalized management strategies for POSA patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn ; No. ChiCTR1900025714 (retrospectively registered).
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Postura , Apneia Obstrutiva do Sono , Apolipoproteínas C , Nível de Alerta , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Polissonografia , Prevalência , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Decúbito DorsalRESUMO
OBJECTIVE: To determine if artificial intelligence-based modification of the Thyroid Imaging Reporting Data System (TI-RADS) would be better than the current American College of Radiology (ACR) TI-RADS for risk stratification of thyroid nodules. METHODS: A total of 2061 thyroid nodules (in 1859 patients) sampled with fine-needle aspiration or operation were retrospectively analyzed between January 2017 and July 2020. Two radiologists blinded to the pathologic diagnosis evaluated nodule features in five ultrasound categories and assigned TI-RADS scores by both ACR TI-RADS and AI TI-RADS. Inter-rater agreement was assessed by asking another two radiologists to score a set of 100 nodules independently. The reference standard was postoperative pathological or cytopathological diagnosis according to the Bethesda system. Inter-rater agreement was determined using intraclass correlation coefficient (ICC). RESULTS: AI TI-RADS assigned lower TI-RADS risk levels than ACR TI-RADS (p < 0.001) and had larger area under receiver operating characteristic curve (0.762 vs. 0.679, p < 0.001). The sensitivities of ACR TI-RADS and AI TI-RADS were similar (86.7% vs. 82.2%, p = 0.052), but specificity was higher with AI TI-RADS (70.2% vs. 49.2%, p < 0.001). AI TI-RADS downgraded 743 (48.63%) benign nodules, indicating that 328 (42.3% of 776 biopsied nodules) unnecessary fine-needle aspirations (FNA) could have been avoided. Inter-rater agreement was better with AI TI-RADS than with ACR TI-RADS (ICC, 0.808 vs. 0.861, p < 0.001). CONCLUSION: AI TI-RADS can achieve meaningful reduction in the number of benign thyroid nodules recommended for biopsy and significantly improve specificity despite a slight decrease in sensitivity. KEY POINTS: ⢠AI TI-RADS assigned lower TI-RADS risk levels than ACR TI-RADS, showing similar sensitivity but higher specificity. ⢠Half of the benign nodules can be downgraded of which 42.3% of biopsy nodules avoided unnecessary fine-needle aspiration (FNA). ⢠AI TI-RADS had a better overall inter-rater agreement.
Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Inteligência Artificial , Estudos Retrospectivos , Biópsia por Agulha Fina , Ultrassonografia/métodosRESUMO
BACKGROUND: Definitive diagnosis of peripheral pulmonary lesions (PPLs) depends on the histological analysis of the pleural biopsy sample. Ultrasound (US)-guided sampling is now standard practice in the clinical setting. However, determining a suitable needle size and sampling times to improve the efficacy and safety of the biopsy remains challenging. Here, we compared the efficacy between 16- and 18-gauge core biopsy needles in US-guided percutaneous transthoracic biopsy for PPLs on histological diagnosis and procedure-related complications. MATERIALS AND METHODS: In total, 1169 patients (767 men, 402 women; mean age, 59.4 ± 13.2 years) who received biopsy for PPLs between September 2011 and February 2019 were included. The propensity score matching (PSM) analysis was performed to adjust the baseline differences, and the rate of successful specimen assessment and complications were compared between the 16-gauge (249 patients) and 18-gauge (920 patients) groups. The number of pleural surfaces crossed (NOPSC) was defined as the number of times the visceral pleural surface was transgressed. Stratified analysis was performed based on NOPSC. RESULTS: The overall success rate was 92.0% (1076/1169). The overall complication rate was 9.6%, including pneumothorax, hemorrhage, and vasovagal reaction, which occurred in 2.5% (29/1169), 6.6% (77/1169), and 0.5% (6/1169) of the patients, respectively. When NOPSC was 1 or > 2, the success and complication rates in the 16-gauge group were comparable to those of the 18-gauge group (all P > 0.05). When the NOPSC was 2, the success rate in the 16-gauge group was significantly higher than that in the 18-gauge group (P = 0.017), whereas the complication rate was comparable (P > 0.05). CONCLUSION: Higher success rate could be achieved using a 16-gauge than an 18-gauge core biopsy needle in the US-guided percutaneous transthoracic biopsy for PPLs when the NOPSC was 2. We recommend using 16-gauge needles with 2 times of needle passes in biopsy for PPLs in clinical practice.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Ultrassonografia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre/efeitos adversos , Feminino , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia/métodos , Adulto JovemRESUMO
This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to quantify the effects of probiotic, prebiotic, and synbiotic supplementation on biomarkers of inflammation and oxidative stress, as well as lipid profiles among patients with chronic kidney disease (CKD). Electronic databases, including PubMed, the Cochrane Database, and the Web of Science were searched from January 1, 2000, to May 15, 2019. All RCTs that investigated the effect of prebiotics, probiotics, and synbiotics on a circulating (serum and plasma) inflammatory marker (C-reactive protein [CRP]), oxidative stress indicators (malondialdehyde [MDA], glutathione [GSH], and total anti-oxidant capacity [TAC]); and lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-c], and high-density lipoprotein cholesterol [HDL-c]) among patients with CKD were included. Data were pooled and expressed as a standardized mean difference (SMD) with a 95% confidence interval (CI). The protocol for this meta-analysis is registered with PROSPERO; No. CRD42019139090. Thirteen trials that included 671 patients were identified for analysis. The methodological quality varied across studies. Meta-analysis indicated that microbial therapies significantly reduced CRP (SMD, -0.75; 95% CI, -1.03 to -0.47; p = 0.000), MDA (SMD, -1.06; 95% CI, -1.59 to -0.52; p = 0.000), TC (SMD, -0.33; 95% CI, -0.52 to -0.13; p = 0.000), and LDL-c (SMD, -0.44; 95% CI, -0.86 to -0.02; p = 0.000) levels; they also increased the GSH (SMD, 0.44; 95% CI, 0.25 to 0.65; p = 0.000), TAC (SMD, 0.61; 95% CI, 0.07 to 1.15; p = 0.000), and HDL-c (SMD, 0.45; 95% CI, 0.03 to 0.87; p = 0.000) levels in CKD patients, as compared to the placebo groups; however, there was no statistically significant TG concentration among patients with CKD. Subgroup analyses showed that other key factors, such as the duration of intervention, participants' baseline body mass index (BMI), type of intervention, and age, had an effect of microbial therapies on outcomes. This meta-analysis supports the potential use of probiotic, prebiotic, and synbiotic supplements in the improvement of established biomarkers of inflammation and oxidative stress, as well as lipid profiles among patients with CKD, which are well-known cardiovascular risk factors. Further research into these interventions should consider the limitations of our study to explore the effect of long-term administration of these supplements in the CKD population.
Assuntos
Probióticos , Insuficiência Renal Crônica , Simbióticos , Suplementos Nutricionais , Humanos , Metaboloma , Prebióticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/terapiaRESUMO
Mesenchymal stromal cells (MSCs) show potential for treating cardiovascular diseases, but their therapeutic efficacy exhibits significant heterogeneity depending on the tissue of origin. This study sought to identify an optimal source of MSCs for cardiovascular disease therapy. We demonstrated that Nestin was a suitable marker for cardiac MSCs (Nes+cMSCs), which were identified by their self-renewal ability, tri-lineage differentiation potential, and expression of MSC markers. Furthermore, compared with bone marrow-derived MSCs (Nes+bmMSCs) or saline-treated myocardial infarction (MI) controls, intramyocardial injection of Nes+cMSCs significantly improved cardiac function and decreased infarct size after acute MI (AMI) through paracrine actions, rather than transdifferentiation into cardiac cells in infarcted heart. We further revealed that Nes+cMSC treatment notably reduced pan-macrophage infiltration while inducing macrophages toward an anti-inflammatory M2 phenotype in ischemic myocardium. Interestingly, Periostin, which was highly expressed in Nes+cMSCs, could promote the polarization of M2-subtype macrophages, and knockdown or neutralization of Periostin remarkably reduced the therapeutic effects of Nes+cMSCs by decreasing M2 macrophages at lesion sites. Thus, the present work systemically shows that Nes+cMSCs have greater efficacy than do Nes+bmMSCs for cardiac healing after AMI, and that this occurs at least partly through Periostin-mediated M2 macrophage polarization.