RESUMEN
BACKGROUND: The COVID-19 pandemic's diverse symptomatology, driven by variants, underscores the critical need for a comprehensive understanding. Employing stochastic models, our study evaluates symptom sequences across SARS-CoV-2 variants on aggregated data, yielding essential insights for targeted interventions. METHODS: We conducted a meta-analysis based on research literature published before December 9, 2022, from PubMed, LitCovid, Google Scholar, and CNKI databases, to investigate the prevalence of COVID-19 symptoms during the acute phase. Registered in PROSPERO (CRD42023402568), we performed random-effects meta-analyses using the R software to estimate pooled prevalence and 95% CI. Based on our findings, we introduced the Stochastic Progression Model and Sequential Pattern Discovery using Equivalence classes (SPADE) algorithm to analyze patterns of symptom progression across different variants. RESULTS: Encompassing a total of 430,100 patients from east and southeast Asia, our results reveal the highest pooled estimate for cough/dry cough across wild-type, Delta, and Omicron variants, with fever (78.18%; 95% CI: 67-89%) being the most prominent symptom for the Alpha variant. Symptoms associated with the Omicron variant primarily manifested in upper respiratory tracts, cardiovascular, and neuropsychiatric systems. Stochastic models indicate early symptoms including dry cough and fever, followed by subsequent development of sleep disorders, fatigue, and more. CONCLUSION: Our study underscores the evolving symptomatology across SARS-CoV-2 variants, emphasizing similarities in fever, cough, and fatigue. The Omicron variant presents a distinct profile characterized by milder symptoms yet heightened neuropsychological challenges. Advanced analytical models validate the observed sequential progression of symptoms, reinforcing the consistency of disease trajectory.
RESUMEN
BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.
RESUMEN
PURPOSE OF REVIEW: There are significant differences in the transmission rate and mortality rate of COVID-19 under environmental conditions such as seasons and climates. However, the impact of environmental factors on the role of the COVID-19 pandemic and the transmission mechanism of the SARS-CoV-2 is unclear. Therefore, a comprehensive understanding of the impact of environmental factors on COVID-19 can provide innovative insights for global epidemic prevention and control policies and COVID-19 related research. This review summarizes the evidence of the impact of different natural and social environmental factors on the transmission of COVID-19 through a comprehensive analysis of epidemiology and mechanism research. This will provide innovative inspiration for global epidemic prevention and control policies and provide reference for similar infectious diseases that may emerge in the future. RECENT FINDINGS: Evidence reveals mechanisms by which natural environmental factors influence the transmission of COVID-19, including (i) virus survival and transport, (ii) immune system damage, (iii) inflammation, oxidative stress, and cell death, and (iiii) increasing risk of complications. All of these measures appear to be effective in controlling the spread or mortality of COVID-19: (1) reducing air pollution levels, (2) rational use of ozone disinfection and medical ozone therapy, (3) rational exposure to sunlight, (4) scientific ventilation and maintenance of indoor temperature and humidity, (5) control of population density, and (6) control of population movement. Our review indicates that with the continuous mutation of SARS-CoV-2, high temperature, high humidity, low air pollution levels, and low population density more likely to slow down the spread of the virus.
Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/prevención & control , Humanos , Contaminación del Aire/efectos adversos , PandemiasRESUMEN
The CC chemokine ligand 2 (CCL2, also known as MCP-1) and its cognate receptor CCR2 have well-characterized roles in chemotaxis. CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability. However, the detailed molecular mechanism underlying this process remains largely unclear. In cultured hippocampal neurons, CCL2 application rapidly upregulated surface expression of GluA1, in a CCR2-dependent manner, assayed using SEP-GluA1 live imaging, surface GluA1 antibody staining, and electrophysiology. Using pharmacology and reporter assays, we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq- and CaMKII-dependent signaling. Consistently, using i.p. injection of lipopolysaccharide to induce neuroinflammation, we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus, an effect blocked in Ccr2-/- mice. Together, these results provide a mechanism through which CCL2, and other secreted molecules that signal through G-protein coupled receptors, can directly regulate synaptic transmission.
RESUMEN
Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). Conclusion: GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.
RESUMEN
The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.
Asunto(s)
COVID-19 , Modelos Animales de Enfermedad , Pandemias , SARS-CoV-2 , Animales , COVID-19/inmunología , COVID-19/terapia , SARS-CoV-2/inmunología , Humanos , Ratones , Neumonía Viral/inmunología , Neumonía Viral/virología , Neumonía Viral/terapia , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/terapia , Betacoronavirus/inmunología , CricetinaeRESUMEN
Porcine epidemic diarrhea virus (PEDV) is one of the most devastating diseases affecting the pig industry globally. Due to the emergence of novel strains, no effective vaccines are available for prevention and control. Investigating the pathogenic mechanisms of PEDV may provide insights for creating clinical interventions. This study constructed and expressed eukaryotic expression vectors containing PEDV proteins (except NSP11) with a 3' HA tag in Vero cells. The subcellular localization of PEDV proteins was examined using endogenous protein antibodies to investigate their involvement in the viral life cycle, including endocytosis, intracellular trafficking, genome replication, energy metabolism, budding, and release. We systematically analyzed the potential roles of all PEDV viral proteins in the virus life cycle. We found that the endosome sorting complex required for transport (ESCRT) machinery may be involved in the replication and budding processes of PEDV. Our study provides insight into the molecular mechanisms underlying PEDV infection. IMPORTANCE: The global swine industry has suffered immense losses due to the spread of PEDV. Currently, there are no effective vaccines available for clinical protection. Exploring the pathogenic mechanisms of PEDV may provide valuable insights for clinical interventions. This study investigated the involvement of viral proteins in various stages of the PEDV lifecycle in the state of viral infection and identified several previously unreported interactions between viral and host proteins. These findings contribute to a better understanding of the pathogenic mechanisms underlying PEDV infection and may serve as a basis for further research and development of therapeutic strategies.
Asunto(s)
Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Proteínas Virales , Replicación Viral , Virus de la Diarrea Epidémica Porcina/fisiología , Animales , Chlorocebus aethiops , Células Vero , Porcinos , Proteínas Virales/metabolismo , Proteínas Virales/genética , Infecciones por Coronavirus/virología , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/metabolismo , EndocitosisRESUMEN
INTRODUCTION: Cardiovascular disease nursing is a critical clinical application that necessitates real-time monitoring models. Previous models required the use of multi-lead signals and could not be customized as needed. Traditional methods relied on manually designed supervised algorithms, based on empirical experience, to identify waveform abnormalities and classify diseases, and were incapable of monitoring and alerting abnormalities in individual waveforms. METHODS: This research reconstructed the vector model for arbitrary leads using the phase space-time-delay method, enabling the model to arbitrarily combine signals as needed while possessing adaptive denoising capabilities. After employing automatically constructed machine learning algorithms and designing for rapid convergence, the model can identify abnormalities in individual waveforms and classify diseases, as well as detect and alert on abnormal waveforms. RESULT: Effective noise elimination was achieved, obtaining a higher degree of loss function fitting. After utilizing the algorithm in Section 3.1 to remove noise, the signal-to-noise ratio increased by 8.6%. A clipping algorithm was employed to identify waveforms significantly affected by external factors. Subsequently, a network model established by a generative algorithm was utilized. The accuracy for healthy patients reached 99.2%, while the accuracy for APB was 100%, for LBBB 99.32%, for RBBB 99.1%, and for P-wave peak 98.1%. CONCLUSION: By utilizing a three-dimensional model, detailed variations in electrocardiogram signals associated with different diseases can be observed. The clipping algorithm is effective in identifying perturbed and damaged waveforms. Automated neural networks can classify diseases and patient identities to facilitate precision nursing.
RESUMEN
Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.
Asunto(s)
Compuestos de Boro , Estructuras Metalorgánicas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Platino (Metal) , Compuestos de Boro/química , Compuestos de Boro/farmacología , Humanos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Platino (Metal)/química , Platino (Metal)/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ratones , Nanopartículas/química , Hipoxia Tumoral/efectos de los fármacos , Peróxido de Hidrógeno/químicaRESUMEN
OBJECTIVE: Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody-positive NMOSD, but high-quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control. METHODS: Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded. RESULTS: Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50-8.38 vs. 5.00-8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30-0.84 vs. 0.95-1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation. DISCUSSION: After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile.
Asunto(s)
Acuaporina 4 , Eliminación de Componentes Sanguíneos , Neuromielitis Óptica , Puntaje de Propensión , Humanos , Femenino , Masculino , Neuromielitis Óptica/terapia , Neuromielitis Óptica/inmunología , Persona de Mediana Edad , Adulto , Acuaporina 4/inmunología , Estudios de Cohortes , Eliminación de Componentes Sanguíneos/métodos , Eliminación de Componentes Sanguíneos/efectos adversos , Resultado del Tratamiento , Intercambio Plasmático/métodos , Intercambio Plasmático/efectos adversos , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Autoanticuerpos/sangre , Estudios ProspectivosRESUMEN
Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.
Asunto(s)
Movimiento Celular , Quimioterapia Combinada , Nanopartículas , Neoplasias , Dióxido de Silicio , Movimiento Celular/efectos de los fármacos , Dióxido de Silicio/química , Quimioterapia Combinada/métodos , Neoplasias/tratamiento farmacológico , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/uso terapéutico , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanopartículas/ultraestructura , Células A549 , Microscopía Electrónica de Transmisión , HumanosRESUMEN
Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM2.5 were analyzed in Xinxiang city, Henan Province. PM2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM2.5. The average seasonal concentrations of WSIIs ranged from 19.62-72.15 µg·m-3, accounting for more than 60% of PM2.5, demonstrating that WSIIs were the major components of PM2.5. The annual concentration value of NO3-/SO42- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH4+]/[NO3-] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca2+ and Mg2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity (T < 8â, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures (T > 24â), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH4NO3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.
RESUMEN
HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.
RESUMEN
A one-target-many-trigger signal model sensing strategy is proposed for quickly, sensitive and on-site detection of the environmental pollutant p-aminophenol (PAP) by use of a commercial personal glucose meter (PGM) for signal readout with the core-shell "loading-type" nanomaterial MSNs@MnO2 as amplifiable nanoprobes. In this design, the mesoporous silica nanoparticles (MSNs) nanocontainer with entrapped signal molecule glucose is coated with redoxable manganese dioxide (MnO2) nanosheets to form the amplifiable nanoprobes (Glu-MSNs@MnO2). When encountered with PAP, the redox reaction between the MnO2 and PAP can induce the degradation of the outer layer of MSNs@MnO2, liberating multiple copies of the loaded glucose to light up the PGM signal. Owing to the high loading capability of nanocarriers, a "one-to-many" relationship exists between the target and the signal molecule glucose, which can generate adequate signal outputs to achieve the requirement of on-site determination of environmental pollutants. Taking advantage of this amplification mode, the developed PAP assay owns a dynamic linear range of 10.0-400 µM with a detection limit of 2.78 µM and provides good practical application performance with above 96.7 ± 4.83% recovery in environmental water and soil samples. Therefore, the PGM-based amplifiable sensor for PAP proposed can accommodate these requirements of environment monitoring and has promising potential for evaluating pollutants in real environmental samples.
Asunto(s)
Aminofenoles , Nanoestructuras , Óxidos , Compuestos de Manganeso , Glucosa , Dióxido de SilicioRESUMEN
Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.
Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Epigénesis Genética , Histonas/metabolismo , ADP-Ribosil Ciclasa 1 , Células Asesinas NaturalesRESUMEN
BACKGROUND: Rituximab effectively targets B cells and reduces relapses in neuromyelitis optica spectrum disorder (NMOSD). But the ideal dosage and treatment intervals remain unanswered. We aimed to assess the efficacy and safety of low and ultralow-dose rituximab in NMOSD. METHODS: We conducted a retrospective analysis of NMOSD patients treated with rituximab at two Chinese tertiary hospitals. Patients received either a low-dose regimen (500 mg reinfusion every 6 months) or an ultralow-dose regimen: 100 to 300 mg rituximab based on CD19+B cells (100 mg for 1-1.5% of peripheral blood mononuclear cells, 200 mg for 1.5-5%, and 300 mg for over 5%). RESULTS: We analyzed data from 136 patients (41 in the low-dose group, 95 in the ultralow-dose group) with median follow-up durations of 43 and 34.2 months, respectively. Both groups exhibited similar sex distribution, age at disease onset, annual relapse rate, and baseline disease duration. Survival analysis showed that ultralow-dose rituximab was noninferior to low-dose rituximab in preventing relapses. Infusion reactions occurred in 20 of 173 (11.6%) low-dose treatments and 9 of 533 (1.7%) ultralow-dose treatments. B-cell re-emergence was observed in 137 of 236 (58.1%) monitors in the low-dose group and 367 of 1136 (32.3%) monitors in the ultralow-dose group. CONCLUSION: Ultralow dose rituximab was noninferior to low-dose rituximab in preventing NMOSD relapses. A randomized controlled trial is essential to validate these findings.
Asunto(s)
Neuromielitis Óptica , Humanos , Rituximab , Factores Inmunológicos , Estudios Retrospectivos , Leucocitos Mononucleares , Recurrencia , Acuaporina 4RESUMEN
OBJECTIVE: To characterize the susceptibility-weighted image (SWI) features including paramagnetic rim and nodular lesions with signal intensity changes and central vein sign (CVS) associated with aquaporin 4 (AQP4)-immunoglobulin G (IgG)-negative neuromyelitis optica spectrum disorder (NMOSD), and explore whether they can be used as potential imaging biomarkers for differentiating multiple sclerosis (MS) from this disorder. METHODS: We prospectively recruited NMOSD with AQP4-IgG-negative (AQP4- NMOSD) and IgG-positive (AQP4+ NMOSD), and MS subjects from the Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE) project (NCT0410683) between 2019 and 2021. The SWI features including paramagnetic rim and nodular lesions with signal intensity changes and CVS were analyzed and compared among groups, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for distinguishing MS from AQP4- NMOSD. RESULTS: We enrolled a total of 160 consecutive patients (22 AQP4- NMOSD, 65 AQP4+ NMOSD, and 73 MS). We observed paramagnetic rim lesion (0/120 lesions, 0 %) and nodular (1/120, 1 %) lesions with hypointense signals on SWI in the AQP4- NMOSD group. These characteristics were similar to those recorded from AQP4+ NMOSD patients (rim: 0/369 lesions, 0 %, P = 1.000; nodular: 10/369 lesions, 2.7 %, P = 1.000), but differed significantly from those observed in the MS group (rim: 162/1665 lesions, 9.7 %, P<0.001; nodular: 392/1665 lesions, 23.5 %, P < 0.001). AQP4- NMOSD patients had fewer average CVS+ rate (12 %) than MS patients (46 %, p<0.001), similar to AQP4+ NMOSD (13 %, p = 1.000). The SWI imaging features denoting lesions with paramagnetic rim or nodular hypointense SWI signals showed 90.4 % sensitivity, 95.5 % specificity, 98.5 % PPV, and 75 % NPV, and the criteria with≥3 CVS lesions showed sensitivity of 91.8 %, specificity of 90.9 %%, PPV of 97.1 %, and NPV of 76.9 % in distinguishing MS from AQP4- NMOSD. DISCUSSION: The SWI imaging features including lesions with paramagnetic rim or nodular hypointense SWI signals and 3 CVS lesions carries useful information in distinguishing MS from AQP4- NMOSD.
Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico , Autoanticuerpos , Esclerosis Múltiple/diagnóstico , Acuaporina 4 , Inmunoglobulina GRESUMEN
RATIONALE AND OBJECTIVES: To evaluate the effect of compressed SENSE (CS) in clinical settings on scan time reduction and image quality. MATERIALS AND METHODS: Ninety-five magnetic resonance imaging (MRI) scans from different anatomical regions were acquired, consisting of a standard protocol sequence (SS) and sequence accelerated with CS. Anonymized paired sequences were randomly displayed and rated by six blinded subspecialty radiologists. Side-by-side evaluation on perceived sharpness, perceived signal-to-noise-ratio (SNR), lesion conspicuity, and artifacts were compared and scored on a five-point Likert scale, and individual image quality was evaluated on a four-point Likert scale. RESULTS: CS reduced overall scan time by 32% while maintaining acceptable MRI quality for all regions. The largest time savings were seen in the spine (mean = 68 seconds, 44% reduction) followed by the brain (mean = 86 seconds, 37% reduction). The sequence with maximum time savings was intracranial 3D-time-of-flight magnetic resonance angiography (202 seconds, 56% reduction). CS was mildly inferior to SS on perceived sharpness, perceived SNR, and lesion conspicuity (mean scores = 2.32-2.96, P < .001 [1: SS superior; 3: equivalent; 5: CS superior]). CS was equivalent to SS for joint and body scans on overall image quality (CS = 3.02-3.37, SS = 3.04-3.68, P > .05, [1: lowest quality and 4: highest quality]). The overall image quality of CS was slightly less for brain and spine scans (mean CS = 2.79-3.05, mean SS = 3.13-3.43, P = .021) but still diagnostic. Good overall clinical acceptance for CS (88%) was noted with full clinical acceptance for body scans (100%) and high acceptance for other regions (68%-95%). CONCLUSION: CS significantly reduced MR acquisition time while maintaining acceptable image quality. The implementation of CS may improve departmental workflows and enhance patient care.
Asunto(s)
Imagenología Tridimensional , Imagen por Resonancia Magnética , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Angiografía por Resonancia Magnética/métodos , Relación Señal-Ruido , Encéfalo/diagnóstico por imagen , ArtefactosRESUMEN
BACKGROUND: Although results from in vitro studies and small randomized controlled trials have shown positive effects of Dazhu hongjingtian injection (DZHJTI) on acute ischemic stroke (AIS), their generalizability to routine clinical practice remains to be established. OBJECTIVE: The primary aim of this study is to evaluate the effectiveness of DZHJTI treatment for AIS with regard to changes in the stroke-related neurological deficit from baseline to outpatient follow-up, mortality, subsequent vascular events, disability, and traditional Chinese medicine syndrome in real-world clinical settings. By monitoring for adverse events or significant changes in vital signs and laboratory parameters, we also aim to assess the safety of DZHJTI. METHODS: This prospective, multicenter cohort study plans to enroll 2000 patients with AIS within 14 days of symptom onset from 30 hospitals across China. Eligible patients will be followed up for 6 months after initiating medication treatments. The primary outcome will be the change in the National Institute of Health Stroke Scale score from baseline to outpatient follow-up. The secondary outcomes include overall mortality, stroke recurrence, new-onset major vascular events, global disability, and improvement of traditional Chinese medicine syndrome in 6 months. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of DZHJTI. An augmented inverse propensity weighted estimator will be used to reduce variability and improve accuracy in average treatment effects estimation. RESULTS: The clinical trial registration was approved in October 2022, and the recruitment and enrollment of participants started in November 2022. The study's outcomes are expected to be published in 2025 in reputable, peer-reviewed health-related research journals. CONCLUSIONS: This real-world cohort study is the first to assess the effectiveness and safety of DZHJTI in treating AIS. It may provide additional clinical evidence, including the duration of response, long-term drug effectiveness, and subgroup efficacy data. The study results will be valuable for clinicians and patients seeking optimal treatment for AIS and could lead to better use of DZHJTI and improved patient outcomes. TRIAL REGISTRATION: ITMCTR ITMCTR2022000005; http://tinyurl.com/554ns8m5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52447.