RESUMEN
Coprinopsis cinerea, a model fungus, is utilized for investigating the developmental mechanisms of basidiomycetes. The development of basidiomycetes is a highly organized process that requires coordination among genetic, environmental, and physiological factors. Oxylipins, a class of widely distributed signaling molecules, play crucial roles in fungal biology. Among oxylipins, the sexual pheromone-inducing factors (psi factors) have been identified as key regulators of the balance between asexual and sexual spore development in Ascomycetes. Linoleate dioxygenases are enzymes involved in the biosynthesis of psi factors, yet their specific physiological functions in basidiomycete development remain unclear. In this study, linoleate dioxygenases in basidiomycetes were identified and characterized. Phylogenetic analysis revealed that linoleate dioxygenases from Basidiomycota formed a distinct clade, with linoleate dioxygenases from Agaricomycetes segregating into three groups and those from Ustilaginomycetes forming a separate group. Both basidiomycete and ascomycete linoleate dioxygenases shared two characteristic domains: the N-terminal of linoleate dioxygenase domain and the C-terminal of cytochrome P450 domain. While the linoleate dioxygenase domains exhibited similarity between basidiomycetes and ascomycetes, the cytochrome P450 domains displayed high diversity in key sites. Furthermore, the gene encoding the linoleate dioxygenase Ccldo1 in C. cinerea was knocked out, resulting in a significant increase in fruiting body formation without affecting asexual conidia production. This observation suggests that secondary metabolites synthesized by CcLdo1 negatively regulate the sexual reproduction process in C. cinerea while not influencing the asexual reproductive process. This study represents the first identification of a gene involved in secondary metabolite synthesis that regulates basidiocarp development in a basidiomycete.
Asunto(s)
Basidiomycota , Cuerpos Fructíferos de los Hongos , Proteínas Fúngicas , Filogenia , Cuerpos Fructíferos de los Hongos/genética , Cuerpos Fructíferos de los Hongos/crecimiento & desarrollo , Cuerpos Fructíferos de los Hongos/enzimología , Basidiomycota/genética , Basidiomycota/enzimología , Basidiomycota/crecimiento & desarrollo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Dioxigenasas/genética , Dioxigenasas/metabolismo , Agaricales/genética , Agaricales/enzimología , Agaricales/crecimiento & desarrollo , Agaricales/metabolismo , Regulación Fúngica de la Expresión Génica , Esporas Fúngicas/crecimiento & desarrollo , Esporas Fúngicas/genética , Esporas Fúngicas/enzimologíaRESUMEN
BACKGROUND: This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula, expanding the differential diagnosis for gastrointestinal bleeding. It emphasizes the importance of considering vascular origins in cases of atypical hematochezia, particularly in the absence of common gastrointestinal causes, and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual presentations. CASE SUMMARY: A 75-year-old man with a history of hypertension presented with 12 d of hematochezia, experiencing bloody stools 7-8 times per day. Initial computed tomography (CT) scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma development. Hemoglobin levels progressively decreased to 7 g/dL. Emergency arterial angiography and iliac artery-covered stent placement were performed, followed by balloon angioplasty. Despite initial stabilization, minor rectal bleeding and abdominal pain persisted, leading to further diagnostic colonoscopy. This identified a neoplasm and potential perforation at the proximal rectum. An exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall, necessitating partial rectal resection, intestinal anastomosis, and ileostomy. Postoperative recovery was successful, with no further bleeding incidents and normal follow-up CT and colonoscopy results after six months. CONCLUSION: In cases of unusual gastrointestinal bleeding, it is necessary to consider vascular causes for effective diagnosis and intervention.
RESUMEN
BACKGROUND: Primary cilia are antenna-like organelles that conduct physical and chemical signals, which affect cell proliferation, migration, and differentiation. Some researchers have reported the correlation between primary cilia-related genes and prognosis of colorectal cancer (CRC). METHODS: The association between single nucleotide polymorphisms (SNPs) of primary cilia-related genes and outcome after the first-line chemotherapy was explored by the Cox regression model. Expression qualitative trait locus (eQTL) analysis was performed to explore the impact of SNPs on gene expression. Tumor Immune Estimation Resource and TISIDB databases were used for investigating the relevance between ODF2L and tumor infiltration immune cells and immunomodulators. RESULTS: We identified that rs4288473 C allele of ODF2L had poor progression-free survival (PFS) and overall survival (OS) of CRC patients in the additive model (adjusted HRPFS = 1.39, 95% CI = 1.14-1.70, p = 1.36 × 10-3 , and adjusted HROS = 1.31, 95% CI = 1.03-1.65, p = 2.62 × 10-2 ). The stratified analysis indicated that rs4288573 CC/CT genotype was involved with poor prognosis in the irinotecan-treated subgroup (PPFS = 1.03 × 10-2 , POS = 3.29 × 10-3 ). Besides, ODF2L mRNA expression level was notably up-regrated in CRC tissues. The C allele of rs4288573 was notably related to higher ODF2L mRNA expression levels based on eQTL analysis. Functionally, knockdown of ODF2L inhibited cell proliferation and decrease the chemoresistance of HCT-116 and DLD-1 cells to irinotecan. CONCLUSION: Our study indicates that rs4288573 in ODF2L is a potential predictor of the chemotherapy prognosis of CRC.
Asunto(s)
Neoplasias Colorrectales , Humanos , Irinotecán/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Cilios/genética , Cilios/patología , Pronóstico , Polimorfismo de Nucleótido Simple , ARN MensajeroRESUMEN
The outstanding photoactive materials are the imperative for the construction of a front-illuminated photoelectrochemical (PEC) biosensor, which is crucial step for improving the detection sensitivity. Yet, the weak and unstable initial PEC signals of the photoelectrodes have limited evidently the detection performance. Herein, a front-illuminated "on-off" PEC immunosensor was constructed based on Mo:BiVO4 as photoactive matrix and Au/CeO2 as signal quencher for sensitive detection of procalcitonin (PCT). Systematic studies reveal that the Mo doped BiVO4 can increase the charge carrier density of BiVO4, leading to much higher initial signal under front illumination than back illumination. Moreover, Mo:BiVO4 was directly grown on conducting substrates, which effectively overcomes the loose combination of sensing substrate ensuring good electrical contact and continuity. Upon coupling with Au/CeO2 as signal quencher, the initial photocurrent signal can be significantly quenched. As a result, the proposed PEC immunosensor presents a wide linear range from 10 fg mL-1 to 50 ng mL-1 with a detection limit of 2.45 fg mL-1. Impressively, this study will open a new avenue for the construction of highly efficient and stable photoelectrode, as well as extend the application of PEC biosensor for biomarkers detection in early disease diagnosis.
Asunto(s)
Técnicas Biosensibles , Polipéptido alfa Relacionado con Calcitonina , Técnicas Electroquímicas , Inmunoensayo , TitanioAsunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Adulto , Humanos , Sistemas de Atención de Punto , Tuberculosis/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Lipopolisacáridos , Infecciones por VIH/diagnóstico , Sensibilidad y Especificidad , EsputoRESUMEN
BACKGROUND: Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. METHODS: Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. FINDINGS: All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. CONCLUSIONS: For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness. FUNDING: This work was funded by the National Natural Science Foundation of China (81761128014).
Asunto(s)
Dibenzotiepinas , Virus de la Influenza A , Gripe Aviar , Gripe Humana , Morfolinas , Piridonas , Síndrome de Dificultad Respiratoria , Sepsis , Triazinas , Animales , Humanos , Gripe Aviar/tratamiento farmacológico , Gripe Aviar/epidemiología , Oseltamivir/uso terapéutico , Subtipo H5N6 del Virus de la Influenza A , Interleucina-18/uso terapéutico , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Sepsis/tratamiento farmacológicoRESUMEN
This article proposes a semi-supervised contrastive capsule transformer method with feature-based knowledge distillation (KD) that simplifies the existing semisupervised learning (SSL) techniques for wearable human activity recognition (HAR), called CapMatch. CapMatch gracefully hybridizes supervised learning and unsupervised learning to extract rich representations from input data. In unsupervised learning, CapMatch leverages the pseudolabeling, contrastive learning (CL), and feature-based KD techniques to construct similarity learning on lower and higher level semantic information extracted from two augmentation versions of the data", weak" and "timecut", to recognize the relationships among the obtained features of classes in the unlabeled data. CapMatch combines the outputs of the weak-and timecut-augmented models to form pseudolabeling and thus CL. Meanwhile, CapMatch uses the feature-based KD to transfer knowledge from the intermediate layers of the weak-augmented model to those of the timecut-augmented model. To effectively capture both local and global patterns of HAR data, we design a capsule transformer network consisting of four capsule-based transformer blocks and one routing layer. Experimental results show that compared with a number of state-of-the-art semi-supervised and supervised algorithms, the proposed CapMatch achieves decent performance on three commonly used HAR datasets, namely, HAPT, WISDM, and UCI_HAR. With only 10% of data labeled, CapMatch achieves F1 values of higher than 85.00% on these datasets, outperforming 14 semi-supervised algorithms. When the proportion of labeled data reaches 30%, CapMatch obtains F1 values of no lower than 88.00% on the datasets above, which is better than several classical supervised algorithms, e.g., decision tree and k -nearest neighbor (KNN).
RESUMEN
A rapid, accurate, non-sputum-based triage test for diagnosing tuberculosis (TB) is a high-priority need. Cepheid developed a novel prototype blood test, Xpert Mycobacterium tuberculosis Host Response (Xpert-MTB-HR), which generates a TB score based on the mRNA expression of three genes. We conducted a case-control study with prospective recruitment to evaluate its accuracy in the clinic of the Wusheng County Centers for Disease Prevention and Control in China. We enrolled 149 TB patients, 248 other respiratory diseases (ORD) patients, and 193 healthy controls. In addition, whole-blood samples taken from TB patients after 2, 5, and 6 months of treatment were tested with Xpert-MTB-HR to evaluate its ability to monitor treatment response. Xpert-MTB-HR discriminated between TB and healthy controls with an area under the curve (AUC) of 0.912 (95% CI, 0.878-0.945). With the specificity of 70% envisioned for a triage test, its sensitivity was 90.1% (84.9%-94.6%). Xpert-MTB-HR discriminated between TB and ORD with an AUC of 0.798 (0.750-0.847), and at specificity of 70%, the sensitivity was only 75.8% (68.5%-82.8%). In patients determined by Ultra to have medium or high sputum bacillary loads, with specificity of 70%, the sensitivity for discriminating patients with TB from healthy controls was 100.0% (100.0-100.0) and from patients with ORD, 95.1% (89.8-100.0). The TB scores generally increased by 2 months of treatment and then remained stable. Xpert-MTB-HR met the criteria for a triage test to discriminate between TB and healthy controls, but not between TB and ORD, except when limited to patients with high sputum bacillary loads. Xpert-MTB-HR showed promise for monitoring response to treatment but needs to be further evaluated in larger prospective studies.
Asunto(s)
Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Estudios Prospectivos , Rifampin , Antibióticos Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Mycobacterium tuberculosis/genética , Esputo/microbiología , ChinaRESUMEN
Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Síndrome del Colon Irritable , Humanos , Animales , Ratones , Microesferas , Fermentación , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mesalamina , Alginatos , Fibras de la DietaRESUMEN
Objective: To determine whether photobiomodulation therapy (PBMT) by class IV Multiwave Locked System laser treatment as an adjunctive therapy could relieve symptoms in patients with Bell's palsy with a duration of greater than 8 weeks. Materials and methods: This nonrandomized controlled trial was conducted from January 2020 to December 2022. Patients were eligible if they had Bell's palsy with a duration of greater than 8 weeks at the out-patient department of otorhinolaryngology in Beijing Tongren Hospital. The control group consisted of patients recruited between January 1, 2020, and December 31, 2020. The PBMT group consisted of patients recruited between January 1, 2021, and December 31, 2022. In this study, the PBM used has a wavelength of 808 and 905 nm, 1.2 W power (808 nm is 1 W, 905 nm is 200 mW), continuous mode emission (808 nm) and pulsed mode emission (905 nm), 8.35 J/cm2 dosimetry, administered 3 times per week, 72 times of total treatment. The primary outcome measures included the House-Brackmann facial nerve grading system, the Sunnybrook facial grading system, and the Facial Clinimetric Evaluation Scale (FaCE). Secondary outcome measures comprised electroneurography, electromyography, and the blink reflex. Results: A total of 54 participants were included (27 in the control group and 27 in the photobiomodulation group). After 6 months, the House-Brackmann grading system [risk difference, -0.59, confidence interval (95% CI), -0.81 to -0.38, relative risk, 0.27, 95% CI, 0.13-0.56, p < 0.001], Sunnybrook facial grading system (21.14, 95% CI, 11.71-30.58; p < 0.001), and FaCE (-0.20, 95% CI, 0.41-0.02; p = 0.07) had significant difference between the two groups. Latency of ala nasi muscle (10.92, 95% CI, 5.58-16.27; p < 0.001) was not statistically significant after treatment compared with the control group; however, most of the electrophysiological examinations have significant difference between the two groups, respectively. Conclusions: The results of this study suggest that PBMT may relieve symptoms for patients with Bell's palsy with a duration of greater than 8 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT05585333.
Asunto(s)
Parálisis de Bell , Parálisis Facial , Terapia por Luz de Baja Intensidad , Humanos , Parálisis de Bell/radioterapia , Fototerapia , Manejo del DolorRESUMEN
Objectives: Lipoarabinomannan (LAM), an abundant cell wall glycolipid of mycobacteria including Mycobacterium tuberculosis (Mtb), is a promising TB diagnostic marker. The current commercially available urine LAM assays are not sufficiently sensitive, and more novel detection strategies are urgently needed to fill the current diagnostic gap. Methods: A proteinase K-pretreated Concanavalin A (ConA)-based ELISA assay was developed. Diagnostic performance was assessed by several bacterial strains and clinical urine samples. Results: The limit of detection (LoD) of the assay against ManLAM was 6 ng/ml. The assay reacted strongly to Mtb H37Rv and M. bovis BCG, intermediately to M. smegmatis mc2155, and weakly to four non-mycobacteria pathogens. This method could distinguish TB patients from healthy controls (HCs) and close contacts (CCs) in 71 urine samples treated with proteinase K, which increases urine LAM antibody reactiveness. In TB+HIV+ and TB+HIV- patients, the sensitivity was 43.8 and 37.5%, respectively, while the specificity was 100.0%. The areas under ROC curves (AUCs) were 0.74 and 0.82, respectively. Conclusion: This study implies that ConA can be paired with antibodies to detect LAM. Proteinase K treatment could effectively enhance the sensitivity by restoring the reactiveness of antibodies to LAM.
RESUMEN
The Xpert MTB/RIF Ultra (Ultra) is not yet used for the diagnosis of tuberculosis (TB) in China. We compared the performance of the Xpert and Ultra for detecting Mycobacterium tuberculosis and rifampicin resistance in a primary-level clinic in rural China. Sputum samples from suspected pulmonary TB patients were collected and subjected to smear microscopy, liquid culture, Xpert and Ultra tests. We then compared the sensitivity and specificity of Xpert and Ultra for diagnosing TB against liquid culture. Whole-genome sequencing was performed to predict rifampicin resistance and the results were compared with the Xpert and Ultra tests. The sensitivities of Xpert and Ultra were 88.1% and 95.1%, and the specificities were 91.9% and 84.4%, respectively. Among the 61 smear-negative culture-positive patients, the sensitivities of Xpert and Ultra were 80.3% and 91.8%. All Xpert-positive patients were Ultra-positive. Among culture-negative Xpert or Ultra-positive patients, 69.6% were taking anti-TB drugs or had a previous history of TB. Of the samples that Ultra classified as trace, nearly 25% were probably false-positives. Both Xpert and Ultra accurately detected all rifampicin-resistant patients. In conclusion, Ultra was more sensitive than Xpert, especially for smear-negative patients but had decreased specificity with more false-positives, especially with Ultra trace results.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Mycobacterium tuberculosis/genética , Rifampin/farmacología , Rifampin/uso terapéutico , Antituberculosos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , China/epidemiologíaRESUMEN
With the increasing accessibility of remote sensing videos, remote sensing tracking is gradually becoming a hot issue. However, accurately detecting and tracking in complex remote sensing scenes is still a challenge. In this article, we propose a collaborative learning tracking network for remote sensing videos, including a consistent receptive field parallel fusion module (CRFPF), dual-branch spatial-channel co-attention (DSCA) module, and geometric constraint retrack strategy (GCRT). Considering the small-size objects of remote sensing scenes are difficult for general forward networks to extract effective features, we propose a CRFPF-module to establish parallel branches with consistent receptive fields to separately extract from shallow to deep features and then fuse hierarchical features adaptively. Since the objects and their background are difficult to distinguish, the proposed DSCA-module uses the spatial-channel co-attention mechanism to collaboratively learn the relevant information, which enhances the saliency of the objects and regresses to precise bounding boxes. Considering the interference of similar objects, we designed a GCRT-strategy to judge whether there is a false detection through the estimated motion trajectory and then recover the correct object by weakening the feature response of interference. The experimental results and theoretical analysis on multiple datasets demonstrate our proposed method's feasibility and effectiveness. Code and net are available at https://github.com/Dawn5786/CoCRF-TrackNet.
RESUMEN
BACKGROUND: The goal was to simply and efficiently predict the indicators of disease severity in knee osteoarthritis (KOA) patients. METHODS: One hundred eighty-four patients with KOA and 126 healthy subjects were included. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was used as a reference index for disease severity in KOA patients, in which WOMAC < 80 was classified as mild and WOMAC ≥ 80 as moderate and severe. Blood routine parameters of the KOA and the healthy groups were analyzed by the Mann Whitney U test. Receiver operating characteristic curves were used to analyze the sensitivity and specificity of mean corpuscular hemoglobin and platelet distribution width ratio (MPR) and monocyte and hemoglobin ratio (MHR) indicators. The correlation between MPR and MHR and disease severity of KOA was determined by bivariate regression analysis. Independent predictors of disease severity in patients with KOA were assessed by multivariate regression analysis. RESULTS: MPR, MHR, and WOMAC were significantly higher in the KOA group. The ROC curve indicated that the cutoff values of MPR and MHR were 2.09 and 0.0030, respectively, with sensitivity of 86.4% and 68.5% and specificity of 99.2% and 79.4%. Bivariate regression analysis found that MPR was better correlated with disease severity than MHR. The results of multivariate regression analysis demonstrated that the MPR values of moderate and severe patients were more than 19 times that of mild patients, and the OR values were 21.695 and 19.558, respectively. CONCLUSIONS: MPR and MHR demonstrated a good correlation with disease severity in patients with KOA. MPR is a potential independent predictor of disease severity in patients with KOA.
Asunto(s)
Osteoartritis de la Rodilla , Índices de Eritrocitos , Pruebas Hematológicas , Humanos , Osteoartritis de la Rodilla/diagnóstico , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The authors have plagiarized/duplicated part of a paper that appeared in Neurosci Lett, 549 (2013) 63-68, (https://doi.org/10.1016/j.neulet.2013.06.002). Several images in the Journal of Ethnopharmacology paper; 3A, 3B, 4A, 4B correspond to figures; 2A, 2B, 3A and 3B respectively as published in Neuroscience Letters. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
RESUMEN
BACKGROUND: Recombinant protein subunit vaccination is considered to be a safe, fast and reliable technique when combating emerging and re-emerging diseases such as coronavirus disease 2019 (COVID-19). Typically, such subunit vaccines require the addition of adjuvants to attain adequate immunogenicity. AS01, which contains adjuvants MPL and saponin QS21, is a liposome-based vaccine adjuvant system that is one of the leading candidates. However, the adjuvant effect of AS01 in COVID-19 vaccines is not well described yet. METHODS: In this study, we utilized a mixture of AS01 as the adjuvant for an S1 protein-based COVID-19 vaccine. RESULTS: The adjuvanted vaccine induced robust immunoglobulin G (IgG) binding antibody and virus-neutralizing antibody responses. Importantly, two doses induced similar levels of IgG binding antibody and neutralizing antibody responses compared with three doses and the antibody responses weakened only slightly over time up to six weeks after immunization. CONCLUSION: These results suggested that two doses may be enough for a clinical vaccine strategy design using MPL & QS21 adjuvanted recombinant protein, especially in consideration of the limited production capacity of COVID-19 vaccine in a public health emergency.
Asunto(s)
Antígenos Virales/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , Lípido A/análogos & derivados , SARS-CoV-2/inmunología , Saponinas/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas de Subunidad/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes de Vacunas/administración & dosificación , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales/metabolismo , Formación de Anticuerpos , COVID-19/virología , Relación Dosis-Respuesta Inmunológica , Combinación de Medicamentos , Femenino , Células HEK293 , Humanos , Inmunización , Inmunogenicidad Vacunal , Lípido A/administración & dosificación , Lípido A/inmunología , Ratones Endogámicos BALB C , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Saponinas/administración & dosificaciónRESUMEN
BACKGROUND: Metoclopramide is frequently prescribed as an adjuvant for the postpyloric placement of nasoenteric tubes (NETs). However, a recent meta-analysis showed that metoclopramide was not beneficial in adults. Thus, this study aimed to reevaluate the effect of metoclopramide on the postpyloric placement of NETs. METHODS: A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data was conducted up to August 2020 for randomized controlled trials (RCTs) comparing metoclopramide with placebo or no intervention. Trial sequential analysis (TSA) was used for the primary outcomes (the success rate of the postpyloric placement of NETs). RESULTS: Seven eligible RCTs that included 520 participants were identified. The results of the pooled effect sizes showed that metoclopramide significantly facilitated the postpyloric placement of NETs (relative risk [RR], 1.48; 95% CI, 1.11-1.97; P = .007; I2 = 37%). However, the risk-of-bias assessment and the TSA results indicated that the qualities of the RCTs and the sample sizes were insufficient to confirm the efficacy of metoclopramide. Further subgroup analysis revealed that successful postpyloric placement was more pronounced in studies in which spiral NETs were employed (RR, 1.85; 95% CI, 1.41-2.43; P < .001; I2 = 0%). Additionally, overall adverse events were minimal. CONCLUSIONS: The evidence accumulated so far was not strong enough to demonstrate metoclopramide's beneficial effects on the postpyloric placement of NETs. Further high-quality, large-sample RCTs are required to elucidate the effects of metoclopramide.