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Objective: Air pollution is a leading public health issue. This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai. Methods: The study monitored 27 asthma outpatients for a year, collecting data on weather, patient self-management [daily asthma diary, peak expiratory flow (PEF) monitoring, medication usage], spirometry and serum markers. To explore the potential mechanisms of any effects, asthmatic mice induced by ovalbumin (OVA) were exposed to PM 2.5. Results: Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma. Acute exposure showed a correlation between PEF and levels of ozone (O 3) and nitrogen dioxide (NO 2). Chronic exposure indicated that interleukin-5 (IL-5) and interleukin-13 (IL-13) levels correlated with PM 2.5 and PM 10 concentrations. In asthmatic mouse models, exposure to PM 2.5 increased cytokine levels and worsened lung function. Additionally, PM 2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways. Conclusion: Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation. Specifically, PM 2.5 significantly contributes to these adverse effects. Further research is needed to elucidate the mechanisms by which PM 2.5 impacts asthma.
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Poluentes Atmosféricos , Asma , Pulmão , Asma/induzido quimicamente , China , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/toxicidade , Animais , Humanos , Feminino , Masculino , Adulto , Camundongos , Pessoa de Meia-Idade , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Camundongos Endogâmicos BALB C , Inflamação/induzido quimicamente , Material Particulado/toxicidade , Material Particulado/efeitos adversos , Citocinas/sangue , Citocinas/metabolismo , OvalbuminaRESUMO
BACKGROUND: Numerous studies have found that patients experiencing sudden sensorineural hearing loss (SSHL), with or without accompanying vertigo, often show impaired vestibular function. However, there is a dearth of studies analyzing vestibular-evoked myogenic potentials (VEMPs) in SSHL patients across various age groups. AIM: To investigate vestibular condition in SSHL patients across various age demographics. METHODS: Clinical data of 84 SSHL patients were investigated retrospectively. Audiometry, cervical vestibular evoked myogenic potentials (c-VEMPs), and ocular vestibular evoked myogenic potentials (o-VEMPs) were conducted on these patients. Parameters assessed included the latencies of P1 and N1 waves, as well as the amplitudes of P1-N1 waves. Moreover, the study evaluated the influence of factors such as sex, affected side, configuration of hearing loss, and presence of accompanying vertigo. RESULTS: Among the 84 SSHL patients, no significant differences were observed among the three groups in terms of gender, affected side, and the presence or absence of vertigo. Group II (aged 41-60 years) had the highest number of SSHL cases. The rates of absent o-VEMPs in the affected ears were 20.83%, 31.58%, and 22.72% for the three age groups, respectively, with no statistically significant difference among them. The rates of absent c-VEMPs in the affected ears were 8.3%, 34.21%, and 18.18% for the three age groups, respectively, with significant differences. In the unaffected ears, there were differences observed in the extraction rates of o-VEMPs in the unaffected ears among the age groups. In the three age groups, no significant differences were noted in the three age groups in the latencies of P1 and N1 waves or in the amplitude of N1-P1 waves for c-VEMPs and o-VEMPs, either on the affected side or on the unaffected side, across the three age groups. CONCLUSION: The extraction rate of VEMPs is more valuable than parameters. Regardless of the presence of vertigo, vestibular organs are involved in SSHL. Notably, SSHL patients aged 41-60 appear more susceptible to damage to the inferior vestibular nerve and saccule.
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BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes. METHODS: A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation. RESULTS: Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4. CONCLUSION: Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.
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Microbioma Gastrointestinal , Lúpus Eritematoso Sistêmico , Subpopulações de Linfócitos T , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/microbiologia , Microbioma Gastrointestinal/imunologia , Feminino , Adulto , Masculino , Subpopulações de Linfócitos T/imunologia , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Adulto Jovem , Células Th17/imunologiaRESUMO
Wide operation temperature is the crucial objective for an energy storage system that can be applied under harsh environmental conditions. For lithium-sulfur batteries, the "shuttle effect" of polysulfide intermediates will aggravate with the temperature increasing, while the reaction kinetics decreases sharply as the temperature decreasing. In particular, sulfur reaction mechanism at low temperatures seems to be quite different from that at room temperature. Here, through in situ Raman and electrochemical impedance spectroscopy studies, the newly emerged platform at cryogenic temperature corresponds to the reduction process of Li2S8 to Li2S4, which will be another rate-determining step of sulfur conversion reaction, in addition to the solid-phase conversion process of Li2S4 to Li2S2/Li2S at low temperatures. Porous bismuth vanadate (BiVO4) spheres are designed as sulfur host material, which achieve the rapid snap-transfer-catalytic process by shortening lithium-ion transport pathway and accelerating the targeted rate-determining steps. Such promoting effect greatly inhibits severe "shuttle effect" at high temperatures and simultaneously improves sulfur conversion efficiency in the cryogenic environment. The cell with the porous BiVO4 spheres as the host exhibits excellent rate capability and cycle performance under wide working temperatures.
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Great effort has been dedicated to the engineering of porous organic cages (POCs) in geometry and topology. Yet, harnessing these cage-like entities as premade building units to construct infinite cage-based superstructures remains elusive. In this study, we design a type of vertex-modified phosphine organic prism by a postfunctionalized approach and use it as a ditopic cage monomer to achieve an intercage supramolecular polymerization via the synergy of metal coordination and π-π dimerization. The resulting cage-by-cage polymers can further hierarchically organize into superstructures of diverse morphologies and dimensionalities, including 1D fibers, 2D lamellae, and 3D vesicles. Control over the cosolvents is capable of well regulating their structural hierarchies and self-assembled shapes. This would pave a way for the creation of cage-based supramolecular assemblies and nanomaterials.
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Significant efforts have been dedicated to designing porous organic cage compounds with geometric complexity and topological diversity. However, the use of these cage molecules as premade building units for constructing infinite cage-based superstructures remains unexplored. Here, we report the use of a panel-decorated phosphine organic cage as a special monomer to achieve supramolecular polymerization, resulting in cage-by-cage noncovalent polymers through the synergy of metal-coordination and intercageπ-πdimerization. At a monomer concentration of 122 mM, the average degree of polymerization reaches 17, corresponding to a molecular weight of 26 kDa. The obtained cage-based supramolecular polymers can further hierarchically self-assemble into vesicular morphologies or one-dimensional nanofiber architectures. Selective control over the cosolvents can regulate their structural hierarchy and assembled morphology. This approach paves a new way for the construction of cage-based hierarchical assemblies and materials.
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OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.
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Leucemia Mieloide Aguda , MicroRNAs , RNA Circular , Fatores de Transcrição SOXC , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , Prognóstico , RNA Circular/genética , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Regulação para Cima/genéticaRESUMO
OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.
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Displasia Broncopulmonar , Recém-Nascido Prematuro , Gêmeos , Humanos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/epidemiologia , Fatores de Risco , Recém-Nascido , Feminino , Estudos Retrospectivos , Masculino , Idade Gestacional , Peso ao Nascer , Modelos LogísticosRESUMO
People have been focusing on how to improve the specific capacity and cycling stability of lithium-sulfur batteries at room temperature, however, on some special occasions such as cold cities and aerospace fields, the operating temperature is low, which dramatically hinders the performance of batteries. Here, we report an iron carbide (Fe3C)/rGO composite as electrode host, the Fe3C nanoparticles in the composite have strong adsorption and high catalytic ability for polysulfide. The rGO makes the distribution of Fe3C nanoparticles more disperse, and this specific structure makes the deposition of Li2S more uniform. Therefore, it realizes the rapid transformation and high performance of lithium-sulfur batteries at both room and low temperatures. At room temperature, after 100 cycles at 1C current density, the reversible specific capacity of the battery can be stabilized at 889 ± 7.1 mAh/g. Even at -40 °C, in the first cycle battery still emits 542.9 ± 3.7 mAh/g specific capacity. This broadens the operating temperature for lithium-sulfur batteries and also provides a new idea for the selection of host materials for sulfur in low-temperature lithium-sulfur batteries.
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In order to explore the unique physiological roles of gas signaling molecules and gasotransmitters inâ vivo, chemists have engineered a variety of gas-responsive polymers that can monitor their changes in cellular milieu, and gas-releasing polymers that can orchestrate the release of gases. These have advanced their potential applications in the field of bio-imaging, nanodelivery, and theranostics. Since these polymers are of different chain structures and properties, the morphology of their assemblies will manifest distinct transitions after responding to gas or releasing gas. In this review, we summarize the fundamental design rationale of gas-responsive and gas-releasing polymers in structure and their controlled transition in self-assembled morphology and function, as well as present some perspectives in this prosperous field. Emerging challenges faced for the future research are also discussed.
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Gases , Polímeros , Polímeros/química , Gases/química , HumanosRESUMO
PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
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Antineoplásicos , Arsênio , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/efeitos adversos , Arsênio/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pandemias , Resultado do TratamentoRESUMO
BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.
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Gastrite Atrófica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Gastrite/epidemiologia , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Gastroscopia , Infecções por Helicobacter/patologia , Estilo de Vida , Dor , Úlcera Gástrica/patologiaRESUMO
The construction of high-asymmetrical structures demonstrates significant potential in improving the functionality and distinctness of nanomaterials, but remains a considerable challenge. Herein, we develop a one-pot method to fabricate regioselective super-assembly of Prussian blue analogue (PBA) -- a PBA anisotropic structure (PBA-AS) decorated with epitaxial modules--using a step-by-step epitaxial growth on a rapidly self-assembled cubic substrate guided by thiocyanuric acid (TCA) molecules. The epitaxial growth units manifest as diverse geometric shapes, which are predominantly concentrated on the {100}, {111}, or {100}+{111} crystal plane of the cubic substrate. The crystal plane and morphology of epitaxial module can be regulated by changing the TCA concentration and reaction temperature, enabling a high level of controllability over specific assembly sites and structures. To illustrate the advantage of the asymmetrical structure, phosphated PBA-AS demonstrates improved performance in the oxygen evolution reaction compared to simple phosphated PBA nanocube. This method offers valuable insights for designing asymmetrical nanomaterials with intricate architectures and versatile functionalities.
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Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for cancer therapy effectiveness. This study explored the effects of a casein protein diet (CTL) versus a free amino acid (FAA)-based diet on CRC progression, gut microbiota, and metabolites using carcinogen-induced (AOM/DSS) and spontaneous genetically induced (ApcMin/+ mice) CRC mouse models. Comprehensive approaches including 16s rRNA gene sequencing, transcriptomics, metabolomics, and immunohistochemistry were utilized. We found that the FAA significantly attenuated CRC progression, evidenced by reduced colonic shortening and histopathological alterations compared to the CTL diet. Notably, the FAA enriched beneficial gut bacteria like Akkermansia and Bacteroides and reversed CRC-associated dysbiosis. Metabolomic analysis highlighted an increase in ornithine cycle metabolites and specific fatty acids, such as Docosapentaenoic acid (DPA), in FAA-fed mice. Transcriptomic analysis revealed that FAA up-regulated Egl-9 family hypoxia inducible factor 3 (Egln 3) and downregulated several cancer-associated pathways including Hippo, mTOR, and Wnt signaling. Additionally, DPA was found to significantly induce EGLN 3 expression in CRC cell lines. These results suggest that FAA modulate gut microbial composition, enhance protective metabolites, improve gut barrier functions, and inhibit carcinogenic pathways.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Animais , Camundongos , RNA Ribossômico 16S , Carcinogênese , Transformação Celular Neoplásica , Carcinógenos , AminoácidosRESUMO
The controllable construction of complex metal-organic coordination polymers (CPs) merits untold scientific and technological potential, yet remains a grand challenge of one-step construction and modulating simultaneously valence states of metals and topological morphology. Here, a thiocyanuric acid (TCA)-triggered strategy is presented to one-step rapid synthesis a double-crystalline Prussian blue analogue hetero-superstructure (PBA-hs) that comprises a Co3[Fe(CN)6]2 cube overcoated with a KCo[Fe(CN)6] shell, followed by eight self-assembled small cubes on vertices. Unlike common directing surfactants, TCA not only acts as a trigger for the fast growth of KCo[Fe(CN)6] on the Co3[Fe(CN)6]2 phase resulting in a PBA-on-PBA hetero-superstructure, but also serves as a flange-like bridge between them. By combining experiments with simulations, a deprotonation-induced electron transfer (DIET) mechanism is proposed for formation of second phase in PBA-hs, differing from thermally and photo-induced electron transfer processes. To prove utility, the calcined PBA-hs exhibits enhanced oxygen evolution reaction performance. This work provides a new method to design of novel CPs for enriching chemistry and material science. This work offers a practical approach to design novel CPs for enriching chemistry and material science.
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Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Anemia Aplástica/diagnóstico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , China/epidemiologia , População do Leste AsiáticoRESUMO
Catalytic performance of single-atom catalysts (SACs) relies fundamentally on the electronic nature and local coordination environment of the active site. Here, based on a machine-learning (ML)-aided density functional theory (DFT) method, we reveal that the intrinsic dipole in Janus materials has a significant impact on the catalytic activity of SACs, using 2D γ-phosphorus carbide (γ-PC) as a model system. Specifically, a local dipole around the active site is a key degree to tune the catalytic activity and can be used as an important descriptor with a high feature importance of 17.1% in predicting the difference of adsorption free energy (ΔGO* - ΔGOH*) to assess the activity of the oxygen evolution reaction. As a result, the catalytic performance of SACs can be tuned by an intrinsic dipole, in stark contrast to those external stimuli strategies previously used. These results suggest that dipole engineering and the revolutionary DFT-ML hybrid scheme are novel approaches for designing high-performance catalysts.
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The rational design of electrocatalysts with well-designed compositions and structures for the oxygen evolution reaction (OER) is promising and challenging. Herein, we developed a novel strategy - a one-step double-cation etching sedimentation equilibrium strategy - to synthesize amorphous hollow Fe-Co-Ni layered double hydroxide nanocages with an outer surface of vertically interconnected ultrathin nanosheets (Fe-Co-Ni-LDH), which primarily depends on the in situ etching sedimentation equilibrium of the template interface. This unique vertical nanosheet-shell hierarchical nanostructure possesses enhanced charge transfer, increased active sites, and favorable kinetics during electrolysis, resulting in superb electrocatalytic performance for the oxygen evolution reaction (OER). Specifically, the Fe-Co-Ni-LDH nanocages exhibited remarkable OER activity in alkaline electrolytes and achieved a current density of 100 mA cm-2 at a low overpotential of 272 mV with excellent stability. This powerful strategy provides a profound molecular-level insight into the control of the morphology and composition of 2D layered materials.
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Following the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (-3.74%-10.75%) in the one-dose cohort and 72.19% (57.33%-81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.
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COVID-19 , SARS-CoV-2 , Humanos , Sprays Nasais , Pandemias , China , Anticorpos Monoclonais , Anticorpos Amplamente Neutralizantes , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
INTRODUCTION: To investigate the levels of nicotinamide-adenine dinucleotide phosphate oxidase 2 (NOX2) in serum and pericardial drainage samples in the early stage after coronary artery bypass grafting (CABG) and determine whether NOX2 is predictive of postoperative atrial fibrillation (POAF). MATERIALS AND METHODS: This prospective pilot study involved 152 adults without history of atrial fibrillation who underwent first-time elective isolated CABG. Serum and pericardial fluid samples were simultaneously obtained from patients at baseline and 4, 12, and 24 h post operation. NOX2 levels were determined using enzyme-linked immunosorbent assays. The heart rhythm of patients was continuously monitored through a Holter monitor until discharge. Logistic regression and receiver-operating characteristic (ROC) curve analyses were performed, as appropriate. RESULTS: Fifty-one patients (33.6%) experienced in-hospital POAF. NOX2 concentration in serum and pericardial drainage samples was increased after surgery, reached its peak at 12 h, and gradually declined thereafter toward the baseline levels by 24 h. At 12 h, patients with POAF had higher levels of serum NOX2 than those without (3.96 ± 0.35 vs. 3.70 ± 0.75 µg/mL, respectively, p = 0.004). There were no discernible differences in pericardial NOX2 between the 2 groups. Multivariate analysis revealed that serum NOX2 at 12 h post operation was the strongest independent predictor of POAF (odds ratio: 2.179, 95% confidence interval: 1.084-4.377). The area under the ROC curve of the POAF predictive model was 0.732 (95% confidence interval: 0.654-0.801). CONCLUSION: Serum NOX2 may be useful in the identification of POAF. Larger studies are warranted to substantiate these findings.