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OBJECTIVE: Exploring the effects of age on microbial community structure and understanding the effects of chronological ageing as well as sun exposure on microbial community diversity. METHOD: The microbial characteristics of the facial skin of 98 adult women aged 18-70 years were studied using 16S rRNA gene sequencing, and differences based on age and reported sun exposure were assessed. RESULTS: The cheek skin's bacterial diversity and richness increased with age. The relative abundance of Cutibacterium decreased with age, while the relative abundance of Corynebacterium, Anaerococcus, Paracoccus, Micrococcus, Kocuria, Kytococcus, and Chryseobacterium increased. In addition, an increase in Micrococcus and a decrease in Cutibacterium were observed in volunteers with more than 2 h of daily sun exposure compared to volunteers with <2 h of daily sun exposure. Under low-sunlight conditions, Cutibacterium was more prevalent in the youth group, and Corynebacterium, Anaerococcus, and Kytococcus were more prevalent in the older group. CONCLUSION: The diversity and composition of the bacterial community on the cheeks are affected by age and extrinsic factors (sun exposure) may also play a role in this.
OBJECTIF: Étudier les effets de l'âge sur la structure de la communauté microbienne et comprendre les effets du vieillissement chronologique ainsi que de l'exposition au soleil sur la diversité de la communauté microbienne. MÉTHODE: Les caractéristiques microbiennes de la peau du visage de 98 femmes adultes âgées de 18 à 70 ans ont été étudiées à l'aide du séquençage génétique de l'ARNr 16S, et les différences basées sur l'âge et l'exposition au soleil rapportée ont été évaluées. RÉSULTAT: La diversité et la richesse bactériennes de la peau des joues ont augmenté avec l'âge. L'abondance relative de Cutibacterium a diminué avec l'âge, tandis que l'abondance relative de Corynebacterium, Anaerococcus, Paracoccus, Micrococcus, Kocuria, Kytococcus et Chryseobacterium a augmenté. De plus, une augmentation de Micrococcus et une diminution de Cutibacterium ont été observées chez des volontaires ayant été exposés au soleil pendant plus de 2 heures par jour par rapport à des volontaires ayant été exposés au soleil pendant moins de 2 heures par jour. Dans des conditions de faible luminosité, Cutibacterium était plus prévalent dans le bras des personnes jeunes, et Corynebacterium, Anaerococcus et Kytococcus étaient plus prévalents dans le bras des personnes plus âgées. CONCLUSION: La diversité et la composition de la communauté bactérienne sur les joues sont affectées par l'âge et des facteurs extrinsèques (exposition au soleil) peuvent également y jouer un rôle.
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BACKGROUND: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. METHODS: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. RESULTS: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. CONCLUSIONS: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Infecciones Comunitarias Adquiridas , Herpesvirus Humano 1 , Pruebas de Sensibilidad Microbiana , Filogenia , Secuenciación Completa del Genoma , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Humanos , Acinetobacter baumannii/genética , Acinetobacter baumannii/patogenicidad , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , China/epidemiología , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Animales , Virulencia/genética , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/patogenicidad , Herpesvirus Humano 1/aislamiento & purificación , Antibacterianos/farmacología , Factores de Virulencia/genética , Herpes Simple/virología , Neumonía Bacteriana/microbiología , Masculino , Genoma Bacteriano , Mariposas Nocturnas/microbiología , Mariposas Nocturnas/virologíaRESUMEN
COVID-19 has emerged as a global pandemic, challenging the world's economic and health systems. Human oral microbiota comprises the second largest microbial community after the gut microbiota and is closely related to respiratory tract infections; however, oral microbiomes of patients who have recovered from COVID-19 have not yet been thoroughly studied. Herein, we compared the oral bacterial and fungal microbiota after clearance of SARS-CoV-2 in 23 COVID-19 recovered patients to those of 29 healthy individuals. Our results showed that both bacterial and fungal diversity were nearly normalized in recovered patients. The relative abundance of some specific bacteria and fungi, primarily opportunistic pathogens, decreased in recovered patients (RPs), while the abundance of butyrate-producing organisms increased in these patients. Moreover, these differences were still present for some organisms at 12 months after recovery, indicating the need for long-term monitoring of COVID-19 patients after virus clearance.
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COVID-19 , Microbiota , Micobioma , Humanos , SARS-CoV-2 , Bacterias/genéticaRESUMEN
CVST is a type of venous stroke that mainly affects young adults with no reliable diagnostic markers and effective treatment strategies for secondary pathologies. However, the underlying pathological molecular mechanisms remain unclear. Here, we systematically analyzed the molecule profiling of the cerebrospinal fluid (CSF) in CVST patients via tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for the diagnosis and treatment of CVST. Five CVST patients and five control patients were selected, and CSF samples were analyzed by TMT proteomics. Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed. Besides, parallel reaction monitoring (PRM) was utilized to validate the DEPs. 468 differentially expressed proteins were screened, 185 of which were up-regulated and 283 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis displayed that these proteins were significantly enriched in multiple pathways related to a variety of pathophysiological processes. PRM verification showed that apolipoprotein E, MMP-2, neuroserpin, clusterin, and several other molecules were down-regulated. These identified proteins reveal unique pathophysiological characteristics secondary to CVST. Further characterization of these proteins in future research could enable their application as potential therapeutic targets and biomarkers in CVST therapy. SIGNIFICANCE: Cerebral venous sinus thrombosis (CVST) is an underrated and potentially fatal cause of stroke with a reported mortality of 5-10% worldwide. Currently, in addition to anticoagulant and thrombolytic therapy, effective treatments targeting the injured brain parenchyma after CVST remain limited. Besides, accurate diagnostic markers are still sorely lacking. In the present study, we will detect the alterations of the CSF protein spectrum of CVST patients by TMT technique, screen differentially expressed proteins, analyze the functions of these signals through bioinformatics methods, and finally validate the key molecules through parallel reaction monitoring (PRM) technique. Collectively, the study aimed to offer a reference for the discovery of specific protein/pathway alterations in the CSF of CVST patients and further reveal the underlying pathogenesis, thereby providing evidence for the diagnosis and treatment of CVST.
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Trombosis de los Senos Intracraneales , Accidente Cerebrovascular , Adulto Joven , Humanos , Proteómica , Trombosis de los Senos Intracraneales/complicaciones , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de los Senos Intracraneales/terapia , Resultado del Tratamiento , Anticoagulantes , Accidente Cerebrovascular/complicacionesRESUMEN
Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.
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COVID-19 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Vacunas , Humanos , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Monoclonales , Anticuerpos ampliamente neutralizantes , Anticuerpos Antivirales , Glicoproteína de la Espiga del CoronavirusRESUMEN
The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.
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Background: The transvenous endovascular approach has become an optimal method for the treatment of cerebrovascular diseases. This procedure might cause iatrogenic damage to the chordae willisii (CW) in the straight sinus. However, little literature has been found to support this hypothesis. Objective: To investigate the possible damage of CW in the straight sinus during a transvenous endovascular procedure. Materials and Methods: The features of the CW from 38 cadaveric heads were observed via an endoscope mimicking a mechanical thrombectomy procedure in the straight sinus. Endoscopic observation and light microscopy examination were used to assess the damage of the CW throughout the procedure. Results: Valve-like lamellae and longitudinal lamellae were found predominantly in the posterior portion of the straight sinus. Trabeculae were present in both the anterior and posterior portions of the straight sinus. Samples treated with a stent had a significantly higher rate of Grade 1 damage during the eight procedures compared with samples treated with a balloon (P = 0.02). The incidence of damage to the CW surface was higher in the stent group than in the balloon group (P = 0.00). The use of stent or balloon did not increase the rate of CW damage during repeated experiments. Conclusions: The stent or balloon navigation through the straight sinus can cause minor damage to the CW. Frequent uses of retrograde navigation through the straight sinus do not seem to increase the possibility of damage to CW.
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Senos Craneales , Procedimientos Endovasculares , Humanos , StentsRESUMEN
BACKGROUND: Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS-STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear. METHODS: A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2'3'-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry. RESULTS: cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS-STING axis. RU.521 decreased the levels of 2'3'-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1ß, and cleaved IL-1ß/pro-IL-1ß. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2'3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA. CONCLUSIONS: Our data demonstrate that repression of the cGAS-STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.
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Inflamasomas , Proteínas de la Membrana/metabolismo , Piroptosis , Animales , Modelos Animales de Enfermedad , Humanos , Inflamasomas/metabolismo , Interferones , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedades Neuroinflamatorias , Nucleotidiltransferasas/metabolismo , ARN Interferente Pequeño/genética , Transducción de Señal/fisiologíaRESUMEN
We know little about the antigen bias in SARS-CoV-2 humoral response and the epitopes of spike recognized by the immune system in asymptomatic (AS) patients and symptomatic (S) patients. Here, we used a microarray to evaluate the humoral immune response in the sera collected from 33 COVID-19-recovered patients up to 1 year. We found that the levels of IgG and IgM induced by the 23 proteins differed significantly in the same patients, and were able to distinguish AS and S patients. The N- and S-specific antibodies were detected even at 12 months after onset. Five epitopes were identified to be associated with the clinical adverse events, and three peptides located in RBD. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses between AS and S recovered patients and provide insights to promote precise development of SARS-CoV-2 vaccines.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Humanos , Inmunidad Humoral , Glicoproteína de la Espiga del CoronavirusRESUMEN
BACKGROUND: Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. METHODS: IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. DISCUSSION: To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.
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Encefalitis , Meningitis , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Humanos , Metagenoma , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVES: Evidence is currently accumulating for the role of inflammation in cerebral venous thrombosis (CVT). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/high-density lipoprotein ratio (MHR), and systematic immune-inflammation index (SII) are easily obtainable indicators of systemic inflammations. However, there were few studies on the relationship between them and CVT. Therefore, we aimed to evaluate the connection between the occurrence of CVT and the inflammatory markers described. MATERIALS AND METHODS: The samples from 150 participants (including 90 CVT and 60 primary headaches as controls) with similar baseline characteristics were collected in this retrospective study. The NLR, PLR, MHR, SII and file records were employed to compare CVT patients with the control group. RESULTS: The levels of NLR (3.93 [2.27, 7.87] vs. 1.65 [1.31, 2.06], P < 0.001), PLR (149.52 [98.39, 198.82] vs. 107.34 [83.31, 129.47], P < 0.001), SII (896.84 [559.89, 1591.87] vs. 382.45 [273.51, 520.92], P < 0.001) and MHR (0.51 [0.40, 0.64] vs. 0.41 [0.29, 0.53], P = 0.001) were significantly higher in the CVT group. After multivariate logistic regression analysis, the SII degree (13.136, [5.675, 30.407], P < 0.001) and MHR degree (2.620, [1.123, 6.113], P < 0.01) were found as independent predictors of CVT. CONCLUSIONS: NLR, PLR, SII, and MHR may be able to assist in the diagnosis of CVT which confirmed that inflammation played an important role in CVT.
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Inflamación , Trombosis Intracraneal , Humanos , Inflamación/epidemiología , Trombosis Intracraneal/epidemiología , Estudios RetrospectivosRESUMEN
Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Acrecentamiento Dependiente de Anticuerpo , Epítopos/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/uso terapéutico , Reacciones Antígeno-Anticuerpo , COVID-19/inmunología , COVID-19/virología , Línea Celular , Niño , Análisis por Conglomerados , Femenino , Humanos , Concentración 50 Inhibidora , Masculino , Persona de Mediana Edad , Dominios Proteicos/inmunología , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto Joven , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: We aimed to identify any differences in the clinical characteristics of patients treated in Zhoushan Hospital and Wuhan Fourth Hospital, Gutian campus to provide insights into measures to better control the coronavirus disease 2019 (COVID-19) pandemic and treat COVID-19 patients. METHODS: All cases included in this retrospective study from January 10, 2020 to March 15, 2020 were confirmed by laboratory detection of SARS-CoV-2. Data of epidemiological characteristics, clinical characteristics, laboratory results, radiological findings, treatments, and outcomes were obtained from electronic medical records and compared between the patient groups. RESULTS: A correlation analysis was performed to detect correlations between the serum C-reactive protein (CRP) level and other laboratory findings. COVID-19 patients treated in Wuhan more commonly had fever and shortness of breath, and less commonly had headache compared to those treated in Zhoushan (P=0.002, 0.039, and 0.015, respectively). The period from illness onset to hospitalization in Wuhan was 11.7±7.2 days, which was longer than that in Zhoushan (4.2±3.7 days; P=0.002), whereas the period from illness onset to shortness of breath in Wuhan was 5.4±5.0 days, which was shorter than that in Zhoushan (14.0±5.6 days; P=0.020). Computed tomography scans showed linear opacities, reticulation, and patchy shadows more commonly in cases treated in Wuhan (P=0.016, 0.013, and 0.008, respectively). The mean CRP level in Zhoushan patients was lower than that in Wuhan patients (P<0.001), and the CRP level was correlated with several laboratory findings related to the immune response. CONCLUSIONS: COVID-19 patients treated at Wuhan Fourth Hospital, Gutian campus had more severe symptoms than those treated at Zhoushan Hospital. Earlier in-hospital treatment, as conducted in Zhoushan, may be beneficial in reducing the severity of illness in COVID-19 patients. Additionally, the correlations between the CRP level and indicators of immune function in COVID-19 patients warrant further investigation.
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COVID-19 , SARS-CoV-2 , Tos , Humanos , Pandemias , Estudios RetrospectivosRESUMEN
BACKGROUND: To explore the kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19. METHODS: This observational study enrolled 20 patients with COVID-19, who were hospitalized between January 20-April 6, 2020, in the two COVID-19 designated hospitals of Zhoushan, Zhejiang and Rushan, Shandong, China, The laboratory findings, imaging, serum response to viral infection, and viral RNA level in the throat and stool samples were assessed from onset to recovery phase in patients with COVID-19. RESULTS: SARS-COV-2 RNA was positive as early as day four. It remained positive until day 55 post-onset in the sputum-throat swabs and became negative in most cases (55%) within 14 days after onset. Lymphocytopenia occurred in 40% (8/20) of patients during the peak infection period and returned to normal at week five. The most severe inflammation in the lungs appeared in week 2 or 3 after onset, and this was completely absorbed between week 6 and 8 in 85.7% of patients. All patients had detectable antibodies to the receptor binding domain (RBD), and 95% of these patients had IgG to viral N proteins. The antibody titer peaked at week four. Anti-S IgM was positive in 7 of 20 patients after week three. CONCLUSIONS: All COVID-19 patients in this study were self-limiting and recovered well though it may take as long as 6-8 weeks. Our findings on the kinetic changes in imaging, serum response to viral infection and viral RNA level may help understand pathogenesis and define clinical course of COVID-19.
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Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/inmunología , Pulmón/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/inmunología , Adolescente , Adulto , Anciano , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Niño , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Proteínas de la Nucleocápside de Coronavirus , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Proteínas de la Nucleocápside/inmunología , Pandemias , Fosfoproteínas , Neumonía Viral/epidemiología , Neumonía Viral/virología , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Esputo/virología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Some structure might be encountered with endovascular procedures within the straight sinus and is not now readily seen on digital subtraction angiography (DSA). We investigated the morphological and histological characteristics of the straight sinus, chordae willisii (CW), and junction between the great cerebral vein (GCV) and straight sinus. A total of 22 cadaveric heads and 135 patients were analyzed with either anatomic dissection or neuroimaging. The morphological features of the CW and the junction between the GCV and straight sinus were analyzed by endoscope. The histology of the junction between the GCV and straight sinus was evaluated under the microscope with staining for elastic fiber, Masson's, and immunohistochemistry. We found that fold, elevation, small bugle, or nodule and CW were detected by endoscope in the straight sinus. The most common type of CW was valve-like lamellae, which comprised 40.46% of all CW. Three different types of junctions between the GCV and straight sinus were identified: type 1 has folds in the GCV and elevation on the floor of the straight sinus; type 2 has folds and a small bugle; and type 3 presents with an intraluminal nodule located at the opening of the GCV. Compared with arachnoid granulation, the nodule consists of smooth muscle fibers and higher rate of elastic fibers. Understanding the detailed anatomy of the straight sinus may help surgeons to avoid procedural difficulties and to achieve higher success rate.
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Cerebral venous sinus thrombosis (CVST) is a rare type of stroke, which is life-threatening in severe cases. However, considerably less attention has been concentrated on the mechanism of neural cell damage after CVST. This study aims to investigate the role of endoplasmic reticulum stress, oxidative stress, and pyroptosis in a well-established rodent model of CVST. Rat brains were harvested at 0 h, 6 h, days 1, days 3, days 7, and days 14 post-CVST for measurement of corresponding indexes. Endoplasmic reticulum stress sensors (including protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme-1α (IRE1α)), oxidative stress markers (thioredoxin-interacting protein (TXNIP) and peroxynitrite), NLRP3, caspase p20, IL-1ß, and gasdermin D (GSDMD, an indicator of pyroptosis) were separately evaluated by Western-blot and Immunohistochemistry/Immunofluorescence. Co-immunoprecipitation and Fluorescent double-labeling were employed to probe into the relationship between TXNIP/peroxynitrite and NLRP3 inflammasome. In the damaged cortex region, profuse p-PERK, p-IRE1α, TXNIP were produced and predominantly localized in neurons accompanied by a small amount expressed in microglia and astrocytes. The levels of 3-nitrotyrosine (3-NT, as a footprint of peroxynitrite), NLRP3, caspase p20, IL-1ß, and GSDMD were distinctly elevated post-CVST and cellular localization of peroxynitrite, NLRP3, caspase p20, and IL-1ß was largely observed in neurons and/or microglia. Importantly, sites of enhanced TXNIP and 3-NT immunoreactivity were colocalized with increased NLRP3 staining, indicating the involvement of TXNIP and peroxynitrite in NLRP3 inflammasome activation and subsequent pyroptosis. Besides, co-immunoprecipitation also hinted that there might be an interaction or causality between TXNIP/peroxynitrite and NLRP3 inflammasome. We concluded that endoplasmic reticulum stress and oxidative stress may jointly lead to neuronal NLRP3 inflammasome activation and pyroptosis after CVST.
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Proteínas de Ciclo Celular/metabolismo , Estrés del Retículo Endoplásmico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo , Piroptosis , Trombosis de los Senos Intracraneales/patología , Animales , Inmunohistoquímica , Inflamasomas , Sistema de Señalización de MAP Quinasas , Masculino , Neuronas/metabolismo , Ácido Peroxinitroso/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient's serum to establish a solid pathogen diagnosis. CASE PRESENTATION: We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69-year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient's abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for 7 days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient's serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure. CONCLUSION: The present case provides strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.
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Mordeduras y Picaduras , Phlebovirus/genética , Filogenia , Síndrome de Trombocitopenia Febril Grave/virología , Garrapatas/virología , Anciano , Animales , China , Resultado Fatal , Humanos , Masculino , Insuficiencia Multiorgánica , Phlebovirus/clasificación , Phlebovirus/patogenicidad , ARN Viral/sangre , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Síndrome de Trombocitopenia Febril Grave/transmisiónRESUMEN
Rapid detection of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for its control and surveillance. In this study, a rapid isothermal real-time reverse-transcription recombinase polymerase amplification (RT-RPA) assay was developed for the detection of SFTSV. The detection limit at 95% probability was 241 copies per reaction. A test of 120 serum samples of suspected severe fever with thrombocytopenia syndrome (SFTS) patients revealed that the sensitivity and specificity of the RT-RPA assay was approximately 96.00% (95%CI: 80.46%-99.79%) and 98.95% (95% CI: 94.28%-99.95%), respectively; the kappa value was 0.9495 (Pï¼0.001). The Bland-Altman analysis showed that 87.50% of the different data points were located within the 95% limits of agreement, indicating a good correlation between the results from RT-RPA assays and those of RT-qPCR assays. In conclusion, the rapid and efficient RT-RPA assay can be a promising candidate for point-of-care detection method of SFTSV.
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Bioensayo/métodos , Recombinasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Síndrome de Trombocitopenia Febril Grave/virología , Humanos , Phlebovirus , Sensibilidad y EspecificidadRESUMEN
Enhanced recovery after surgery (ERAS) is a multiprofessional, multidisciplinary and evidence-based program that aims to reduce complications, improve overall prognosis, shorten hospital stays, and promote fast recovery following major surgery. Nurses play a crucial role in the successful implementation of the ERAS program. Therefore, this research focuses on the trajectory optimized and acquired by nurses in the enhanced recovery of elderly patients undergoing radical surgery for lung cancer. This study concludes that the implementation of the proposed ERAS preoperative point-of-care trajectory is highly beneficial for improved outcomes and enhanced recovery of geriatric patients following lung surgery.
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Recuperación Mejorada Después de la Cirugía/normas , Tiempo de Internación/estadística & datos numéricos , Neoplasias Pulmonares/enfermería , Neoplasias Pulmonares/cirugía , Atención Perioperativa , Procedimientos Quirúrgicos Pulmonares/métodos , Proyectos de Investigación , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Background and Purpose- The relationship between infarct dimensions and neurological progression in patients with acute pontine infarctions remains unclear. This study aimed to investigate the morphometric predictive value of magnetic resonance imaging for early neurological deterioration (END) in acute pontine infarction. Methods- We included all patients admitted to our department having an acute ischemic stroke in the pons. The ventrodorsal length multiplied by thickness was measured as parameters of infarct size. END was defined as an incremental increase in the National Institutes of Health Stroke Scale score by ≥1 point in motor power, or ≥2 points in the total score within the first week after admission. Results- We enrolled 407 patients, and 114 (28.0%) patients were diagnosed with END. Adjusted logistic regression analyses showed the maximum length multiplied by thickness was independently associated with END (odds ratio, 4.580 [95% CI, 2.909-7.210]). The sensitivity, specificity, and area under the curve were 77.2%, 79.2%, and 0.843, respectively, in the receiver operating characteristic curve analysis of maximum length multiplied by thickness for predicting END. Conclusions- These results suggest that the maximum length multiplied by thickness may be a possible predictor in the evaluation of progression with isolated acute pontine infarction. The extent of the pontine infarction along the conduction tract may contribute to deterioration.