Nucleic acid aptamer-based electrochemical sensor for the detection of serum P-tau231 and the instant screening test of Alzheimer's disease.

The instant screening of patients with a tendency towards developing Alzheimer's disease (AD) is significant for providing preventive measures and treatment. However, the current imaging-based technology cannot meet the requirements in the early stage. Developing biosensor-based liquid biopsy technology could be overcoming this bottleneck problem. Herein, we developed a simple, low-cost, and sensitive electrochemical aptamer biosensor for detecting phosphorylated tau protein threonine 231 (P-tau231), the earliest and one of the most efficacious abnormally elevated biomarkers of AD. Gold nanoparticles (AuNPs) were electrochemically synthesized on a glassy carbon electrode as the transducer, exhibiting excellent conductivity, and were applied to amplify the electrochemical signal. A nucleic acid aptamer was designed as the receptor to capture the P-tau231 protein, specifically through the formation of an aptamer-antigen complex. The proposed biosensor showed excellent sensitivity in detecting P-tau 231, with a broad linear detection range from 10 to 107 pg/mL and a limit of detection (LOD) of 2.31 pg/mL. The recoveries of the biosensor in human serum ranged from 97.59 to 103.26%, demonstrating that the biosensor could be used in complex practical samples. In addition, the results showed that the developed biosensor has good repeatability, reproducibility, and stability, which provides a novel method for the early screening of AD.

Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model.

Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood-brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/ß-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain-blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/ß-catenin pathway.

Analysis of Related Factors Affecting Facial Nerve Function after Acoustic Neuroma Surgery.

Objective: To investigate the factors affecting facial nerve function after acoustic neuroma surgery and to provide theoretical reference for clinicians to preserve facial nerve function better after surgery. Methods: A retrospective cohort study was conducted to analyze the correlation between postoperative facial nerve function and surgical approach, age, sex, tumor size and adhesion degree of facial nerve in 152 patients with acoustic neuroma. Results: In the choice of surgical approach, there was no significant difference in the anatomy of the complete facial nerve in labyrinth path, retrosigmoid sinus path, and middle cranial fossa path. There was no statistically significant difference between the middle cranial fossa path and the retrosigmoid sinus path in facial nerve function preservation 7 days after surgery. The difference between middle cranial fossa path and labyrinthine path was statistically significant (P < 0.01). There were statistically significant differences between labyrinth path and retrosigmoid sinus path (P < 0.05). Logistic multivariate regression analysis showed that the operative approach and the degree of adhesion between tumor and facial nerve were the risk factors affecting functional preservation of facial nerve 7 days after surgery. Age and the degree of adhesion between tumor and facial nerve were the risk factors for functional preservation of facial nerve 1 year after operation. Conclusion: The facial nerve function injury in patients with acoustic neuroma may be related to the choice of surgical approach, the adhesion degree of tumor and facial nerve, and their age. Clinicians need to comprehensively evaluate the risk factors before surgery, so as to achieve individualized treatment to protect the integrity of postoperative facial nerve function of patients.

16SrDNA-Based Detection Technology in Patients with Chronic Pharyngitis to Analyze the Distribution Characteristics of Pharyngeal Bacteria.

In order to analyze the distribution characteristics of pharyngeal bacteria in patients with chronic pharyngitis (CP) by 16SrDNA-based detection technology, a prospective study is conducted to collect pharyngeal secretion samples from patients diagnosed with CP who are admitted to the Otorhinolaryngology Department of The Third People's Hospital of Shenzhen from May 2021 to September 2021. Among them, 11 cases are chronic simple pharyngitis (CSP), 11 cases are chronic hypertrophic pharyngitis (CHP), and 8 cases are healthy subjects. All samples are detected by the 16SrDNA technique and analyzed by bioinformatics. 55724.64 ± 1772.80, 53697.73 ± 2252.19, and 55177.5 ± 1661.80 optimized sequences are obtained by 16SrDNA sequencing. The α diversity analysis of pharyngeal microflora showed that the abundance index SOBS of pharyngeal microflora is upregulated in patients with CHP compared with normal controls (NC), but the diversity index of pharyngeal bacteria in the three groups is not significantly changed, indicating that the abundance of pharyngeal bacteria in the CHP group is increased. The ß diversity analysis of pharyngeal microflora showed that the three groups are similar in structure and composition, and there is no significant statistical difference. The structural difference analysis of pharyngeal flora combined with LEfSe difference analysis showed that at the phylum level, the relative abundance of Spirochaetes and Synergistetes in the CHP group is significantly higher than that in the CSP group. At the genus level, the relative abundance of opportunistic pathogens such as Selenomonas and Campylobacter increased significantly in the CSP group. The relative abundance of Escherichia, Mycoplasma, and Porphyromonas are significantly increased in the CHP group. The abundance of beneficial symbiotic bacteria decreased significantly in patients with CP. The pharyngitis of patients with CP is characterized by an increase in the abundance of pharyngitis, changes in the structure of pharyngitis, a decline in the symbiotic beneficial bacteria, and an increase in the content of opportunistic pathogens, which may be closely related to the onset and development of CP.

Approaching Otolaryngology Patients During the COVID-19 Pandemic.

Objective. To describe coronavirus disease 2019 (COVID-19) patient presentations requiring otolaryngology consultation and provide recommendations for protective measures based on the experience of ear, nose, and throat (ENT) departments in 4 Chinese hospitals during the COVID-19 pandemic. Study Design. Retrospective case series. Setting. Multicenter. Subjects and Methods. Twenty hospitalized COVID-19 patients requiring ENT consultation from 3 designated COVID-19 hospitals in Wuhan, Shanghai, and Shenzhen were identified. Data on demographics, comorbidities, COVID-19 symptoms and severity, consult reason, treatment, and personal protective equipment (PPE) use were collected and analyzed. Infection control strategies implemented for ENT outpatients and emergency room visits at the Eye and ENT Hospital of Fudan University were reported. Results. Median age was 63 years, 55% were male, and 95% were in severe or critical condition. Six tracheotomies were performed. Posttracheotomy outcomes were mixed (2 deaths, 2 patients comatose, all living patients still hospitalized). Other consults included epistaxis, pharyngitis, nasal congestion, hyposmia, rhinitis, otitis externa, dizziness, and tinnitus. At all hospitals, powered air-supply filter respirators (PAPRs) were used for tracheotomy or bleeding control. PAPR or N95-equivalent masks plus full protective clothing were used for other complaints. No inpatient ENT providers were infected. After implementation of infection control strategies for outpatient clinics, emergency visits, and surgeries, no providers were infected at the Eye and ENT Hospital of Fudan University. Conclusions and Relevance. COVID-19 patients require ENT consultation for many reasons, including tracheotomy. Otolaryngologists play an indispensable role in the treatment of COVID-19 patients but, due to their work, are at high risk of exposure. Appropriate protective strategies can prevent infection of otolaryngologists.

A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer's Disease.

BACKGROUND Alzheimer's disease (AD) is the most common type of dementia. The objective of this paper is to propose a novel method to identify differential pathways in hippocampus AD. MATERIAL AND METHODS We proposed a combined method by merging existed methods. Firstly, pathways were identified by four known methods (DAVID, the neaGUI package, the pathway-based co-expressed method, and the pathway network approach), and differential pathways were evaluated through setting weight thresholds. Subsequently, we combined all pathways by a rank-based algorithm and called the method the combined method. Finally, common differential pathways across two or more of five methods were selected. RESULTS Pathways obtained from different methods were also different. The combined method obtained 1639 pathways and 596 differential pathways, which included all pathways gained from the four existing methods; hence, the novel method solved the problem of inconsistent results. Besides, a total of 13 common pathways were identified, such as metabolism, immune system, and cell cycle. CONCLUSIONS We have proposed a novel method by combining four existing methods based on a rank product algorithm, and identified 13 significant differential pathways based on it. These differential pathways might provide insight into treatment and diagnosis of hippocampus AD.