179 research outputs found

    Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

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    Background: Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy (IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy (SST). Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors. Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group (n = 25) or the treatment group (n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST. Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies (250-8000 Hz) compared with the control group (P  0.05). Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL

    Analysis of cognitive function and its related factors after treatment in Meniere’s disease

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    A growing body of research recently suggested the association between vestibular dysfunction and cognitive impairment. Meniere’s disease (MD), a common clinical vestibular disorder, is usually accompanied by hearing loss and emotional stress, both of which may mediate the relationship between vestibule dysfunction and cognition. It is currently unknown whether the cognitive decline in MD patients could improve through treatment and how it relates to multiple clinical characteristics, particularly the severity of vertigo. Therefore, in the present study, the MD patients were followed up for 3, 6, and 12 months after treatment, and the cognitive functions, vertigo symptoms, and related physical, functional, and emotional effects of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and Dizziness Handicap Inventory (DHI), aiming to explore the change in cognition before and after therapy and the correlation with various clinical features. It was found that cognitive decline in MD patients compared to healthy controls before therapy. Importantly, this cognitive impairment could improve after effective therapy, which was related to the severity of vertigo, especially in functional and physical impacts. Our results support the view that vestibular dysfunction is a potentially modifiable risk factor for cognitive decline

    Efficient exon skipping by base-editor-mediated abrogation of exonic splicing enhancers

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    Summary: Duchenne muscular dystrophy (DMD) is a severe genetic disease caused by the loss of the dystrophin protein. Exon skipping is a promising strategy to treat DMD by restoring truncated dystrophin. Here, we demonstrate that base editors (e.g., targeted AID-mediated mutagenesis [TAM]) are able to efficiently induce exon skipping by disrupting functional redundant exonic splicing enhancers (ESEs). By developing an unbiased and high-throughput screening to interrogate exonic sequences, we successfully identify novel ESEs in DMD exons 51 and 53. TAM-CBE (cytidine base editor) induces near-complete skipping of the respective exons by targeting these ESEs in patients’ induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Combined with strategies to disrupt splice sites, we identify suitable single guide RNAs (sgRNAs) with TAM-CBE to efficiently skip most DMD hotspot exons without substantial double-stranded breaks. Our study thus expands the repertoire of potential targets for CBE-mediated exon skipping in treating DMD and other RNA mis-splicing diseases

    Economic evaluations of 13-valent pneumococcal conjugate vaccine: a systematic review

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    Introduction Studies on economic evaluations of the 13-valent pneumococcal conjugate vaccine (PCV13) have been increasing over the last decade. No systematic reviews have synthesized the evidence of economic evaluations of the PCV13. Areas covered We systematically searched the literature which published on peer-reviewed journals from January 2010 to June 2022. The literature search was conducted in the following electronic databases: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database. We identified 1827 records from the database search. After excluding 511 duplicates, 1314 records were screened, of which 156 records were retained for the full-text reviews. A total of 44 studies were included in the review. Among the included studies, 33 studies were economic evaluations of PCV13 among children, and 11 studies were conducted among adults. The literature search initiated in April, 2022, and updated in June 2022. Expert opinion Vaccination with PCV13 was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccine or several other pneumococcal vaccines (e.g. PCV10, PPV23). Future research is advised to expand economic evaluations of PCV13 combined with dynamic model to enhance methodologic rigor and prediction accuracy

    SWDPM: A Social Welfare-Optimized Data Pricing Mechanism

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    Data trading has been hindered by privacy concerns associated with user-owned data and the infinite reproducibility of data, making it challenging for data owners to retain exclusive rights over their data once it has been disclosed. Traditional data pricing models relied on uniform pricing or subscription-based models. However, with the development of Privacy-Preserving Computing techniques, the market can now protect the privacy and complete transactions using progressively disclosed information, which creates a technical foundation for generating greater social welfare through data usage. In this study, we propose a novel approach to modeling multi-round data trading with progressively disclosed information using a matchmaking-based Markov Decision Process (MDP) and introduce a Social Welfare-optimized Data Pricing Mechanism (SWDPM) to find optimal pricing strategies. To the best of our knowledge, this is the first study to model multi-round data trading with progressively disclosed information. Numerical experiments demonstrate that the SWDPM can increase social welfare 3 times by up to 54\% in trading feasibility, 43\% in trading efficiency, and 25\% in trading fairness by encouraging better matching of demand and price negotiation among traders

    Protective effect of dexmedetomidine on lung injury during one-lung ventilation in elderly patients undergoing radical esophagectomy

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    This study investigated the protective effect of dexmedetomidine (Dex) on lung injury during one-lung ventilation (OLV) in elderly patients undergoing radical esophagectomy with remote ischemic preconditioning (RIPC). Fifty-four esophageal cancer patients undergoing radical esophagectomy were divided into control, RIPC and RIPC+Dex group. During the anesthesia and ventilation in surgery, the RIPC was performed in RIPC group, and the intravenous infusion of Dex based on RIPC was conducted in RIPC+Dex group. At the time immediately before OLV beginning (T1), 60 min of OLV (T2) and end of surgery (T3), the oxygenation index (OI) and respiratory index (RI) were recorded, and the serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were determined. Results showed that, compared with RIPC group, in RIPC+Dex group the OI at T2 and T3 increased, the RI at T2 and T3 decreased, the serum SOD level at T3 increased, the serum MDA level at T3 decreased, the serum TNF-α and IL-6 levels at T2 and T3 decreased (all P < 0.05). In conclusion, for elderly patients undergoing radical esophagectomy with RIPC, Dex can effectively inhibit the oxidative stress and inflammatory response during OLV, thus alleviating the lung injury and reducing the postoperative complications

    Value of a novel Y-Z magnetic totally implantable venous access port in improving the success rate of one-time needle insertion

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    Background and objectivesA totally implantable venous access port (TIVAP) is a commonly used intravenous infusion device for patients receiving chemotherapy or long-term infusion therapy. To improve the success rate of one-time insertion of the Huber needle, we developed a novel Y-Z magnetic TIVAP (Y-Z MTIVAP), which we produced using three-dimensional printing technology.Materials and methodsThe Y-Z MTIVAP includes a magnetic port body and a magnetic positioning device. For testing, we established four venous port implantation models using the two types of TIVAPs and two implantation depth ranges (≤5 mm and >5 mm). Twenty nurses performed Huber needle puncture with the four models, and we recorded the number of attempts required for successful needle insertion, the operation time, and the operator's satisfaction.ResultsThe success rate for one-time needle insertion with the Y-Z MTIVAP was significantly higher than that with the traditional TIVAP at either depth range (100% vs. 75% at ≤5 mm, p = 0.047; 95% vs. 35% at >5 mm, p < 0.001). With increasing implantation depth, the success rate for one-time insertion was significantly reduced with the traditional TIVAP (75% at ≤5 mm vs. 35% vs. >5 mm, p = 0.025), but the success rate with the Y-Z MTIVAP was not significantly affected (100% vs. 95%, p = 1.000). The operation time with the Y-Z MTIVAP was significantly shorter than that with the traditional TIVAP at either depth range (both p < 0.001), and 90% of operators reported that the Y-Z MTIVAP was superior to the traditional TIVAP.ConclusionsThe theoretical design of Y-Z MTIVAP is feasible, and the preliminary in vitro simulation experiment shows that it can significantly improve puncture success rate and shortened operation time

    5-Aminolevulinic acid mitigates the chromium-induced changes in Helianthus annuus L. as revealed by plant defense system enhancement

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    Chromium (Cr) in the soil is one of the major pollutants for agricultural production. This study examined the efficiency of sunflower plants to remediate Cr-contaminated soils using a plant growth regulator, 5-aminolevolinic acid (ALA). At six leaf stage, sunflower plants were exposed to soil-applied Cr (0.15 g kg−1), manganese (Mn, 0.3 g kg−1) and trisodium (S,S)-ethylenediamine-N,N′-disuccinic acid (EDDS, 2.5 mmol kg−1), ALA (10 mg L−1) was sprayed. After ALA treatment, the plants were harvested for further biochemical analyses. Results showed that EDDS and Mn improved the Cr accumulation but restrained plant growth. Conversely, ALA improved the growth of Cr-stressed plants by promoting chlorophyll concentration in the top fully expanded leaves. The bioaccumulation quantity and removal efficiency of sunflowers treated by Cr + EDDS + ALA was improved by 47.92% and 47.94%, respectively, as compared to the Cr treatment. This was further supported by qRT-PCR analysis, where the expression of heavy metal transport genes such as ZIP6 and NRAMP6 and subsequently Cr accumulation in sunflower tissues increased by EDDS, Mn, and ALA application. However, compared with other treatments, ALA ameliorated cellular injury from Cr-stress by uptake or movement of Cr prevention, modulation of antioxidant enzymes, and elimination of reactive oxygen species. Our study suggested that ALA as an ideal option for the phytoremediation of Cr-contaminated soils.The research was sponsored by the Science and Technology Program of Zhejiang Province (2022C02034), and Fundamental Research Funds of Zhejiang Sci-Tech University (14042216-Y). We thank Dr. Li Xie at Bio-ultrastructure Analysis Laboratory of Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University. We also thank Rui Sun from the Agricultural Experiment Station of Zhejiang University for his assistance

    AMPK-Dependent YAP Inhibition Mediates the Protective Effect of Metformin against Obesity-Associated Endothelial Dysfunction and Inflammation

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    Hyperglycemia is a crucial risk factor for cardiovascular diseases. Chronic inflammation is a central characteristic of obesity, leading to many of its complications. Recent studies have shown that high glucose activates Yes-associated protein 1 (YAP) by suppressing AMPK activity in breast cancer cells. Metformin is a commonly prescribed anti-diabetic drug best known for its AMPK-activating effect. However, the role of YAP in the vasoprotective effect of metformin in diabetic endothelial cell dysfunction is still unknown. The present study aimed to investigate whether YAP activation plays a role in obesity-associated endothelial dysfunction and inflammation and examine whether the vasoprotective effect of metformin is related to YAP inhibition. Reanalysis of the clinical sequencing data revealed YAP signaling, and the YAP target genes CTGF and CYR61 were upregulated in aortic endothelial cells and retinal fibrovascular membranes from diabetic patients. YAP overexpression impaired endothelium-dependent relaxations (EDRs) in isolated mouse aortas and increased the expression of YAP target genes and inflammatory markers in human umbilical vein endothelial cells (HUVECs). High glucose-activated YAP in HUVECs and aortas was accompanied by increased production of oxygen-reactive species. AMPK inhibition was found to induce YAP activation, resulting in increased JNK activity. Metformin activated AMPK and promoted YAP phosphorylation, ultimately improving EDRs and suppressing the JNK activity. Targeting the AMPK–YAP–JNK axis could become a therapeutic strategy for alleviating vascular dysfunction in obesity and diabetes

    Table_5_The increasing incidence and high body mass index-related burden of gallbladder and biliary diseases–A results from global burden of disease study 2019.pdf

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    BackgroundGallbladder and biliary diseases are common gastrointestinal conditions associated with huge socioeconomic costs and are considered risk factors for cardiovascular diseases and digestive system cancers. The prevalence and incidence of gallbladder and biliary diseases have not received enough attention from 1990 to 2019. Several non-communicable diseases were associated with the incidence of gallbladder and biliary diseases. It is necessary to clarify the change in the incidence and disability burden of gallbladder and biliary diseases worldwide.MethodsData on high body mass index (BMI)-related disease burden and incidence, years of life lost prematurely, and years lived with disability (YLDs) due to gallbladder and biliary diseases were obtained from the Global Burden of Disease 2019. The estimated annual percentage change was calculated to qualify the gallbladder and biliary disease burden change.ResultsThe global age-standardized incidence rate has increased from 585.35 per 100,000 (95% UI: 506.05–679.86) in 1990 to 634.32 per 100,000 (95% UI: 540.21–742.93) in 2019. And the increase in incidence was positively correlated with rising high BMI-related summary exposure value. The high BMI-related YLDs of gallbladder and biliary diseases have increased worldwide over time. Globally, the 25–49 age group suffered a rapid rise in incidence and high BMI attributable to the YLDs rate of gallbladder and biliary diseases.ConclusionThe global incidence and high BMI-related YLDs of gallbladder and biliary diseases remain prominent to increase over the past 30 years. Notably, the incidence and high BMI-related YLDs among people aged 25–49 years have rapidly increased over time. Therefore, high BMI should be emphasized in strategic priorities for controlling gallbladder and biliary diseases.</p