oral treatment

口腔治疗
  • 文章类型: Journal Article
    这项研究解决了通过遗传密码扩展在无义突变的位点特异性抑制中利用次优非天然氨基酸(UAA)的挑战,这对于蛋白质修复和精确的属性定制至关重要。通过将UAA转化为离子液体,开发了一种简便且经济的口服液体制剂。显着提高其生物利用度和组织积累。经验数据显示生物利用度增加10倍,局灶性组织积累增加13倍,以及UAA注册效率的显著提高。在mdx小鼠中口服4周,杜氏肌营养不良症(DMD)的模型,展示了该配方前所未有的治疗潜力,高达40%的肌营养不良蛋白表达恢复和75%的正常纤维功能恢复,超越现有的治疗方法,并表现出实质性的长期安全性。这项研究提出了一种有效的口服剂型,可以显着改善体内UAA掺入靶蛋白,在无义突变介导的疾病的治疗方面取得了重大进展,并为临床翻译提供了可观的希望。
    This investigation addresses the challenge of suboptimal unnatural amino acid (UAA) utilization in the site-specific suppression of nonsense mutations through genetic code expansion, which is crucial for protein restoration and precise property tailoring. A facile and economical oral liquid formulation is developed by converting UAAs into ionic liquids, significantly enhancing their bioavailability and tissue accumulation. Empirical data reveal a 10-fold increase in bioavailability and up to a 13-fold rise in focal tissue accumulation, alongside marked improvements in UAA incorporation efficiency. A 4-week oral administration in mdx mice, a model for Duchenne muscular dystrophy (DMD), demonstrates the formulation\'s unprecedented therapeutic potential, with up to 40% dystrophin expression restoration and 75% recovery of normal fiber functions, surpassing existing treatments and exhibiting substantial long-term safety. This study presents a potent oral dosage form that dramatically improves UAA incorporation into target proteins in vivo, offering a significant advance in the treatment of nonsense mutation-mediated disorders and holding considerable promise for clinical translation.
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  • 文章类型: Clinical Trial
    背景:瘢痕疙瘩的治疗仍然是一个棘手而复杂的临床问题,尤其是伤口诱发的多发性瘢痕疙瘩,严重烧伤,种族背景或文化行为,或无法解释的皮肤愈合。主流治疗在治疗多发性瘢痕疙瘩方面具有有限的功效。由于没有无痛苦和方便的口服治疗,应制定口腔治疗策略。
    目的:本研究旨在探讨托法替尼口服治疗瘢痕疙瘩的疗效及机制。
    方法:我们招募了7例瘢痕疙瘩患者,每天两次口服5mg托法替尼,最长随访12周。患者和观察者疤痕评估量表(POSAS)温哥华疤痕量表(VSS),ANTERA3D摄像机,和DUB皮肤扫描仪75用于评估病变的特征。进行免疫组织化学以评估胶原蛋白合成,扩散,和相对分子途径。此外,在体外评估了托法替尼对瘢痕疙瘩成纤维细胞的影响.
    结果:口服托法替尼12周后,POSAS的显著改进,VSS,皮肤病学生活质量指数(DLQI)评分(p<0.05)。音量,病变高度,瘢痕疙瘩真皮厚度降低(p<0.05)。此外,胶原蛋白I的表达显着下降,给药12周后观察Ki67、p-STAT3和p-SMAD2。体外实验表明,托法替尼治疗通过抑制STAT3和SMAD2途径抑制成纤维细胞增殖和胶原蛋白I合成。
    结论:托法替尼,一种治疗瘢痕疙瘩的新候选口服药物,可以通过抑制胶原蛋白合成和抑制成纤维细胞增殖来减少瘢痕疙瘩的体积,并减轻瘙痒和疼痛,以获得更好的生活质量。
    BACKGROUND: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated.
    OBJECTIVE: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients.
    METHODS: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro.
    RESULTS: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway.
    CONCLUSIONS: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.
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  • 文章类型: Journal Article
    母猪免疫球蛋白A(IgA)对于评估仔猪对猪流行性腹泻病毒(PEDV)的保护能力至关重要。这里,我们报道了由中国仓鼠卵巢(CHO)细胞表达的治疗性嵌合抗PEDVIgG/IgA,用于口服治疗PED。嵌合抗PEDVIgG/IgA由CHO细胞系产生,其中通过结合VH构建重链,PEDVIgGmAb8A3的Cγ1和铰链区,以及小家鼠免疫球蛋白α链的Cα2和Cα3结构域。嵌合抗PEDVIgG/IgA可中和CV777(G1)株,P014(G2)和HN1303(G2)在体外有效,显示广谱中和活性。体内激发实验表明,在CHO细胞上清液中产生的嵌合抗PEDVIgG/IgA(9C4)可以减轻仔猪中PEDV感染的临床腹泻症状。总的来说,我们的研究表明,从CHO细胞系上清液产生的嵌合抗PEDVIgG/IgA可以有效地减轻仔猪的PEDV感染,这也为通过J链引入来构建功能齐全的分泌型IgA以最大化抗体治疗效果奠定了基础。
    Immunoglobulin A (IgA) of sows is critically important for assessing piglets\' protective capacity against porcine epidemic diarrhea virus (PEDV). Here, we report a therapeutic chimeric anti-PEDV IgG/IgA expressed by Chinese hamster ovary (CHO) cells for oral treatment of PED. The chimeric anti-PEDV IgG/IgA was produced by the CHO cell lines, in which the heavy chain was constructed by combining the VH, Cγ1 and hinge regions of PEDV IgG mAb 8A3, and the Cα2 and Cα3 domains of a Mus musculus immunoglobulin alpha chain. The chimeric anti-PEDV IgG/IgA could neutralize the strains of CV777 (G1), P014 (G2) and HN1303 (G2) in vitro effectively, showing broad-spectrum neutralization activity. The in vivo challenge experiments demonstrated that chimeric anti-PEDV IgG/IgA (9C4) produced in the CHO cell supernatant could alleviate clinical diarrhea symptoms of the PEDV infection in piglets. In general, our study showed that chimeric anti-PEDV IgG/IgA produced from CHO cell line supernatants effectively alleviates PEDV infection in piglets, which also gives the foundation for the construction of fully functional secretory IgA by the J chain introduction to maximize the antibody therapeutic effect.
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  • 文章类型: Journal Article
    OBJECTIVE: Explore how to manage oral healthcare during the COVID-19 outbreak.
    METHODS: In order to solve oral healthcare during the COVID-19 outbreak, our hospital has taken effective measures: build a team of experts, which provide a 24-h hotline, online video consultation, and online training and push popular science articles on WeChat. For the treatment of emergency patients aside from routine epidemic prevention measures, some special measures for oral treatment need to be added.
    RESULTS: From January 23, 2020, to March 2, 2020, a total of 3035 patients received oral therapy during the COVID-19 epidemic in our hospital. To our knowledge, no oral health worker or patient has been infected with COVID-19 due to oral treatment, and no patients have complained about the suspension of treatment by complaints hotline.
    CONCLUSIONS: COVID-19 is a novel challenge for oral healthcare. Attention should be paid to oral healthcare during the outbreak of COVID-19.
    CONCLUSIONS: These experiences of oral healthcare can be used as a reference by stomatological hospitals and oral clinics during public health emergencies.
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  • 文章类型: Journal Article
    Obstructive sleep apnea syndrome (OSAS) is a common clinical disease with high incidence and low treating proportion, difficult evaluation, and complicated nosogenesis. OSAS can cause systematic impairments. Various treatment methods were applied in clinical setting with the tendency of cross-disciplinary promotion. Oral treatment plays an exceedingly important role in OSAS research and therapy. This study reports the oral treatment involving OSAS therapy.
    阻塞性睡眠呼吸暂停综合征(OSAS)是临床常见病和多发病,患病率高,求医率低,难以评判治疗效果;该病的发病机制复杂,可引起全身多系统性损伤;其治疗方法种类繁多,并呈现出多学科参与和多学科交叉的发展趋势。随着口腔医学对OSAS诊断与治疗研究的逐渐深入,口腔治疗在OSAS的作用已愈来愈重要。本文就OSAS治疗方法的研究进展、争议情况以及口腔治疗的方法与发展进行了总结。.
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  • 文章类型: Journal Article
    The number of disabled persons increases in the course of human life and in the aging population. The high prevalence, low treatment rate, long therapy period, and sophisticated procedures prevent most of disabled individuals from availing dental services. Moreover, special dental institutions for the disabled are insufficient, and a certain treatment standard is commonly not complied. This study performed analysis and evaluation, including treatment features, pretreatment procedures, patient communication, treatment factors, and treatment standards to provide a targeted solution for the special requirements of the oral therapy for disabled patients.
    随着人类预期寿命的增加和社会老龄化,残障人必将有所增加。大多数的残障人口腔疾病患病率高、治疗率低,对残障人的口腔疾病治疗需要花费更多的时间与沟通,治疗程序也更为复杂,国内外都少有专注残障人口腔医疗的专门机构,对残障人的口腔治疗技术也没有固定的原则与规范可寻。本文就残障人口腔疾病患病情况,临床治疗特点,治疗前的准备与医患沟通,口腔疾病治疗影响因素评估,治疗规范与原则进行全面分析,针对不同种类的残障人,提出在口腔疾病治疗中的特殊需求和注意事项等针对性的处理原则。.
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  • 文章类型: Journal Article
    OBJECTIVE: To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factor.
    METHODS: Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies.
    RESULTS: Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged >60 years was 1.4% (95% CI: 0.5%-4.2%) and 3.2% (95% CI: 1.1%-8.7%) respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% (95% CI: 4.5%-7.2%).
    CONCLUSIONS: Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.
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