本研究由重庆市卫生健康委员会和重庆市科学技术局联合开展的医学研究重点项目（2022ZDXM037）、武汉市卫生健康委员会中医药科研基金重点项目（WZ22A03）和重庆市自然科学基金（cstc2020jcyj-msxmX0592）提供资金支持。

所有涉及人类参与者的研究程序均符合重庆市中医院伦理委员会的伦理标准和《赫尔辛基宣言》（1964年）及其后续修正案的原则，并已获得上述伦理委员会的批准。图像数据收集是在患者的口头和书面同意下进行的，并且作为检查的常规部分，为教学目的拍摄的照片是使用多光谱皮肤镜获得的。
1. 患者选择
<ol><li>设置以下纳入标准5:<ol><li>根据面部浅色至深棕色、边界明确的斑块的存在来选择患者，通常具有对称分布、无炎症和脱屑。</li>
		<li>根据是否存在明显的主观症状（如瘙痒、灼热和疼痛）来选择患者。</li>
		<li>考虑到黄褐斑主要发生在女性身上，主要是在青春期之后，选择患者。</li>
		<li>在选择患者时，应考虑病情的季节性变化 - 通常在夏季更严重，在冬季较温和。</li>
		<li>如果存在可能导致色素沉着过度的其他疾病（如颧颧梭蓝痣、Riehl 黑变病和色素性日光性皮炎），则排除患者。</li>
	</ol></li>
</ol>2.滚筒微针治疗的准备工作
<ol><li>术前沟通<ol><li>了解患者的治疗目标和美容愿望，并收集完整的病史，包括用药史、过敏史、禁忌症和过去的美容治疗。</li>
		<li>告知患者治疗的效果、步骤、潜在并发症、恢复时间、持续时间和费用。讨论具体的治疗计划和替代方案，以确保所有患者的疑问都得到解决，帮助他们建立切合实际的期望并实现更高的满意度。</li>
		<li>要求患者签署知情同意书。</li>
	</ol></li>
	<li>环境要求<ol><li>留出一个安静、光线充足的治疗室用于操作滚筒微针，并在手术前用紫外线消毒 30 分钟。</li>
		<li>要求患者在进入治疗室时戴上鞋套和帽子。</li>
	</ol></li>
	<li>准备治疗所需的物品和药物<ol><li>检查并准备 物料清单中列出的所有材料。</li>
	</ol></li>
	<li>卸妆和清洁<ol><li>如果治疗区域被化妆品覆盖，请在清洁前用卸妆液彻底卸妆。</li>
		<li>对于不化妆的人，请用温和的清洁产品清洁治疗区域。</li>
	</ol></li>
	<li>多光谱皮肤镜检查记录 注意: 多光谱皮肤镜使用不同的光源来捕捉面部超高像素图像。<ol><li>治疗前和三次治疗后，使用多光谱皮肤镜从三个不同角度拍摄患者的前部、左侧（45°）和右侧（45°）的照片，并记录患者的紫外线浅层和深层斑点和褐色斑点的值</li>
	</ol></li>
	<li>局部麻醉的应用<ol><li>将5%利多卡因乳膏均匀涂抹在治疗区域，总剂量为30-40g，并用保鲜膜包裹以增强麻醉效果40-60分钟。 注意:一些患者可能会表现出对局部麻醉剂过敏的症状。患者可能会在应用部位出现严重的瘙痒、灼热或刺痛。如果发生此类反应，请立即移除麻醉剂并提供适当的对症治疗。</li>
		<li>在下次治疗之前，请确保在麻醉应用区域对皮肤进行适当的滋润。</li>
	</ol></li>
	<li>微针溶液的制备<ol><li>使用注射器提取 5 mL 5% 氨甲环酸溶液，并将其放在一边使用。</li>
	</ol></li>
	<li>微针器械的制备<ol><li>选择0.5mm滚筒微针（图1），并将其浸泡在0.1%苯扎溴铵溶液中约20分钟以消毒。</li>
		<li>用生理盐水冲洗微针 3 次以去除消毒剂。 注意:通过为每个患者使用单个滚筒微针来避免交叉污染，以防止由于钝针而对皮肤造成不必要的伤害，并防止疾病在患者之间传播。</li>
	</ol></li>
	<li>去除局部麻醉<ol><li>在局部麻醉应用足够长的时间后，取下保鲜膜并用刮刀刮掉麻醉剂。使用浸泡在0.9%生理盐水溶液中的纱布擦去面部残留的麻醉剂。</li>
	</ol></li>
	<li>消毒<ol><li>露出治疗区域，治疗面部时用消毒毛巾包裹头发，用0.1%苯扎溴铵棉球从顶部到发际线边缘，到下颌边缘和下巴3次消毒面部皮肤，遵循"自下而上，向内向外"的原则，防止感染。</li>
	</ol></li>
</ol>3. 滚筒微针手术
<ol><li>让治疗师洗手，戴上帽子、口罩和无菌手套。</li>
	<li>在告知患者开始手术后，指导患者闭上眼睛，按照左脸颊、右脸颊、前额、下巴、上唇和鼻子的顺序进行治疗。用注射器将适量氨甲环酸溶液注射到皮肤上，用手均匀涂抹，然后用生理盐水冲洗滚筒微针，在治疗区域沿水平、垂直、倾斜方向短距离滚动。</li>
	<li>逐渐在不同区域进行治疗，在滚动时涂抹溶液以增强吸收。在一个区域重复 3-5 次，最好是皮肤潮红且没有明显出血。均匀地用力，不要太重也不要太轻，不要用微针在皮肤上拖动。</li>
</ol>4.功效评价
<ol><li>使用滚筒微针和局部氨甲环酸溶液的组合 3 次治疗黄褐斑，每 4 周一次，作为一个疗程。</li>
	<li>治疗前后使用多光谱皮肤镜，3x，根据患者紫外线浅深斑点和褐色斑点的值观察疗效。值越小，黄褐斑越轻。</li>
	<li>统计分析处理前后UV浅层和深层斑点以及褐色斑点的变化。</li>
</ol>

用氨甲环酸和微针疗法加强黄褐斑治疗

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黄褐斑的发病机制复杂，治疗方法包括全身用药、局部脱色剂、化学换肤和激光疗法。不幸的是，没有一种治疗方法对所有患者都普遍有效，不能总是保证满意的结果6.光疗治疗黄褐斑呈下降趋势，部分患者在光疗后黄褐斑恶化。这是由于炎症性黄褐斑中皮肤敏感和皮肤屏障功能受损的个体增加。针对黑色素的激光或其他治疗可能会加剧皮肤的炎症反应，导致黄褐斑症状加重。因此，黄褐斑治疗的最新进展侧重于安全性和非刺激性方法，特别强调恢复皮肤屏障功能作为治疗的新目标。
滚筒微针联合氨甲环酸的优点 与其他透皮给药方法相比，微针治疗具有显着优势，并发症发生率低，停留时间最短7。此外，它还可以应用于有色皮肤（Fitzpatrick 皮肤类型 IV-VI）8 的患者。滚筒微针对皮肤造成的微损伤极小，微小的穿刺伤口是局部的，保留了周围的正常组织，为皮肤修复提供了良好的基础。治疗后，出血很少或没有出血，渗出量极少，并形成浅表结痂。炎症反应轻微，愈合迅速，副作用最小。与不可避免地导致热损伤的光疗相比，治疗后色素沉着过度的风险在一定程度上降低了。这种"微损伤修复"过程刺激胶原蛋白再生并增强细胞新陈代谢，同时具有最小的不利影响。疤痕和色素沉着过度是罕见的，使其成为一种安全有效的治疗方法。黄褐斑的滚筒微针治疗每 4 周进行一次，在治疗过程中进行 3 次。经过一个疗程后，每4周进行一次维持治疗，直到黄褐斑消退。
除了抗出血和抗纤维蛋白溶解作用外，氨甲环酸还具有抗炎和美白皮肤的特性。这是第一种用于治疗黄褐斑的全身性药物。有大量证据支持口服氨甲环酸治疗黄褐斑的疗效;然而，它可能导致全身性副作用9.氨甲环酸的局部应用已被证明与黄褐斑的标准治疗（例如，外用对苯二酚）一样有效，但副作用较少10,11。虽然氨甲环酸治疗黄褐斑的确切机制和生化途径尚不完全清楚，但其对减少皮肤色素沉着的影响已经得到充分证实。它可以减少黑色素的产生，并被认为通过抑制纤溶酶和碱性成纤维细胞生长因子12,13 来减少黄褐斑中的血管和红斑数量。此外，氨甲环酸在表皮屏障中起作用14,15。
微针治疗可促进成纤维细胞增殖和真皮胶原蛋白重建，修复黄褐斑中的真皮和基底膜损伤。它减少了真皮中促黑色素生成信号的释放，增加了表皮黑色素的更新，并促进色素沉着过度区域的皮肤结构的正常化16。微针治疗在皮肤中形成微通道，使氨甲环酸能够输送到皮肤中。当与氨甲环酸联合使用时，微针治疗可改善黄褐斑，与单独局部应用相比，可能优于皮内注射氨甲环酸6。目前，黄褐斑的可用治疗方案显示出次优的结果，色素清除不完全和高复发率。Saleh等观察外用氨甲环酸联合微针治疗黄褐斑的疗效，12周时，黄褐斑面积和严重程度指数（MASI）改善率为62.1%17。滚筒微针是黄褐斑局部治疗的有用辅助方法。对于具有挑战性的局限性黄褐斑患者，临床医生在开始化学换肤、激光治疗或全身用药之前，应考虑将微针治疗作为一种升级选择18.
滚筒微针操作的限制和注意事项 在滚筒微针操作过程中，必须考虑患者的禁忌症，并评估他们的皮肤状况是否适合微针治疗。禁忌症包括皮肤感染（细菌性、真菌性和病毒性感染）、皮肤过敏（红斑、水肿、渗出、溃疡）、全身感染（如HIV、梅毒、各种肝炎）、可能诱发同构反应的皮肤病（如活动期白癜风）、严重高血压、心脏病、糖尿病、凝血障碍、妊娠;在哺乳期和月经期间以及有形成增生性疤痕倾向的个体中，必须谨慎使用滚筒微针4.
提供舒适的环境、适当的温度和照明、操作员和患者之间的有效沟通、缓解患者的紧张情绪、管理治疗后的不良反应，以及在手术后实施严格的防晒和感染预防，这些都是需要考虑的关键方面。红斑可能在治疗后立即发生，其持续时间取决于治疗强度和患者的皮肤反应。大多数红斑会在治疗后 3 天内自行消退。如果治疗后瘙痒明显，则必须用冰袋冷敷 20-30 分钟，或使用温和的外用类固醇乳膏，例如丁酸氢化可的松乳膏，用于更严重的情况。如果手术后出现感染症状，则必须对致病病原体和症状进行相应治疗。必须局部使用硼酸溶液，每天两次使用抗生素或抗病毒软膏。在严重的情况下，可能需要口服抗生素或抗病毒药物。
真菌感染很少见。瘢痕形成很少见，通常由感染引起。对于已有感染的患者，应尽早采取上述措施进行治疗，以防止瘢痕形成。对于已有疤痕的患者，治疗选择包括色素激光、强脉冲光 （IPL）、点阵激光、局部注射、局部抗疤痕乳膏或贴剂。由于在滚筒微针治疗过程中皮肤角质层的破坏，皮肤可能会暂时出现干燥、发红、瘙痒和烦躁不安。角质层较薄和皮肤敏感的患者可能对外部刺激更敏感，并且可能会出现轻微的灼热感或不适感。医用修复面膜和专门的修复霜可以应用于敏感皮肤。如有必要，可以使用冷喷剂或红光和黄光照射。建议延长后续治疗之间的时间，直到皮肤稳定并且屏障功能恢复。在此期间，必须避免其他可能加重敏感性的侵入性治疗。
虽然微针治疗期间的感染风险很小，但如果术前消毒不彻底、手术过程中没有严格遵守无菌原则或术后患者护理不足，仍然存在风险。随着微针材料和氨甲环酸外用制剂的不断改进，滚筒微针和外用药物的组合有望为黄褐斑产生更好的治疗效果。

黄褐斑，也称为黄褐斑，是一种慢性和获得性面部色素沉着过度的皮肤病。临床上，它表现为对称的浅棕色至深棕色斑块，边界不清晰，分布在脸颊、前额和下颌线。亚洲育龄妇女的发病率可高达 30%1。这种疾病很容易诊断，但很难治愈。黄褐斑的发病机制尚不完全清楚，但有三个主要因素促成了黄褐斑的发展:遗传易感性、暴露在阳光下和荷尔蒙变化。黑色素合成增加、皮肤病变部位的血管增生、炎症反应和皮肤屏障功能受损都在黄褐斑2 的发生中起作用。
目前，黄褐斑的治疗选择包括激光疗法和药物治疗，其中透皮给药是一种广泛使用的方法。然而，主要的挑战在于角质层的屏障功能，它阻碍了药物的渗透。微针疗法在短时间内在皮肤中产生多个微通道，破坏角质层，诱导胶原蛋白的产生，并增加皮肤的通透性。这种方法有望使药物扩散到皮肤中，然后迅速重新封闭，从而避免引入有毒或刺激性物质3.
常用的微针工具包括电子水光注射微针、滚筒微针、电助纳米晶微针、梅花微针和单针微针4。滚筒式微针的特点是创伤小，疗效好，操作方便，可以与其他一些药物合用治疗黄褐斑。对黄褐斑具有良好的治疗前景，在临床上值得进一步推广和使用。本文介绍了滚筒微针联合氨甲环酸治疗黄褐斑的操作和注意事项，并通过临床案例论证了滚筒微针联合氨甲环酸治疗黄褐斑的疗效。

<table><tbody><tr><td>5 mL syringe</td><td></td><td></td><td></td></tr><tr><td>Benzalkonium bromide solution</td><td>Chongqing Traditional Chinese Medicine Hospital</td><td>H20050531</td><td>0.1%</td></tr><tr><td>cling film</td><td></td><td></td><td></td></tr><tr><td>Compound lidocaine cream</td><td>Beijing Ziguang Pharmaceutical Co., Ltd.</td><td>H20063466</td><td>5.0%</td></tr><tr><td>disinfectant towel</td><td></td><td></td><td></td></tr><tr><td>disposable curved disc</td><td></td><td></td><td></td></tr><tr><td>Multispectral Dermoscope</td><td>CBS Medical Skin Analysis, Wuhan, China</td><td>CBS-2022</td><td></td></tr><tr><td>Roller microneedle</td><td>Guangzhou Yuanxiang Biotechnology Co., Ltd</td><td>221001</td><td>(model: 0.22 x 0.5 mm, Figure 1)</td></tr><tr><td>Sodium chloride solution</td><td>Hubei Tiansheng Pharmaceutical Co., Ltd.</td><td>H42021838</td><td>0.9%</td></tr><tr><td>sterile cotton swab</td><td></td><td></td><td></td></tr><tr><td>sterile gauze</td><td></td><td></td><td></td></tr><tr><td>sterile gloves</td><td></td><td></td><td></td></tr><tr><td>tongue depressor</td><td></td><td></td><td></td></tr><tr><td>Tranexamic acid solution</td><td>Shanghai Hyundai Hasen (Shangqiu) Pharmaceutical Co., Ltd.</td><td>H20184047</td><td>5.0%</td></tr><tr><td>treatment vehicle</td><td></td><td></td><td></td></tr></tbody></table>

roller microneedle combined with tranexamic acid solution in treating melasma

黄褐斑是一种常见的获得性面部色素沉着性皮肤病，临床诊断简单明了，但在有效管理方面存在挑战。黄褐斑的确切根本原因仍然难以捉摸，目前的治疗方法主要包括药物和激光干预，疗效有限。透皮给药是黄褐斑的一种普遍治疗方法，通常通过使用微针来促进。其中，氨甲环酸作为一种常用的治疗剂出现。微针的一个子集，称为滚筒微针，在这种方法中发挥着重要作用，它用多根细针巧妙地刺穿表皮，与药物输送协同作用。这种方法不仅可以增强药物吸收，还可以提高治疗效果，同时最大限度地减少组织创伤。这些特性预示着治疗黄褐斑的有希望的途径。本文主要介绍滚筒微针和氨甲环酸溶液联合治疗黄褐斑的情况，并通过临床案例论证了滚筒微针和氨甲环酸溶液治疗黄褐斑的疗效。

病例1为57岁女性，有10年病史，选取治疗及疗效评价。在治疗前和三个治疗疗程（图 2、 Figure 3 和 Figure 4）后评估滚筒微针和氨甲环酸溶液组合的疗效，并使用多光谱皮肤镜从不同角度观察。在正面视图中，紫外线浅斑点、紫外线深点和棕色区域分别减少了 35.91 mm2、163.32 mm2 和 82.4 mm2 。在45°的右侧视图中，UV浅斑、UV深斑和棕色区域分别减少了57.7 mm2、42.68 mm2和48.52 mm2 。在 45° 的左侧侧视图中，UV 浅斑、UV 深斑和棕色区域分别减少了 24.3 mm2、51.39 mm2 和 47.39 mm2 。
病例 2 为一名 44 岁女性，有 2 年病史，3 个疗程后也显示出治疗效果（图 5、 图 6 和 图 7）。在正面视图中，紫外线浅斑点、紫外线深点和棕色区域分别减少了 119.4 mm2、61.39 mm2 和 3.81 mm2 。在45°的右侧视图中，UV浅斑、UV深斑和棕色区域分别减少了46.89 mm2、8.11 mm2和34.29 mm2 。在 45° 的左侧侧视图中，UV 浅斑、UV 深斑和棕色区域分别减少了 15.52 mm2、20.47 mm2 和 28.45 mm2 。
在用滚筒微针结合氨甲环酸溶液进行三次处理后，两种病例的棕色斑块都变浅了，紫外线浅点和深层斑点的数量也减少了，棕色区域也减少了。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66015/66015fig01.jpg"> 图 1:滚筒微针 （0.22 x 0.5 mm）。 <a href="https://www.jove.com/files/ftp_upload/66015/66015fig01large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66015/66015fig02.jpg"> 图 2:案例 1 的正面视图。 （A-C） 治疗前和 （D-F） 三次治疗后，在多光谱皮肤镜下。（A） 图像显示处理前的紫外线浅斑点:210.58 mm2;（B）处理前紫外线深斑的图像:1,834.53 mm2;（C）图像显示处理前的棕色区域:925.47 mm2.（D） 图像显示三次治疗后的紫外线浅斑点:174.67 mm2;（E） 三次治疗后的图像呈现紫外线深斑点:1,671.21 mm2;（F）图像显示了三次处理后的棕色区域:843.07 mm2。<a href="https://www.jove.com/files/ftp_upload/66015/66015fig02large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66015/66015fig03.jpg"> 图 3:案例 1 45° 的右侧视图。 （A-C） 治疗前和 （D-F） 三次治疗后，在多光谱皮肤镜下。（A） 图像显示处理前的紫外线浅斑点:338.4 mm2;（B）处理前图像呈现紫外深斑点:479.29 mm2;（C）图像显示处理前的棕色区域:544.9 mm2.（D） 图像显示三次治疗后的紫外线浅斑点:280.7 mm2;（E） 三次治疗后图像呈现紫外线深斑点:436.61 mm2;（F）图像显示了三次处理后的棕色区域:496.38 mm2。<a href="https://www.jove.com/files/ftp_upload/66015/66015fig03large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/66015/66015fig04.jpg"> 图 4:案例 1 45° 处的左侧侧视图。 （A-C） 治疗前和 （D-F） 三次治疗后，在多光谱皮肤镜下。（A） 图像显示处理前的紫外线浅斑点:142.49 mm2;（B）处理前图像呈现紫外深斑点:578.22 mm2;（C）处理前的棕色区域图像:532.19 mm2.（D） 图像显示三次治疗后的紫外线浅斑点:118.19 mm2;（E）三次治疗后的图像呈现紫外线深斑点:526.83 mm2;（F）图像显示了三个疗程后的棕色区域:484.8 mm2。<a href="https://www.jove.com/files/ftp_upload/66015/66015fig04large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/66015/66015fig05.jpg"> 图 5:案例 2 的正面视图。 （A-C） 治疗前和 （D-F） 三次治疗后，在多光谱皮肤镜下。（A） 图像显示处理前的紫外线浅斑点:600.28 mm2;（B）处理前图像呈现紫外深斑点:589.42 mm2;（C）图像显示处理前的棕色区域:42.67 mm2.（D） 图像显示三次处理后的紫外线浅斑点:480.88 mm2;（E） 三次处理后的图像呈现紫外线深斑点:528.03 mm2;（F）图像显示了三次处理后的棕色区域:38.86 mm2。<a href="https://www.jove.com/files/ftp_upload/66015/66015fig05large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/66015/66015fig06.jpg"> 图 6:案例 2 45° 的右侧视图。 （A-C） 治疗前和 （D-F） 三次治疗后，在多光谱皮肤镜下。（A） 图像显示处理前的紫外线浅斑点:232.11 mm2;（B）处理前图像呈现紫外深斑点:90.93 mm2;（C）图像显示处理前的棕色区域:384.98 mm2.（D） 图像显示三次处理后的紫外线浅斑点:185.22 mm2;（E） 三次治疗后的图像呈现紫外线深斑点:82.82 mm2;（F） 图像显示了三个疗程后的棕色区域:350.69 mm2.<a href="https://www.jove.com/files/ftp_upload/66015/66015fig06large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>
<img alt="Figure 7" class="xfigimg" src="/files/ftp_upload/66015/66015fig07.jpg"> 图 7:案例 2 45° 的左侧侧视图。 （A-C） 治疗前和 （D-F） 三次治疗后，在多光谱皮肤镜下。（A） 图像显示处理前的紫外线浅斑点:90.94 mm2;（B）处理前图像呈现UV-深斑点:229.85 mm2;（C）图像显示处理前的棕色区域:319.38 mm2.（D） 图像显示三次治疗后的紫外线浅斑点:75.42 mm2;（E）三次处理后的图像呈现紫外线深斑点:209.38 mm2;（F）图像显示了三次处理后的棕色区域:290.93 mm2。<a href="https://www.jove.com/files/ftp_upload/66015/66015fig07large.jpg" target="_blank">请点击这里查看此图的较大版本.</a>

Watch this Scientific Journal Video about Roller Microneedle Combined with Tranexamic Acid Solution in Treating Melasma at JoVE.com

作者聚焦: 黄褐斑的非手术治疗 – 氨甲环酸微针

本文提出了一种通过使用滚筒微针结合氨甲环酸溶液进行黄褐斑治疗的方案，并评估疗效。

滚筒微针联合氨甲环酸溶液治疗黄褐斑

Melasma, a common, acquired facial pigmentation skin disorder, presents a straightforward clinical diagnosis but poses challenges in terms of effective ...

我们的研究重点是色素性疾病的非手术治疗。我们测试了滚筒微针联合氨甲环酸溶液治疗黄褐斑的疗效。我们将研究使用滚筒微针和氨甲环酸溶液组合治疗黄褐斑的有效性和最大难易程度。

roller-microneedle-combined-with-tranexamic-acid-solution-treating

Nanyang Technological University

Research

JoVE Journal

Medicine

Roller Microneedle Combined with Tranexamic Acid Solution in Treating Melasma

786 次观看.  Chongqing Hospital of Traditional Chinese Medicine. 我们的研究重点是色素性疾病的非手术治疗。我们测试了滚筒微针联合氨甲环酸溶液治疗黄褐斑的疗效。我们将研究使用滚筒微针和氨甲环酸溶液组合治疗黄褐斑的有效性和最大难易程度。

视频: 作者聚焦: 黄褐斑的非手术治疗 – 氨甲环酸微针

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Cutaneous melanoma is well known as the most aggressive skin cancer. Although the risk factors and major genetic alterations continue to be documented with increasing depth, the incidence rate of cutaneous melanoma has shown a rapid and continuous increase during recent decades. In order to find effective preventative methods, it is important to understand the early steps of melanoma initiation in the skin. Previous data has demonstrated that follicular melanocyte stem cells (MCSCs) in the adult skin tissues can act as melanoma cells of origin when expressing oncogenic mutations and genetic alterations. Tumorigenesis arising from melanoma-prone MCSCs can be induced when MCSCs transition from a quiescent to active state. This transition in melanoma-prone MCSCs can be promoted by the modulation of either hair follicle stem cells&#39; activity state or through extrinsic environmental factors such as ultraviolet-B (UV-B). These factors can be artificially manipulated in the laboratory by chemical depilation, which causes transition of hair follicle stem cells and MCSCs from a quiescent to active state, and by UV-B exposure using a benchtop light. These methods provide successful spatial and temporal control of cutaneous melanoma initiation in the murine dorsal skin. Therefore, these in vivo model systems will be valuable to define the early steps of cutaneous melanoma initiation and could be used to test potential methods for tumor prevention.

The following procedure describes a method for spatial and temporal control of melanocytic tumor initiation in murine dorsal skin, using a genetically engineered mouse model. This protocol describes macroscopic as well as microscopic cutaneous melanoma initiation.

突变黑色素细胞干细胞引发小鼠黑色素瘤的时空控制

Cutaneous melanoma is well known as the most aggressive skin cancer. Although the risk factors and major genetic alterations continue to be documented ...

科研

癌症研究

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Fairness of skin, UV sensitivity and skin cancer risk all correlate with the physiologic function of the melanocortin 1 receptor, a Gs-coupled signaling protein found on the surface of melanocytes. Mc1r stimulates adenylyl cyclase and cAMP production which, in turn, up-regulates melanocytic production of melanin in the skin. In order to study the mechanisms by which Mc1r signaling protects the skin against UV injury, this study relies on a mouse model with "humanized skin" based on epidermal expression of stem cell factor (Scf). K14-Scf transgenic mice retain melanocytes in the epidermis and therefore have the ability to deposit melanin in the epidermis. In this animal model, wild type Mc1r status results in robust deposition of black eumelanin pigment and a UV-protected phenotype. In contrast, K14-Scf animals with defective Mc1r signaling ability exhibit a red/blonde pigmentation, very little eumelanin in the skin and a UV-sensitive phenotype. Reasoning that eumelanin deposition might be enhanced by topical agents that mimic Mc1r signaling, we found that direct application of forskolin extract to the skin of Mc1r-defective fair-skinned mice resulted in robust eumelanin induction and UV protection 1. Here we describe the method for preparing and applying a forskolin-containing natural root extract to K14-Scf fair-skinned mice and report a method for measuring UV sensitivity by determining minimal erythematous dose (MED). Using this animal model, it is possible to study how epidermal cAMP induction and melanization of the skin affect physiologic responses to UV exposure.

Epidermal melanin is induced by topical application of forskolin in a murine model of the fair-skinned UV-sensitive human. Pharmacologic manipulation of cAMP levels in the skin and epidermal darkening strongly protect against UV-mediated inflammation (sunburn) as measured by the minimum erythematous dose (MED) assay.

表皮黑色素和防止晒斑的人性化小鼠模型的诱导药物

Fairness of skin, UV sensitivity and skin cancer  risk all correlate with the physiologic function of the melanocortin 1  receptor, a Gs-coupled signaling ...

医学

Polymeric Microneedle Array Fabrication by Photolithography

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a photomask consisting of embedded micro-lenses. Embedded micro-lenses were found to influence MN geometry (sharpness). Robust MN arrays with tip diameters ranging between 41.5 &#181;m &#177; 8.4 &#181;m and 71.6 &#181;m &#177; 13.7 &#181;m, with two different lengths (1,336 &#181;m &#177; 193 &#181;m and 957 &#181;m &#177; 171 &#181;m) were fabricated. These MN arrays may provide potential applications in delivery of low molecular and macromolecular therapeutic agents through skin.

Here, we present a protocol describing a mold-free fabrication process of the polymeric microneedles by photolithography.

聚合物微针阵列制造用光刻

This manuscript describes the fabrication of polymeric microneedle (MN) arrays by photolithography. It involves a simple mold-free process by using a ...

生物工程

Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA approved in April 2011 for the treatment of patients 22 years or older with rGBM. The device delivers alternating electric fields and is programmed to ensure maximal tumor cell kill1.
Glioblastoma is the most common type of glioma and has an estimated incidence of approximately 10,000 new cases per year in the United States alone2. This tumor is particularly resistant to treatment and is uniformly fatal especially in the recurrent setting3-5. Prior to the approval of the TTF System, the only FDA approved treatment for rGBM was bevacizumab6. Bevacizumab is a humanized monoclonal antibody targeted against the vascular endothelial growth factor (VEGF) protein that drives tumor angiogenesis7. By blocking the VEGF pathway, bevacizumab can result in a significant radiographic response (pseudoresponse), improve progression free survival and reduce corticosteroid requirements in rGBM patients8,9. Bevacizumab however failed to prolong overall survival in a recent phase III trial26. A pivotal phase III trial (EF-11) demonstrated comparable overall survival between physicians&#8217; choice chemotherapy and TTF Therapy but better quality of life were observed in the TTF arm10.
There is currently an unmet need to develop novel approaches designed to prolong overall survival and/or improve quality of life in this unfortunate patient population. One appealing approach would be to combine the two currently approved treatment modalities namely bevacizumab and TTF Therapy. These two treatments are currently approved as monotherapy11,12, but their combination has never been evaluated in a clinical trial. We have developed an approach for combining those two treatment modalities and treated 2 rGBM patients. Here we describe a detailed methodology outlining this novel treatment protocol and present representative data from one of the treated patients.

A novel methodology that is employed for the treatment of recurrent glioblastomas is described. This treatment approach employs the application of alternating electric tumor treating fields (TTFields), known as TTF Therapy in combination with bevacizumab, a targeted agent that is currently FDA approved as monotherapy.

肿瘤治疗领域的治疗与联合贝伐单抗治疗复发性胶质母细胞瘤的治疗

A novel device that employs TTF therapy has recently been developed and is currently in use for the treatment of recurrent glioblastoma (rGBM). It was FDA ...

Apparatus for Harvesting Tissue Microcolumns

This manuscript describes the production process for a laboratory apparatus, made from off-the-shelf components, that can be used to collect microcolumns of full-thickness skin tissue. The small size of the microcolumns allows donor sites to heal quickly without causing donor site scarring, while harvesting full-thickness tissue enables the incorporation of all cellular and extracellular components of skin tissue, including those associated with deeper dermal regions and the adnexal skin structures, which have yet to be successfully reproduced using conventional tissue engineering techniques. The microcolumns can be applied directly into skin wounds to augment healing, or they can be used as the autologous cell/tissue source for other tissue engineering approaches. The harvesting needles are made by modifying standard hypodermic needles, and they can be used alone for harvesting small amounts of tissue or coupled with a simple suction-based collection system (also made from commonly available laboratory supplies) for high-volume harvesting to facilitate studies in large animal models.

Here we describe a protocol for producing harvesting needles that can be used to collect full-thickness skin tissue without causing donor site scarring. The needles can be combined with a simple collection system to achieve high-volume harvesting.

水样组织的采集装置

This manuscript describes the production process for a laboratory apparatus, made from off-the-shelf components, that can be used to collect microcolumns ...

Intense Pulsed Light for the Treatment of Dry Eye Owing to Meibomian Gland Dysfunction

Dry eye disease (DED) is an increasingly common condition and one of the most common complaints of patients. The vast majority of DED is caused by the so-called &#34;evaporative&#34; subtype, that is mainly caused by meibomian gland dysfunction (MGD). Intense pulsed light (IPL) devices employ high intensity pulses of polychromatic lights with a broad range of wavelength (515-1200 nm). IPL treatment has been utilized for years in the field of dermatology, and then its use was applied to ophthalmology for the treatment of MGD. Recently, a new device employing IPL was specifically designed for the periocular application. This procedure determines the thermal selective coagulation and ablation of superficial blood vessels and telangiectasias of the eyelids skin, reducing the release of inflammatory mediators and tear cytokines levels, and improving meibomian glands outflow. IPL treatment is noninvasive and easy to perform, lasts for only a few minutes and can be conducted in an office setting. In the present study, 19 patients underwent 3 sessions of IPL treatment. After treatment, both mean noninvasive break-up time and lipid layer thickness grade significantly increased, as a result of an improvement of tear film stability and quality, respectively. Conversely, no statistically significant changes were found for meibomian gland loss and tear osmolarity. Furthermore, the vast majority of the treated patients (17/19; 89.5% of the total) perceived an improvement of their ocular discomfort symptoms after IPL treatment. Although IPL treatment provides an improvement of both ocular surface parameters and ocular discomfort symptoms after one cycle of three sessions, regular repeated treatments are usually required to maintain the persistence over the time of its beneficial effects.

Dry eye disease is an increasingly common condition, which strongly impair patients&#39; life quality. Recently, a new device employing intense pulsed light, specifically designed for the periocular area, has been shown to improve tear film stability and ocular discomfort symptoms in dry eye disease owing to meibomian gland dysfunction.

梅博米安腺体功能障碍治疗干眼症的强脉冲光

Dry eye disease (DED) is an increasingly common condition and one of the most common complaints of patients. The vast majority of DED is caused by the ...

用于生物医学应用中外泌体持续递送的微针贴片

Fabrication and Characterization of Microneedle Patches for Loading and Delivery of Exosomes

Exosomes, as emerging &#34;next-generation&#34; biotherapeutics and drug delivery vectors, hold immense potential in diverse biomedical fields, ranging from drug delivery and regenerative medicine to disease diagnosis and tumor immunotherapy. However, the rapid clearance by traditional bolus injection and poor stability of exosomes restrict their clinical application. Microneedles serve as a solution that prolongs the residence time of exosomes at the administration site, thereby maintaining the drug concentration and facilitating sustained therapeutic effects. In addition, microneedles also possess the ability to maintain the stability of bioactive substances. Therefore, we introduce a microneedle patch for loading and delivering exosomes and share the methods, including isolation of exosomes, fabrication, and characterization of exosome-loaded microneedle patches. The microneedle patches were fabricated using trehalose and hyaluronic acid as the tip materials and polyvinylpyrrolidone as the backing material through a two-step casting method. The microneedles demonstrated robust mechanical strength, with tips able to withstand 2 N. Pig skin was used to simulate human skin, and the tips of microneedles completely melted within 60 s after skin puncture. The exosomes released from the microneedles exhibited morphology, particle size, marker proteins, and biological functions comparable to those of fresh exosomes, enabling dendritic cells uptake and promoting their maturation.

作者聚焦：用于增强外泌体递送和稳定性的创新微针策略

Exosomes possess significant clinical potential, but their practical application is limited due to easy in vivo clearance and poor stability. Microneedles present a solution by enabling localized delivery by puncturing physiological barriers and dry-state preservation, thereby addressing the limitations of exosome administration and expanding their clinical utility.

用于加载和递送外泌体的微针贴片的制造和表征

Exosomes, as emerging &#34;next-generation&#34; biotherapeutics and drug delivery vectors, hold immense potential in diverse biomedical fields, ranging ...

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ

Here, we describe a protocol to induce switchable in vivo photogeneration of endogenous reactive oxygen species (ROS) in mouse skin. This transient production of ROS in situ efficiently activates cell proliferation in stem cell niches and stimulates tissue regeneration as strongly manifested through the acceleration of burn healing and hair follicle growth processes. The protocol is based on a regulatable photodynamic treatment that treats the tissue with precursors of the endogenous photosensitizer protoporphyrin IX and further irradiates the tissue with red light under tightly controlled physicochemical parameters. Overall, this protocol constitutes an interesting experimental tool to analyze ROS biology.

The aim of this protocol is to induce transient in vivo production of nonlethal levels of reactive oxygen species (ROS) in mouse skin, further promoting physiological responses in the tissue.

通过可切换原卟啉IX依赖性原位活性氧物种光生成刺激小鼠皮肤中的干细胞壁龛和组织再生

Here, we describe a protocol to induce switchable in vivo photogeneration of endogenous reactive oxygen species (ROS) in mouse skin. This transient ...

滚筒微针联合氨甲环酸溶液治疗黄褐斑

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突变黑色素细胞干细胞引发小鼠黑色素瘤的时空控制

表皮黑色素和防止晒斑的人性化小鼠模型的诱导药物

聚合物微针阵列制造用光刻

肿瘤治疗领域的治疗与联合贝伐单抗治疗复发性胶质母细胞瘤的治疗

水样组织的采集装置

梅博米安腺体功能障碍治疗干眼症的强脉冲光

用于加载和递送外泌体的微针贴片的制造和表征

用于加载和递送外泌体的微针贴片的制造和表征

用于加载和递送外泌体的微针贴片的制造和表征

通过可切换原卟啉IX依赖性原位活性氧物种光生成刺激小鼠皮肤中的干细胞壁龛和组织再生