背景
    UVB光疗是包括白癜风在内的浅表性皮肤病的重要治疗手段，发光二极管（Light Emitting Diode，LED）是一种高亮度、低成本的新型光源。研究显示，LED光治疗躯干白癜风的疗效和安全性与308 nm准分子光（Monochromatic Excimer Light, MEL）相当，但在面部白癜风治疗方面的尚无报道。光疗所导致的长期不良反应（光老化）是影响光疗患者依从性的重要因素，目前光老化缺乏有效治疗手段。tRNA衍生的小RNA（tsRNA）是非编码RNA（ncRNA）的一种重要类型，目前已有研究表明多种tsRNA在光老化中差异表达，其中一种5′tiRNA-Glu-TTC在光老化模型中表达升高，但其参与光老化的具体作用机制尚未进行研究。因此，本研究旨在评估308nm LED治疗面部白癜风的疗效是否与308nm准分子光相当，并对其长期不良反应光老化展开机制和防治靶点探索。
方法
    1、将145处面部非节段型稳定期白癜风皮损随机分为两组，分别接受2个月308nm LED光或308nm准分子光治疗，在第1个月和第2个月治疗结束后，由两名独立研究者对复色效果进行分级评估。
    2、采用UVB诱导人真皮成纤维细胞（Human Dermal Fibroblast，HDF）和小鼠光老化模型，通过RT-qPCR检测5′tiRNA-Glu-TTC表达水平，利用tiRNA mimic/inhibitor转染HDF研究其对光老化表型的影响，并在小鼠模型中皮内注射腺相关病毒抑制其表达，分析其对小鼠光老化表型的作用。
    3、通过miRanda、Targetscan、RT-qPCR、Western Blot确定5′tiRNA-Glu-TTC
下游靶基因并过表达靶基因探索对HDF光老化表型的影响。
    4、通过KEGG分析、Western Blot进一步探究5′tiRNA-Glu-TTC参与光老化的具体分子机制。
结果
    1、308 nm LED组共纳入76处皮损，308 nm MEL组共纳入69处皮损。两种光源在1个月和2个月治疗后面部白癜风皮损的疗效相似（p = 0.349；p = 0.416），两组急性副作用发生率相当（p = 0.332）。两组患者中均观察到长期不良反应光老化的发生。
    2、在由UVB所诱导的光老化HDF、小鼠模型中，5′tiRNA-Glu-TTC表达升高；其模拟物诱导HDF产生光老化样改变，而敲低其表达可以改善UVB所诱导的HDF以及小鼠皮肤光老化表型。
    3、对miRanda以及Targetscan预测结果取交集后再通过实验证实5′tiRNA-Glu-TTC靶向 TRPV3，降低其表达。同时，过表达TRPV3可以改善由5′tiRNA-Glu-TTC模拟物诱导HDF光老化样改变。
    4、针对5′tiRNA-Glu-TTC的KEGG通路富集分析显示出PI3K/AKT信号通路的显著富集，Western Blot结果表明其模拟物可以激活HDF中PI3K/AKT信号通路，并且过表达TRPV3后可以减少光老化HDF中PI3K/AKT信号通路的激活。
结论
    308 nm LED治疗面部非节段型稳定期白癜风皮损的疗效和安全性与308 nm MEL相似，且两种光源均可导致局部皮肤光老化。在UVB所诱导的皮肤光老化过程中，5′tiRNA-Glu-TTC表达升高，并通过靶向作用于TRPV3介导其表达降低，同时激活PI3K/AKT信号通路参与光老化过程，这表明5′tiRNA-Glu-TTC以及TRPV3可以作为防治皮肤光老化的潜在靶点。

Background 
 UVB phototherapy is key for treating vitiligo and other superficial skin diseases. LEDs, 
known for high brightness and low cost, are a novel light source. Studies have shown that 
LED light therapy demonstrates comparable efficacy and safety to 308 nm MEL for treating 
vitiligo on the trunk, but its effectiveness for facial vitiligo remains unreported. Photoaging 
caused by phototherapy can reduce patient compliance, and current treatments for it are 
limited. tsRNAs, a type of non-coding RNA (ncRNA), are implicated in photoaging. Research 
has found that multiple tsRNAs are differentially expressed in photoaging, with 5′tiRNAGlu-TTC
 being significantly upregulated in photoaging models, though its role is unclear. 
This study aims to assess if 308 nm LED treatment for facial vitiligo matches MEL's efficacy 
and to explore the mechanisms and preventive targets of photoaging caused by long-term 
phototherapy. 
Methods 
1.145 facial lesions of non-segmental stable vitiligo were randomly assigned to two 
groups, each receiving treatment for 2 months of 308 nm LED or MEL treatment. At the end 
of the first and second months of treatment, two independent researchers evaluated the 
repigmentation effects. 
2. UVB-induced photoaging HDFs and mouse models were used. RT - qPCR measured 
5′tiRNA-Glu-TTC expression. TiRNA mimic/inhibitor transfection was studied to determine 
its impact on HDF photoaging phenotypes. Intra-dermal AAV injection in mouse models 
investigated its role in mouse photoaging. 
3. The downstream target gene of 5′tiRNA-Glu-TTC was identified through miRanda, 
Targetscan, RT-qPCR, and Western Blot. The effects of overexpressing the target gene on the 
photoaging phenotype of HDF were explored. 
4. KEGG analysis and Western Blot were used to further investigate the specific 
molecular mechanisms by which 5′tiRNA-Glu-TTC is involved in photoaging. 
Results 
 1. A total of 76 lesions were included in the 308 nm LED group, and 69 lesions were 
included in the 308 nm MEL group. The efficacy of the two light sources in treating facial 
vitiligo lesions was similar after one month and two months of treatment (p = 0.349; p = 
0.416). The two groups had comparable incidences of acute adverse reactions (p = 0.332). 
Photoaging was observed as a long-term adverse reaction in both patient groups.  
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2. In UVB-induced photoaging HDF and mouse models, the expression of 5′tiRNA-GluTTC
 was increased. Its mimic induced photoaging-like changes in HDF, while knockdown 
of its expression improved the photoaging phenotype in UVB-induced HDF and mouse skin. 
3. The intersection of prediction results from miRanda and Targetscan was 
experimentally confirmed to show that 5′tiRNA-Glu-TTC targets TRPV3 and reduces its 
expression. Overexpression of TRPV3 improved the photoaging-like changes induced by the 
5′tiRNA-Glu-TTC mimic in HDF. 
4. KEGG pathway enrichment analysis targeting 5′tiRNA-Glu-TTC showed significant 
enrichment of the PI3K/AK signaling pathway. Western Blot results indicated that its mimic 
could activate the PI3K/AKT signaling pathway in HDF, and overexpression of TRPV3 
reduced the activation of the PI3K/AKT signaling pathway in photoaged HDF. 
Conclusion 
 The efficacy and safety of 308 nm LED treatment for facial non-segmental stable vitiligo 
lesions are similar to those of 308 nm MEL, and both light sources can cause local skin 
photoaging. In UVB-induced skin photoaging, the expression of 5′tiRNA-Glu-TTC is 
increased. It targets TRPV3 to mediate its downregulation and activates the PI3K/AKT 
signaling pathway to participate in the photoaging process. This suggests that 5′tiRNA-GluTTC
 and TRPV3 can be potential targets for the prevention and treatment of skin photoaging.