Volume 139 · Issue 06 · 2026

基因融合是肿瘤发生和进展的常见机制。在非小细胞肺癌(NSCLC)中，常见的融合基因变异包括间变性淋巴瘤激酶(ALK)、ROS原癌基因1受体酪氨酸激酶(ROS1），在转染过程中重排（RET)、神经营养素受体激酶(NTRK）和神经调节蛋白-1（NRG1）合并。近年来，国内外均有针对多个融合基因的靶向药物获批并应用于临床，显著改善了携带这些融合突变的非小细胞肺癌患者的预后。因此，融合基因检测越来越受到重视。目前，临床上检测融合基因的方法有免疫组化（IHC）、荧光原地杂交（FISH）、逆转录聚合酶链反应和下一代测序（NGS）。IHC使用特异性单克隆抗体来检测融合蛋白的表达。它快速、廉价且易于自动化，因此经常被选为某些融合的伴随诊断（例如，ALK使用VENTANA平台上的克隆D5F3)或作为筛选工具(例如，用于ROS1或者NTRK合并）。然而，当高度特异性抗体不可用时，IHC携带高假阳性率和高假阴性率(例如，对于RET合并）。因此，通过IHC获得的任何阳性筛选结果都必须用正交分子测定法确认。FISH使用荧光标记的DNA探针来识别靶序列，并可以揭示拷贝数增加和染色体结构变化，如重排。该方法可靠且稳健，即使在5'配偶体未知的情况下也能检测融合。TheALK例如，分离FISH分析仍然被认为是金标准ALK-融合测试。然而，FISH有局限性：比最小距离更近的罕见或新颖的断点；FISH可以检测突变，但可能会产生假阴性结果；复杂的信号模式需要相当多的解释专业知识。逆转录聚合酶链反应可以高灵敏度和特异性地鉴定准确的5’和3’融合配偶体，但它只会检测序列已知的融合体。与其他技术相比，NGS提供了高通量、高准确性和检测罕见融合的能力，而其缺点是成本较高和周转时间较长。

临床上不稳定的上颈椎病变常需要内固定以恢复稳定性；然而，由于其复杂的解剖结构和靠近关键的神经血管结构，该区域的手术干预是高风险的。传统的依赖于外科医生的方法受到诸如重复荧光透视的辐射暴露和精度不足等问题的限制。^[1,2,3]机器人技术通过微创切口实现精确的手术操作，有助于限制软组织损伤，减少术中失血，加速术后恢复，最终改善患者预后。^[4]此外，机器人系统允许针对患者的手术策略，并有助于建立脊柱手术的标准化平台。它们支持临床数据收集，简化手术工作流程，并作为教育工具，缩短了初级外科医生的学习曲线。^[5,6]

The gut-brain axis is a complex, bidirectional network of communication systems that integrates neural, endocrine, and immune pathways, as well as metabolic processes, to regulate homeostasis and maintain physiological and cognitive equilibrium. Central to this axis is the gut microbiota, which exerts a profound influence on brain function through microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acids. Disruption of this microbial balance, known as dysbiosis, has been implicated in the onset and progression of major neuropsychiatric and neurodegenerative disorders, including depression, Alzheimer’s disease, and Parkinson’s disease. This review critically examines the mechanistic underpinnings of the gut-brain axis, emphasizing metabolic, immunological, and neuroendocrine signaling as key mediators. Furthermore, it explores how dietary components, particularly fiber, polyphenols, and fermented foods, modulate gut microbial composition and function to influence brain health. Emerging therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, are discussed, along with the potential of personalized targeted intervention. By integrating current findings, this review underscores the gut-brain axis as a dynamic interface that not only influences neurological and psychiatric outcomes but also represents a promising target for therapeutic intervention.

Pediatric health is the foundation for people’s lifelong health. The co-evolution of host genetics and the gut microbiome fosters a symbiotic relationship that is important for pediatric growth and the pathogenesis of various diseases. However, a comprehensive overview of the human genetics-gut microbiome axis in pediatric diseases remains unavailable. This review summarizes the human genetic variants that are associated with pediatric diseases, affecting the nervous, respiratory, and immune systems, as well as those linked to preterm birth (PTB), as identified by genome-wide association studies (GWAS). As the gut microbiome plays a crucial role in pediatric health, we have systematically discussed microbial biomarkers associated with the onset and progression of pediatric diseases, with an emphasis on their clinical impact across four key axes: the gut-brain, gut-lung, gut-skin, and gut-immune axes. The GWAS on the gut microbiome revealed numerous genetic variants that intricately regulate its composition. These variants predispose individuals to gut microbiome dysbiosis, potentially initiating or exacerbating pediatric disease manifestations. Moreover, the underrepresentation of populations from low- and middle-income countries in existing microbiome-related data, coupled with technical challenges, limits our understanding of the association between microbiome and health. Finally, we emphasize the promising potential of elucidating and modulating host gene-gut microbiome interactions to offer novel insights for advancing precision pediatric medicine and developing innovative therapeutic strategies.

Pancreatic ductal adenocarcinoma (PDAC), the deadliest epithelial malignancy, is increasingly prevalent and contributes significantly to cancer-related mortality. Research over the past decade has demonstrated that microbiota may play a pivotal role in both PDAC oncogenesis and its resistance to chemotherapy. Emerging preclinical and clinical data highlight the impact of microbiota on therapeutic outcomes in PDAC patients. This review systematically explores the role and underlying mechanisms of microbiota in PDAC, with a particular focus on their clinical implications and translational potential in disease progression and therapeutic responses. Finally, this review addresses the potential of microbiome-based therapies to enhance the efficacy of PDAC treatments.

Severe white matter lesions (WMLs) have been linked to poorer functional outcomes following endovascular therapy (EVT) in patients with acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). However, the absence of a control group in previous studies has limited the ability to determine the benefit of EVT to patients with severe WMLs.

This work is a secondary analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT) trial, a multicenter, randomized controlled trial conducted at 46 comprehensive stroke centers across China, which enrolled 456 patients with AIS with anterior-circulation LVO and large ischemic cores between October 2020 and May 2022. WML severity was graded using the van Swieten Scale on pretreatment noncontrast computed tomography (CT). For supplementary analyses, WML severity was further assessed using T2 fluid-attenuated inversion recovery (T2-FLAIR) magnetic resonance imaging (MRI) and graded according to the Fazekas scale, with WMLs categorized into periventricular and deep subtypes. Treatment effect on the primary outcome (90-day modified Rankin Scale [mRS] score) was assessed using multivariable ordinal logistic regression, and a treatment-by-WML interaction term was tested to evaluate effect modification.

In patients with absent-to-moderate WMLs, EVT was associated with a favorable shift in the distribution of 90-day mRS scores (adjusted common odds ratio [cOR] 2.15, 95% confidence interval [CI, 1.48-3.13], P <0.001). However, this benefit was less pronounced in those with severe WMLs (adjusted cOR 2.25, 95% CI [0.95-5.30], P = 0.065). No significant interaction between WML severity and treatment effect was detected (P_interaction = 0.888). Similarly, only among patients with absent-to-moderate WMLs, EVT significantly increased rates of mRS scores of 0-2 (adjusted OR 4.86, 95% CI [2.66-8.86], P <0.001), the rates of mRS scores of 0-3 (adjusted OR 2.23, 95% CI [1.39-3.57], P = 0.001), and the rates of early neurological improvement (adjusted OR 5.22, 95% CI [1.31-20.79], P = 0.019) compared to medical management alone. Supplementary analyses using T2-FLAIR MRI to stratify patients by WML burden yielded results consistent with those of the primary analyses.

EVT significantly improved functional outcomes in patients with LVO-AIS with absent-to-moderate WMLs, while the benefit in those with severe WMLs appeared less pronounced. However, estimates within subgroups were underpowered. Future pooled analyses of randomized clinical trials with adequate statistical power are needed to clarify the impact of WML severity on EVT outcomes and to refine patient selection criteria.

Senescence significantly participates in shaping the pathobiological process underlying chronic obstructive pulmonary disease (COPD). Currently, the mechanisms underlying the anti-aging effects of hydrogen sulfide (H₂S) in COPD are not fully illustrated.

Immunohistochemistry (IHC) staining was performed on human lung tissue to detect the expression levels of sirtuin 3 (Sirt3), cyclin-dependent kinase 4 inhibitor (P16), and cystathionin gamma lyase (CTH). An animal COPD model including wild-type (WT) and Sirt3 knockout (KO) mice was established by exposing them to cigarette smoking (CS) for 24 weeks, with or without intraperitoneal injection of sodium hydrosulfide (NaHS, 50 µmol·L^-1·kg^-1) 30 min prior to CS exposure. Lung function was assessed. The expression levels of P16, cyclin-dependent kinase inhibitor 1A (P21), Sirt3, manganese superoxide dismutase (SOD2), manganese acetylated superoxide dismutase (ac-SOD2), interleukin-6 (IL-6), IL-8, malondialdehyde (MDA), and glutathione (GSH), as well as the activity of SOD2 and Sirt3, were evaluated. Human bronchial epithelial BEAS-2B cells were subjected to diverse cigarette smoking extract (CSE) concentrations for 48 h with or without sodium hydrosulfide (NaHS). Subsequently, the levels of total intracellular reactive oxygen species (T-ROS), mitochondrial reactive oxygen species (mitoROS), mitochondrial membrane potential (MMP), senescence-associated β-galactosidase (SA-β-gal) staining positive cells, and related marker proteins and cytokines were assessed. Furthermore, the Sirt3-specific inhibitor 3-TYP and small interfering RNAs (siRNAs) of Sirt3 were used to examine the mechanisms whereby H₂S inhibits oxidative stress and senescence in COPD.

IHC showed a significant reduction of CTH and Sirt3 protein levels in the lung tissue of COPD with smoking patients and smokers without COPD compared to non-smokers. Furthermore, the expression of the aging marker protein P16 was notably elevated in the COPD with smoking group compared to the smokers without COPD and non-smoker groups. Furthermore, our results demonstrated that exposure to CS resulted in imbalanced oxidative and cellular senescence, including elevated mitoROS, T-ROS, MDA, and ac-SOD2, along with increased proportions of SA-β-gal staining positive cells and the increased expression levels of IL-6, IL-8, P21, and P16, as well as decreased GSH levels, SOD2 and Sirt3 activities, and Sirt3 expression, which ultimately contribute to emphysema development and impaired lung function. However, pretreatment with NaHS effectively reversed these detrimental effects. Nevertheless, the protective effect of NaHS was alleviated in Sirt3 KO mice and in cellular models treated with Sirt3 siRNA and 3-TYP.

Our study indicates that H₂S inhibits oxidative stress and cellular senescence by modulating the Sirt3/SOD2 signaling pathway, therefore attenuating the emphysema and impaired lung function induced by CS.

Cardiopulmonary bypass-associated acute kidney injury (CPB-AKI) is a serious and common complication following cardiopulmonary bypass (CPB), leading to worse outcomes and higher mortality. However, the underlying pathological mechanisms of CPB-AKI remain largely unknown. This study aimed to investigate the role of long non-coding RNA H19 (H19) in regulating CPB-AKI.

We examined the expressions of H19 and mitophagy-related proteins in a CPB-AKI rat model and HK-2 cells following oxygen-glucose deprivation/reperfusion (OGD/R). In vivo, lentiviral-mediated overexpression of H19 was induced in the kidney through tail vein injection. We then evaluated renal functions, kidney pathological damage, levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, and IL-10), neutrophil infiltration, and the activation of PTEN-induced putative kinase 1 (Pink1)/Parkin-mediated mitophagy following CPB-AKI. In vitro, small interfering RNA (siRNA) was used to downregulate H19 expression in HK-2 cells. We also examined cell viability, apoptosis, inflammation, and Pink1/Parkin-mediated mitophagy after OGD/R.

We demonstrated an increase in H19 expression and activation of Pink1/Parkin-mediated mitophagy in the rat model of CPB-AKI and HK-2 cells following OGD/R. In the rat models of CPB-AKI, lentivirus-mediated overexpression of H19 significantly attenuated renal injury, characterized by better renal function, reduced tissue damage, decreased neutrophil infiltration, and lower inflammatory cytokine release (P <0.05). Notably, overexpression of H19 significantly activated Pink1/Parkin-mediated mitophagy. Furthermore, in vitro, downregulation of H19 by specific siRNA in HK-2 cells significantly decreased cell viability, worsened HK-2 injury after OGD/R, increased inflammatory cytokine release, and decreased Pink1/Parkin-mediated mitophagy activity, promoting cell apoptosis (P <0.05).

These findings suggest that H19 overexpression may protect against CPB-AKI by activating Pink1/Parkin-mediated mitophagy and decreasing inflammatory responses and cellular apoptosis. Thus, H19 overexpression might be a promising therapeutic target for treating CPB-AKI.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by a multifactorial etiology and limited therapeutic options. Recent advancements in plant-derived exosome-like nanoparticles (PDENs) have demonstrated promising potential for UC treatment. This study explored the therapeutic efficacy of Andrographis paniculata-derived exosome-like nanoparticles (APELNs) in alleviating dextran sodium sulfate (DSS)-induced colitis.

APELNs were isolated and purified using sucrose gradient centrifugation and subsequently characterized through visualization techniques. Their stability was assessed under simulated stomach-like and intestine-like conditions. The therapeutic potential of APELNs was evaluated through both in vivo and in vitro experiments. In addition, the biosafety of APELNs was comprehensively analyzed in these settings.

APELNs exhibited excellent stability and biosafety, with a targeted accumulation in inflamed colonic tissues under gastrointestinal conditions. The nanoparticles displayed a desirable size (about 180 nm) and a negative zeta potential (-40 mV). Treatment with APELNs significantly ameliorated colonic pathologies in vivo and suppressed the expression of pro-inflammatory cytokines in vitro. Mechanistically, APELNs enhanced gut microbiota richness and diversity, fostering the growth of the probiotic Lactobacillus murinus. Moreover, APELNs reduced intestinal permeability and preserved intestinal barrier integrity by upregulating tight junction proteins, including Claudin-1, zonula occludens-1, Mucin2, and anti-occludin. Importantly, oral administration of APELNs shifted macrophage polarization in the colon, inhibiting the pro-inflammatory M1 subset while promoting the anti-inflammatory M2 subset. This polarization was mediated through the activation of the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) and Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways and the upregulation of interleukin-4 receptor expression.

These findings highlighted the potential of APELNs as a novel therapeutic strategy for UC, offering a promising alternative for effective disease management.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) improves beta-cell function in animals and humans with diabetes. Herein, we aimed to investigate the effects of SGLT2i on beta-cell regeneration, trace the origin of regenerated beta cells, and reveal the potential mechanism.

Type 2 and type 1 diabetic mice were treated with canagliflozin (10 mg/kg), dapagliflozin (1 mg/kg), or vehicle. Islet morphology was evaluated to investigate beta-cell regeneration. Inducible pancreatic neurogenin 3 (Ngn3)⁺ progenitor lineage-tracing mice and alpha-cell lineage-tracing mice were used to trace the origin of regenerated cells. Mouse and human islets, alpha cells, and beta cells were incubated with dapagliflozin (12.5 µmol/L) or vehicle. Insulin and glucagon-like peptide-1 (GLP-1) release, gene expression, and RNA sequencing analysis were performed to clarify the direct actions of SGLT2i and to screen potential targets. Alpha cells were transfected with peroxisome proliferator-activated receptor-γ coactivator 1α (Ppargc1α) plasmid or with Ppargc1α siRNA, followed by incubation with or without dapagliflozin to confirm the effects of Ppargc1α in alpha-cell phenotype conversion.

SGLT2i increased islet and beta-cell areas in type 2 diabetic mice and showed a similar trend in type 1 diabetic mice. SGLT2i induced alpha-cell dedifferentiation into Ngn3⁺ progenitors and promoted progenitor differentiation toward beta cells. In cultured diabetic mouse and human islets and in stressed alpha cells, SGLT2i increased supernatant insulin and active GLP-1 levels, downregulated alpha-cell-specific marker expression, and upregulated the expression of endocrine progenitor- and beta-cell-specific markers, including prohormone convertase 1/3. Although dapagliflozin did not affect beta cells directly, it affected alpha cells (457 upregulated and 235 downregulated genes). Ppargc1α, a coactivator participating in oxidative phosphorylation, was identified as a potential target. By using overexpression and knockdown, we confirmed that Ppargc1α participated in SGLT2i-induced regulation of alpha-cell phenotype conversion.

Alpha-cell regression to progenitors and progenitor differentiation toward beta cells represent a novel pathway for beta-cell neogenesis induced by SGLT2i in diabetes, with Ppargc1α playing a role in this process.

Visual input supports locomotion through sensorimotor integration. However, the neural mechanisms underlying how the brain adapts to degraded vision are not well understood. This study investigated the effects of visual occlusion on interactions between regions within the sensorimotor network.

Twelve healthy young adults (8 males, 4 females; mean age 24.0 ± 2.1 years) were recruited from the Department of Ophthalmology at Peking University Third Hospital between December 2024 and September 2025. Pattern-reversal visual evoked potentials were recorded under both normal vision and visual occlusion condition (Snellen 20/60 acuity). We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data to calculate the amplitude of low-frequency fluctuations (ALFF) and seed-based functional connectivity (FC) focused on visuomotor integration regions. A one-way repeated-measures analysis of variance was conducted with three within-subject conditions: seated rest, level walking with normal vision, and level walking with visual occlusion.

Stimuli consisted of checkerboard patterns with large (1°) and small (15′) checks. Under 1° visual stimulation, visual occlusion prolonged binocular P100 latency (117.00 ± 8.55 ms vs. 111.81 ± 5.12 ms; 116.78 ± 9.79 ms vs. 110.96 ± 4.28 ms; all P <0.05) and reduced N75-P100 amplitude (5.798 ± 2.372 µV vs. 8.613 ± 3.949 µV; 6.230 ± 2.459 µV vs. 7.453 ± 2.692 µV, all P <0.05). For 15′ stimulation, occlusion decreased both binocular N75-P100 (5.935 ± 3.500 µV vs. 10.794 ± 5.249 µV; 3.991 ± 1.585 µV vs. 10.361 ± 3.143 µV, all P <0.001) and P100-N135 amplitudes (6.218 ± 3.516 µV vs. 12.499 ± 4.236 µV; 4.427 ± 2.218 µV vs. 10.767 ± 4.904 µV, all P <0.001). Rs-fMRI analysis showed reduced ALFF in the right paracentral lobule after walking (peak Montreal Neurological Institute [MNI] coordinates: 3, -39, 66; P <0.001, F = 14.009). Walking activated multiple visuomotor pathways (all P <0.001), including the bilateral calcarine and middle temporal gyri, the right calcarine and middle frontal gyri, the bilateral supplementary motor area and right cuneus, and the bilateral precentral gyrus and right cerebellar lobule VI. The visual occlusion strengthened FC between the right precentral and the right middle frontal gyri (peak MNI: 27, 57, 27; F = 16.456, P <0.001).

Basic visuomotor pathways demonstrate consistent activation to maintain locomotion. Increased functional connectivity between the right precentral and middle frontal gyri serves as a compensatory mechanism for reduced visual input.

致编辑：肺癌是世界范围内最常见的恶性肿瘤之一，也是癌症相关死亡的主要原因。非小细胞肺癌（NSCLC）占所有肺癌的80%以上，人类表皮生长因子受体2（HER2)在约2-4%的非小细胞肺癌患者中发现。^[1,2]目前，化疗已成为HER2-突变型NSCLC。近年来，免疫检查点抑制剂（ICIs）在非小细胞肺癌的治疗方面取得了重大进展。然而，ICIs在HER2-突变型非小细胞肺癌患者仍不确定。^[2,3,4]因此，我们进行了一项多中心、真实世界的回顾性研究，以评估化疗单独或联合ICIs在晚期HER2-突变型NSCLC患者。

致编辑：肝硬化是以肝组织纤维化和肝功能受损为特征的各种慢性肝病的终末期。^[1]这种情况现在已经成为一个巨大的全球健康负担，具有显著的发病率和死亡率。^[1,2,3]确定影响肝硬化发生、发展和预后的危险因素非常重要。最近，被认为是肺纤维化早期阶段的间质性肺异常（ILAs）的概念被提出。鉴于ILAs作为间质性肺病（ILD）的前驱物，与肝硬化具有纤维化性质，并考虑到ILD与肝硬化之间的记录关联，ILAs与肝硬化之间可能存在潜在联系，但这种联系在当前文献中仍未探讨。因此，在本研究中，我们旨在探索（1）肝硬化人群中ILAs患者的比例；（2）伴有或不伴有ILAs的肝硬化患者的死亡率；以及（3）根据中国的回顾性队列研究，ILAs的存在是否是肝硬化患者死亡率的独立预测因素。

致编辑：下呼吸道感染（LRIs）是全球死亡率的重要原因。二手烟（SHS）含有7000多种化学物质，其中70种是致癌的，会加剧呼吸系统的脆弱性。SHS暴露仍然是导致LRIs的重要风险因素，对易感人群，尤其是儿童和老年人的影响不成比例。尽管先前的研究已经量化了SHS对哮喘和肺癌的负担，但对LRIs的研究仍然有限。本研究旨在量化1990年至2021年间SHS暴露导致的全球、区域和国家LRIs负担，并预测到2035年的未来趋势。

致编辑糖尿病肾病(DKD)是糖尿病的一种严重且日益普遍的并发症。早期临床干预可有效减轻肾脏损害，促进疾病逆转，尤其是肾功能基本保留的微量白蛋白尿患者。^[1]最近的临床研究表明，黄秋葵（A.manihot）花（黄葵胶囊）在原发性肾小球疾病、IgA肾病和DKD的治疗中显示出良好的潜力。^[2]先前的研究也表明，A.木薯在降低DKD和大量白蛋白尿患者的尿蛋白方面发挥与厄贝沙坦相当的作用。^[2]然而，没有证据表明A.木薯影响微量白蛋白尿患者的尿蛋白水平，尽管其在中国广泛用于治疗慢性肾脏疾病的蛋白尿。^[3]因此，我们进行了一项以氯沙坦为阳性对照的多中心随机临床试验，以评估是否A.木薯在治疗伴有微量白蛋白尿的2型糖尿病方面与氯沙坦一样有效。

致编辑：类固醇诱导的股骨头坏死(SIONFH)是一种使人虚弱的骨科疾病，其特征是进行性髋关节疼痛、不可逆的股骨头塌陷和最终残疾，^[1]给患者带来相当大的身体和社会经济负担。尽管其确切的发病机制仍不完全清楚，但越来越多的证据强调了两个相互关联的驱动因素：破骨细胞活性过多和活性氧（ROS）的过量产生。先前的研究^[2]报道了股骨头坏死区域破骨细胞活化升高和抗氧化酶表达降低。这种不平衡破坏了骨重塑稳态，而抗氧化防御不足不能减轻ROS诱导的细胞损伤，从而加速坏死和塌陷。在氧化应激下，Kelch样ECH相关蛋白1(Keap1），一种氧化还原敏感的生物传感器，经历降解，使核因子红系2相关因子2(Nrf2）易位到细胞核中^[3]并与抗氧化反应元件(ARE)结合，随后诱导抗氧化基因的转录以恢复ROS介导的破骨细胞稳态。^[4]

致编辑：包含1（MAMLD1人类孟德尔遗传[OMIM]#300120)是46，XY性发育障碍(DSDs)的致病基因。先前的研究表明MAMLD1可能通过影响睾丸间质细胞中睾酮的合成导致46，XY DSDs。然而，这种机制MAMLD1影响T生物合成尚不清楚。在本研究中，我们确定了5例46，XY DSDs患者，旨在探讨MAMLD1变体和46，XY DSD。总体而言，我们发现MAMLD1在调节清道夫受体B类成员1的转录中发挥新作用（SCARB1;OMIM#601040)，从而影响小鼠睾丸间质细胞系中的胆固醇稳态。这些结果为深入了解MAMLD1在46中，XY DSDs。

致编辑：黄褐斑是一种慢性、获得性和色素沉着过度疾病，其中患者表现为面部色素斑，影响全球8.8%至40%的人口。^[1]目前，该病症的主要治疗是应用局部药物，其中包含0.01%氟轻松、4%氢醌和0.05%维a酸的三联组合乳膏(TCC)(Tri-Luma，Galderma)，这是1975年首次提出的Kligman-Willis配方的改进，^[2]于2002年获得食品药品监督管理局批准。这种面霜在白种人和其他种族中显示出有希望的功效。但其疗效尚未在中国患者中得到证实，中国市场上也没有获批的制剂。在拟定的III期试验（ChiCTR2100043798）中，我们旨在采用双盲、安慰剂对照设计研究TCC的疗效和安全性。