Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications.

The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.

Neoadjuvant Photodynamic Therapy: An Updated Therapeutic Approach for Non-Melanoma Skin Cancers.

OPINION STATEMENT: Non-melanoma skin cancers (NMSCs) are the most common malignancy and surgical excision is considered treatment of choice for the majority of cases. However, surgery can be very extensive in cases of large, multiple, or cosmetic-sensitive tumors located on areas such as scalp and face or genital region, leading to significant functional and cosmetic deficit. Aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a widely used approach in a variety of skin diseases, demonstrating remarkable efficacy in treatment of actinic keratosis, Bowen disease and basal cell carcinoma. Besides, when employed as a preoperative intervention, ALA-PDT effectively reduces tumor size and minimizes subsequent local surgical morbidity. With its minimally invasive nature and proven effectiveness, ALA-PDT holds significant promise as a neoadjuvant treatment option for NMSCs. In cases where the tumor is large, invasive, multiple, or located in cosmetically and functionally sensitive areas, or when considering patient factors such as age, comorbidity, willingness to undergo surgery, and post-operative quality-of-life, surgical intervention or radiotherapy alone may be impracticable or unacceptable. In such scenarios, neoadjuvant ALA-PDT can offer remarkable outcomes. In order to further ensure the maximum benefit of patients from neoadjuvant PDT, collaboration with multidisciplinary teams and whole-process management may be in need.

Real-world data of 5-aminolevulinic acid-mediated photodynamic therapy for Bowen's disease: A 10-year retrospective study in the skin of color patients (2011-2021).

BACKGROUND: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen's disease (BD). However, reported data on 5-aminolevulinic acid-mediated PDT (ALA-PDT) with red light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. METHODS: Medical records of BD patients who received ALA-PDT with red light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were performed to identify risk predictors. RESULTS: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first two years following ALA-PDT. CONCLUSION: ALA-PDT is an effective treatment for BD in the skin of color patients. Well-executed operation and effective pre-treatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, two years of follow-up is necessary following ALA-PDT.

YAP1/Piezo1 involve in the dynamic changes of lymphatic vessels in UVR-induced photoaging progress to squamous cell carcinoma.

BACKGROUND: UV-induced cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The constant alterations of the lymphatic-centered immune microenvironment are essential in transforming from photoaging to cSCC. Studying the mechanism will be beneficial for new targets exploration to the early prediction of cSCC. AIMS: To investigate the dynamic changes and mechanism of the lymphatic-centered immune microenvironment in transforming from photoaging to cSCC induced by ultraviolet irradiation (UVR). METHODS: TIMER2.0 was used to analyze whether YAP1/VEGFC signaling pathway is involved in lymphangiogenesis in head and neck squamous cell carcinoma (HNSCC). Meanwhile, lymphatic-centered immune microenvironments alterations and the related cumulative survival time were also analyzed. With the accumulated UVR, skin photoaging developed and gradually progressed into actinic keratosis and cSCC on SKH-1 hairless mice. The skin lymphatic-centered immune microenvironment was evaluated at the 0th, 8th, 12th, 16-18th, and 20-24th week of UVR. Skin phenotype was assessed using optical coherence tomography (OCT) and skin image. H&E and Masson's trichrome staining evaluated epidermis and dermis. The structure of lymphatic vessels (LVs), blood vessels, and different types of T cells were evaluated by immunohistochemistry staining. The expression of Piezo1 whose deletion in adult lymphatics led to substantial valve degeneration, VE-cadherin that maintained the permeability of LVs, and YAP1 were evaluated by immunohistochemistry staining as well. Besides, the drainage function of LVs was assessed by Evans Blue assay in vivo. RESULTS: The lymphatic function and immune cell infiltration underwent adaptive changes under continuous UVR. TIMER2.0 analysis indicated that VEGFC genes high expressed in HNSCC. YAP1 gene expression was positive correlated with VEGFC in HNSCC. LV density increased in human cSCC. More LVs in HNSCC were beneficial to prolong the survival time. VEGFC gene overexpression was positive correlated to CD8+T cell infiltration. More CD8A+T cells and CD8B+T cell infiltration in HNSCC extended survival time. When YAP1 gene overexpression and high infiltration of endothelial cells took place simultaneously might prolong the survival time of HNSCC patients. And high infiltration of CD8+T cells prolonged the survival time as well. In animal studies, UVR-induced eight weeks (photoaging) and 16-18 weeks (precancerous) were two turning points. The density of LVs in UV-8w was the least. When photoaged skin developed into AK lesions (UV-16-18w), LV slightly exceeded healthy skin and proliferated sharply in cSCC (UV-20-24w). YAP1 expression was almost consistent with LV but rose after the photoaging stage. The drainage of cSCC mice induced by UVR was better than that of photoaged skin and worse than that of health skin. The dynamic alterations of LVs number, Piezo1 expression, and collagen might be reasons for it. The expression of Piezo1 was in the highest point after 8 weeks of UVR, then gradually descended to the platform. The total T cells increased slowly, but the infiltration of CD4+T cells increased, and CD8+T cells decreased after eight weeks of UVR. The CD8+T cells and CD4+T cells increased sharply in UV-16-18w and UV-20-24w groups. CONCLUSION: The lymphatic-centered immune microenvironment underwent adaptive changes under continuous UVR via regulating YAP1/VEGFC and Piezo1. During the formation of cSCC, there are two turning points, eight weeks (photoaging) and 16-18 weeks (precancerous). YAP1, Piezo1, LVs, and immune cells constantly changed with the skin state induced by UVR. According to these changes the process of cSCC can be identified in advance and intervene timely.

Signaling mechanisms underlying lymphatic vessel dysfunction in skin aging and possible anti-aging strategies.

Aging-related skin diseases are gradually increasing due to the imbalance of cutaneous homeostasis in the aging population. Skin aging-induced inflammation promotes systemic inflammation and may lead to whole-body aging. Lymphatic vessels play an important role in maintaining fluid and homeostasis balance. In intrinsically aged skin, the number of lymphatic vessels decrease and their functions decline, which is related to the reduced adhesion junctions between lymphatic endothelial cells, particularly VE-cadherin. VEGFC/VEGFR-3 signal pathway plays an important role in remodeling and expansion of lymphatic vessels; the downregulation of this pathway contributes to the dysfunction of lymphatic vessels. Meanwhile, we proposed some additional mechanisms. Decline of the pumping activity of lymphatic vessels might be related to age-related changes in extracellular matrix, ROS increase, and eNOS/iNOS disturbances. In extrinsically aged skin, the hyperpermeability of lymphatic vessels results from a decrease in endothelial-specific tight junction molecules, upregulation of VEGF-A, and downregulation of the VEGFC/VEGFR-3 signaling pathway. Furthermore, some of the Phyto therapeutics could attenuate skin aging by modulating the lymphatic vessels. This review summarized the lymphatic vessel dysfunction in skin aging and anti-aging strategies based on lymphatic vessel modulation.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

5-Aminolevulinic acid photodynamic therapy versus minocycline for moderate-to-severe rosacea: A single-center, randomized, evaluator-blind controlled study.

BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) showed potential to treat rosacea according to recent studies; however, a lack of clinical evidence and unclear adverse effects limit its use. OBJECTIVE: To compare the effect of ALA-PDT vs minocycline on rosacea. METHODS: In this single-center, randomized, evaluator-blind, controlled study, patients with moderate-to-severe rosacea were allocated to receive 3 to 5 sessions of ALA-PDT or 8 weeks of 100 mg daily minocycline treatment, followed by a 24-week follow-up. RESULTS: Of all the 44 randomized patients, 41 received complete treatment (ALA-PDT: 20 and minocycline: 21 patients). At the end of treatment, ALA-PDT showed noninferior improvement of papulopustular lesions and Rosacea-specific Quality of Life compared with minocycline (median reduction of lesion count: 19 vs 22, median change of Rosacea-specific Quality of Life score: 0.48 vs 0.53). The Clinician's Erythema Assessment success of ALA-PDT was lower than that of minocycline's (35% vs 67%). Demodex density and relapse rate were comparable in both groups. Erythema, mild pain, and exudation were the most common adverse reactions of ALA-PDT. LIMITATIONS: Limited sample size restricted us from drawing further conclusions. CONCLUSION: As minocycline does, ALA-PDT can improve rosacea mainly in papulopustular lesions and patients' quality of life, indicating a new option for rosacea.

Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study.

BACKGROUND: Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris. OBJECTIVE: To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris. METHODS: A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy. RESULTS: A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group. LIMITATIONS: Limitations of this study included relatively low numbers of participants and high withdrawal rate. CONCLUSION: M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO.

Paroxetine is an effective treatment for refractory erythema of rosacea: Primary results from the Prospective Rosacea Refractory Erythema Randomized Clinical Trial.

BACKGROUND: Patients with refractory erythema of rosacea have limited treatment options. OBJECTIVE: To evaluate the efficacy and safety of a 12-week course of paroxetine for moderate-to-severe erythema of rosacea. METHODS: In a multicenter, randomized, double-blinded, placebo-controlled trial, patients with refractory erythema of rosacea were randomly assigned (1:1) to receive paroxetine 25 mg daily or placebo for 12 weeks. RESULTS: Overall, 97 patients completed the study (paroxetine: 49; placebo: 48). The primary end point was the proportion of participants achieving Clinical Erythema Assessment success (defined as Clinical Erythema Assessment score of 0, 1, or ≥2-grade improvement from baseline) at week 12; this was significantly greater in the paroxetine group than in the placebo group (42.9% vs 20.8%, P = .02). Some secondary end points were met, such as flushing success with point reductions ≥2 (44.9% vs 25.0%, P = .04) and improvement in overall flushing (2.49 ± 3.03 vs 1.68 ± 2.27, P = .047), burning sensation (46.9% vs 18.8%, P = .003), and depression (P = .041). The most reported adverse events associated with paroxetine were dizziness, lethargy, nausea, dyspepsia, and muscle tremors. LIMITATIONS: Only a single-dosage regimen of paroxetine within a 12-week study was evaluated. CONCLUSIONS: Paroxetine is an effective and well-tolerated alternative treatment for moderate-to-severe erythema of rosacea.

Modified painless photodynamic therapy for facial multiple actinic keratosis in China: A prospective split-face control study.

BACKGROUND: Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for multiple actinic keratosis (AK). However, PDT-induced pain often discontinues the therapy to reduce its efficacy, limiting its application. If modified painless PDT schedule with shorter photosensitizer dressing and higher dose illumination could achieve good efficacy in AK, it is still unknown. OBJECTIVES: To explore the efficacy and pain tolerance of the modified painless PDT (M-PDT) in facial multiple AK. METHODS: A split-face controlled clinical study including 14 patients with facial multiple AK was conducted. The patients received conventional PDT (C-PDT) on the left and M-PDT in the contralateral area. The left area (C-PDT) was illuminated by a red light-emitting diode light (144 J/cm2 ) after applying the 10% ALA cream for 3 h; the other had illumination for a total light dose of 288 J/cm2 after applying the 10% ALA cream for 0.5 h. The primary endpoint was the lesion clearance rate at 1-month postthree sessions of PDT. Secondary endpoints included pain scores, the incidence of adverse events during treatment, and cosmetic outcomes. RESULTS: At 1 month following three treatments, the total lesion clearance rate was comparable between M-PDT and C-PDT (91.6% vs. 89.0%). While the lesion clearance rate of M-PDT was higher than that of C-PDT in the Grade III lesions (86.5% vs. 72.0%, respectively) (p < 0.05). M-PDT achieved a 100% lesion clearance rate for Grade I lesions earlier than C-PDT, with M-PDT treated twice and C-PDT treated thrice. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (p < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT. CONCLUSIONS: M-PDT is comparable to C-PDT's efficacy for treating facial multiple AK, resulting in much lower pain scores.

Comparison of red light and blue light therapies for mild-to-moderate acne vulgaris: A randomized controlled clinical study.

BACKGROUND: Red and blue light therapies are safe and effective treatments for mild-to-moderate acne vulgaris. However, very few previous studies have directly compared the characteristics of these two methods. OBJECTIVE: To compare the efficacy and side effects of red light (RL) and blue light (BL) for acne vulgaris and to assess these two therapies in different types of lesions. MATERIALS AND METHODS: A total of 28 subjects with mild-to-moderate acne vulgaris were randomized into the RL group or the BL group. Subjects in each group received different light treatments, and they were followed up regularly until 2 weeks after the last treatment. The improvement rates of different types of acne lesions were compared between the 2 groups, as well as the incidence of adverse reactions. RESULTS: At the 2-week follow-up, the average improvement rate of total acne lesions was 36.2% in the RL group and 30.7% in the BL group (p > .05). The average improvement rate of inflammatory and non-inflammatory lesions was 51.5% and 17.3% in the RL group, compared with 26.4% and 10.0% in the BL group (all p > .05). Treatment-related adverse reactions were observed distinctly in the BL group. CONCLUSIONS: Red light and BL therapies have similar efficacy in mild-to-moderate acne vulgaris, especially for inflammatory lesions. RL had advantages with fewer adverse reactions compared with BL.

Fluorescence kinetics study of twice laser irradiation based HpD-PDT for nonmelanoma skin cancer.

BACKGROUND: Hematoporphyrine injection (HpD)-based photodynamic therapy (HpD-PDT) has emerged as a promising cancer therapy. However, its tumor-targeting ability and metabolokinetics in nonmelanoma skin cancer (NMSC) have not been well explored. Importantly, photodynamic diagnosis is widely used for cancer lesion assessment and positioning to ensure effective therapy, while the photosensitizer metabolic kinetics study is utilized for biosafety assessment and light-protection instruction. These are particularly important for the optimization of therapeutic parameters. OBJECTIVES: In the present study, NMSC patients were subjected to twice laser irradiation-based HpD-PDT strategy. Broadly, the study aimed to assess long-term variations in fluorescence (FL) intensity in vivo in NMSC patients after intravenous (i.v.) administration of HpD, and thus obtain information regarding metabolism, biosafety, and light-protection instruction for HpD during the therapy. METHODS: In vitro experiments were used for the evaluation of absorption and fluorescent characterization of HpD in aqueous solution and cutaneous squamous cell carcinoma (SCC) cells. For in vivo assessment, 20 patients with NMSC, including SCC, basal cell carcinoma (BCC), Bowen disease (BD), extramammary Paget's disease (EMPD), and malignant proliferating tricholemmoma (APT), were recruited, and treated with HpD-PDT. To evaluate the selectivity and pharmacokinetics of HpD in vivo, relative changes in FL intensity for lesional, perilesional, and nonlesional skin of nonmelanoma skin cancer patients, before and after HpD injection, were semiquantitatively analyzed for 1 month, using the FL detection system and Wood's lamp. RESULTS: The absorption and FL spectra were detected and semiquantitatively analyzed in HpD diluted solution and SCC cells after coincubation with HpD. After i.v. administration of HpD in EMPD patients, FL was detected in the skin lesions at 24 hours, and it was characterized by clear edges. Importantly, FL intensity in the skin lesions increased significantly at 48 and 72 hours postinjection, which was suitable for HpD-PDT. After 72 h, it decreased gradually and reached close to the baseline value at 4 weeks postinjection. No severe side effects were observed during HpD injection and the therapy. Urinary tract infection was recorded in one patient (with a previous history of recurrent urinary tract infections) after HpD-PDT, and the patient was cured afterward. Transient light was observed in two patients after HpD-PDT and they soon recovered after therapy. CONCLUSIONS: The present study reported a significant increase in FL intensities at 48 and 72 hours after i.v. administration of HpD in patients with nonmelanoma skin cancers, which indicated accumulation of HpD at the cancer site. Importantly, HpD was found to be safe for NMSC patients. After therapy, FL intensities decreased, which indicated expending and metabolization of HpD. Thus, the results of the present study highlighted the suitability of a twice red-light laser irradiation strategy for the application of HpD-PDT in nonmelanoma skin cancer treatment.

Hydrogen-Peroxide-Responsive Protein Biomimetic Nanoparticles for Photothermal-Photodynamic Combination Therapy of Melanoma.

BACKGROUND AND OBJECTIVES: Recently, there has been a rapid increase in the incidences of melanoma, which represents a serious threat to human health. Generally, tumor-microenvironment-responsive nanoparticle-based photothermal-photodynamic combination therapy (PTT-PDT) is characterized by intratumoral response and tumor targeting. In this study, we designed and synthesized hydrogen-peroxide-responsive protein biomimetic nanoparticles (MnO2 -ICG@BSA) for the treatment of melanoma. STUDY DESIGN/MATERIALS AND METHODS: Briefly, MnO2 -ICG@BSA was prepared using a mild protein synthesis method by loading indocyanine green (ICG) into a bovine serum albumin-manganese dioxide complex (MnO2 @BSA); next, its characteristics were determined. In addition, in vitro biocompatibility and antitumor efficacy were assessed using the classic cell counting kit-8 assay. Moreover, in vivo high-frequency ultrasound and thermal imaging were used to evaluate the oxygen-production capacity and photothermal conversion effect of MnO2 -ICG@BSA at the tumor site, and Singlet Oxygen Sensor Green (SOSG) was used to measure singlet oxygen levels in the tumor. The antitumor efficacy was assessed based on relative tumor size, bodyweight, survival curves, and hematoxylin and eosin staining. RESULTS: The results showed that MnO2 -ICG@BSA has a high photothermal conversion efficiency, a strong singlet oxygen-generation ability, and high photothermal stability. In addition, in vitro PTT-PDT experiments showed that MnO2 -ICG@BSA has a significant inhibitory effect on the proliferation of B16F10 melanoma cells. Meanwhile, in vivo experiments showed that MnO2 -ICG@BSA has a significant inhibitory effect on melanoma in mice. Preliminary toxicity studies indicated that MnO2 -ICG@BSA exhibits low toxicity. CONCLUSION: From the results, we can conclude that MnO2 -ICG@BSA could be used in PTT-PDT to treat melanoma, making it a good candidate material for PTT-PDT. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

[Analysis of NF1 gene variant in a sporadic case with neurofibromatosis type 1].

OBJECTIVE: To explore the genetic basis for a sporadic case with neurofibromatosis type 1 (NF1). METHODS: Peripheral blood samples were collected from the patient, his unaffected parents and 100 healthy controls. The NF1 gene was detected by PCR and direct sequencing. RESULTS: The patient was found to carry a novel nonsense variant c.4339C>T (p.Q1447X) in exon 33 of the NF1 gene. The same variant was not found in his unaffected parents and the 100 healthy controls. CONCLUSION: The c.4339C>T (p.Q1447X) variant probably underlies the pathogenesis of NF1 in this patient.

Latent Demodex infection contributes to intense pulsed light aggravated rosacea: cases serial.

Intense pulsed light (IPL) is a good option for erythema and telangiectasia of rosacea. Demodex, which is light and heat sensitive, is an important risk of Rosacea. Sometimes, IPL can induce rosacea aggravation. Here, we show two cases of erythema rosacea aggravated as pustule in several hours after IPL. Both cases show high density of Demodex after IPL. Neither of them had photosensitivity, systemic disease, or any other contraindication for IPL. One of the patients received IPL again after Demodex infection relieved and this time there was no inflammation induction. We need to attract more attention to IPL-induced rosacea aggravation and latent Demodex infection may act as a cofactor.

Laser immunotherapy for cutaneous squamous cell carcinoma with optimal thermal effects to enhance tumour immunogenicity.

BACKGROUND: Laser immunotherapy is a new anti-cancer therapy combining photothermal therapy and immunostimulation. It can eliminate the tumours by damaging tumour cells directly and promoting the release of damage-associated molecular patterns (DAMPs) to enhance tumour immunogenicity. The aim of this study was to investigate the thermal effects of laser immunotherapy and to evaluate the effectiveness and safety of laser immunotherapy for cutaneous squamous cell carcinoma (cSCC). METHODS: The cell viability and the DAMPs productions of heat-treated cSCC A431 cells in different temperatures were investigated. Laser immunotherapy with the optimal thermal effect for DAMPs production was performed on SKH-1 mice bearing ultraviolet-induced cSCC and a patient suffering from a large refractory cSCC. RESULTS: The temperature in the range of 45-50 °C killing half of A431 cells had an optimal thermal effect for the productions of DAMPs. The thermal effect could be further enhanced by local application of imiquimod, an immunoadjuvant. Laser immunotherapy eliminated most tumours and improved the survival rate of the ultraviolet-induced cSCC-bearing SKH-1 mice (p < 0.05). The patient with cSCC treated by laser immunotherapy experienced a significant tumour reduction after laser immunotherapy increased the amounts of infiltrating lymphocytes in the tumour. No obviously adverse effect was observed in the mice experiment or in the clinical application. CONCLUSIONS: Our results strongly indicate that laser immunotherapy with optimal thermal effects is an effective and safe treatment modality for cSCC.

Enhancement of Photodynamic Therapy for Bowen's Disease Using Plum-Blossom Needling to Augment Drug Delivery.

BACKGROUND: Bowen's disease (BD) is treated effectively with 5-aminolevulinic acid (ALA)-photodynamic therapy (ALA-PDT). Plum-blossom needling (PBN) may enhance topical drug delivery. OBJECTIVE: To compare the effects of and adverse reactions to PBN and ALA-PDT of BD with those associated with ALA-PDT alone. MATERIALS AND METHODS: Forty-three lesions from 24 patients were randomly assigned to 2 groups. The PBN-ALA-PDT group underwent vertical skin tapping with PBN before applying 10% ALA cream and narrow-band light-emitting diode irradiation (λ = 633 ± 10 nm; 100-200 J/cm). The ALA-PDT group received ALA cream and irradiation only. RESULTS: At 6 weeks, the PBN-ALA-PDT and ALA-PDT groups achieved complete response (CR) rates of 77.78% (14/18 lesions) and 40% (7/20 lesions), respectively, (p < .05), and 2/18 and 10/20 lesions, respectively, achieved CRs after further treatment; 2.9 ± 0.8 sessions and 3.4 ± 0.7 sessions, respectively, were required for the lesions to achieve CRs. The PBN-ALA-PDT group required fewer treatment sessions and had higher protoporphyrin IX fluorescence levels (p < .05). CONCLUSION: Plum-blossom needling may improve the efficacy of ALA-PDT by enhancing ALA delivery for BD treatment.