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.

A review on ferroptosis and photodynamic therapy synergism: Enhancing anticancer treatment.

Ferroptosis is an iron-dependent programmed cell death modality, which has showed great potential in anticancer treatment. Photodynamic therapy (PDT) is widely used in clinic as an anticancer therapy. PDT combined with ferroptosis-promoting therapy has been found to be a promising strategy to improve anti-cancer therapy efficacy. Fenton reaction in ferroptosis can provide oxygen for PDT, and PDT can produce reactive oxygen species for Fenton reaction to enhance ferroptosis. In this review, we briefly present the importance of ferroptosis in anticancer treatment, mechanism of ferroptosis, researches on PDT induced ferroptosis, and the mechanism of the synergistic effect of PDT and ferroptosis on cancer killing.

A prospective, split-face, randomized controlled trial of intense pulsed light-photodynamic therapy for seborrhea.

BACKGROUND: Seborrhea poses a common cosmetic concern in adolescents and young adults, often accompanied by enlarged pores, and contributing to various skin conditions, including acne vulgaris and seborrheic dermatitis. At present, there is a lack of effective treatment for this problem, and the potential of photodynamic therapy (PDT) in reducing sebum remains inconclusive. OBJECTIVE: This exploratory, prospective, single-center, double-blinded, randomized split-face controlled trial aimed to compare the efficacy and safety of intense pulsed light-photodynamic therapy (IPL-PDT) versus IPL therapy for seborrhea. METHODS: Participants with seborrhea underwent 3 times of IPL treatment (590 nm, 15-17 J/cm2 based on patient's tolerance) for one hemifacial part and IPL-PDT treatment for the other. Follow-up assessment was conducted up to 8 weeks after the final treatment. RESULTS: Compared with single IPL treatment, IPL-PDT can significantly inhibit sebum secretion and decrease pore size. PDT group exhibited no additional damage to the skin barrier, with even lower transepidermal water loss (TEWL). Additionally, the PDT group showed superior improvement in scores of porphyrins, red areas, and ultraviolet (UV) spots. Both groups experienced only mild topical adverse effects, well tolerated by the participants. CONCLUSION: IPL-PDT is a more effective method than IPL in the treatment of seborrhea, as well as on the improvement of the skin barrier function.

IPL-PDT as an effective treatment for mild-to-moderate acne vulgaris: A prospective, single-center, self-controlled study.

BACKGROUND: High recurrence rate of mild-to-moderate acne vulgaris following traditional therapy poses a significant challenge. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) with intense pulsed light (IPL) has emerged as a promising intervention. OBJECTIVES: This study aimed to evaluate the efficacy and safety of IPL-PDT for the treatment of mild-to-moderate acne vulgaris. METHODS: In this prospective, self-controlled study, eligible patients aged from 18 to 45 years old with Pillsbury grade Ⅰ-III facial acne were included. Patients were treated with three sessions of IPL-PDT at three-week interval, with follow-ups at 3 weeks and 2 months after the final treatment. RESULTS: A total of 31 patients were enrolled. At 3 weeks post-treatment, the mean count of acne lesions decreased significantly (P < 0.001), with 87.1 % of patients achieving treatment success (defined as ≥ 75 % clearance rate of acne lesions). Recurrence rate at 2-month follow-up was 9.68 %. No severe adverse reactions were observed. LIMITATIONS: This study is a single-center, self-controlled study. Multi-center study designed as randomize controlled trials involving a larger patient cohort is necessary. CONCLUSIONS: IPL-PDT is a promising therapy for mild-to-moderate acne vulgaris, exhibiting high efficacy, minimal adverse effects, and a low recurrence rate.

Oroxylin A suppress LL-37 generated rosacea-like skin inflammation through the modulation of SIRT3-SOD2-NF-κB signaling pathway.

Rosacea is a long-term inflammatory skin disease associated with the dysfunction of vascular and immunological systems. Treatment options for rosacea are difficult to implement. Oroxylin A(OA), a traditional Chinese medicine, has anti-inflammation effects in a variety of inflammatory diseases. However, it is not known that whether OA exerts protective effects against LL-37-induced rosacea. In this study, bioinformatics analyses showed that the mechanisms of rosacea and the pharmacological targets of OA were highly overlapped. Subsequently, it was shown that the administration of OA resulted in a notable amelioration of rosacea-like skin lesions, as evidenced by a reduction in immune cell infiltration, modulation of cytokine production, and inhibition of angiogenesis. Plus, it was shown that OA effectively suppressed the generation of ROS generated by LL-37, as well as the subsequent activation of NF-κB signaling pathway. To explore further, we found that OA inhibited LL-37-induced ROS production via SIRT3-SOD2 signaling pathway in keratinocytes. Based on the aforementioned evidence, it can be inferred that OA exhibits a mitigating effect on the inflammatory response in rosacea by modulating the SIRT3-SOD2-NF-κB signaling pathway.

Curcumin-mediated photodynamic therapy for mild to moderate Acne: A self-controlled split-face randomized study.

OBJECTIVE: To evaluate the effectiveness and safety of Curcumin-mediated Photodynamic Therapy (Curcumin-PDT) in the treatment of mild to moderate acne. METHODS: In this randomized split-face controlled study, 11 patients with mild to moderate acne were randomly divided into two groups. One side received a single 445 nm LED light exposure of 36 J/cm2, while the other side received Curcumin-PDT. The process of Curcumin-PDT involves the application of a mask containing 1 % curcumin for 20 min, followed by exposure to 445 nm LED light at 36 J/cm². The treatment consists of sessions spaced every 3 days, with a total of 2 treatments per week, administered continuously for 2 weeks. Efficacy assessment and comparison were conducted on both groups of patients before treatment and 2 weeks after the last treatment, and adverse reactions were observed and recorded. RESULTS: At the 2-week follow-up after the last treatment, the total lesion clearance rates for Curcumin-PDT and monotherapy light were 54.7 ± 21.5 % and 28.1 ± 19.9 %, respectively (P = 0.001). The clearance rates for non-inflammatory lesions were 32.3 ± 25.7 % and 21.9 ± 14.0 % for Curcumin-PDT and monotherapy light sides (P = 0.252), while for inflammatory lesions, the clearance rates were 59.3 ± 28.2 % and 36.5 ± 21.6 % (P = 0.013). Both groups experienced mild erythema after treatment, which subsided within 1-2 h. Two patients developed mild localized pigmentation, which self-resolved after 1 month of follow-up. Both groups did not exhibit edema, crust formation, scaling, pigment reduction, or scarring. CONCLUSION: Curcumin-PDT can be considered a safe and effective method for the treatment of mild to moderate acne.

Modified 5-aminolevulinic acid photodynamic therapy induces cutaneous squamous cell carcinoma cell pyroptosis via the JNK signaling pathway.

Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) is a novel therapeutic modality for cutaneous squamous cell carcinoma (cSCC) that is reported to be effective and well tolerated. However, the mechanisms underlying its antitumor effects are not fully understood. In this research, we investigated the effects of M-PDT on pyroptosis, a form of programmed cell death characterized by cell swelling, ruptures of cell membrane, and inflammatory cytokine release, in two human cSCC cell lines, SCL-1 and HSC-5. We found that M-PDT triggered pyroptosis in a dose-dependent manner, as evidenced by increased lactate dehydrogenase release, propidium iodide staining, and expression of pyroptosis-related proteins, such as NLR family pyrin domain containing 3 (NLRP3), N-terminal of gasdermin D (N-GSDMD), cleaved caspase-1, and mature interleukin 1 beta (IL-1B) in both cell lines. This process was inhibited by treatment with MCC950, an NLRP3-specific inhibitor, suggesting the involvement of the NLRP3 inflammasome in M-PDT-induced pyroptosis. We also demonstrated that M-PDT activated c-Jun N-terminal kinase (JNK) signaling, which is required for pyroptosis induction, as treatment with SP600125, a JNK inhibitor, suppressed the expression of pyroptosis-related proteins after M-PDT. JNK activation enhanced M-PDT-induced pyroptosis, highlighting the significance of the JNK pathway in M-PDT. Moreover, M-PDT increased intracellular reactive oxygen species (ROS) levels, which are responsible for JNK activation and pyroptosis induction. In summary, our results revealed that M-PDT triggers pyroptosis through ROS-mediated JNK activation and subsequent NLRP3 inflammasome activation in cSCC cells, providing a better understanding of the molecular mechanism of M-PDT and promoting its clinical application.

The combination of holmium laser and ALA-PDT for Bowenoid Papulosis with diffuse large B-cell lymphoma.

Bowenoid Papulosis (BP) is an anogenital pre-malignancy. BP with immunosuppression may recur, worsen, or possibly evolve into squamous cell carcinoma or Bowen's disease (BD), and it may also become resistant to conventional treatment. Here, we describe a complex case of BP together with BD and Diffuse Large B-Cell Lymphoma that was effectively treated with a holmium laser in conjunction with 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT). The lesion totally vanished and the affected area remained intact with no recurrence at five years.

Dermoscopy combined with reflectance confocal microscopy as a noninvasive involvement for monitoring Cutaneous Rosai-Dorfman: A case report.

Cutaneous Rosai-Dorfman disease(CRDD) is an extremely rare entity and features histiocytic proliferation in the skin. Dermoscopy and reflectance confocal microscopy(RCM) reports on CRDD are rare. We reported a case of CRDD and summarized the dermoscopy(FotoFinder Medicare 800HD, FotoFinder-Systems GmbH, Birbach Germany) and RCM(VivaScope® 1500, V Caliber Imaging and Diagnostics) features of CRDD. The dermoscopic features of CRDD showed red-orange background with pale yellowish roundish areas similar to millet, surrounded by branched blood vessels. Sometimes the white structureless materials of CRDD could be observed by dermoscopy, which may be a hint of spontaneous regression. The RCM features of CRDD revealed dense highly refractile roundish or ovoid structures(inflammatory cells), and multiple larger structures with central low refraction and moderately refractive peripheral semicircle or circle(engulfed inflammatory cells), together with low refractive branched structures(blood vessels). Dermoscopic and RCM features of CRDD can help the dermatologists recognize and follow-up the disease in real time.

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.

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.

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.

[Effects of Long-term Tillage on Soil Bacterial Community Structure and Physicochemical Properties of Dryland Wheat Fields in Northern China].

To explore the effects of long-term tillage on bacterial community structure in different soil layers of dryland wheat fields and its relationship with soil physicochemical properties, a long-term field experiment was conducted from 2016 to 2021 in Wenxi Experimental Demonstration Base of Shanxi Agricultural University, Shanxi Province. We studied the effects of no-tillage (NT), subsoiling-tillage (ST), and deep plowing (DP) on soil physicochemical properties; α and ß diversity of the bacterial community; and dominant and different species of phyla and genera in different soil layers. Additionally, PICRUSt2 was used to predict the metabolic function of soil bacterial community. The results revealed that subsoiling-tillage and deep plowing significantly increased the soil water content in the 20-40 cm soil layer and significantly decreased the soil organic carbon content in the 0-20 cm soil layer compared with that under no-tillage for five consecutive years. Compared with that under deep plowing, subsoiling-tillage significantly increased soil water content, soil organic carbon content, dissolved organic carbon content, and dissolved organic nitrogen content in the 0-20 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing increased the α diversity of the soil bacterial community in the 0-40 cm soil layer, and subsoiling-tillage was higher than deep plowing. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundances of Acidobacteria and Nitrospirae in the 0-20 cm soil layer and Acidobacteria, Chloroflexi, Gemmatimonadetes, Rokubacteria, GAL15, and Nitrospirae in the 20-40 cm soil layer. Compared with that under no-tillage, subsoiling-tillage and deep plowing significantly increased the relative abundance of Nitrospira in the 0-20 cm soil layer and Rubrobacter and Streptomyces in the 20-40 cm soil layer. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundance of Acidobacteria and Gemmatimonadetes in the 0-40 cm soil layer. Redundancy analysis demonstrated that the contents of soil organic carbon, dissolved organic carbon, and dissolved organic nitrogen in the 0-20 cm soil layer exerted positive effects on Actinobacteria and Blastococcus, and the soil water content in the 0-40 cm soil layer exerted positive effects on Acidobacteria, Chloroflexi, and Gemmatimonadetes under subsoiling-tillage. The results of PICRUSt2 prediction showed that subsoiling-tillage and deep plowing significantly increased the relative abundance of amino acid metabolism and the metabolism of cofactors and vitamins but decreased the relative abundance of lipid metabolism of bacterial communities in the 20-40 cm soil layer compared with that under no-tillage. Compared with that under deep plowing, subsoiling-tillage significantly increased the relative abundances of amino acid metabolism in the 0-40 cm soil layer and other amino acid metabolism in the 0-20 cm soil layer. In conclusion, subsoiling-tillage or deep plowing could increase the soil water content, α diversity of the soil bacterial community, and their metabolic capacity in the dryland wheat fields during the summer fallow period. The relative abundance of Acidobacteria and Gemmatimonadetes and the ability of amino acid metabolism of the bacterial community were increased by subsoiling-tillage, and thus the contents of soil dissolved organic carbon and dissolved nitrogen can be increased.

5-aminolevulinic acid sonodynamic therapy for cutaneous squamous cell carcinoma.

BACKGROUND: The treatment of deep-invasive cutaneous squamous cell carcinoma (cSCC) is difficult. Sonodynamic therapy (SDT) has showed advantages in large penetration depth, small trauma, good repeatability, high targeting selectivity and effective protection for intact structure and function of tissues and organs. OBJECTIVE: To study the efficacy and safety of 5-aminolevulinic acid SDT (ALA-SDT) in the treatment of cSCC. METHODS: The absorption and transformation of ALA after co-incubation with cSCC were detected by UV-Vis and fluorescence absorption. The production of reactive oxygen species (ROS) when protoporphyrin IX (PpIX) excited with ultrasound was detected by ROS detection probe. Cytotoxicity of ALA-SDT to cSCC was detected with cytotoxicity indicators. The tumor volume changes and tumor weight of mice after ALA-SDT were detected. The effects of ALA-SDT on the growth of mice were evaluated through the changes in body weight of mice. Biosafety of treatment was further evaluated by histopathology to determine whether the tissues and organs of mice were affected after ALA-SDT. RESULTS: ALA can be absorbed and converted into PpIX when incubated with cSCC cells and produces ROS with ultrasound irradiation. ALA-SDT showed a significant cytotoxicity on cSCC cells. With one session of ALA-SDT in vivo, tumor growth was slowed but not stopped and would proceed once treatment was ended. ALA-SDT had no significant effect on body weight changes and major tissues and organs of the mice. CONCLUSION: ALA-SDT could safely and reduce cSCC cells growth both in vitro and in vivo.

Exploring the Pathogenesis and Mechanism-Targeted Treatments of Rosacea: Previous Understanding and Updates.

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments.

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.

Single cell transcriptome profiling reveals cutaneous immune microenvironment remodeling by photodynamic therapy in photoaged skin.

Background: The immune microenvironment plays a critical role in maintaining skin homeostasis, which is closely related to the dysfunction in photoaged skin such as autoimmunity and tumorigenesis. Several recent studies have demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in alleviating photoaging and skin cancer. However, the underlying immune mechanisms and the immune microenvironment change by ALA-PDT remain largely unknown. Methods: To illustrate the effects of ALA-PDT on immune microenvironment in photoaged skin, single cell RNA sequencing (scRNA-seq) analysis of photoaged skin on the extensor side of the human forearm before and after ALA-PDT was performed. R-packages of Seurat, clusterProfiler, Monocle, CellChat were used for cell clustering, differentially expressed genes analysis, functional annotation, pseudotime analysis and cell-cell communication analysis. The gene sets related to specific functions were extracted from the MSigDB database, which were used to score the functions of immune cells in different states. We also compared our result with published scRNA-seq data of photoaged skin of the eyelids. Results: The increase score of cellular senescence, hypoxia and reactive oxygen species pathway in immune cells and the decrease of immune receptor activity function and proportion of naive T cells were found in skin photoaging. Moreover, the function of T cell ribosomal synthesis was also impaired or down regulated and function of G2M checkpoint was up regulated. However, ALA-PDT showed promising results in reversing these effects, as it improved the above functions of T cells. The ratio of M1/M2 and percentage of Langerhans cells also decreased with photoaging and increased after ALA-PDT. Additionally, ALA-PDT restored the antigen presentation and migration function of dendritic cells and enhanced cell-cell communication among immune cells. These effects were observed to last for 6 months. Conclusion: ALA-PDT has potential to rejuvenate immune cells, partially reversed immunosenescence and improved the immunosuppressive state, ultimately remodelling the immune microenvironment in photoaged skin. These results provide an important immunological basis for further exploring strategies to reverse skin photoaging, chronological aging and potentially systemic aging.

Identification of different types of tumors based on photoacoustic spectral analysis: preclinical feasibility studies on skin tumors.

Significance: Collagen and lipid are important components of tumor microenvironments (TME) and participates in tumor development and invasion. It has been reported that collagen and lipid can be used as a hallmark to diagnosis and differentiate tumors. Aim: We aim to introduce photoacoustic spectral analysis (PASA) method that can provide both the content and structure distribution of endogenous chromophores in biological tissues to characterize the tumor-related features for identifying different types of tumors. Approach: Ex vivo human tissues with suspected squamous cell carcinoma (SCC), suspected basal cell carcinoma (BCC), and normal tissue were used in this study. The relative lipid and collagen contents in the TME were assessed based on the PASA parameters and compared with histology. Support vector machine (SVM), one of the simplest machine learning tools, was applied for automatic skin cancer type detection. Results: The PASA results showed that the lipid and collagen levels of the tumors were significantly lower than those of the normal tissue, and there was a statistical difference between SCC and BCC (p<0.05), consistent with the histopathological results. The SVM-based categorization achieved diagnostic accuracies of 91.7% (normal), 93.3% (SCC), and 91.7% (BCC). Conclusions: We verified the potential use of collagen and lipid in the TME as biomarkers of tumor diversity and achieved accurate tumor classification based on the collagen and lipid content using PASA. The proposed method provides a new way to diagnose tumors.