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Hidroacanthoma simplex (HS) is a rare skin appendage tumor that typically appears on the trunk and lower limbs in the elderly. Although HS is a predominantly benign condition, the presence of cellular atypia and dermal infiltration on histological examination indicates malignant HS (MHS). 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) uses a photosensitizer and corresponding light source to cause irreversible damage or death of target cells through a photochemical reaction. Here, we reported the successful treatment of a MHS patient with ALA-PDT using plum-blossom needle pretreatment combined with CO 2 laser. After five courses of ALA-PDT, the lesions were completely resolved, and the autonomic activity and smooth surface of the left ring finger were restored. This suggests that ALA-PDT is an effective, minimally invasive and safe treatment modality for MHS., (Copyright © 2024. Published by Elsevier B.V.)

Background: Melanoma is an aggressive cancer with poor response to traditional therapies. A combination of photothermal therapy and topical immunotherapy is expected to eliminate melanoma effectively., Materials and Methods: C57BL/6 mice with early stage and metastatic melanoma were treated with laser immunotherapy (LIT), combining near-infrared laser-based photothermal therapy (PTT) and topical imiquimod (IMQ)-based immunotherapy. The volume of primary and abscopal melanoma, animal survival, tissue temperature, transcriptome, and immune cell response were investigated to evaluate the effect of LIT., Results: LIT could eliminate primary tumors, inhibited abscopal tumors, and prolonged animal survival. The tumor tissues were selectively destroyed under a photothermal gradient between 38.2 ± 3.7°C and 73.0 ± 2.3°C. Gene expression analysis showed a significant increase in the expression of damage associated molecular patterns. Additionally, the expression of mature dendritic cells, CD4 + T cells, and CD8 + T cells were increased, while myeloid-derived suppressor cells were downregulated after LIT., Conclusion: The study showed that LIT inhibited the growth of both primary and abscopal melanoma by activating systemic antitumor immune responses and reversing the immunosuppressive tumor microenvironment, making LIT a potential method for advanced melanoma treatment., Competing Interests: Declaration of competing interest The authors declare no financial or commercial conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

The escalating threat of antimicrobial resistance underscores the imperative for innovative therapeutic strategies. Host defense peptides (HDPs), integral components of innate immunity, exhibit profound antimicrobial and immunomodulatory properties. Various dietary compounds, such as short-chain fatty acids, vitamins, minerals, sugars, amino acids, phytochemicals, bile acids, probiotics, and prebiotics have been identified to enhance the synthesis of endogenous HDPs without provoking inflammatory response or compromising barrier integrity. Additionally, different classes of these compounds synergize in augmenting HDP synthesis and disease resistance. Moreover, dietary supplementation of several HDP-inducing compounds or their combinations have demonstrated robust protection in rodents, rabbits, pigs, cattle, and chickens from experimental infections. However, the efficacy of these compounds in inducing HDP synthesis varies considerably among distinct compounds. Additionally, the regulation of HDP genes occurs in a gene-specific, cell type-specific, and species-specific manner. In this comprehensive review, we systematically summarized the modulation of HDP synthesis and the mechanism of action attributed to each major class of dietary compounds, including their synergistic combinations, across a spectrum of animal species including humans. We argue that the ability to enhance innate immunity and barrier function without triggering inflammation or microbial resistance positions the nutritional modulation of endogenous HDP synthesis as a promising host-directed approach for mitigating infectious diseases and antimicrobial resistance. These HDP-inducing compounds, particularly in combinations, harbor substantial clinical potential for further exploration in antimicrobial therapies for both human and other animals., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to develop models for predicting prolonged postoperative length of stay (PPOLOS) in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS) by utilizing machine-learning techniques. These models aim to offer valuable insights for clinical decision-making., Methods: This retrospective cohort study analyzed a dataset of lung cancer patients who underwent VATS, identifying 25 numerical features and 45 textual features. Three classification machine-learning models were developed: XGBoost, random forest, and neural network. The performance of these models was evaluated based on accuracy (ACC) and area under the receiver operating characteristic curve, whereas the importance of variables was assessed using the feature importance parameter from the random forest model., Results: Of the 6767 lung cancer patients, 1481 patients (21.9%) experienced a postoperative length of stay of > 4 days. The majority were male (4111, 60.8%), married (6246, 92.3%), and diagnosed with adenocarcinoma (4145, 61.3%). The Random Forest classifier exhibited superior prediction performance with an area under the curve (AUC) of 0.792 and ACC of 0.804. The calibration plot revealed that all three classifiers were in close alignment with the ideal calibration line, indicating high calibration reliability. The five most critical features identified were the following: surgical duration (0.116), age (0.066), creatinine (0.062), hemoglobin (0.058), and total protein (0.054)., Conclusions: This study developed and evaluated three machine-learning models for predicting PPOLOS in lung cancer patients undergoing VATS. The findings revealed that the Random Forest model is most accurately predicting the PPOLOS. Findings of this study enable the identification of crucial determinants and the formulation of targeted interventions to shorten the length of stay among lung cancer patients after VATS, which contribute to optimize the allocation of healthcare resources., (© 2024 The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Enterococcus cecorum (EC) has been associated with septicemia and early mortality in broiler chickens. There is limited research investigating the pathogenicity of EC field strains obtained from affected birds. The purpose of this study was to evaluate the effect of in-ovo administration into the amnion with different EC field isolates at d 18 of embryogenesis (DOE18). In Exp 1, 7 EC field isolates alone or in combination (EC1-EC3, EC4-EC5, EC6, and EC7) were selected based on phenotypic characteristics and evaluated at different concentrations (1 × 10 2 , 1 × 10 4 , and 1 × 10 6 CFU/200 µL/embryo) to assess the impact on early performance and macroscopic lesions. Three isolates (n = 3; EC2, EC5, EC7) were selected for additional evaluation based on the significant (P < 0.05) BWG reduction (d 0-21) compared to the negative control (NC) and the presence of macroscopic lesions observed during posting sessions at d 14 and d 21. An additional isolate associated with enterococcal spondylitis was included in Exp 2 (EC11B). Treatment groups for Exp 2 include: 1) NC, 2) EC2, 3) EC5, 4) EC7, and 5) EC11B (n = 90-120/embryos/group). Groups 2 to 5 were challenged at 1 × 10 2 CFU/200 µL/embryo by in-ovo injection into the amnion at DOE18. Chicks were placed in battery cages for the duration of the study (21 d), and pen weights were recorded at d 0, d 7, d 14, and d 21 to calculate average BW and BWG. At d 14 and d 21 posthatch, liver, spleen, free thoracic vertebrae (FTV), and femoral head (FH) were aseptically collected to enumerate Enterococcus spp. using Chromagar Orientation as the selective media. Cecal contents were collected at d 21 to evaluate the effect of EC challenge on the cecal microbiome composition. There was a significant (P < 0.05) reduction in BW at d 21, and BWG from d 14 to 21 and d 0 to 21, for EC7 and EC11B. Enterococcus cecorum was recovered from the FTV of all challenged groups at d 14 and d 21. The most representative lesions were pericarditis, hydropericardium, focal heart necrosis, and FH osteomyelitis. However, lesions were not uniform across challenged groups or ages (d 14 and d 21). Alpha diversity of the cecal contents was markedly lower in EC5 and EC11B compared to all treatment groups suggesting that EC exposure during late embryogenesis affect the cecal microbiome up to 21 d posthatch. Additionally, these results highlight the differences in pathogenicity of EC strains isolated from field cases and suggest that hatchery exposure to EC during late embryogenesis is a potential route of introduction into a flock., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The land surface has been drying over recent decades, which is inconsistent with the greening of the Earth. The extent and spatial variation in the sensitivity of vegetation to aridity changes in drylands and humid regions remain unclear. In this study, satellite observation and reanalysis data were used to analyze the relationship between vegetation growth and atmospheric aridity changes in different climatological regions on a global scale. Our results showed that the leaf area index (LAI) increased at a rate of 0.032/decade from 1982 to 2014, while the aridity index (AI) increased slightly at a rate of 0.005/decade. Over the past three decades, the sensitivity of the LAI to AI has decreased in drylands and increased in humid regions. Thus, the LAI and AI were decoupled in drylands, whereas the effect of aridity on vegetation was enhanced in humid regions during the study period. The physical and physiological effects of increasing CO 2 concentration are responsible for the divergent responses of vegetation sensitivity to aridity in drylands and humid regions. The results of the structural equation models showed that the effect of increasing CO 2 concentration via LAI and temperature, with respect to decreasing AI, enhanced the negative relationship between LAI and AI in humid regions. The greenhouse effect of increasing CO 2 concentration resulted in an increase in temperature and a reduction in aridity, whereas the fertilization effect of CO 2 increased LAI, thus creating an inconsistent trend with LAI and AI in drylands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In order to accurately identify the morphological features of different differentiation stages of induced Adipose Derived Stem Cells (ADSCs) and judge the differentiation types of induced ADSCs, a morphological feature recognition method of different differentiation stages of induced ADSCs based on deep learning is proposed. Using the super-resolution image acquisition method of ADSCs differentiation based on stimulated emission depletion imaging, after obtaining the super-resolution images at different stages of inducing ADSCs differentiation, the noise of the obtained image is removed and the image quality is optimized through the ADSCs differentiation image denoising model based on low rank nonlocal sparse representation; The denoised image is taken as the recognition target of the morphological feature recognition method for ADSCs differentiation image based on the improved Visual Geometry Group (VGG-19) convolutional neural network. Through the improved VGG-19 convolutional neural network and class activation mapping method, the morphological feature recognition and visual display of the recognition results at different stages of inducing ADSCs differentiation are realized. After testing, this method can accurately identify the morphological features of different differentiation stages of induced ADSCs, and is available., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a reliable treatment for actinic keratosis (AK), but its effect needs to be enhanced in thick lesions. Plum-blossom needle is a traditional Chinese cost-effective instrument for enhancing the transdermal delivery of ALA. However, whether it could improve the efficacy of AK treatment has not yet been investigated., Objective: To compare the efficacy and safety of plum-blossom needle-assisted PDT in facial AK in the Chinese population., Methods: In this multicenter, prospective study, a total of 142 patients with AKs (grades I-III) were randomized into the plum-blossom needle-assisted PDT group (P-PDT) and control PDT group (C-PDT). In the P-PDT group, each AK lesion was tapped vertically by a plum-blossom needle before the application of 10% ALA cream. In the C-PDT group, each lesion was only wiped with regular saline before ALA cream incubation. Then, 3 hours later, all the lesions were irradiated with light-emitting diode (LED) at a wavelength of 630 nm. PDT was performed once every 2 weeks until all lesion patients achieved complete remission or completed six sessions. The efficacy (lesion response) and safety (pain scale and adverse events) in both groups were evaluated before each treatment and at every follow-up visit at 3-month intervals until 12 months., Results: In the P-PDT and C-PDT groups, the clearance rates for all AK lesions after the first treatment were 57.9% and 48.0%, respectively (P < 0.05). For grade I AK lesions, the clearance rates were 56.5% and 50.4%, respectively (P = 0.34). For grade II AK lesions, the clearance rates were 58.0% and 48.9%, respectively (P = 0.1). For grade III AK lesions, the clearance rates were 59.0% and 44.2%, respectively (P < 0.05). Moreover, grade III AK lesions in the P-PDT group required fewer treatment sessions (P < 0.05). There was no significant difference in the pain score between the two groups (P = 0.752)., Conclusion: Plum-blossom needle tapping may enhance the efficacy of ALA-PDT by facilitating ALA delivery in the treatment of AK., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objectives: Although most cutaneous squamous cell carcinoma (cSCC) cases are generally nonlethal and manageable with surgical excision, there ares till significant hazards for patients who are ineligible for surgical resection. We sought to find a suitable and effective treatment for cSCC., Methods: We modified chlorin e6 by adding a hydrogen chain with a six-carbon ring to the benzene ring and named this new photosensitizer as STBF. We first investigated the fluorescence characteristics, cellular uptake of STBF and subcellular localization. Next, cell viability was detected by CCK-8 assay and the TUNEL staining was performed. Akt/mTOR-related proteins were examined by western blot., Results: STBF-photodynamic therapy (PDT) inhibits cSCC cells viability in a light dose dependent manner. The antitumor mechanism of STBF-PDT might be due to the suppression of the Akt/mTOR signaling pathway. Further animal investigation determined that STBF-PDT led to a marked reduction in tumor growth., Conclusions: Our results suggest that STBF-PDT exerts significant therapeutic effects in cSCC. Thus, STBF-PDT is expected to be a promising method for the treatment of cSCC and the photosensitizer STBF may be destined for a wider range of applications in photodynamic therapy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) is an effective therapy in treating inoperable cutaneous squamous cell carcinoma (cSCC) in China. However, its exact mechanism in treating cSCC is still unclear. Here, we analyzed expression profiles of lncRNAs and mRNAs of cSCC after ALA-PDT in a mouse model using Mouse Transcriptome Assay 1.0 chip. A total of 592 and 828 differentially expressed genes were identified in comparisons of ALA-PDT after 3 h vs. control, ALA-PDT after 6 h vs. control respectively. Regarding the lncRNAs analysis, a total of 185 and 410 differentially expressed lncRNAs were sought out. Bioinformatics analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, pathway relation network, and gene set enrichment analysis revealed that the pathways of ALA-PDT in treating cSCC were mainly associated with immune regulation, NF-κB signaling pathway, TLR signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and MAPK signaling pathway, which was validated by western blot analysis. Furthermore, a lncRNA-mRNA co-expression network revealed 118 network pairs comprising 36 lncRNAs and 68 mRNAs. These findings provide a basis for investigations into the treatment mechanisms of ALA-PDT in treating cSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Obesity develops from an imbalance of energy homeostasis and is associated with the development of metabolic disorders, including insulin resistance and type 2 diabetes. Identification of the underlying molecular mechanisms and effective therapeutic approaches is highly needed. Lysine-specific demethylase 1 (LSD1), an flavin adenine dinucletide-dependent amine oxidase, is implicated in a wide variety of biological processes, including tumorigenesis, stem cell fate decisions, and embryonic development. Recent studies have suggested a vital role of LSD1 in regulating adaptive thermogenesis, mitochondrial biogenesis, glucose, and lipid metabolism. More recently, LSD1 activity was found to be regulated by nutrients, energy status, and hormonal signals, suggesting that it may act as a novel sensor for nutritional regulation of metabolic health. Here, we first discuss the effects of LSD1 on physiological phenotypes, including body weight, fat mass, body temperature, and glucose homeostasis. We also summarize recent understanding of the physiological roles and underlying mechanisms of LSD1 in controlling metabolic functions of adipose and other tissues. Hopefully, a better understanding of the roles of LSD1 in metabolic regulation may provide new perspectives for the nutritional prevention and treatment of obesity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: The aims of this study were to examine the symptom severity and interference among patients with lung cancer treated with PD-1 immunotherapy, explore whether those symptoms were clustered together, and identify factors associated with symptom clusters., Methods: A cross-sectional study was conducted. Data were collected by demographic and clinical characteristic questionnaires and the M.D. Anderson Symptom Inventory Lung Cancer Module. Symptom clusters were identified using exploratory factor analysis, and stepwise linear regression was applied to analyze the factors affecting the symptom clusters., Results: A total of 148 patients with lung cancer treated with PD-1 immunotherapy participated in this study. The overall symptom burdens of these patients were mainly at a mild level. The patient symptom clusters identified in this study were a general cluster, a treatment-related cluster, a pulmonary cluster, a gastrointestinal cluster, and a neural cluster. The patients' Karnofsky performance status (KPS) score ( β  ​= ​-2.758, P  ​< ​0.001) and having a history of chemotherapy ( β  ​= ​4.384, P  ​= ​0.001) were significant predictors of the general cluster. Their KPS scores ( β  ​= ​-1.202, P  ​< ​0.001) and having a history of chemotherapy ( β  ​= ​-1.957, P  ​= ​0.001) were significant predictors of the pulmonary cluster. Their monthly income ( β  ​= ​-0.316, P  ​= ​0.030) and KPS scores ( β  ​= ​-0.357, P  ​= ​0.045) were significant predictors of the gastrointestinal cluster. Having a history of chemotherapy ( β  ​= ​1.868, P  ​< ​0.001) was the predictor of the neural cluster., Conclusions: The symptom burdens of patients with lung cancer and treated with PD-1 immunotherapy were at a mild level and appeared to be clustered. In addition, because the symptoms that comprise a cluster are interrelated, the diagnosis and management of each symptom in a cluster should not be performed in isolation, and each symptom in a cluster should be treated either simultaneously or in an orderly manner., Competing Interests: None declared., (© 2022 The Author(s).)

Background: 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for cutaneous diseases, such as precancers, superficial non melanoma skin cancers and certain inflammatory or viral conditions. However, the absence of a complete picture of adverse reactions limits the promotion of ALA-PDT., Objective: To systemically investigate the detailed evidence of adverse reactions relating to ALA-PDT for skin diseases., Methods: A retrospective study performed at the Shanghai Skin Disease Hospital., Results: In the retrospective study, 439 patients were included. Incidences of adverse reactions, including in-treatment pain (98.8%), erythema (92.4%), edema (35.0%), exudation (23.0%), hyperpigmentation (27.3%) were clarified. Edema was more common in female patients (P<0.05). Patients with HPV-related skin diseases were more likely to suffer erythema, edema or exudation (P<0.05). Hyperpigmentation was more likely to occur in skin appendage disorders (P<0.05). Fever (2.4%) and hypopigmentation (1.9%) are two neglected adverse reactions analyzed in detail. Fever is more prevalent in female patients. Hypopigmentation occurred predominantly in elderly with skin cancer or precancerosis lesions., Conclusion: The results outline detailed information about the adverse reactions, including systemic reactions following ALA-PDT, assisting dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction., (Copyright © 2022. Published by Elsevier B.V.)

Cutaneous squamous cell carcinomas (cSCC) is one of the most common types of non-melanoma skin cancer (NMSC), and surgical excision is the primary regimen in most cases. However, in some circumstances of special lesion locations like lips, eyelids or vulva, old age or patient choice non-surgical therapy may be alternative. This is a case of one 93-year-old female cSCC patient who declined surgery. Treatment of hematoporphyrin derivatives photodynamic therapy (HpD-PDT) consisting of both intravenous and topical photosensitizers plus red light irradiation was prescribed. Clinical remission was achieved without evidence of recurrence and most cosmetic function was preserved., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Acne vulgaris is a chronic inflammatory skin disease around pilosebaceous unit. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is an effective therapy for severe acne vulgaris. However, the lack of detailed information of adverse reactions limits the promotion of ALA-PDT in clinic., Objective: To systemically investigate the adverse reactions relating to ALA-PDT for acne vulgaris., Methods: A prospective study was performed at the Shanghai Skin Disease Hospital., Results: In the prospective study, 35 patients with acne vulgaris completed the trial. The adverse reactions were first divided into acute-phase adverse reactions, including erythema (94.3%), post-treatment pain (91.4%), burning skin (91.4%), dry skin (91.4%), itching (85.7%), pustule (82.9%), edema (20%) and blister (11.4%), or recovery-phase adverse reactions, which included crust (65.6%), exudation (48.6%) and hyperpigmentation (42.7%). Younger patients were more likely to have pustules (P<0.05). Male patients were represented itching more often than female patients (P<0.05). The efficacy of ALA-PDT for severe acne was positively related to the severity of acute-phase adverse reactions. The duration of pain was shortest. Crusting and hyperpigmentation lasted considerably longer., Conclusion: In the present study, we recorded the relative incidence of various adverse reactions following ALA-PDT for acne vulgaris. The severity of adverse reactions tended to decrease with increased patient age, except for itching and hyperpigmentation. Light-to-moderate adverse reactions might be the inflammatory reactions of ALA-PDT, predicting a good efficacy. A form for evaluation of adverse reactions based on the present study could assist dermatologists in predicting and managing adverse reactions for greater efficacy and higher patient satisfaction., (Copyright © 2022. Published by Elsevier B.V.)

Background: Extramammary Paget's Disease (EMPD) is an intraepithelial cancer that is prone to recurrence and sometimes refractory to therapy. A few EMPD cases have been treated with Photodynamic therapy (PDT), which reported high complete remission (CR) rates and low recurrence with hematoporphyrin derivatives (HpD) The aim of this study was to further explore the efficacy and safety of HpD-PDT for EMPD patients., Methods: Open-label, single arm, pilot study was designed to investigate the role of HpD-PDT in EMPD. The HpD sensitizer was given intravenously at a dose of 3 or 5 mg/kg 48 h before light irradiation with a laser 630 nm red light at a dose level of 150-200 J/cm 2 . Clinical parameters involving gender, age, disease course, previous treatment, tumor thickness, long diameter of lesion, TNM staging, EMPD staging, HpD dosage, Visual Analogue Scale (VAS) score, 1st month visit result, subsequent treatment, follow up period and endpoint outcomes were collected to evaluate efficacy and safety of the intervention., Results: Eleven patients with pathologic confirmed EMPD were treated with HpD-PDT. The thickness of skin lesions which were located in vulva, penis, scrotum, and perianal area is 0.8∼6.7 mm (mean thickness 2.9 mm). All patients were followed up for an average of 17.4 months (12∼27 months). Complete remission (CR) rate and partial remission (PR) rate at the 1st month were 90.1% (10/11) and 9.1% (1/11) respectively. At the end of follow-up, 72.7% of the subjects (8/11) showed CR. Pain, infection, photosensitivity and uroschesis are recorded as adverse events (AEs) in this population, and no event of hepatic impairment was reported. After treatment, all the eleven patients showed different degrees of scar in the treatment site, but none of them had any structural or functional abnormalities., Conclusions: According to our study, HpD-PDT in EMPD is able to offer acceptable disease outcomes including relatively high CR rate, with good cosmetic and functional outcomes, and could be considered a potential recommended therapy for patients with EMPD., Trial Registration: Chinese Clinical Trial Register (ChiCTR-1900024965)., (Copyright © 2021. Published by Elsevier B.V.)

Actinic keratosis(AK) is a common premalignant skin lesion that can progress to invasive squamous cell carcinoma(iSCC). Clinically, AK presents as reddish or brownish macules, papules, or hyperkeratotic plaques. AK cannot be reliably predicted whether it will transform into invasive carcinomas, so skin biopsy is currently a gold standard for identifying suspicious malignancy. Currently, there are non-invasive methods to help diagnose and determine the difference between AKs and iSCC. For example, dermoscopy and ultrasound can be very useful in diagnosing and monitoring skin diseases non-invasively. Therefore, we report a case of multiple facial AKs with poorly differentiated skin squamous cell carcinoma, which was diagnosed early through dermoscopy and ultrasound, and confirmed by histopathology., (Copyright © 2021. Published by Elsevier B.V.)

Seborrheic keratosis (SK) is a common benign lesion in which malignancies like cutaneous squamous cell carcinoma (cSCC) can arise rarely. We report a case of an 81-year-old man who presented a well-demarcated reddish-brown plaque with central raised coarse nodules on the top of his head. Dermoscopy and reflectance confocal microscopy (RCM) showed the possibility of malignant transformation. cSCC was confirmed by histopathology and immunohistochemistry. Considering the fact of local low-risk cSCC within a large SK lesion, carbon dioxide (CO 2 ) laser was used to treat the SK lesion, and reduce the thickness of local cSCC simultaneously. Three sessions of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) were performed after CO 2 laser. Finally, no atypical cells were found by multi-point biopsy after treatment, and follow-up was continued for one year. Therefore, malignant changes of SK are relatively uncommon, but should be suspected when abnormal appearance or symptoms occurred. ALA-PDT combined with CO 2 is a safe, effective, and minimally invasive treatment for cSCC arising from a huge SK., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Objectives: Androgenetic alopecia (AGA) is one of the most common hair loss disorders. Treatment options for AGA are limited . New therapies for AGA are clinically needed. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is widely applied in diseases involving the pilosebaceous unit. However, limited research has explored the efficacy of ALA-PDT in treating alopecia. Some studies reported hair regrowth after PDT in alopecia areata patients, but the efficacy of ALA-PDT on AGA remains unclear. The objective of this study is to evaluate the efficacy and safety of ALA-PDT for the treatment of AGA., Methods: A randomized, placebo-controlled, split-scalp clinical study was conducted. Subjects with AGA received six sessions of 5% ALA-PDT on one half of their scalp and the red-light therapy on the other half. The treatments were applied every two weeks for six sessions on each subject., Results: There were 7 subjects enrolled in this study. No significant difference in hair density was observed between the red-light treatment and ALA-PDT treatment. The hair density in the ALA-PDT treated half of the scalp significantly decreased 1 week after the treatment, then it increased, and no statistical difference was found at 12 weeks after the last treatment compared to the baseline. There was no significant improvement in hair growth according to a 7-point scale and the subjects' self-assessments. The main adverse effects in ALA-PDT treatment were mild edema and tolerable pain, and no adverse effect was observed in red-light treatment., Conclusions: 6 sessions of 5% ALA-PDT did not increase the hair growth of AGA patients, but slightly suppressed the sebum secretion on the scalp. The adverse effects of ALA-PDT were mild, which indicated safety and tolerability of this treatment., (Copyright © 2021. Published by Elsevier B.V.)

Background: Squamous cell carcinoma (SCC) of the lip removed by surgery may cause lip dysfunction and scar. ALA-PDT (5-Aminolevulinic acid photodynamic therapy) is a minimally invasive treatment for superficial SCC in situ. However, few studies reported the use of topical ALA-PDT to manage lip SCC., Methods: Between 2015 and 2017, 6 patients with Tis to T2 lip squamous cell carcinoma without evidence of lymph node spread, were treated with topical ALA-PDT at Shanghai Skin Disease Hospital. Clinical responses and side effect were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) at 1 month, 6 months, 12 months and 24 months after ALA-PDT., Results: All of the 6 patients achieved complete response (CR) by 2-7 sessions of ALA-PDT. There was no relapse during 24 months follow up for 4 patients. Two out of 6 patients relapsed at 10 months and 20 months post PDT but achieved CR again by 1-3 more sessions of PDT. There was no functional or aesthetic problem., Conclusion: Topical 5-Aminolevulinic acid photodynamic could be considered a potential alternative therapeutic option for early-stage lip squamous cell carcinoma without lymph node spread., (Copyright © 2021 Elsevier B.V. All rights reserved.)

5-aminolaevulinic acid photodynamic therapy (ALA-PDT) has emerged as a non-invasive treatment modality for premalignant and malignant skin lesions. It has the advantage of better tolerance and providing better cosmetic outcomes than conventional treatment methods. Herein, we report a patient who suffered from multiple cutaneous squamous cell carcinoma (cSCC) in situ and actinic keratosis (AK) scattered in the body's sun-exposed areas, which had led him to undergo multiple surgical resections since the age of 16. Next-generation sequencing-based on a targeted gene capture panel revealed compound heterozygous mutations c.G559A and c.G1389A in the TMC8 gene. Combined with the typical clinical manifestations and mutation analysis, the patient was diagnosed with Epidermodysplasia verruciformis (EV). Due to the multiple AK and cSCC in situ lesions, ALA-PDT was applied. After 8 courses of ALA-PDT all lesions were successfully cleared without causing any scarring. Therefore, the use of ALA-PDT treatment may constitute a very promising and effective therapeutic modality for multiple cSCC in situ and AK secondary to EV., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Basal cell carcinoma (BCC) is a common non-melanoma skin malignancy arising in sun exposure area. Patients with multiple BCCs have a high-risk factor for recurrence and are very difficult to  treat with current methods. 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) treat superficial type of BCCs with superior efficacy and an excellent cosmetic result, but deep tumor success is limited. Herein, a case of numerous nodular BCCs scattered on the face and head, which was treated with the combination of topical curettage and modified ALA-PDT is reported. Curettage was to rapidly scalp away nodular tumors and contributed to ALA transdermal depth to the tumor base. Modified ALA-PDT as an advanced treatment was nearly painless and can cure multiple BCCs of face and head combing curettage., (Copyright © 2021. Published by Elsevier B.V.)

Estimating the influence of dust aerosol on clouds, especially deep convective clouds which is closely related to heavy precipitation, still has large uncertainties due to the lack of adequate direct measurements. In this study, a typical dust storm along with thunderstorm (referred to dust-rain storm), occurred in Northwest India on May 2, 2018, was selected to explore the possible effects of dust aerosol on deep convective cloud by combining a series of satellite retrievals and reanalysis data. Results showed that dust aerosol and moisture were carried to Northwest India by southwesterly wind at 700 hPa and easterly wind along south foothill of Himalayas at 850 hPa, respectively, and then were lifted to upper level of the cloud by robust updraft induced by the deep convection and secondary circulation driven by the upper-level westerly jet. The injection of dust is likely to transfer supercooled water cloud into ice cloud as effective ice nuclei, hence increasing the cloud ice water path and cloud optical depth but decreasing ice particle radius in the cloud. The latent heat released by this phase-change process would enhance the deep convection and further cause heavy rainfall in northern India by drawing moisture from surrounding region. Although we cannot eliminate the effect of large-scale dynamics, this study highlighted the role of dust aerosol in invigorating the deep convective clouds as ice nuclei, providing observation evidence for the investigation of aerosol-cloud-precipitation interaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epidermodysplasia verruciformis (EV) is a rare autosomal recessive disorder. Individuals with EV are more susceptible to the development of cutaneous neoplasia in sun-exposed regions. This disease should be closely observed for cutaneous squamous cell carcinoma (cSCC) or pre-cancerous lesions - if neoplasia is found, it should be removed. A 68-year-old woman with EV had a post-operative recurrent, invasive cSCC growing on her upper-left eyelid. Although the standard treatment for cSCC is surgical excision, it is challenging to reach the deepest regions. Herein, we reported a case of a recurrent, invasive cSCC effectively treated by a combination of non-invasive 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and deep-penetrative holmium laser. The results were satisfactory without any adverse effects to the patient., (Copyright © 2021. Published by Elsevier B.V.)

Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome characterized by (a) capillary malformations, such as port-wine stain (PWS), and (b) pigmented lesions, such as pigmented trichoepidermal nevus, café-au-lait spots, and dermal melanocytosis with or without systemic damage. Severe pruritus has not previously been reported among PPV patients. Here, we report a pediatric case of PPV with severe pruritus, which was refractory to various long-term oral antiallergic agents and topical tacrolimus but was temporarily responsive to hematoporphyrin monomethyl ether-mediated photodynamic therapy (HMME-PDT). HMME-PDT is the latest technology used in treating PWS following the basic principle of targeted photodynamic destruction of the vascular wall of the lesion. Furthermore, many studies have confirmed the safety and efficacy of HMME-PDT for PWS in both adults and children. Specific pathophysiologic mechanisms and treatment methods must be further explored to advance our understanding of the disease and improve the quality of life in PPV patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is not only the first-line treatment for actinic keratosis (AK), but also demonstrated to improve photoaging during AK field treatment. However, its long-term effect on photoaging remains elusive., Objective: To evaluate the long-term improvement effect of ALA-PDT on photoaging., Methods: The data of 10 patients with AK who received field-directed ALA-PDT on one side of the face and lesion-directed ALA-PDT on the other side were retrospectively reviewed. Their clinical photographs were evaluated with Global scores of photoaging (GSP) assessment independently by two dermatologists at baseline and 1 month, 6 months and 24 months after ALA-PDT., Results: GSP evaluation was performed after 24 months of follow-up. Improvements in the fine line and mottled pigmentation were observed (p < 0.05). All the 10 patients achieved complete response of AK lesions and had no relapse during the 24-month follow-up period., Limitation: A small sample size., Conclusion: Photoaging can be effectively alleviated in the long-term follow-up after ALA-PDT treatment for AK. The present study may inspire new treatment strategies for photoaging., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Squamous cell carcinoma (SCC) of thelip is conventionally treated by extended surgery or radiotherapy, which may cause deformities and dysfunction due to this special location. Topical 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) for SCC in situ is effective and non-invasive, and may preserve normal morphological structure. However, the effectiveness is limited by tumor size and depth due to the permeability of photosensitizer and penetration depth of the therapeutic light source. We successfully treated two cases of lip invasive SCC (tumor size is 22.4 mm × 16.1 mm × 11.9 mm and 23 mm × 15 mm × 5 mm) with superficial resection surgery to reduce tumor load and sequential ALA-PDT (20 % ALA, 3 h incubation, 200 J/cm 2 ) to remove residual tumor. During the treatment, ultrasonography was used to monitor the tumor invasion depth and assess the therapeutic efficacy. Both cases showed tumor free at 12 months of follow-up. These two cases suggest that ALA-PDT combined with minimal invasive surgery is a viable treatment for special cases of lip SCC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Pain is a major concern associated with conventional photodynamic therapy (C-PDT)., Objective: To evaluate the efficacy, pain and safety of modified photodynamic therapy(M-PDT) for the treatment of condylomata acuminata., Methods: A prospective, randomized, self-controlled study was conducted. Warts were randomized to the M-PDT or C-PDT side. 5-aminolevulinic acid (ALA; 20 %) was incubated for 3 h before patients were exposed to LED red light (100 J/cm2) on the C-PDT side and for 30 min before being exposed to LED red light (300 J/cm2) on the M-PDT side. Treatment was administered with 1-week interval for three weeks. The clearance rates were determined at one week and the recurrence rates at 4, 8, and 12 weeks after treatment. The pain and other side effects were also investigated., Results: A total of 24 patients with condylomata acuminata were enrolled in this trial. Twenty patients completed the trial. The clearance rates were 98.17 % in the M-PDT side and 98.20 % in the C-PDT side(P > 0.05). The recurrence rates were 11.11 % and 10.53 % (P > 0.05). However, M-PDT was almost painless (mean score 0.3 ± 0.47, range 0∼1), which was significantly less than that on the C-PDT side (mean score 3.6 ± 0.94, range 0∼1) (P < 0.05). Local erythema, mild edema and erosion were observed on both sides., Conclusion: The modified PDT is basically painless with similar efficacy to conventional PDT, which is a major breakthrough of pain management in PDT., (Copyright © 2020. Published by Elsevier B.V.)

We used 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) combined with plum-blossom needle (PBN) on a 3.5 cm × 3.0 cm pretibial region to treat an elderly woman suffering from Bowen's disease (BD). Before the application of ALA, the PBN was inserted 3-4 times vertically starting at 5 cm above the lesion. Then, 20 % 5-ALA cream was applied with an incubation time of 3.5 h. A semiconductor laser at a wavelength of 635 nm was used to illuminate the lesion at 100 J/cm 2 using 60 mW/cm 2 . A total of three sessions of ALA-PDT were performed at 2-3-week intervals, thus removing the lesion of BD. However, a 1.5 cm × 1.0 cm ulceration occurred 2 weeks after the third session when the PBN was used. Therefore, PBN percussion or other methods for promoting ALA penetration should be carefully applied to avoid ulceration, especially on the sites with less subcutaneous tissue., (Copyright © 2020. Published by Elsevier B.V.)

Background: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is a reliable treatment for actinic keratosis (AK), though the concentration of 20 % is applied in most ALA-PDT for the treatment of AK, it was found that 10 % ALA could achieve similar outcome during clinical practice. However, there are limited number of reports comparing the efficacy and the safety of ALA-PDT with different ALA doses when treating AK., Objectives: This study was designed to compare the efficacy, the adverse effects and the costs of 10 % and 20 % ALA-PDT for AK treatment., Methods: We reviewed the records of patients who had received ALA-PDT in our department between January 1, 2012, and April 30, 2017, the efficacy, the adverse effects were recorded, and the costs were analyzed. Follow-up data were collected until April 30, 2018., Results: A total of 59 AK patients' records were analyzed for the efficacy, the adverse events, the recurrence and the costs. All the AK lesions were tapped with plum-blossom needle as a pre-treatment before receiving ALA-PDT. There was no statistical difference between 10 % ALA-PDT and 20 % ALA-PDT in terms of efficacy and adverse events. In the 10 % ALA group, there was one recurrence out of 34 patients and in the 20 % group there were none. The average treatment cost of each lesion was significantly lower in 10 % ALA group than in 20 % ALA group., Conclusions: 10 % ALA-PDT has similar efficacy and adverse effects as 20 % ALA-PDT with lower costs. Taken together, this supports the use of 10 % ALA-PDT in clinical practice., (Copyright © 2019. Published by Elsevier B.V.)

Background: Photodynamic therapy (PDT) is an effective and safe treatment modality for acne vulgaris, and a variety of light sources have been investigated. Sunlight has been used as a PDT light source in a limited number of acne studies . However, to date, a comparative study of conventional PDT (C-PDT) and daylight PDT (DL-PDT) on acne is still lacking., Objectives: This study aims to assess the efficacy and safety of DL-PDT vs. C-PDT in the treatment of acne vulgaris., Methods: Eighty patients with facial moderate-to-severe acne vulgaris were randomly assigned to either DL-PDT group or C-PDT group. All patients got two to three treatment sessions at two-week intervals. The lesions were photographed with VISIA digital imaging system at baseline and weeks 2, 4, and 6. Follow-up monthly for 3 months. The endpoints include efficacy (lesion response), safety (VAS pain score) and patient satisfaction., Results: A total of 77 patients completed the study. There was no statistical difference in objective response rate between DL-PDT group and C-PDT group at weeks 2, 4, and 6, respectively (40.0 %, 90.0 %, and 94.7 % vs. 45.0 %, 85.0 %, and 92.3 %, p > 0.05). The IGA score of DL-PDT group has no difference from C-PDT at baseline and at weeks 6, respectively (3.3 ± 0.4, 1.5 ± 0.7 vs. 3.4 ± 0.5, 1.6 ± 0.7, p > 0.05). The VAS pain score of DL-PDT group was lower than that of C-PDT group (1.8 ± 0.2, vs. 5.8 ± 0.3, p < 0.05). Adverse reactions such as mild burning sensation, erythema, dryness, crusting, scales and hyperpigmentation were all tolerated. Patient satisfaction was similar between the two groups (p > 0.05)., Conclusions: DL-PDT is an effective and well-tolerated regimen for moderate-to-severe acne vulgaris compared with C-PDT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 72-year old woman who has a history of refractory vulvar lichen sclerosus(VLS) was treated with ALA-PDT for 3 times every other week,then holmium laser and ALA-PDT were combined to treat the same areas at a time.Satisfactory result was noted without any unbearable adverse effects.The combination of holmium laser therapy and ALA-PDT may further improve the efficacy with good tolerance of VLS patients., (Copyright © 2020. Published by Elsevier B.V.)

Objective: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with a carbon dioxide laser (CO 2 laser + PDT) versus CO 2 laser for the treatment of low-grade vaginal intraepithelial neoplasms (vaginal LSIL)., Methods: We recruited 40 patients with vaginal LSIL and persistent HR-HPV infection and divided these individuals into two groups. The CO 2 laser + PDT group (20 patients) received one CO 2 laser treatment and three treatments of ALA-PDT over a one-week interval. The CO 2 laser group (20 patients) received up to three CO 2 laser treatments. All patients were followed up at 1 month, 3 month, 6 month and 1 year. Hybrid capture HPV DNA assay and colposcopic biopsy were performed for both groups before treatment and during each of the follow-ups. Adverse effects were also assessed., Results: The complete remission (CR) rates were 65 % (13/20) in the CO 2 laser group and 85 % (17/20) in the CO 2 laser + PDT group (p > 0.05). HR-HPV remission rates were 25 % (5/20) in the CO 2 laser group and 95 % (19/20) in the CO 2 laser + PDT group (p < 0.05) at one year after treatment. In the CO 2 laser group, one patient experienced severe bleeding during treatment. Twelve patients had varying degrees of adhesions and vaginal scar stenosis. One patient underwent vaginal "dead angle" after repeated CO 2 laser treatment. No severe adverse events or systemic side effects were observed in the CO 2 + PDT group., Conclusion: Topical ALA-PDT combined with CO 2 laser is an effective, safe, and well-tolerated treatment for vaginal LSIL and HR-HPV infections., Competing Interests: Declaration of Competing Interest The authors state no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is effective in skin tumours. Studies have demonstrated that the therapy has anti-tumour immunity in squamous cell carcinoma (SCC). Exosomes play an important role in tumour microenvironment (TME) crosstalk. Nevertheless, whether exosomes mediate the ALA-PDT anti-tumour effect is unclear. This study aims to investigate whether exosomes secreted from ALA-PDT-treated squamous carcinoma cells (SCCs) demonstrate an anti-tumour effect by inducing dendritic cell (DCs) maturation., Method: In this study, we used electron microscopy, nanoparticle tracking analysis and western blotting to identify exosomes. Subsequently, BCA assay and fluorescence staining were used to evaluate the biological activity of exosomes. Exosomes derived from ALA-PDT-treated SCCs were incubated with SCCs, fibroblasts and immature DCs, separately. A CCK-8 kit was used to analyse the cytotoxicity of exosomes to SCCs. ELISA was utilised to analyse IL-6, VEGF, MMP-3, and TGF-β1 secreted from fibroblasts. FACS and ELISA were used to analysed DC phenotypic maturation (CD80, MHC-II) and IL-12 secretion., Result: Herein we show that exosomes secreted from SCCs after ALA-PDT cannot exert cytotoxicity towards SCCs. However, exosomes derived from ALA-PDT-treated SCCs could induce DCs maturation and IL-12 secretion. Furthermore, exosomes secreted from SCCs after ALA-PDT promote the secretion of TGF-β1 from fibroblast., Conclusion: In conclusion, we found that exosomes derived from ALA-PDT-treated SCCs have the ability to stimulate DC maturation and fibroblast secretion of TGF-β1, which results in the elevation of anti-tumour immunity. These findings provide a new promising strategy of anti-tumour immune response for ALA-PDT in treating SCCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: Anal canal condylomata acuminata is a disease caused by the human papilloma virus. Conventional cauterizing laser treatment cannot achieve a satisfactory result owing to a high recurrence rate, and the application of 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) also has limitations in the anal canal. Holmium yttrium aluminum garnet (Ho: YAG) laser with fiber is found to be effective at removing canal lesions, and may create suitable conditions for ALA-PDT. We aim to investigate the feasibility of Ho: YAG laser combined with ALA-PDT and to explore a more optimal therapy in refractory anal canal condylomata., Methods: Data of 37 patients with anal canal condylomata (number of warts≥ 10 lesions) from May 2017 to March 2019 were reviewed. In total 17 cases were treated with Ho: YAG laser plus ALA-PDT, and 20 patients treated with CO 2 laser plus ALA-PDT were selected as control. Wart clearance and recurrence rates were evaluated as well as laser complications., Results: Most warts (88.23 %) were removed after a session of Ho: YAG laser pretreatment. The average number of laser sessions required to clear all warts was 1.94 in the Ho: YAG laser plus ALA-PDT group. Meanwhile, no wound infections or defecation disfunctions were found. Ho: YAG laser with ALA-PDT could significantly reduce wart recurrence rates (17.6 %) in comparison with CO 2 laser with ALA-PDT (55 %)., Conclusions: Ho: YAG laser combined with ALA-PDT raised the cure rate of refractory anal canal condylomata and has important guidance implications for clinical application., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

The emergence of drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), has brought great difficulties to clinical treatment. Antibacterial photodynamic therapy (aPDT) is a new non-antibiotic treatment strategy for a variety of drug-resistant bacteria. However, there are few studies on the antimicrobial mechanism of a PDT mediated by 5-aminolevulinic acid (ALA-PDT) for MRSA. In this study, we observed the bactericidal effect of ALA-PDT on MRSA. We found that ALA-PDT had the strongest bactericidal effect when ALA was at 0.05 mM, and the bactericidal activity of aPDT increased with the increase of light dose. MRSA was almost completely eliminated at 0.05 mM and 384 Jcm -2 . In addition, the bactericidal morphology was also observed under a fluorescence microscope using a LIVE/DEAD® BacLight™ Bacterial Viability Kit and an electron microscope. It was also found that proteins and DNA were damaged by ALA-PDT. Finally, the transcription level of the specific gene of MRSA, nuc, was decreased by 0.74-fold (P < 0.05) after ALA-PDT treatment by qRT-PCR analysis. The findings suggest that ALA-PDT can effectively inhibit MRSA by damaging cell membrane, cytoplasm, proteins and nucleic acid., (Copyright © 2019. Published by Elsevier B.V.)

Cancer-associated fibroblasts (CAFs) are important components of the tumor microenvironment, affecting the biological behavior of tumor cells and playing critical roles in tumor growth, invasion, and metastasis. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an established approach for the treatment of non-melanoma skin cancers. It is reported that ALA-PDT treating cutaneous squamous cell carcinoma(cSCC) also induce antitumor immune effect and has an impact on tumor microenvironment. However, the effect of ALA-PDT on CAFs is not well known. In this study, the data showed that the expression of α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP), as well as migratory ability, were elevated in 3T3 fibroblasts co-cultured with tumor cells. Western blot, qRT-PCR and transwell cell migration assay were performed to detect these findings. In vivo, the rate of tumor growth in mice injected with a mixture of tumor cells and 3T3 fibroblasts was higher than that in mice injected with tumor cells only. Furthermore, both in co-cultured 3T3 fibroblasts and CAFs, a reduction in the expression of a-SMA and FAP was observed after ALA-PDT. Same with migratory ability. The findings indicated an inhibitory effect of ALA-PDT on the activation of CAFs in cSCC., (Copyright © 2019. Published by Elsevier B.V.)

Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm arising in apocrine rich area of the skin. Surgery is the standard treatment but relapse is common. The postoperative skin defects, penile reconstruction, functional effects and old age are also challenges for curing disease. Herein, a case of postoperative recurrent EMPD, which was treated by combination therapy of non-invasive repeatable ALA-PDT and deep penetrated holmium laser is reported. Ultrasonography monitor of lesions showed light vascularity and the formerly hypoechoic lesion disappeared after treatment., (Copyright © 2019. Published by Elsevier B.V.)