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Background: In November 2023, our hospital confirmed a case of Mycolicibacterium mucogenicum infection in the right back. The patient sought medical attention at our hospital due to "a right back lump for 2 months, ruptured for 1 month." Two months ago, the patient's back collided with a fire hose and developed a local walnut sized lump. The lump was soft, painless when pressed, and there was no obvious redness or swelling around it. The patient went to a private hospital for incision and drainage treatment on their own. One month later, the condition did not improve and there was yellow pus exuding from the incision site. For additional diagnosis and treatment, the patient went to our hospital for treatment. Methods: Back MRI (Magnetic Resonance Imaging) and abdominal ultrasound. Right back abscess incision and drainage surgery, pus pathogen examination: pus bacterial smear, bacterial culture, and identification. Auxiliary examinations: urine routine, blood routine, liver function, kidney function, blood lipids, and blood sugar. Results: Back MR: Abnormal signal shadow of subcutaneous soft tissue in the lower back, suggesting inflammatory lesions with abscess formation. Acid fast staining of pus: positive. Culture and identification of pus bacteria (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS): Mycolicibacterium mucogenicum. Clinical treatment plan: Clarithromycin 500 mg bid po+ minocycline 100 mg bid po, abscess incision and drainage, 5-aminolevulinic acid photodynamic therapy (ALA-PDT) qd. After 14 days of treatment, the patient's incision base tissue showed excellent activity, no obvious bleeding or exudation, slight redness and swelling around the wound, and normal skin temperature. The patient improved and was discharged. Conclusions: This article reports a case of Mycolicibacterium mucogenicum infection in the right back. The Mycolicibacterium mucogenicum was quickly and accurately identified by MALDI-TOF MS, and clinical treatment with antibiotics combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) was used. The patient improved and was discharged. I hope that in the future, this study can provide assistance for the clinical diagnosis and treatment of Mycolicibacterium mucogenicum. [ABSTRACT FROM AUTHOR]

Background: In December 2023, our hospital confirmed a case of finger infection with Mycobacterium marinum. The patient sought medical attention at our hospital due to a hard scratch on her left middle finger, which was red, swollen, and ulcerated for one month. Physical examination: A lesion of approximately 1.5 cm x 2 cm in the patient's left middle finger, surrounded by redness and swelling, unclear boundaries, surface rupture, partial scabbing, and no tenderness during compression. She was treated at the previous clinic, common infectious diseases were considered, and was given intravenous infusion treatment: cefotaxime and clarithromycin, and erythromycin ointment was applied externally. She came to our hospital after poor treatment results. The patient has had hypertension for 3 years, no other systemic diseases, no similar medical history among family members, no history of drug or food allergies. Methods: Clean the wound and remove the scab from the affected area, and use a surgical blade to scrape off necrotic tissue. Send the scraped tissue for pathogen testing: tissue bacterial culture+identification (matrix assisted laser desorption/ionization time-of-flight mass spectrometry, MALDI-TOF), tissue acid fast staining, and tissue metagenomic next-generation sequencing (mNGS). Other auxiliary examinations: blood routine, urine routine, blood fat, liver function, and kidney function. Results: Tissue bacterial culture+identification: growth of Mycobacterium marinum; Acid fast staining of tissue: positive; Tissue mNGS: Mycobacterium marinum. Clinical treatment plan: clarithromycin 0.5 g bid po+rifampicin 0.45 g qd po+5-aminolevulinic acid photodynamic therapy (ALA-PDT) qw+boric acid wash wet compress tid. After 14 days of treatment, the area of redness and swelling significantly decreased, and the degree of redness and swelling was significantly reduced compared to admission. The degree of ulcer edge protrusion was also reduced compared to admission. There was a small amount of exudation from the wound, and no necrotic tissue was observed. The patient improved and was discharged. Conclusions: This article reports a case of finger infection with Mycobacterium marinum. Mycobacterium marinum was quickly and accurately identified by mNGS, and reasonable treatment measures were adopted clinically. The patient improved and was discharged. This study has important reference significance for the clinical diagnosis and treatment of Mycobacterium infection. In addition, mNGS as a novel detection method has considerable prospects for rapid diagnosis of pathogens. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms. Methods: Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152–3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152–3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo. Results: ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152–3p. JAK1 was identified as a direct target of miR-152–3p, and ALA-PDT was found to regulate the expression levels of miR-152–3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152–3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152–3p/JAK1/STAT1 pathway expression. Conclusions: ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152–3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer.

Background: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. Methods: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. Results: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. Conclusions: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

Background: Mycobacterium abscessus skin infections have emerged as a major medical issue. Traditional antibiotic treatments are challenging, prolonged, and often lead to recurrence, creating an urgent need for new therapies. This study investigates the effectiveness of aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics in treatmenting M. abscessus, using both in vitro and in vivo methods. Methods: We treated eight patients with M. abscessus skin infections following cosmetic surgery, using ALA-PDT (ALA concentration: 20 %; red light: 80 J/cm2) combined with oral or intravenous antibiotics,including clarithromycin, moxifloxacin and amikacin, to treat 8 patients with M. abscessus skin infection after medical cosmetic surgery, and assessed the treatment outcomes. Additionally, four bacterial strains (MAB-A1, MAB-A2, MAB-B1, and MAB-B2) isolated from patients were tested in vitro for ALA-PDT efficacy to determine the optimal ALA-PDT dosage. Furthermore, the strains’ single colony morphology, biofilm formation, and genome characteristics of were analyzed to explore the factors influencing ALA-PDT's bactericidal effects. Finally, a combined ALA-PDT and antibiotics sterilization experiment was conducted in vitro. Results: Clinically, ALA-PDT combined with antibiotics showed strong efficacy in treating M. abscessus skin infections, with no recurrence observed during follow-up. In vitro, ALA-PDT effectively killed M. abscessus, although MAB-B1 and MAB-B2 required a higher ALA-PDT dose compared with MAB-A1 and MAB-A2. Compared to MAB-A1 and MAB-A2, MAB-B1 and MAB-B2 exhibited stronger biofilm formation capabilities and bacterial virulence as well as genome mutations primarily affecting fatty acid synthesis and metabolism, potentially explaining their increased ALA-PDT dosage requirement. Notably, the combination of ALA-PDT and antibiotics exerted markedly higher bactericidal effects in vitro compared with antibiotics alone. Conclusions: ALA-PDT combined with antibiotics emerged as an effective treatment for M. abscessus skin infections. However, optimal dosage and antibiotic combinations should be tailored to the characteristics of specific clinical strains.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24–51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL. [ABSTRACT FROM AUTHOR]

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3–5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase. [ABSTRACT FROM AUTHOR]

Background: Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS. Methods: Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted. Results: Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT. Conclusion: ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions.

Jingjing Wei, Lingyun Du, Zhiqiang Cao, Mingming Li, Chunhong Zhang, Chunmin Zhang, Liya Meng Department of Dermato-Venereology, The Second Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Liya Meng, Department of Dermato-venereology, The Second Hospital of Shandong University, 247 Beiyuan Dajie Street, Jinan, 250033, People’s Republic of China, Tel +86-531-85875027, Fax +86-531-88962544, Email mly0706@sina.comBackground: Acne is a chronic inflammatory disease of the pilosebaceous unit. Improper treatment of acne can lead to skin lesions in some people. Acne hypertrophic scar is relatively rare, but it significantly affects the appearance and beauty, and usually has a great psychological and social impact on patients.Objective: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with 5-fluorouracil (5-FU) injection and triamcinolone acetonide (TAC) solution in the treatment of acne hypertrophic scars.Methods: This article included 13 outpatients with acne accompanied by acne hypertrophic scar who were treated from September 2018 to September 2022. All patients received ALA-PDT combined with intralesional injection of 5-FU and TAC. At first, patients received ALA-PDT once every two weeks. After the third ALA-PDT, 5-FU and TAC were mixed in a ratio of 3:7, and then immediately injected in the local scars. The effect was observed after 1 month. If the effect is not obvious, a further injection of 5-FU and TAC to the lesion is necessary. The patients were followed up for 6 months. The Vancouver Scars Scale (VSS) was used to evaluate the efficacy before and after treatment and photos of patients were collected.Results: After ALA-PDT combined with intralesional 5-FU and TAC, all patients achieved good clinical efficacy. 23.08% of patients received one local injection and 76.92% received two local injections. After treatment, the scar lesions were reduced and flattened, and the scars became soft. The total score of VSS after treatment was significantly lower than before, and the difference was statistically significant (P< 0.05). The main adverse reactions were pain, erythema, and pigmentation, which can subside within 3 weeks. There was no recurrence after 6 months of follow-up.Conclusion: ALA-PDT combined with intralesional injection of 5-FU and TAC significantly affects acne hypertrophic scars, which is worthy of further in-depth and large-scale research.Keywords: acne hypertrophic scars, ALA-PDT, 5-FU, TAC, acne

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24–51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.

Bowen’s disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3–5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen’s disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.

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. [ABSTRACT FROM AUTHOR]

Objective To assess the clinical efficacy and safety of sequential therapy for nodular cystic acne. Methods Forty three patients with nodular cystic acne were divided into sequential and control groups. In the sequential group, 22 patients were treated with ALA-PDT every two weeks for 3 times, and oral antibiotics in the first stage, followed by chemical peeling once every two weeks for 3 times, and oral isotretinoin in the second stage. Finally, oral isotretinoin alone was given in the last stage. While 21 patients in the control group were treated with isotretinoin alone. The treatments lasted for 16 weeks. After each treatment course, the efficacy and adverse effect were compared between the two therapies. The patients in both groups were followed up for 6 months, and the relapse rate and adverse reactions were recorded. Results In the first stage of treatment, effective rates after the second and the third treatment course were 9.09% and 22.73%, respectively, in the sequential group, and 0 and 4.76%, respectively, in the controls. In the second stage, the effective rates after each treatment course were higher in sequential groups than in the controls (1st treatment course: 50.00% vs. 23.81%; 2nd treatment course: 90.90% vs. 42.86%, and the 3rd treatment course: 100% vs. 66.67%. P

Keratoacanthoma‐like squamous cell carcinoma (KA‐like SCC) is a malignant classification of KA. We report here a case of surgical combined with 5‐aminolevulinic acid‐photodynamic therapy (ALA‐PDT) to treat KA‐like SCC in an elderly male with successful tumor removal. The tumor resection was performed before ALA‐PDT. One week later, the lesion site was further treated with 20% ALA for 3 h when it was unknown whether the tumor was resected entirely or not. The irradiation was performed with a 633 nm light‐emitting diode lamp at 100 mW/cm2 for 200 J/cm2 after wiping off the ALA cream. Two sessions of ALA‐PDT were performed at a 2 weeks interval. One month after ALA‐PDT, the surgical trace of the lesion was found to have disappeared entirely, with a little scab, and the cancer did not recur. After 1 year of follow‐up, there was no recurrence. The combination with surgery and ALA‐PDT may provide a new idea for the treatment of KA‐like SCC for a wide range of patients. [ABSTRACT FROM AUTHOR]

Abstract Keratoacanthoma‐like squamous cell carcinoma (KA‐like SCC) is a malignant classification of KA. We report here a case of surgical combined with 5‐aminolevulinic acid‐photodynamic therapy (ALA‐PDT) to treat KA‐like SCC in an elderly male with successful tumor removal. The tumor resection was performed before ALA‐PDT. One week later, the lesion site was further treated with 20% ALA for 3 h when it was unknown whether the tumor was resected entirely or not. The irradiation was performed with a 633 nm light‐emitting diode lamp at 100 mW/cm2 for 200 J/cm2 after wiping off the ALA cream. Two sessions of ALA‐PDT were performed at a 2 weeks interval. One month after ALA‐PDT, the surgical trace of the lesion was found to have disappeared entirely, with a little scab, and the cancer did not recur. After 1 year of follow‐up, there was no recurrence. The combination with surgery and ALA‐PDT may provide a new idea for the treatment of KA‐like SCC for a wide range of patients.

The schematic summarizes the underlying mechanisms by which ALA-PDT ameliorates acne in mice. ALA-PDT attenuated tissue injury by suppressing ear swelling and chronic inflammation caused by P. acnes infection. ALA-PDT reduced sebocyte proliferation and lipid synthesis by inducing mitochondrial stress and oxidative stress. [Display omitted] • The proliferative activity of Propionibacterium acnes was inhibited by ALA-PDT in vitro. • ALA-PDT significantly ameliorated ear inflammation caused by Propionibacterium acnes in mice. • ALA-PDT inhibited sebocyte proliferation and lipid secretion by inducing oxidative stress in sebocytes. Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) −based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT. [ABSTRACT FROM AUTHOR]

• Protothecosis , an uncommon cutaneous infection, lacks a unified standard of treatment. • Conventional treatments for cutaneous protothecosis often involve prolonged courses of antifungal medications, highlighting the need for novel therapeutic approaches. • The study successfully utilized the combination of 5-aminolevylinic acid photodynamic therapy (ALA-PDT) and itraconazole to treat a case of cutaneous protothecosis, and in vitro experiments confirmed that ALA-PDT can reduce the MIC of Prototheca against drugs by disrupting their cell walls, thus presenting a promising therapeutic strategy. As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro , ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii , which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro , and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis. [ABSTRACT FROM AUTHOR]

• ALA-PDT significantly inhibited the viability while promoted apoptosis of human cervical cancer SiHa cells. • ALA-PDT remarkably suppressed SiHa cell migration, invasion and epithelial-mesenchymal transition (EMT). • The anti-tumor activities of ALA-PDT on SiHa cells appeared to be via suppressing miR-152–3p and thereby activiating JAK1/STAT1 pathway in vitro and vivo. • The study elucidated the underlying molecular mechanism of ALA-PDT on cervical cancer SiHa cells. Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms. Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152–3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152–3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo. ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152–3p. JAK1 was identified as a direct target of miR-152–3p, and ALA-PDT was found to regulate the expression levels of miR-152–3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152–3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152–3p/JAK1/STAT1 pathway expression. ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152–3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer. [ABSTRACT FROM AUTHOR]

Yan Jing Chen,&ast; Qin Yi,&ast; Yi Ming Li, Li Li Department of Dermatology and Venereology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li LiDepartment of Dermatology and Venereology, West China Hospital, Sichuan University, Guoxue Alley No. 37, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel +86 18980601692Email lilihx_scu@scu.edu.cnAbstract: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant-inherited disease characterized by multiple basal cell carcinomas, multiple keratocystic odontogenic tumors, palmar and/or plantar pits. A 50-year-old male patient presented to our hospital with multiple plaques and maculopapular lesions on his face and trunk for more than 20 years. A skin biopsy revealed a number of discrete nests of basaloid cells in the dermis where the peripheral cells are arrayed like a palisade. Multiple odontogenic keratocysts and falx cerebri calcification were found. The diagnosis of NBCCS was made. We treated this patient with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with red light activation, 5% imiquimod cream and surgical excision for the basal cell carcinomas. All the skin lesions on his face improved substantially after eight sessions of red-light ALA-PDT from clinical observation. Red-light ALA-PDT proved to be a good therapeutic method for NBCCS in this case.Keywords: nevoid basal cell carcinoma syndrome, basal cell carcinomas, ALA-PDT, renal cysts

Background: Mycobacterium abscessus skin infections have emerged as a major medical issue. Traditional antibiotic treatments are challenging, prolonged, and often lead to recurrence, creating an urgent need for new therapies. This study investigates the effectiveness of aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics in treatmenting M. abscessus, using both in vitro and in vivo methods., Methods: We treated eight patients with M. abscessus skin infections following cosmetic surgery, using ALA-PDT (ALA concentration: 20 %; red light: 80 J/cm 2 ) combined with oral or intravenous antibiotics,including clarithromycin, moxifloxacin and amikacin, to treat 8 patients with M. abscessus skin infection after medical cosmetic surgery, and assessed the treatment outcomes. Additionally, four bacterial strains (MAB-A1, MAB-A2, MAB-B1, and MAB-B2) isolated from patients were tested in vitro for ALA-PDT efficacy to determine the optimal ALA-PDT dosage. Furthermore, the strains' single colony morphology, biofilm formation, and genome characteristics of were analyzed to explore the factors influencing ALA-PDT's bactericidal effects. Finally, a combined ALA-PDT and antibiotics sterilization experiment was conducted in vitro., Results: Clinically, ALA-PDT combined with antibiotics showed strong efficacy in treating M. abscessus skin infections, with no recurrence observed during follow-up. In vitro, ALA-PDT effectively killed M. abscessus, although MAB-B1 and MAB-B2 required a higher ALA-PDT dose compared with MAB-A1 and MAB-A2. Compared to MAB-A1 and MAB-A2, MAB-B1 and MAB-B2 exhibited stronger biofilm formation capabilities and bacterial virulence as well as genome mutations primarily affecting fatty acid synthesis and metabolism, potentially explaining their increased ALA-PDT dosage requirement. Notably, the combination of ALA-PDT and antibiotics exerted markedly higher bactericidal effects in vitro compared with antibiotics alone., Conclusions: ALA-PDT combined with antibiotics emerged as an effective treatment for M. abscessus skin infections. However, optimal dosage and antibiotic combinations should be tailored to the characteristics of specific clinical strains., Competing Interests: Declaration of competing interest No conflict of interests exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the listed authors have approved the manuscript that is enclosed. Xiaoyu Wang, Xiao Wang, Zhenyu Kou, Kedai Sun, Yang Tan, Jinyi Chen, Yang He, Wen Ding, Hong Liu, Yi Liang, Lingfei Li, Xia Lei., (Copyright © 2024. Published by Elsevier B.V.)

Photodynamic Therapy (PDT) is a non-invasive treatment that has shown its usefulness in eliminating low grade squamous intraepithelial lesion (LSIL) and Human Papilloma Virus (HPV) infection. The response to PDT is variable, how patient´s immunology works during human PDT is unclear and therefore, the main of this work was to characterize the local immune response during treatment with PDT in patients with LSIL and / or persistent HPV infection. Two groups divided into Complete Response and Non Response patients to PDT, which were treated with a scheme of 12% δ-aminolevulinic acid (ALA), 2 irradiations 48 h apart at a total energy dose of 200 J/cm2, their local immune response were analyzed by Cytometric Bead Array (CBA) and spectral Cytometry before and after each irradiation. Cytokine mostly expressed previously PDT was IL-8 in all groups. PDT stimulates the increase in IL-6 and IL-8 concentrations at 48 h, being greater in the group of responding patients as well as IL-6 and IL-10 proving the host immune stimulus to remit diagnosis. Complete Response group has a higher percentage of total CD45+ cells before treatment than Non Response. A decrement pattern of CD8+ were observed on Non Response group during treatment. An increase tendency was observed on CD14+ and HLADR-ABC+ cells in both response groups. PDT is able to stimulate immune response, being important to treatment effectiveness increasing innate immune cells and their activation, such as monocytes, cytotoxic lymphocytes. A multiple HPV infection could be related to a less expression of cytokines during PDT.

Photodynamic therapy (PDT) is a non-surgical treatment that has been approved for its human medical use in many cancers. PDT involves the interaction of a photosensitizer (PS) with light. The amino acid 5- aminolevulinic acid (ALA) can be used as a pro-PS, leading to the synthesis of Protoporphyrin IX. Hydrogen sulfide (H 2 S) is an endogenously produced gas that belongs to the gasotransmitter family, which can diffuse through biological membranes and have relevant physiological effects such as cardiovascular functions, vasodilatation, inflammation, cell cycle and neuro-modulation. It was also proposed to have cytoprotective effects. We aimed to study the modulatory effects of H 2 S on ALAPDT in the mammary adenocarcinoma cell line LM2. Exposure of the cells to NaHS (donor of H 2 S) in concentrations up to 10 mM impaired the response to ALA-PDT in a dose-dependent manner. The addition of 3 doses of NaHS showed the highest effect. This decreased response to the photodynamic treatment was correlated to an increase in the GSH levels, catalase activity, a dose dependent reduction of PpIX and increased intracellular ALA, decreased levels of oxidized proteins and a decrease of PDT-induced ROS. NaHS also reduced the levels of singlet oxygen in an in vitro assay. H 2 S also protected other cells of different origins against PDT mediated by ALA and other PSs. These results suggest that H 2 S has a role in the modulation of the redox state of the cells, and thus impairs the response to ALA-PDT through multifactor pathways. These findings could contribute to developing new strategies to improve the effectiveness of PDT particularly mediated by ALA or other ROS-related treatments. [Display omitted] • H 2 S generated from NaHS make cells less sensitive to ALA-PDT. • H 2 S has multifactorial effects on ALA-PDT. • Supraphysiological but non-toxic concentrations of H 2 S have antioxidant activity. • Endogenous PpIX levels from ALA, decreases after NaHS treatment. [ABSTRACT FROM AUTHOR]

• Monotherapy with ALA-PDT reduced the DCS symptom. • ALA-PDT decreased the inflammatory cell count in DCS lesions. • ALA-PDT caused sebaceous gland atrophy in DCS lesions. • The immunomodulatory effect of ALA-PDT could have broader applications. Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS. Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted. Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT. ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions. [ABSTRACT FROM AUTHOR]

• ALA-PDT and LEEP were used to treat 120 CIN2 patients. • Total effective rate of LEEP during the first 6 months after treatment is better. • Full recovery rates of ALA-PDT exceeded LEEP at 6–12 months. • ALA-PDT is more promising for better CIN2 degradation especially after 6 months. • ALA-PDT is better in high-risk HPV negativity, and greater fertility conservation. Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat high-grade squamous intraepithelial lesions. However, the clinical efficacy and safety of these two therapies have rarely been compared. Thus, this study aimed to compare the clinical efficacy and safety of the two treatment regimens. One hundred and twenty patients in two groups (60 + 60) with grade 2 cervical intraepithelial neoplasia (CIN2) were voluntary treated with photodynamic therapy or LEEP between June 2020 and December 2022. Follow-up was conducted at 3, 4–6, and 7–12 months after treatment. Although the total effective rate of LEEP was higher during the first 6 months after treatment, both the total effective rate of lesion degradation and the double-negative rate of high-risk HPV16/18 and liquid-based cervical cytology by ALA-PDT treatment increased with time and finally exceeded those of LEEP at 7–12 months. ALA-PDT may be more promising than LEEP for treating patients with CIN2 because of the better CIN2 degradation and high-risk HPV negativity, less damage, and greater fertility conservation, especially after 6 months. [ABSTRACT FROM AUTHOR]

Objective To analyze the influencing factors of ineffective treatment of facial basal cell carcinoma (BCC) through ella photodynamic therapy (ALA-PDT) combined with surgery. Methods Fifty patients with BCC underwent surgery combined with ALA-PDT treatment from January 2016 to December 2019 were selected. The ALA-PDT treatment was performed at the day of stitche sremoval at 1 week after surgery. The therapeutic effect was evaluatedat 6 weeks after ALA-PDT treatment, and all patients were divided into effective group and ineffective group. The baseline data between 2 groups were counted and compared, and the influencing factors of ineffective treatment were analyzed by logistic regression. Results After treatment, there were 45 patients in the effective group (90.0% effective) and 5 patients in the ineffective group (10.0% ineffective). Single logistic regression analysis showed that there was no significant difference in age, sex, duration of illness, lesion size, lesion location and number of lesions between the effective group and the ineffective group (P>0.05). The proportion of pathological type (nodular type), previous main working environment (outdoor) and Skin Grown Classification (Ⅱ aggressive activetype) in the ineffective group were higher than those in the effective group (P<0.05). Multiple logistic regression analysis showed that nodular type [OR=9.360, 95% CI (2.010,43.594)], previous main working environment (outdoor) [OR=8.167, 95% CI (2.388,27.927)], Ⅱ aggressive active type [OR=9.743, 95% CI (2.565,37.003)] were the influencing factors for the failure of surgery combined with ALA-PDT in patients with facial BCC. Conclusion There is still a certain risk of ineffective treatment of surgery combined with ALA-PDT for facial BCC. The nodular type, previous main working environment (outdoor) and Ⅱ aggressive active type may be the influencing factors of ineffective treatment. Patients with the above factors should be paid more attention clinically. [ABSTRACT FROM AUTHOR]

We reported a case of cystic acne occurring after 20% GAP in a patient with hyperandrogenism, treated successfully by topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT), pulsed dye laser (PDL), and oral antiandrogen drugs. Keywords: acne; ALA-PDT; complication; glycolic acid peel; hyperandrogenism EN acne ALA-PDT complication glycolic acid peel hyperandrogenism 184 187 4 03/23/22 20220301 NES 220301 ACKNOWLEDGMENTS The patient mentioned in this manuscript has given written informed consent for publication of her case details. ALA-PDT and pulsed dye laser combined with oral antiandrogen drug in the treatment of cystic acne in a patient with hyperandrogenism. [Extracted from the article]

Background: Actinic keratosis (AK) occurs frequently in sun‐exposed skin while its diagnosis and treatment were still in exploration. Materials and methods: Thirty two patients with facial AK lesions were selected and examined with reflective confocal microscopy (RCM) firstly, followed by biopsy at the same site. RCM was used to observe AK lesions before 5‐aminolevulinic acid photodynamic therapy (ALA‐PDT) treatment, after the first treatment, after 4 treatments, and at 1 and 6 months follow‐up. Retrospective analysis of RCM images was performed. Results: Thirty two AK cases showed initial RCM microscopic features including disorderly arranged epidermal cells (100%), atypical keratinocytes (100%), and blurry border between the epidermis and dermis (100%). 4 patients quitted trail. After treatments, 24 cases showed basically regular arrangement of epidermal cells, absent atypical keratinocytes, and clear border between epidermis and dermis, while 4 cases improved little. At 1 and 6 months follow‐up, 23 cases remained relapse‐free while 1 case developed recurrent symptoms. Effective rate of 4 ALA‐PDT treatments for AK was 100%; recurrence and cure rates were 4.2% and 82.1%, respectively. Conclusion: ALA‐PDT is effective to treat AK, while RCM can be recommended for in vivo evaluating and monitoring the effect of ALA‐PDT on AK. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a chronic inflammatory cutaneous disease. 5‐Aminolaevulinic acid photodynamic therapy (ALA‐PDT) is a novel and effective approach for severe acne vulgaris treatment. However, its specific treatment mechanism still remains unclear. In the present study, we investigated the potential mechanism of how ALA‐PDT regulated intense inflammatory response in acne vulgaris. It appeared that ALA‐PDT suppresses proliferation and lipid secretion of primary human sebocytes. Besides, ALA‐PDT could up‐regulate the expression of CXCL8 in vivo and in vitro, amplifying the inflammatory response by recruiting T cells, B cells, neutrophils and macrophages. We also found that ALA‐PDT elevated the expression of CXCL8 via p38 pathway. SB203580, a p38 pathway inhibitor, decreased the expression of CXCL8 in sebocytes after ALA‐PDT. These findings indicate that ALA‐PDT amplifies the intense inflammatory response in the treatment of acne vulgaris via CXCL8. Our data decipher the mechanism of intense inflammatory response after ALA‐PDT for acne vulgaris. [ABSTRACT FROM AUTHOR]

• 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been shown to be an effective treatment for moderate to severe acne, but the specific mechanism is not clear. • ALA-PDT activated the NLRP3 inflammasome pathway in human SZ95 sebocytes and enhanced caspase-1 activity and IL-1β secretion, which in turn led to cell death. • PDT dose-dependently leads to an increase in reactive oxygen species (ROS) levels in human SZ95 sebocytes. • Antioxidant NAC and caspase inhibitor Z-VAD-FMK reduced cell death and expression and secretion of proteins associated with pyroptosis in a dose-dependent manner. • ALA-PDT induced sebaceous gland cell death can reduce sebum secretion, while it may exacerbate the local inflammatory response and break chronic inflammation to achieve the effect of treating acne. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for pilosebaceous inflammatory diseases, such as acne vulgaris. In this study, we explored ALA-PDT's mechanisms against acne in vitro. We treated human SZ95 sebocytes with ALA (0.2 mM) and subjected them to varied PDT doses (0, 5, 10, 20 J/cm²) over 12 h. We assessed cell viability post-treatment using the Annexin V FITC/PI apoptosis kit. ROS accumulation in the sebocytes was detected with a DCFDA probe. We quantified NLRP3 and caspase-1 mRNA via quantitative PCR and determined IL-1β release following ALA-PDT by ELISA. Western blotting helped identify the levels of proteins associated with pyroptosis (NLRP3, caspase-1, and IL-1β). To elucidate the mechanisms, we re-evaluated these parameters after administering various concentrations of NAC antioxidants (0, 0.4, 2, 10 mM) and the caspase inhibitor Z-VAD-FMK (0, 5, 10, 20 μM). Increasing PDT dose inversely affected SZ95 sebocyte survival, with a corresponding rise in ROS and pyroptosis-related proteins (NLRP3, caspase-1, and IL-1β). Furthermore, NAC and Z-VAD-FMK modulated the expression and secretion of these molecules in a dose-responsive manner. Our findings suggest ALA-PDT's potential mechanism of action on sebaceous glands could involve ROS induction, leading to NLRP3 inflammasome assembly, thereby heightening caspase-1 activation and IL-1β secretion. This cascade may amplify the local inflammatory response to break chronic inflammation in acne vulgaris treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the clinical efficacy of ALA-PDT, Bacillus Calmette-Guerin ( BCG)polysaccharide nucleic acid injection combined with Thymosin enteric-coated tablets in the treatment of condyloma acuminatum. METHODS: Totally 174 patients with condyloma acuminatum admitted into Zhuhai People’s Hospital from Jul. 2017 to Jul. 2020 were extracted to be divided into the thymosin treatment group and the drug combination group via the random number table, with 87 cases in each group. The thymosin treatment group was treated with Thymosin enteric-coated tablets, while the drug combination group was given ALA-PDT, BCG polysaccharide nucleic acid injection combined with Thymosin enteric-coated tablets. Levels of tumor necrosis factor α ( TNF-α), lymphotactin ( LTN), substance P ( SP), T lymphocyte subsets and transforming growth factor β1 ( TGF-β1) in both groups were detected. The treatment effect and incidence of adverse drug reactions were observed and statistically analyzed. RESULTS: After treatment, compared with the thymosin treatment group, the level of LTN of the drug combination group increase significantly, the level of SP decreased significantly, the levels of CD3+ and CD4+ increased significantly, the levels of CD8+ decreased significantly, the level of TGF-β1 increased significantly and the level of TNF-α decreased significantly, with statistically significant differences ( P ＜ 0. 05). The total effective rate of the drug combination group was 96. 15% ( 75/78), compared with 87. 18% ( 68/78) of the thymopeptide treatment group, the difference was statistically significant ( P ＜ 0. 05). The incidence of adverse drug reactions in the thymosin treatment group and the drug combination group group was respectively 7. 69% ( 6/78) and 12. 82% ( 10/78), with no statistically significant difference ( P ＞ 0. 05). CONCLUSIONS: The efficacy of ALA-PDT, BCG polysaccharide nucleic acid injection combined with Thymosin enteric-coated tablets in the treatment of condyloma acuminatum is significant, which can effectively promote the immunity of patients and improve the immune system. [ABSTRACT FROM AUTHOR]

Summary: Chromoblastomycosis (CBM) is a chronic granulomatous fungal infection caused by melanised or brown‐pigmented fungi. It can lead to chronic persistent infections and may cause incapacity for labour in some severe clinical forms. The optimal therapy for CBM is still uncertain. Here, we reported the case of a 66‐year‐old male who has had red plaque and recurrent keratinised protrusions on his right forearm for 20 years. He was treated orally with terbinafine, itraconazole and isotretinoin. He also received carbon dioxide(CO2) laser to eradicate the keratinised protrusions and promote the penetration of photosensitiser. After the CO2 laser, 5‐aminolevulinic acid‐based photodynamic therapy (ALA‐PDT) was adopted immediately to inhibiting the growth of fungi in subcutaneous tissue. The patient received an important improvement with a plaque and crust reduction after 4 months. For such recalcitrant case of chromoblastomycosis, the use of retinoid, CO2 laser combined with ALA‐PDT may be a new adjuvant therapy. We further reviewed the cases of chromoblastomycosis treated with laser, photodynamic therapy or retinoic acid. [ABSTRACT FROM AUTHOR]

Objectives: The study examines the changes in dermoscopic features of actinic keratosis (AK) after photodynamic therapy, and delineates the association between AK dermoscopic and histopathological findings. Methods: A total of 21 patients (23 lesions) with pathologically confirmed actinic keratosis who received 5‐aminolaevulinic acid (ALA) photodynamic therapy (ALA‐PDT) were enrolled. The numbers of PDT treatments were: 1, n = 1; 2, n = 2; 3, n = 10; 4, n = 6; 5, n = 2; 6, n = 2). The dermoscopic features before and after the PDT were compared. Results: There were statistically significant decreases in the positive rates of dermoscopic features including scales (P < 0.001), follicular plugs with whitish halo (P = 0.013), and red pseudonetwork (P = 0.022) among patients treated with ALA‐PDT. Dermoscopic feature was significantly associated with pathological grade (P < 0.001). Histopathological hyperkeratosis was significantly associated with dermoscopic red pseudonetwork (P = 0.034) and wavy vessel (P = 0.005). Parakeratosis was associated with wavy vessels (P = 0.001). For vascular hyperplasia in dermal papillae, the significant correlates included scales (P = 0.011), follicular plugs with whitish halo (P = 0.011), red pseudonetwork (P < 0.001); coiled vessels (P = 0.003) and rosette sign (P = 0.004). Wavy vessels was the only feature correlating keratosis pilaris (P = 0.003). Conclusions: The findings of the present study support dermoscopy as having potential to be useful for diagnosing and monitoring of actinic keratosis. [ABSTRACT FROM AUTHOR]

5‐Aminolevulinic acid‐based photodynamic therapy (ALA‐PDT) comprises photochemical and biological reactions, finally generating tumor destruction. Tumor selectivity of ALA‐PDT relies on the disturbed heme synthesis pathway in neoplastic cells. Tumor pretreatment with ALA induces two reactions: the first, self‐activation of the key enzyme porphobilinogen synthase and then protoporphyrin (PpIX) synthesis at low Fe++ availability. We emphasize that the toxic mechanism of ALA‐PDT triggered by 1O2 targets intracellular organelle destruction death pathways. PpIX fluorescence of tumors, particularly in glioblastoma, is used clinically for fluorescence guidance during neurosurgery. Targeting residual and metastatic cancer stem cells is a crucial challenge of ALA‐PDT, plausibly combined with other therapeutic modalities to encounter metastatic recurrences. We overview the different aspects of ALA‐PDT mechanism and future research and prospects. [ABSTRACT FROM AUTHOR]

• The adult kerion and tinea faciei secondary to ulcers caused by trichophyton rubrum is uncommon. • Topical or oral antifungal agents have side effects and resistance for treating kerion and tinea faciei secondary to ulcers. • ALA-PDT has shown its antibiotic properties and has been commonly used in dermatophytoses. • The combination of antifungals and ALA-PDT is an effective and safe strategy for treating patients with adult kerion and facial ulcer caused by trichophyton rubrum. Dermatophytosis is the most common fungal infectious disease in the world, which is commonly caused by Trichophyton rubrum in China. The traditional therapies for treating dermatophytosis include topical and oral antifungal agents like terbinafine, griseofulvin, and azole antifungal drugs. However, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) as a new alternative therapy avoids the side effects and drug resistance of traditional antifungal agents. We report two cases diagnosed as kerion and tinea faciei secondary to ulcers with CARD 9 deficiency, both of whom were infected by T.rubrum. They were both successfully treated by ALA-PDT combined with antifungal drugs, providing a feasible strategy for therapeutic choice for adult kerion and ulcer treatment. [ABSTRACT FROM AUTHOR]

• We reported a case of BD developed in BP with DLBCL. • A holmium laser and ALA-PDT treatment was effective. • Combination treatment can simultaneously address aesthetic and therapeutic goals. 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. [ABSTRACT FROM AUTHOR]

• ALA-PDT induced significantly morphological changes of hypertrophic scar fibroblast. • The cell viability of fibroblasts was significantly decreased for ALA-PDT treatment. • ALA-PDT can significantly alleviate the contractile capacity of fibroblasts. • ALA-PDT induced K48 ubiquitination and degradation of Smad4 in TGF-β1 signaling. Hypertrophic scars, an abnormal wound-healing response to burn injuries, are characterized by massive fibroblast proliferation and excessive deposition of extracellular matrix and collagen. 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is a promising therapy for hypertrophic scar, details of the mechanisms remain to be elucidated. In this study, we aimed to investigate the molecular mechanisms involved in ALA-PDT against hypertrophic scar fibroblasts. The morphologies of hypertrophic scar fibroblasts (HSFs) treated with ALA-PDT were observed under a light microscopy. The viability of HSFs was detected using the CCK-8 assay. HSFs-populated collagen gel contraction assays were conducted to examine the fibroblast contractility and the cytotoxicity of HSFs in 3D collagen tissues were observed using confocal microscopy. The effect of ALA-PDT on TGF-β1/Smad2/3/4 signaling pathway activation and effector gene expression were verified by immunoprecipitation, western blot and real-time quantitative PCR analysis. We observed significant changes in cell morphology after ALA-PDT treatment of HSFs. As ALA concentration and light dose increased, the viability of HSFs significantly decreased. ALA-PDT can significantly alleviate the contractile capacity and promote the death of HSFs induced by TGF-β1 treatment in a three-dimensional collagen culture model. TGF-β1 treatment of HSFs can significantly induce phosphorylation of Smad2/3 (p-Smad2/3) in whole cells, as well as p-Smad2/3 and Smad4 proteins into the nucleus and increase the mRNA levels of collagen 1/3 and α-SMA. ALA-PDT hampers the TGF-β1-Smad2/3/4 signaling pathway activation by inducing K48-linked ubiquitination and degradation of Smad4. Our results provide evidence that ALA-PDT can inhibit fibroblast contraction and promote cell death by inhibiting the activation of the TGF-β1 signaling pathway that mediates hypertrophic scar formation, which may be the basis for the efficacy of ALA-PDT in the treatment of hypertrophic scars. [ABSTRACT FROM AUTHOR]

• Innovative treatment Approach: ALA-PDT and low-dose corticosteroids in CRDD. • Promising Results: successful management of severe facial CRDD with combined therapy. • Rare dermatological Condition: CRDD responds favorably to this novel treatment combination. Cutaneous Rosai-Dorfman Disease (CRDD), a rare form of Rosai-Dorfman Disease (RDD), lacks established treatment guidelines. In this case report, we detailed a successful case of CRDD management in a 50-year-old woman with facial lesions. Our treatment included 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and low-dose oral corticosteroids. Remarkable improvement was evident after six ALA-PDT courses, and a one-year follow-up confirmed sustained remission. This case highlights the potential of combining ALA-PDT with low-dose corticosteroids as a promising therapeutic strategy for CRDD. Further research is necessary to fully elucidate its mechanisms and effectiveness. [ABSTRACT FROM AUTHOR]

• ALA-PDT is a reliable therapy for AK with large area or multiple lesions. • ALA-PDT has an excellent cosmetic results for AK lesions. • Various factors can impede the selection of ALA-PDT therapy in clinical practice. • Pain and higher cost in short-term as the two most significant limitations for AK. Numerous clinical studies have demonstrated the effectiveness of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) in treating actinic keratosis (AK). This therapy has achieved an average lesion clearance rate of approximately 80 % and has also shown to produce satisfactory cosmetic outcomes. However, in our clinical practice, the utilization and adherence to ALA-PDT treatment among AK patients has been lower than anticipated, possibly due to various factors. The objectives of this study are twofold: (1) To analyze the actual therapeutic effects of ALA-PDT treatment on AK lesions in clinical practice; and (2) To identify the factors that hinder acceptance of ALA-PDT therapy among AK patients with large area or multiple lesions situated on the head and face. This study included a group of 20 AK patients, comprising 15 females and 5 males, with an age range of 57–87 years. All patients received a complete course of ALA-PDT therapy, consisting of 3–6 treatments. The study analyzed various factors, including the cure rate, recurrence rate, cosmetic effects, and adverse reactions following treatment. To investigate the factors affecting the acceptance of ALA-PDT treatment among AK patients with large or multiple lesions on the head and face, we also examined a separate group of 43 AK patients. This group included individuals who either had incomplete courses of ALA-PDT treatment or declined the therapy for the first time. The factors potentially influencing patients' acceptance of PDT were analyzed based on the outcomes of these investigations. Among the 20 patients who completed the full course of ALA-PDT treatment, the cure rate was 95 % (19/20). The recurrence rates at 1 month, 3 months, and 6 months were 0 %, 5 %, and 10 %, respectively. Out of the 19 cured patients, only 2 experienced heavy pigmentation, and no scarring was reported 1–3 months post-treatment. Based on the survey of 43 patients who either had an incomplete course of ALA-PDT treatment or declined the therapy initially, several factors were identified as limiting their choice of PDT therapy. These factors include: (1) Intolerable adverse effects of treatment. (2) Higher treatment cost than expected. (3) Inconvenient transportation. (4) Coexistence of other senile diseases. (5) Unsatisfactory clinical efficacy observed. (6) Inadequate understanding of AK. (7) Lost to follow-up. The study concludes that ALA-PDT is a beneficial and aesthetically pleasing treatment for AK patients, particularly those with extensive or multiple lesions on the head and face. However, various factors can impede the selection of ALA-PDT therapy, potentially depriving patients of the most suitable option. The study aims to assist dermatologists and AK patients in considering treatment plans and exploring alternative options. Overall, the findings of this study may provide valuable guidance for improving treatment outcomes and patient satisfaction. [ABSTRACT FROM AUTHOR]

• There is an urgent urgency to find more effective treatments for hidradenocarcinoma. • We are the first to report ALA-PDT combined with local narrow margin excision for the treatment of hidradenocarcinoma. • ALA-PDT combined with local narrow margin excision may provide a less painful and more effective solution for the treatment of hidradenocarcinoma. Hidradenocarcinoma is a rare malignancy of sweat gland differentiation. It is known for its high rate of recurrence and metastasis, which has a serious impact on human health and aesthetics. However, the treatment options for this disease are limited, making prompt and appropriate treatment is a daunting challenge. In this report, we present the first successful cure of hidradenocarcinoma using 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with local narrow margin excision on the left side of the forehead in an elderly woman. No recurrence during one year of follow-up after the combined therapy. This case will provide a valuable reference for more efficient management of similar cases in clinic. [ABSTRACT FROM AUTHOR]

Objectives: Condyloma acuminatum are the most common sexually transmitted diseases worldwide, and they are closely associated with human papillomavirus (HPV) infection. Urethral meatus is one of the places that warts occur. Many treatments for uretheral warts have limitations. In this study, we performed 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) on patients and investigated the effectiveness of reducing HPV viral loads. Materials and Methods: In our study, 21 patients diagnosed with urethral condyloma acuminatum were included. After 4 h treatment of ALA, patients received PDT. Each patient received HPV test before every PDT cycle. The frequency of PDT was dependent on viral load changes. Results: All patients achieved complete clinical remission after the last session of ALA-PDT. There were significant differences in HPV viral loads between pretherapy and after one or three rounds of PDT treatment. Conclusions: ALA-PDT is a safe and effective method for treatment of condyloma acuminatum in urethra meatus. Dynamic monitoring of HPV viral loads can more objectively demonstrate the effectiveness and guide the treatment of PDT. [ABSTRACT FROM AUTHOR]

• Cancer-associated fibroblasts (CAFs) are important components of the tumor microenvironment. CAFs affect the biological behavior of tumor cells and play critical roles in growth, invasion, and metastasis of tumor. • Cutaneous squamous cell carcinoma (cSCC) is one of the common skin cancers. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is established approach for cSCC in situ and can induce effective antitumor immune response. • This research provides preliminary evidence that ALA-PDT can affect CAFs in the tumor microenvironment and highlights that ALA-PDT can induce a reversal of the activated state of CAFs, thereby suppressing the growth of cSCC. 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. [ABSTRACT FROM AUTHOR]

• This study investigated the effects of low-dose ALA-PDT on photoaging in human dermal fibroblasts (HDFs). • To explore the effect and mechanism of transcription factor Nrf2 in the treatment of photoaging fibroblasts with low-dose ALA-PDT. • This study has played an active role in revealing the effects and mechanisms of PDT under different conditions. Objectives: To investigate the effects of low-dose aminolevulinic acid photodynamic therapy (ALA-PDT) on photoaging in human dermal fibroblasts (HDFs) and to explore the mechanism of Nuclear factor erythroid 2-related factor 2(Nrf2)-mediated photorejuvenation in vitro. Methods: A photoaging model was established through repeated exposure of HDFs to UVA. Total superoxide dismutase (SOD) expression was detected by a SOD activity assay. Nrf2 was knocked down through adenovirus infection, and successful knockdown was confirmed by Western blot analysis and quantitative polymerase chain reaction. Results: Sustained exposure to UVA induced photoaging in HDFs. Total SOD activity was significantly increased by low-dose aminolevulinic acid (ALA)-PDT. Upon application of low doses of ALA-PDT to photoaging HDFs, Nrf2 was translocated to the nucleus; in addition, the expression of Nrf2, transforming growth factor-β1 (TGF-β1), type I and III collagen (COL1 and COL3), heme oxygenase 1 (HO-1), and p-ERK was increased, while the expression of matrix metalloproteinase 9 (MMP-9) was decreased. However, after Nrf2 was knocked down in HDFs, the expression of TGF-β1, COL1, COL3, and HO-1 was significantly decreased, while the expression of MMP-9 was increased. Conclusion: This study revealed that low-dose ALA-PDT decreases UVA-mediated photoaging through an Nrf2-mediated antioxidant effect. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infection is linked to several diseases, the most prominent of which are cervical cancer and genital condyloma acuminatum. Previous studies have suggested an effective role for 5-aminolevulinic acid photodynamic therapy (ALA-PDT) against various cancers by the induction of autophagy and apoptosis. However, few reports have focused on the effectiveness of ALA-PDT on HPV related disorders. To identify the role of ALA-PDT in the context of HPV infection, we initially investigated 111 patients suffering from genital condyloma acuminatum. HPV viral load detected before and after ALA-PDT treatment was compared during this procedure; a significant difference was noted. HeLa (HPV18) cells were exposed to ALA-PDT in vitro to further explore the underlying mechanisms. Western blot analysis showed that ALA-PDT induces LC3II and p62 expression, along with the up regulation of caspase-3 and cleaved caspase-3. Our study also demonstrated that ALA-PDT treatment inhibits the proliferation of HeLa cells in a dose dependent manner and effectively reduces HPV viral load via autophagy and apoptosis by regulating the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways. Hydroxychloroquine (HCQ), although it inhibited autophagy degradation, functioned to activate reactive oxygen species (ROS) levels of ALA-PDT to enhance the observed effect. These findings suggest strategies for the improvement of PDT efficacy in patients. • ALA-PDT reduces HPV viral load via autophagy and apoptosis in a time- and dose-dependent manner. • Autophagy inhibitor HCQ could enhance ALA-PDT efficacy and activate ROS levels in HeLa cells. • These findings could be suitable for better ALA-PDT applications in HPV related diseases. [ABSTRACT FROM AUTHOR]

Highlights • ALA-PDT treatment has differential effects on HPV-positive and negative cervical cancer cell lines. • ALA-PDT treatment inhibits cervical cancer by regulating miR-34a/HMGB1 axis mediated DCs maturation. • Downregulation of miR-34a might modulate cervical cancer immunity by increasing HMGB1 exosomes secretion. Abstract 5-Aminolevulinic acid photodynamic therapy(ALA-PDT) has been widely used for cervical cancer treatment, but the mechanisms are still not fully delineated. Here we showed that ALA-PDT significantly upregulated HMGB1 while downregulated miR-34a expression levels in cervical cancer tissues, and the percentages of mature DCs(mDCs) were increased in ALA-PDT treated patients' peripheral blood. After treating HPV-positive Hela, SiHa, Caski and HPV-negative C33 A cervical cancer cell lines with ALA-PDT, HPV-positive cells' proliferative ability was significantly inhibited and apoptosis rates were elevated, while no significant changes were found in HPV-negative C33 A cell line. Most importantly, in HPV-positive cells, we found that miR-34a were downregulated in cytoplasm, and both cytoplasm and exosome HMGB1 were significantly elevated comparing to cancer cells without ALA-PDT treatment, and it could be reversed by miR-34a mimic transfection, which indicated that HPV infection and miR-34a downregulation might be vital for ALA-PDT treatment. Based on the HMGB1 is the potential target of miR-34a and an inverse correlation between miR-34a and HMGB1 in ALA-PDT treated cancer tissues, we verified that HMGB1 could be targeted and downregulated by miR-34a mimic, and ALA-PDT promotes HMGB1 secretion by inhibiting miR-34a expression. By co-culturing cervical cancer cell lines with immature DCs(imDCs) in the Transwell systems, we found that ALA-PDT induced HMGB1 exosomes could promote DCs maturation, which could be reversed by silencing HMGB1 in HPV-positive cervical cancer cells. In vivo animal experiments also proved that ALA-PDT inhibited tumor growth in tumor bearing mice, which was reversed by co-transfected with miR-34a mimic or silencing HMGB1 in HPV-positive cells. Hence we concluded that ALA-PDT treatment specifically inhibited HPV-positive cervical cancer cells' proliferative ability, promoted cell apoptosis and modulated DCs maturation by regulating miR-34a mediated HMGB1 exosomes secretion. [ABSTRACT FROM AUTHOR]

Highlights • IGF-1 had counter effects of ALA-PDT on SZ95 cells. • Rapamycin enhanced the effects of ALA-PDT on SZ95 cells. • ALA-PDT suppressed the cell growth in SZ95 cells through Akt-/Erk- mTOR pathway. • PRAS40-/RagC- mTOR pathway shows no effect in ALA-PDT suppressing SZ95 cell growth. Abstract Background Topical 5-aminolevulinic acid mediated photodynamic therapy (PDT) is known to be an effective method in treating acne vulgaris and other sebaceous gland-related diseases. The therapeutic mechanisms of ALA-PDT still remain undetermined. Our team has reported that ALA-PDT suppressed the cell growth in SZ95 sebocytes by mTOR-p70 S6K signaling. In this study, we aimed to investigate upstream of the mammalian target of rapamycin (mTOR) signaling cascade after ALA-PDT on cell growth of human SZ95 sebocytes. Material and methods Human SZ95 sebocytes were treated with different concentration of 5-ALA PDT. Western blotting was used to detect and analyze the protein expression level of P-Akt (T308)/Akt, P-Akt (S473)/Akt, P-Erk/Erk, P-AMPKα (T172)/AMPK, P-AMPKα1 (S485)/AMPKα2 (S491)/AMPK, P-PRAS40/PRAS40, RagC. Meanwhile, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences of P-p70 S6K/p70 S6K after ALA-PDT. Results mTOR pathway inhibitor rapamycin decreased the level of P-p70 S6K reduced by ALA-PDT. Conversely, mTOR pathway activator IGF-1. ALA-PDT reduced the level of P-Akt (T308), P-Erk, P-AMPKα (T172), P-AMPKα1 (S485)/AMPKα2 (S491) and P-PRAS40, and no change was observed in the level of Rag C. Conclusion ALA-PDT suppresses the cell growth in SZ95 cells through Akt-/Erk- mTOR -p70 s6k pathway rather than PRAS40-/RagC- mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Genital warts are the manifestation of the human papillomavirus (HPV) infection, which may last for weeks or months before the clinical presentation. The primary aim of the study was the correlation of the DNA HPV genotypes eradication with the treatment response in male patients with persistent genital warts. Methods: Twenty-one male patients (age range: 22–58) after failure of cryotherapy and podophyllotoxin treatment were enrolled in the study. Genetic tests (Real Time - PCR method) analyzed the presence of DNA-HPV before and 6 months after four sessions (4 weeks apart) of photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT). The treatment efficacy was evaluated before each PDT session and at the end of the study. Results: The single HPV DNA type was present in 15/21 of the patients (13/15 HPV6). The high-risk HPV types were found in 8/21 subjects, of which 6/8 had several types. Six months after four sessions of PDT, complete response was found in 16/21 (76.19%; p = 0.0007) of patients, and DNA HPV clearance was found in 66.67% (p = 0.03). The eradication rate differed among patients with primary low-risk and high-risk HPV types—76.92% (10/13; p = 0.0003) and 50% (4/8; p = 0.05) respectively. Conclusion: ALA-PDT is an effective treatment even after the failure of previous modalities. The persistence of clinical lesions and high oncological risk HPV types should be an indication for treatment prolongation.

• CA patients with multiple-type of HPV infections required more times of ALA-PDT. • HPV DNA detection helps individualize ALA-PDT treatment for CA patients. • HPV DNA detection is effective in identifying recurrent and reinfection cases. Aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) is increasingly applied for the treatment of condyloma acuminata (CA). However, the determinants for the sessions and end points of ALA-PDT treatment remains unclear. Here, we recorded HPV screening, evaluated the frequency and efficacy of ALA-PDT in different types of CA, in order to individualize ALA-PDT treatment to CA. A total of 227 CA patients with HPV infection and visible warts were recruited. Prior to PDT, visible lesions were removed by radio frequency or microwave. HPV DNA detection were performed before each PDT treatment and at follow-up. Treatment was ended after two consecutive negative HPV DNA detection. Of the 227 patients, 119 patients received ALA-PDT and 116 patients completed all treatments. We found that CA patients with multiple-site infection, intra-luminal infection or multiple-type of HPV infection required more sessions of ALA-PDT. The recurrence rate was 8.62% (10/116). Viral load was significantly lower after six PDT treatments compared to viral load after three PDT treatments. Gender, HPV subtypes and warts location had no significant effect on the recurrence rate. Comprehensive evaluation of HPV infection state helps to individualize ALA-PDT treatment scheme for CA patients and predict the therapeutic efficacy. [ABSTRACT FROM AUTHOR]

• Compared with CO 2 laser therapy, 5-ALA-PDT can effectively treat multifocal VAIN1 and has apparent advantages in HPV clearance simultaneously. • Compared with CO 2 laser therapy, 5-ALA-PDT can better maintain the structural and functional integrity of the vaginal wall, with less trauma and a lower incidence of adverse reactions. • Compared with CO 2 laser therapy, 5-ALA-PDT can provide a safer and more effective treatment for women with VAIN1 combined with hr-HPV infection. To evaluate the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and CO 2 laser therapy of low-grade vaginal intraepithelial neoplasia (VAIN1) combined with high-risk human papillomavirus (hr-HPV) infection. A total of 163 patients with VAIN1 and hr-HPV infection were divided into PDT Group (n = 83) and CO 2 laser Group (n = 80). The PDT Group received six times of ALA-PDT treatments and the CO 2 laser Group received once CO 2 laser treatment. HPV types, cytology, colposcopy, and pathological examinations were carried out before and after treatment. The differences in HPV clearance rate, VAIN1 regression rate, and adverse reactions between the two groups were analyzed during 6-month follow-up. The overall HPV clearance rate of the PDT Group was significantly higher than that of the CO 2 laser Group (65.06% vs 38.75%, P = 0.0008) although similar result was obtained for 16/18-related HPV infection patients (54.55% vs 43.48%, P = 0.4578). The VAIN1 regression rate of the PDT Group was significantly higher than that of the CO 2 laser Group (95.18% vs 83.75%, P = 0.0170). In patients ≥ 50 years old, ALA-PDT showed better HPV clearance rate and VAIN1 regression rate than CO 2 laser therapy (P < 0.05). The adverse reactions in the PDT Group were significantly lower than that in the CO 2 laser Group (P > 0.05). The efficacy of ALA-PDT appears better than CO 2 laser for VAIN1 patients. However, the long-term effect of ALA-PDT for VAIN1 still needs to be explored. As a non-invasive treatment, ALA-PDT is a highly effective therapeutic procedure for VAIN1 with hr-HPV infection. [ABSTRACT FROM AUTHOR]

• This case confirms the good effects of ALA-PDT in the treatment of phaeohyphomycosis. • The skin lesions of phaeohyphomycosis greatly improved after 3 times of ALA-PDT. • To the patients with recalcitrant local subcutaneous fungal infection, PDT was suggested as an effective adjuvant treatment option combining with antifungal agents. An 80-year-old women complained of painful erythema, papules, nodules on her right wrist for 9 months. Granuloma and inflammatory infiltrates with septate fungal hyphae were observed in pathological sections. Growth of demaciatious fungus on SDA was confirmed to be Exophiala spinifera by microscopic appearance and ITS rDNA sequencing. The diagnosis of phaeohyphomycosis due to E. spinifera was established. The patient had a poor response to oral itraconazole (200 mg/d) combining with terbinafine (250 mg/d) for 6 weeks. Then, following three courses of ALA-PDT, used as adjuvant therapy, skin lesions greatly improved and remained stable after 3 months follow-up. The case suggests that ALA-PDT is an effective adjuvant treatment option for patients with recalcitrant local subcutaneous fungal infection. [ABSTRACT FROM AUTHOR]