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

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

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

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

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

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

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

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

Mortality risk of people living with HIV under hypothetical intervention scenarios of PM2.5 and HIV severity: a prospective cohort study.

This study estimated and compared mortality risks among people living with HIV (PLWH) under the real-world and hypothetical scenarios of PM2.5 concentrations and HIV severity. An open cohort from all PLWH receiving antiretroviral therapy in Sichuan during 2010-2019 was constructed, resulting in 541,515 person-years. Annual mean concentrations of PM2.5 were estimated and linked to PLWH by their residential address. The parametric g-formula were used to assess 3- and 5-year mortality risks under the real-world and hypothetical scenarios of PM2.5 (10-35, 35-50, 50-75 µg/m3) and CD4 concentrations (0-200, 200-500, 500-800, 800-1100 counts/µl). The estimated 3- and 5-year mortality risks among the PLWH were 14.43 % and 19.38 %, respectively, which would decrease substantially when annual PM2.5 concentration were reduced to between 10 and 35 µg/m3 (risk difference [RD] = -3.23 % and - 4.06 %) and would increase when PM2.5 concentration were elevated to between 50 and 75 µg/m3 (RD = 3.59 % and 5.04 %). The mortality risk would increase when CD4 concentration were reduced to <200 counts/µl (RD = 15.90 % and 20.27 %) and would decrease when CD4 concentration were ≥ 200 counts/µl, especially to between 800 and 1100 counts/µl (RD = -9.01 % and - 11.75 %). The elevated concentration of PM2.5 may disproportionately affect individuals with immune deficiency, especially those with more severity. The findings would serve as justifications for future intervention design and policy making to alleviate air pollution and improve environmental justice and health equity.

Electrospun nanofibers applications in caries lesions: prevention, treatment and regeneration.

Dental caries is a multifactorial disease primarily mediated by biofilm formation, resulting in a net loss of mineral content and degradation of organic matrix in dental hard tissues. Caries lesions of varying depths can result in demineralization of the superficial enamel, the formation of deep cavities extending into the dentin, and even pulp infection. Electrospun nanofibers (ESNs) exhibit an expansive specific surface area and a porous structure, closely mimicking the unique architecture of the natural extracellular matrix (ECM). This unique topography caters to the transport of small molecules and facilitates localized therapeutic drug delivery, offering great potential in regulating cell behavior, and thereby attracting interest in ESNs' applications in the treatment of caries lesions and the reconditioning of the affected dental tissues. Thus, this review aims to consolidate the recent developments in ESNs' applications for caries lesions. This review begins with an introduction to the electrospinning technique and provides a comprehensive overview of the biological properties and modification methods of ESNs, followed by an introduction outlining the basic pathological processes, classification and treatment requirements of caries lesions. Finally, the review offers a detailed examination of the research progress on the ESNs' application in caries lesions and concludes by addressing the limitations.

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

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

Novel biomimetic peptide-loaded chitosan nanoparticles improve dentin bonding via promoting dentin remineralization and inhibiting endogenous matrix metalloproteinases.

OBJECTIVE: This study aims to synthesize novel chitosan nanoparticles loaded with an amelogenin-derived peptide QP5 (TMC-QP5/NPs), investigate their remineralization capability and inhibitory effects on endogenous matrix metalloproteinases (MMPs), and evaluate the dentin bonding properties of remineralized dentin regulated by TMC-QP5/NPs. METHODS: TMC-QP5/NPs were prepared by ionic crosslinking method and characterized by dynamic light scattering method, scanning electron microscopy, transmission electron microscope, atomic force microscope, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The encapsulation and loading efficiency of TMC-QP5/NPs and the release of QP5 were examined. To evaluate the remineralization capability of TMC-QP5/NPs, the mechanical properties, and the changes in structure and composition of differently conditioned dentin were characterized. The MMPs inhibitory effects of TMC-QP5/NPs were explored by MMP Activity Assay and in-situ zymography. The dentin bonding performance was detected by interfacial microleakage and microshear bond strength (µSBS). RESULTS: TMC-QP5/NPs were successfully synthesized, with uniform size, good stability and biosafety. The encapsulation and loading efficiency of TMC-QP5/NPs was respectively 69.63 ± 2.22% and 13.21 ± 0.73%, with a sustained release of QP5. TMC-QP5/NPs could induce mineral deposits on demineralized collagen fibers and partial occlusion of dentin tubules, and recover the surface microhardness of dentin, showing better remineralization effects than QP5. Besides, TMC-QP5/NPs significantly inhibited the endogenous MMPs activity. The remineralized dentin induced by TMC-QP5/NPs exhibited less interfacial microleakage and higher µSBS, greatly improved dentin bonding. SIGNIFICANCE: This novel peptide-loaded chitosan nanoparticles improved resin-dentin bonding by promoting dentin remineralization and inactivating MMPs, suggesting a promising strategy for optimizing dentin adhesive restorations.

3D-printed coloured tooth model for inlay preparation in pre-clinical dental education.

INTRODUCTION: Accurate inlay preparation is extremely important in pre-clinical training. However, there is a lack of tools to guide students to efficiently practise inlay preparation. Therefore, a 3D-printed coloured tooth model for inlay preparation was designed to guide beginners to practise inlay preparation by themselves according to different colour prompts. This study aimed to evaluate the benefits of using a 3D-printed coloured tooth model in the pre-clinical training on inlay preparation. MATERIALS AND METHODS: Twenty-eight students in their fourth-year undergraduate dental program participated in this study. The participants were randomly assigned to two groups for the inlay preparation. Group 1 prepared a plain tooth model for the first and fourth attempts and a 3D-printed coloured tooth model for the second and third attempts (n = 14). Group 2 prepared four plain tooth models (n = 14). The first and fourth tooth models prepared by both groups were scored using an evaluation system (Fair Grade 2000, NISSIN). Next, questionnaires answered by students were used to evaluate the benefits of using a 3D-printed coloured tooth model and self-evaluate hands-on ability using a grading system (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). The scores were evaluated statistically using the Mann-Whitney U test, and the given grades are displayed as percentages and mean values. RESULTS: There was an overall increase in the clinical confidence of all students after repeated attempts to prepare an inlay; however, students from group 1, who had used the 3D-printed coloured tooth model, had more positive experiences and comments. The 3D-printed coloured tooth model for inlay preparation has been widely praised by participants. Comparing the average score of the first and fourth preparations, the average score of group 1 increased by 12% (Ø 54.46 ± 8.33, Ø 61.11 ± 7.13, p = .090), while that of group 2 increased by 0.72% (Ø 56.39 ± 9.59, Ø 56.80 ± 8.46, p = .925). CONCLUSION: Students favoured the use of the 3D-printed coloured tooth model, and this improved the average score for inlay preparation. The 3D-printed coloured tooth model for inlay preparation is expected to play an important role in dental education in the future.

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

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

Encapsulation of a novel peptide derived from histatin-1 in liposomes against initial enamel caries in vitro and in vivo.

OBJECTIVES: Biomimetic mineralization mediated by proteins and peptides is a promising strategy for enamel repair, and its specific application model needs more research. In this work, we exploited a liposomal delivery system for a novel peptide (DK5) derived from histatin-1 (DK5-Lips) as a new biomimetic mineralization strategy against initial enamel caries. MATERIALS AND METHODS: The DK5-Lips was prepared using calcium acetate gradient method and then the in vitro release, salivary stability, and cytotoxicity were studied. Initial enamel caries was created in bovine enamel blocks and subjected to pH-cycling model treated with DK5-Lips. Surface microhardness testing, polarized light microscopy (PLM), and transverse microradiography (TMR) were analyzed. Then the biocompatibility of DK5-Lips was evaluated in the caries model of Sprague-Dawley rats, and the anti-caries effect was assessed using Micro-CT analysis, Keyes scores, and PLM in vivo. RESULTS: DK5-Lips provided a mean particle size of (97.63 ± 4.94)nm and encapsulation efficiency of (61.46 ± 1.44)%, exhibiting a sustained release profile, excellent stability in saliva, and no significant toxicity on human gingival fibroblasts (HGFs). The DK5-Lips group had higher surface microhardness recovery, shallower caries depth, and less mineral loss in bovine enamel. Animal experiments showed higher volume and density values of residual molar enamel, lower Keyes score, and shallower lesion depth of the DK5-Lips group with good biocompatibility. CONCLUSION: As a safe and effective application model, DK5-Lips could significantly promote the remineralization of initial enamel caries both in vitro and in vivo. CLINICAL RELEVANCE: The potential of liposome utilization as vehicle for oral delivery of functional peptides may provide a new way for enamel restoration.

Unveiling the mechanism of an amelogenin-derived peptide in promoting enamel biomimetic remineralization.

Amelogenin and its derived peptides have exhibited excellent efficacy in promoting enamel biomimetic remineralization. However, little is known about their specific action mechanisms. Herein, by combining experiments and computer simulation, the mechanism of an amelogenin-derived peptide QP5 in regulating enamel biomimetic remineralization is unveiled for the first time. In experiments, peptide QP5 was separated into (QPX)5 and C-tail domains, the interactions of peptide-minerals in nucleation solution and the regulation of peptide on enamel biomimetic remineralization were explored. QP5 exhibited an unordered conformation when mineral ions existed, and it could adsorb on minerals through its two domains, thereby inhibiting spontaneous nucleation. The remineralized enamel regulated by C-tail showed better mechanical properties and formed more biomimetic crystals than that of (QPX)5, indicating the C-tail domain of QP5 played an important role in forming enamel-like crystals. The simulation results showed that the conformation of QP5 changed greatly, mainly exhibiting ß-bend, ß-turn, and coil structures, and it eventually adsorbed on enamel through negatively charged residues of the C-tail domain, then captured Ca2+ from solution to promote enamel remineralization. This study improved the evaluation methods of the mechanism of biomimetic peptides, and laid a theoretical basis for the amelioration and clinical transformation of peptide QP5.

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

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

Construction and application of dental virtual reality simulation teaching system in China: Necessity and strategies.

INTRODUCTION: Following worldwide progress in digital technology, the utilization of advanced technology to update the concept and mode of education has become an important way to improve the quality and scale of talent training. Adoption of virtual reality technology has a positive effect on dental education. Virtual reality technology has been introduced into Chinese dental education nearly 10 years ago, and a holistic teaching system that employs virtual simulation technology to assist instructors in teaching and students in learning has gradually been formed. MATERIALS AND METHODS: Based on the work of the West China School of Stomatology, Sichuan University, we introduced the necessity and advantages of the application of virtual simulation technology in talent training in dentistry and the status of this teaching system. RESULTS: A virtual dental simulation teaching system was constructed and applied in China. Virtual reality technology was incorporated into the four elements of the teaching system. This reformed system carried out educational informatization in terms of the construction of a virtual simulation teaching platform, development of virtual simulation teaching resources, improvement of the student training model, and upgrading of teaching management. CONCLUSION: The holistic teaching system implemented at the West China School of Stomatology, Sichuan University, highlights the successful incorporation of virtual reality technology into various aspects of dental education. The construction of this system reflects the deep integration of modern information technology and dental education, with the aim of helping dental educators promote teaching methods and management model in the future.

Green Tea-Derived Catechins Suppress the Acid Productions of Streptococcus mutans and Enhance the Efficiency of Fluoride.

Green tea-derived catechins, which can be divided into galloylated (epicatechin gallate: ECG, epigallocatechin gallate: EGCG) and non-galloylated (catechin: C, epicatechin: EC, epigallocatechin: EGC) catechins, are considered to be the main contributors to the caries control potential of green tea. In this study, we intended to compare the antimicrobial effects of these representative green tea-derived catechins and their combined effects with fluoride on the acid production and aggregation of Streptococcus mutans. The effects of different catechins on the growth, aggregation and acid production of S. mutans, and the combined effect of catechins and potassium fluoride (2 mm at pH 7.0, 0.3 mm at pH 5.5) on S. mutans acid production were measured by anaerobic culture, turbidity changes due to aggregation, and pH-stat methods. Molecular docking simulations were also performed to investigate the interactions between catechins and membrane-embedded enzyme II complex (EIIC), a component of the phosphoenolpyruvate-dependent phosphotransferase system (sugar uptake-related enzyme). ECG or EGCG at 1 mg/mL significantly inhibited the growth of S. mutans, induced bacterial aggregation, and decreased glucose-induced acid production (p < 0.05). All catechins were able to bind to EIIC in silico, in the following order of affinity: EGCG, ECG, EGC, EC, and C. Furthermore, they enhanced the inhibitory effects of fluoride at pH 5.5 and significantly inhibited S. mutans acid production by 47.5-86.6% (p < 0.05). These results suggest that both galloylated and non-galloylated catechins exhibit antimicrobial activity, although the former type demonstrates stronger activity, and that the caries control effects of green tea may be due to the combined effects of multiple components, such as catechins and fluoride. The detailed mechanisms underlying these phenomena and the in vivo effect need to be explored further.

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

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

Impact of multi-source data augmentation on performance of convolutional neural networks for abnormality classification in mammography.

Introduction: To date, most mammography-related AI models have been trained using either film or digital mammogram datasets with little overlap. We investigated whether or not combining film and digital mammography during training will help or hinder modern models designed for use on digital mammograms. Methods: To this end, a total of six binary classifiers were trained for comparison. The first three classifiers were trained using images only from Emory Breast Imaging Dataset (EMBED) using ResNet50, ResNet101, and ResNet152 architectures. The next three classifiers were trained using images from EMBED, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), and Digital Database for Screening Mammography (DDSM) datasets. All six models were tested only on digital mammograms from EMBED. Results: The results showed that performance degradation to the customized ResNet models was statistically significant overall when EMBED dataset was augmented with CBIS-DDSM/DDSM. While the performance degradation was observed in all racial subgroups, some races are subject to more severe performance drop as compared to other races. Discussion: The degradation may potentially be due to ( 1) a mismatch in features between film-based and digital mammograms ( 2) a mismatch in pathologic and radiological information. In conclusion, use of both film and digital mammography during training may hinder modern models designed for breast cancer screening. Caution is required when combining film-based and digital mammograms or when utilizing pathologic and radiological information simultaneously.

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

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

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

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