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Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection.

Background: Perianal Paget disease (PPD), an uncommon extramammary Paget disease, is characterized by intraepidermal pagetoid spread of atypical Paget cells in the perianal skin. PPDs can be primary or secondary. Secondary PPDs have poorer prognosis due to progression of the underlying anorectal carcinoma. Objectives: We analyzed the clinicopathological features of PPDs to determine the primary versus secondary PPD. Methods: We reviewed the clinicopathological features, including evidence of underlying anorectal carcinomas, tumor immunoprofiles, treatments, and outcomes of 8 cases of PPD diagnosed in our department during 1992–2019. Results: Colonoscopy was performed in 6 cases; rectal adenocarcinoma and anal canal adenocarcinoma were detected in 2 cases each. Three patients had local recurrence(s). Based on the detection of underlying anorectal cancers and immunoprofiles, 2 cases were classified as primary (one with perianal squamous cell carcinoma), 4 secondary, and 2 inconclusive for primary or secondary PPD. The immunoprofiles were CK7(+)/CK20(−)/GCDFP-15(−)/CDX2(−) in the primary PPDs; CK7(+/−)/CK20(+)/GCDFP-15(−)/CDX2(+) in the secondary and inconclusive PPDs. Eventually, all patients with secondary PPD died of the disease; one primary PPD and one inclusive PPD cases died of unrelated causes. Conclusion: We report the clinicopathological features of 8 cases of PPD in Taiwanese and first describe differential CK7 expression in the epidermal and dermal tumor cells in 2 cases of secondary PPDs, which may provide a clue to the diagnosis of secondary PPD. Since an underlying anorectal carcinoma in PPDs may be undetectable by colonoscopy, it is essential to consider anoscopy and/or anal canal mucosal biopsy to search for an occult anorectal carcinoma.

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 “FLASH” randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided.

Abstract. Rationale:. Although single-cytokine inhibitors can be considered in treating severe or refractory Behçet disease (BD), these biologic agents are associated with potential therapeutic failure due to the multi-cytokine pathogenesis involving Th1- and Th17-type cytokines with activated Janus kinase/signal transducer and activator of transcription signaling pathways. Notably, there is an increasing trend toward the use of small-molecule targeted drug tofacitinib (TOF), a pan-Janus kinase inhibitor, with immediate-release formulations for treating patients with severe or refractory systemic vasculitis involving different vessel sizes. Despite no reported efficacy of extended-release formulations in refractory BD yet, such a dosage form has pharmacokinetic parameters that are comparable to those of conventional immediate-release formulations. Patient concerns and diagnosis:. We report the case of a 27-year-old local woman with recurrent manifestations of arthritis, orogential ulcerations, papulopustular lesions, and anterior uveitis. She was diagnosed with BD for more than 3 years, and received long-term corticosteroids plus immunosuppressants therapy with the complication of opportunistic candidiasis infection. Interventions and outcomes:. Under extended-release TOF 11 mg once-daily therapy, the patient achieved disease remission while sparing the use of corticosteroids during follow-up. Lessons:. Our clinical observations implicate the oral convenience and therapeutic efficacy of extended-release TOF formulations in controlling the disease activity of BD.

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

There are limited studies regarding childhood and adolescent psoriasis in Taiwan. A total of 86 pathologically confirmed cases diagnosed from 1989 to 2017 were retrospectively reviewed. Mean disease onset age was 10.51 years, and plaque psoriasis was the most common type. Compared to studies on Caucasian and other Asian populations, we found a lower estimated prevalence, higher rate of psoriasis limited to the nail at presentation, and higher prevalence of psoriatic arthritis. The most common comorbidities were related to atopy and metabolic syndrome. Positive family history of psoriasis and psoriasis preceded by infection were significantly associated with moderate-to-severe disease.

Background/Objectives: Plaque psoriasis is a debilitating condition that significantly affects patient well-being. Limited data are available regarding the effect of psoriasis and treatment on health-related quality of life (HRQoL) and work ability among Taiwanese patients.To document and compare HRQoL, treatment satisfaction, and work disability among Taiwanese patients with current and past moderate-to-severe plaque psoriasis. Methods: This was a multicenter, non-interventional, cross-sectional study of adult patients with moderate-to-severe plaque psoriasis. During a single clinic visit, each patient was assessed for body surface area (BSA) involvement, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), Euro Quality of Life-5 Dimensions (EQ-5D), 10-level satisfaction scale for psoriasis treatment, and Working Productivity and Activity Impairment (WPAI). Multivariate regression was used to identify factors associated with HRQoL and work disability. Results: A total of 305 patients were included within the analysis. The mean PASI score was 11.83, and the mean BSA involvement was 20.90%. The mean EQ-5D score was 65.68 and the mean DLQI score was 12.55. Fewer than half of patients (45.68%) indicated they were satisfied with the standard therapy they were currently receiving. Among employed patients, the mean reduction in on-the-job effectiveness was 32.09% and the mean reduction in overall productivity was 33.48%. The regression analysis indicated that patients with more severe psoriasis defined by PASI scores show a greater impact in quality of life and impairment in work disability; and that patients who were satisfied with current standard treatment had a better quality of life. Conclusion: The effect of psoriasis on HRQoL among patients with psoriasis in Taiwan is substantial, with fewer than half of patients reporting satisfaction with therapeutic options. Keywords: DLQI, EQ-5D, Health-related quality of life, Psoriasis, WPAI

BackgroundReal-world clinical data on psoriasis patients receiving different biological agents is needed, especially in Asian populations.ObjectivesOur aim is to compare and analyze the efficacy and safety profile of four biological agents (etanercept, adalimumab, ustekinumab and secukinumab) in a real-world setting in Taiwan.MethodsWe retrospectively analyzed the clinical data of all patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥ 10) who received etanercept, adalimumab, ustekinumab or secukinumab between January 2011 and December 2018 in a tertiary hospital in Taiwan.ResultsA total of 119 treatment episodes in 75 patients were included in this study. Ustekinumab was used in 49 treatment episodes, followed by secukinumab in 46 treatment episodes, adalimumab in 14 treatment episodes and etanercept in 10 treatment episodes. The proportion of the biologic-naïve was highest in etanercept (100%) and lowest in secukinumab (23.9%). The PASI-75, -90 and -100 were the highest in secukinumab (91.3%, 82.6%, 41.3%, respectively), followed by ustekinumab (79.6%, 44.9%, 16.3%), adalimumab (64.3%, 28.6%, 7.1%) and etanercept (50.0%, 30.0%, 0%). The rate of adverse events that required treatment was highest for secukinumab (15.2%), followed by adalimumab (14.3%), ustekinumab (8.2%), and etanercept (0%), including 4 cases of infections, 2 cases of cardiovascular diseases and 4 cases of cancers.ConclusionsThis real world data showed differential efficacy and safety of the four biological agents.

Background: Antimicrobial photodynamic therapy (APDT) has become a potential regimen to treat multidrug-resistant bacterial infections. Limited data showed indocyanine green (ICG), a safe and inexpensive contrast medium for eye angiography and hepatic function examination, is an effective photosensitizer in APDT to kill methicillin-resistant Staphylococcus aureus (MRSA) after excitation with laser. Objective: We investigated the potentials of ICG-APDT with an inexpensive, non-coherent commercial near infrared (NIR) lamp against MRSA. Methods: The inhibition of MRSA was studied after exposing bacteria to NIR with different light doses and concentrations of ICG. The selectivity on MRSA was examined on human fibroblasts. Bacterial virulence including the activities of coagulase and enterotoxin was investigated. The effects of singlet oxygen scavengers (tryptophan and ascorbic acid) and H2O2 on cell survival were evaluated. The morphology of bacteria after PDT was observed by transmission electron microscopy. Results: ICG-PDT inhibited the growth of bacteria by 5 log (99.999% inhibition) with 200 J/cm2 at 65.5 mW/cm2 in the presence of 100 μg/mL ICG. Adding 0.1% H2O2 at a lower PDT dose (25 μg/mL ICG and 100 J/cm2) increased its efficacy by 5 log. This PDT dose was not toxic to human fibroblasts. PDT significantly reduced the level of bacterial virulence factors. The inhibition effects were decreased by tryptophan and ascorbic acid suggested singlet oxygen involved in the process. TEM showed severe non-selective cell destruction immediately after irradiation. Conclusion: The study reveals ICG-PDT has the potential to treat MRSA by using a clinical accessible NIR lamp and photosensitizer.

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.

The delayed healing response of diabetic wounds is a major challenge for treatment. Negative pressure wound therapy (NPWT) has been widely used to treat chronic wounds. However, it usually requires a long treatment time and results in directional growth of wound healing skin tissue. We investigated whether nonthermal microplasma (MP) treatment can promote the healing of skin wounds in diabetic mice. Splint excision wounds were created on diabetic mice, and various wound healing parameters were compared among MP treatment, NPWT, and control groups. Quantitative analysis of the re-epithelialization percentage by detecting Ki67 and DSG1 expression in the extending epidermal tongue (EET) of the wound area and the epidermal proliferation index (EPI) was subsequently performed. Both treatments promoted wound healing by enhancing wound closure kinetics and wound bed blood flow; this was confirmed through histological analysis and optical coherence tomography. Both treatments also increased Ki67 and DSG1 expression in the EET of the wound area and the EPI to enhance re-epithelialization. Increased Smad2/3/4 mRNA expression was observed in the epidermis layer of wounds, particularly after MP treatment. The results suggest that the Smad-dependent transforming growth factor β signaling contributes to the enhancement of re-epithelialization after MP treatment with an appropriate exposure time. Overall, a short-term MP treatment (applied for 30 s twice a day) demonstrated comparable or better efficacy to conventional NPWT (applied for 4 h once a day) in promoting wound healing in diabetic mice. Thus, MP treatment exhibits promise for treating diabetic wounds clinically.

Background: Effective management of psoriasis is a cause for much concern. In Taiwan, there is a lack of consensus on management strategies for psoriasis, especially the principles of drug prescribing in psoriatic patients. Objectives: The Taiwanese Dermatological Association convened Expert Panel meetings three times between 2012 and 2015 to discuss the management strategies for treatment of psoriasis in order to fill the knowledge gap and provide a reference tool for Taiwanese dermatologists. Results: This paper reports the final output from the three meetings, with the aim of aiding clinical decision making in terms of principles of prescribing, including dosing strategies, efficacy profiles, and safety concerns in connection with eight categories of antipsoriatic treatment: topical agents, phototherapy, nonbiologic conventional systemic agents, licensed biologic systemic agents, newly emerging therapies, combination therapy, transitional therapy, and traditional Chinese medicine. Conclusion: The Expert Panel, comprising distinguished Taiwanese dermatologists, succeeded in developing a consensus about the management of psoriasis in Taiwanese patients. Unavailability of data in certain areas may suggest a possibility of new directions in research.

Photodynamic therapy (PDT) works through photoactivation of a specific photosensitizer (PS) in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with other treatments, and can be repeated as needed. A large amount of reactive oxygen species (ROS) and singlet oxygen is generated in a cancer cell during PDT, which destroys the tumor effectively. However, the efficacy of PDT in treating a deep-seated tumor is limited due to three main reasons: Limited light penetration depth, low oxygen concentration in the hypoxic core, and poor PS accumulation inside a tumor. Thus, PDT treatments are only approved for superficial and thin tumors. With the advancement of nanotechnology, PDT to treat deep-seated or thick tumors is becoming a reachable goal. In this review, we provide an update on the strategies for improving PDT with nanomedicine using different sophisticated-design nanoparticles, including two-photon excitation, X-ray activation, targeting tumor cells with surface modification, alteration of tumor cell metabolism pathways, release of therapeutic gases, improvement of tumor hypoxia, and stimulation of host immunity. We focus on the difficult-to-treat pancreatic cancer as a model to demonstrate the influence of advanced nanomedicine in PDT. A bright future of PDT application in the treatment of deep-seated tumors is expected.

Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves.

Background/Objectives: Recently, fibrotic diseases such as hypertrophic scar, keloid, and scleroderma have been treated with UV-A1 radiation with encouraging results. However, conventional UV light sources are bulky and expensive. In this study, we aimed to verify the effectiveness of a portable UV-A1 radiation device in treating hypertrophic scars. Materials and methods: A light-emitting diode array that emitted 365 ± 5 nm (UV-A1) was used to irradiate fibroblasts and hypertrophic scar in a rabbit model. Results: In cell cultures, UV-A1 light exposure inhibited post-wound cell migration and reduced the total amount of soluble collagen production in fibroblasts. Type I collagenase production and its activity increased after treatment. On the rabbit ear, UV-A1 light irradiation reduced the thickness of hypertrophic scars, confirming the antifibrotic effect in vivo. Conclusion: These results support the potential of a portable UV-A1 light device in treating hypertrophic scar.

Secondary intention healing on concave areas of the face may provide acceptable cosmetic outcome after tumor excision but is underused. We evaluated cosmetic outcome and tumor recurrence of this technique in 10 patients with nodular basal cell carcinoma and one patient with basosquamous carcinoma on the face. The average size of these tumors was 1 cm. Subjective evaluations included patients' satisfaction on the degree of wound pain, ease of wound care, and satisfaction with cosmetic outcome. Objective evaluations included physician's scoring on the time to complete wound healing, wound infection, cosmetic outcome, and tumor recurrence after operation. The operations were completed in 30 minutes on average. All wounds healed well without infection within 4 weeks. Postoperation wound pain was absent to mild. Wound care was neither difficult nor troublesome. All patients were satisfied with the cosmetic outcome. Physicians scored good or excellent cosmetic outcome in 91% of patients. No tumor recurred during 3–60 months (median, 13 months) of follow-up. Secondary intention healing appears to be a good option after excision of nodular basal cell carcinomas located on concave areas of the face. Good to excellent cosmetic results can be expected after wound healing.

Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro-plasma has potential to be used to promote the healing of skin wounds clinically.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor involving the dermis and subcutaneous tissue with a high local recurrence rate after standard excision. Mohs micrographic surgery offers a lower recurrence rate. However, the procedure requires multiple stages of excision with intraoperative histopathological mapping, which is time consuming and expensive. We report our experience of using circumferential scouting punch biopsy technique in five patients to determine in advance the resection margins for DFSP prior to wide excision. Multiple 4 mm punches, usually eight in number, were performed 1–2.5 cm around the palpable borders of DFSP to delineate the resection margins in five consecutive patients. Tumors were excised at a later date along the margin defined by these biopsies and the wounds were repaired with skin graft. The operation was completed in 2 hours in all cases excluding one that required frozen sections for deep margin. No recurrence was noted 2–10 years after the operations. The results suggest that circumferential scouting punch biopsies before wide excision may be an alternative method to define the resection margins for DFSP when Mohs surgery is not available.

In situ photoimmunotherapy (ISPI) can be a treatment option for selected cutaneous malignancies in patients who are not surgical candidates. We herein report the case of a large, ulcerating poorly differentiated squamous cell carcinoma (SCC) affecting the foot of an elderly woman with chronic arsenicosis. The tumor failed radiotherapy, intralesional methotrexate, and 5-aminolevulinic acid photodynamic therapy (PDT). Because the patient was reluctant to undergo amputation, the recurrent tumor was treated with ISPI using topical imiquimod application followed by PDT. Despite some initial improvement in the superficial part of the tumor, tumor invasion to the underlying bone was detected. This case illustrates the lack of efficacy of ISIP in treating a high-risk invasive SCC.

Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. In particular, the detection of a superoxide anion radical (O2•−), a reactive oxygen species (ROS), and the inactivation of Acinetobacter baumannii (A. baumannii)—including a carbapenem-resistant A. baumannii (CRAB)—was investigated during the photoreaction of catechin hydrate. Following basification with blue light irradiation, the transparent solution of catechin hydrate turned yellowish, and a chromogenic catechin dimer was separated and identified as a proanthocyanidin. Adding ascorbic acid during the photolytic treatment of catechin hydrate decreased the dimer formation, suggesting that ascorbic acid can suppress the photosensitive oxidation of catechin. When catechin hydrate was irradiated by blue light in an alkaline solution, O2•− was produced via photosensitized oxidation, enhancing the inactivation of A. baumannii and CRAB. The present findings on the photon-induced oxidation of catechin hydrate provides a safe practice for the inactivation of environmental microorganisms.

ABSTRACT: Photodynamic therapy (PDT) is an evolving cancer treatment with promising results in treating malignant tumors by photoactivation of a photosensitizer with a specific wavelength. The second generation photosensitizer mono-L-aspartyl chlorin e6 (NPe6) was reported to have significant efficacy in killing cancer cells in vitro and in vivo. Though topical application might yield a higher local concentration and less systemic side effect, no data concerning topical absorption of NPe6 is available even though the drug has already been used in clinical trial for several years. To evaluate the possibility of topical delivery of NPe6 via an animal model, escalated concentrations of NPe6 were applied to BALB/c mouse skin for a different time periods after barrier disruption with tape stripping. Since NPe6 fluorescence intensity and drug concentration in tissue was well correlated, we evaluated drug penetration depth with frozen sections of treated and non-treated skin under a fluorescence microscope. An on-line fluorescence imaging system was used to monitor the NPe6 fluorescence kinetics in the skin. The fluorescence microscope confirmed successful topical delivery of NPe6 in mouse skin with or even without barrier disruption. Orange to red NPe6 fluorescence appeared at the epidermis, dermis, and even the muscular layer when using 10 mg/ml NPe6 application. The fluorescence intensity peaked at 1 h and revealed a dose-dependent response pattern. NPe6 treated versus non-treated skin showed a statistically significant difference by Student’s t-test (P