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BACKGROUND Oral tranexamic acid (TA) has been an effective treatment for melasma with unclear mechanism. OBJECTIVE The present study aimed to demonstrate the effect of TA on melanogenesis via regulation of TGF-β1 expression in keratinocytes. METHODS We firstly determined the expression level of TGF-β1 in TA-treated keratinocyte-conditioned medium (KCM). Then the mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein-1 (TRP-1) of human epidermal melanocytes (NHEMs) in presence of TA-treated KCM were evaluated via RT-PCR and Western blot analysis. Moreover, melanin content and tyrosinase activity were quantified. TGF-β1 gene was knocked down by small interfering RNA (siRNA) in keratinocytes. RESULTS The mRNA and protein levels of TGF-β1 in keratinocytes were significantly increased after TA treatment. Melanin contents, tyrosinase activity, protein and mRNA levels of TYR, MITF, and TRP-1 were downregulated in NHEMs in the presence of TA-treated KCM. Knockdown of TGF-β1 in keratinocytes could attenuate the inhibitory effect of TA-treated KCM on melanogenesis. CONCLUSION TA could stimulate TGF-β1 expression in keratinocytes, which further inhibits melanogenesis through the paracrine signaling.

Ziqi Jiang,* Shanglin Jin,* Xiaoyao Fan, Ke Cao, Ye Liu, Xuan Wang, Ying Ma, Leihong Xiang Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Leihong Xiang; Ying Ma, Department of Dermatology, Huashan Hospital, Fudan University, No. 12 Wulumuqizhong Road, Shanghai, 200040, People’s Republic of China, Tel: +86 21 52889999, Fax: +86 21 62489191, Email flora_xiang@vip.163.com; alle_ma@163.comBackground: Acne is a common inflammatory skin disease, while cannabidiol (CBD) is a representative non-psychoactive phytocannabinoid which has been proved to exert universal anti-inflammatory properties. This study aimed to explore the effect of CBD on acne inflammation induced by Cutibacterium acnes-derived extracellular vesicles (CEVs) in keratinocytes and reveal the underlying mechanisms.Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated by CEVs in the presence of CBD or vehicle. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels were examined by RT-PCR and ELISA. The expression of cannabinoid type-2 (CB2) receptor and transient receptor potential vanilloid type-1 (TRPV1) was detected by Western blotting. TNF-α levels in the presence of CB2 receptor antagonist (AM630) or TRPV1 antagonist (Capsazepine) were detected by RT-PCR. The activation of MAPK and NF-κB signaling pathways and the nuclear translocation of NF-κB p65 upon CBD treatment were analyzed by Western blotting and immunofluorescence assay, respectively.Results: The expression of inflammatory cytokines (IL-6, IL-8 and TNF-α) in CEVs-stimulated NHEKs was suppressed by CBD. CB2 receptor expression was upregulated by CBD, whereas CEVs-promoted TRPV1 expression was downregulated by CBD. AM630 reversed TNF-α levels inhibited by CBD. Capsazepine exerted an inhibitory effect on CEVs-induced inflammation and had synergistic effect with CBD. The phosphorylation of ERK1/2 and NF-κB p65 and nuclear translocation of NF-κB p65 were induced by CEVs but reduced by CBD.Conclusion: The results indicated that CBD could inhibit inflammation induced by CEVs in NHEKs, which was mediated by activation of CB2 receptor and enhanced by the TRPV1 antagonist, through inactivation of the MAPK and NF-κB signaling pathways. CBD might be a potential novel strategy for acne treatment in the future.Keywords: cannabidiol, acne, inflammation, Cutibacterium acnes, keratinocytes

Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

Background Robust evidence regarding the efficacy of topical tranexamic acid (TA) on melasma in Chinese population is lacking. Objective To evaluate the efficacy and safety of 1.8% liposomal TA and microneedling with 5% TA solution on melasma. Methods Sixty melasma patients were enrolled and randomized to receive 1.8% liposomal TA twice daily, microneedling with 5% TA solution weekly or 2% hydroquinone every night. Objective and subjective assessments were obtained at baseline, 4, 8 and 12 weeks. Results 27.8% of patients of liposomal TA group, 33.3% of microneedling with TA solution group and 30.0% of hydroquinone group were recognized as "more than 50% improvement". At the endpoint, the melanin index (MI) in all treatment groups were significantly decreased, while the improvement of MI in microneedling with TA solution group and hydroquinone group is higher than liposomal TA group. The erythema index (EI) was significantly diminished in liposomal TA group and microneedling with TA solution group. Dermatoscopy and reflectance confocal microscopy revealed decreased brown granules in all groups and reduced telangiectasia in liposomal TA group and microneedling with TA solution group. Conclusion 1.8% liposomal TA and microneedling with 5% TA solution are both effective and safe on melasma.

Background 585 nm light-emitting diodes have been proven to suppress melanogenesis in melanocytes. However, whether LEDs will influence normal human epidermal keratinocytes (NHEKs) and paracrine effect of LEDs-irradiated NHEKs in melanogenesis remains unknown. Objective To elucidate the possible mechanisms in vitro of anti-melanogenic activity of 585 nm LEDs on paracrine effect of NHEKs and its exosomes. Methods NHEKs irradiated with different fluences of 585 nm LEDs were evaluated the cell viability by CCK8 assay. Irradiated medium of NHEKs was co-cultured with melanocytes. Melanin content, tyrosinase activity and melanogenic enzymes activities were detected. Exosomes from NHEKs medium were isolated and characterized by electron microscopy and nanoparticle tracking analysis. The expression changes of H19 and its encoded exosomal miR-675 were analyzed. Results Irradiation with 585 nm LEDs from 0 J/cm2 to 20 J/cm2 had no cytotoxic effect on NHEKs. After co-cultured with irradiated medium of NHEKs, melanin content and tyrosinase activity were reduced and the melanogenic activities were downregulated on both mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). H19 and its derived exosomal miR-675 from NHEKs, which has been proven relevant to melanogenesis, were significantly upregulated after irradiation. Furthermore, H19 knockdown and miR-675 inhibition in NHEKs could attenuate the inhibition effect of 585 nm LEDs on melanogenesis. Conclusions This study demonstrated that 585 nm LEDs could inhibit melanogenesis via the up-regulation of H19 and its derived exosomal miR-675 from NHEKs, which was considered as a novel paracrine factor in regulating melanogenesis.

Postinflammatory hyperpigmentation (PIH) is a common disfiguring complication following inflammatory dermatoses and cosmetic procedures in dark-skinned individuals. Anti-inflammatory and repairing agents targeting primary inflammation and injury are becoming promising choices for preventing PIH. The aim of this active-controlled, assessor-blinded, intra-individual monocentric study was to evaluate the preventive effect of a wound-dressing biomaterial, mussel adhesive protein (MAP) in the suction blister-induced PIH model. Twenty Chinese patients underwent suction blister epidermal grafting had defined wound areas to receive a topical MAP spray or a potent corticosteroid cream once daily for seven consecutive days after operation. In situ semi-quantitative evaluations of inflammation and pigmentation were achieved by Mexameter, reflectance confocal microscopy and dermoscopy on week 1, week 4, and week 12. Topical application of MAP exerted remarkably inhibitory effect on PIH comparable to fluticasone propionate, manifested as significantly lower melanin index and papillary contrast measured by Mexameter and confocal microscopy on week 12 compared to untreated sites. Although MAP exhibited moderate anti-inflammatory effect weaker than fluticasone propionate, MAP-treated sites healed faster than steroid-treated and untreated sites. The biological activity of MAP was further studied in UVB-irradiated HaCaT cell model, which revealed MAP decreased the expression of UVB-induced α-melanocyte stimulating hormone (α-MSH) and pro-inflammatory cytokines (IL-1α, IL-6, COX-2). It also protected HaCaT cells from UVB-induced cell death and apoptosis. In conclusion, MAP could be a novel postoperational wound dressing preventing PIH associated with skin inflammation and injury.

Laser is being widely used in treating pigmented lesions nowadays. Linear and whorled nevoid hypermelanosis (LWNH) is a rare pigmentary anomaly, and there are only a handful of cases of successful treatment, all with QS 532- and 755-nm laser. The objective of this study was to examine the clinical outcome of QS 694-nm ruby laser in the treatment of LWNH. We report on a 4-year-old boy presented with asymptomatic macular hyperpigmentation over the entire cheek who underwent 3 treatment sessions with QS 694-nm ruby laser. One month after the last treatment, the patient demonstrated significant improvement to the treatment area. Aside from post-procedural purpura lasting approximately 1 week, the patient experienced no serious adverse effects. No recurrence was observed during the 3-month follow-up. Given the excellent results seen in our patients, we recommended the use of QS 694-nm ruby laser as a safe and effective treatment in patients with LWNH.

Oxidative stress represents an imbalance between the generation of reactive oxygen and nitrogen species and the ability of antioxidant systems to decompose those products. Oxidative stress is implicated in the pathogenesis of hyperpigmentation, hypopigmentation, melanoma, and other skin diseases. Regulatory networks involving oxidative stress and related pathways are widely represented in hypopigmentation diseases, particularly vitiligo. However, there is no complete review into the role of oxidative stress in the pathogenesis of hyperpigmentation disorders, especially regarding associations involving oxidative stress and cellular signaling pathways. Here, we review oxidative and antioxidant systems, oxidative stress-induced signal transduction mechanisms, and effects of antioxidant drugs used in preclinical and clinical settings in hyperpigmentation disorders.

Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of pigmentation. Among various hypotheses proposed for the pathogenesis of vitiligo, oxidative stress-induced immune response that ultimately leads to melanocyte death remains most widely accepted. Oxidative stress which causes elevated levels of reactive oxygen species (ROS) can lead to dysfunction of molecules and organelles, triggering further immune response, and ultimately melanocyte death. In recent years, a variety of cell death modes have been studied, including apoptosis, autophagy and autophagic cell death, ferroptosis, and other novel modes of death, which will be discussed in this review in detail. Oxidative stress is also strongly linked to these modes of death. Under oxidative stress, ROS could induce autophagy by activating the Nrf2 antioxidant pathway of melanocytes. However, persistent stimulation of ROS might eventually lead to excessive activation of Nrf2 antioxidant pathway, which in turn will inactivate autophagy. Moreover, ferroptosis may be triggered by oxidative-related transcriptional production, including ARE, the positive feedback loop related to p62, and the reduced activity and expression of GPX4. Therefore, it is reasonable to infer that these modes of death are involved in the oxidative stress response, and that oxidative stress also acts as an initiator for various modes of death through some complex mechanisms. In this study, we aim to summarize the role of oxidative stress in vitiligo and discuss the corresponding mechanisms of interaction between various modes of cell death and oxidative stress. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of vitiligo.

Post-inflammatory hyperpigmentation (PIH) is a common acquired pigmentary disorder occurring after skin inflammation or injury. Ultraviolet B irradiation could exaggerate PIH clinically due to its effect on promoting cutaneous inflammation and melanogenesis in keratinocytes and melanocytes, respectively. Solamargine (SM), a steroidal alkaloid glycoside extracted from

Background/Aim: Hydrogen sulfide (H2S) has been found to act as a physiological intercellular messenger to regulate cell survival. In this study, we evaluated whether H2S could promote cell proliferation and melanin synthesis in human epidermal melanocytes (HEMs). Methods: Primary HEMs were cocultured with sodium hydrosulfide (NaHS, the most widely used H2S donor) or endogenously overexpressed with cystathionine-γ-lyase (CSE) gene, which is the most predominant H2S-producing enzyme. Then, cell viability, intracellular melanin content, tyrosinase (TYR) activity, and expression of microphthalmia-associated transcription factor (MITF), TYR, together with TYR-related protein 1 (TRP-1) in both transcript and protein levels, were detected. Results: We first confirmed that NaHS (10–100 μm) increased cell viability, intracellular melanin content, and TYR activity in a dose-dependent manner. Then, we found that endogenous H2S production also promoted cell proliferation, intracellular melanin content, and TYR activity. In addition, we observed the mRNA and protein expression of MITF, TYR, and TRP-1 was significantly up-regulated after NaHS treatment and CSE gene transfection. Conclusions: This study demonstrates that H2S promotes cell proliferation and melanin synthesis in HEMs, which indicates pharmacologic regulation of H2S may be potential treatment for skin disorders caused by loss of melanocytes or dysfunction of melanogenesis.

Background Post-inflammatory hyperpigmentation (PIH) reflects a dynamic process from primary injury and cutaneous inflammation to subsequent melanogenesis and hyperpigmentation, of which pathogenesis remains unclear, hindering the development of targeted therapies. Aims To observe the dynamic development of PIH; determine the starting point and peak point of the inflammatory phase and pigmentary phase; clarify the timing of anti-inflammatory and anti-pigmentary treatment. Methods Thirty healthy volunteers with Fitzpatrick skin types III-IV were enrolled and underwent suction blisters. The non-invasive evaluation of inflammation and hyperpigmentation on suction-blister sites were performed via spectrophotometry (CM2600d and SIAscope) and RCM for the following 24 weeks. Results We successfully observed suction blister-induced PIH lasting over 24 weeks. The inflammatory phase started soon after the procedure and lasted for 8-12 weeks, manifested by significantly elevated a* values and erythema index detected by spectrophotometry, as well as inflammatory infiltration and angiogenesis shown in RCM images. Meanwhile, melanogenesis was accelerated after week 3 and reached peek on week 8, manifested by significantly accumulated melanin granules and bright pigment rings in different depths under RCM, which was in parallel with elevated melanin index. The darkening skin tone in PIH actually presented a mixture of inflammatory erythema, angiogenesis and hyperpigmentation. The inflammation and pigmentation phases of PIH were not sequential but partially overlap. Conclusion The duration of suction blister induced-PIH is more than 24 weeks. The inflammatory phase partially overlaps with the pigmentary phase, and those drugs with anti-inflammatory and anti-pigmentary dual effects are potential choices.

Loss of melanocytes (MCs) is the most notable feature of vitiligo. Hence, it is critical to clarify the mechanisms of MC destruction in vitiligo. Apoptosis is most widely studied cell death pathways in vitiligo. In addition, the other two forms of cell death, conventional necrosis and autophagy seem to be involved in the death of vitiligo MCs under certain situations. Moreover, new types of regulated cell death including necroptosis, pyroptosis, and ferroptosis may also participate in the pathogenesis of vitiligo. Anoikis is likely to be connected with the death of detached MCs, which is provoked specifically by loss of anchorage. Primary phagocytosis, later called phagoptosis can execute death of viable cells, probably partly responsible for the loss of MCs in vitiligo. In this review, we aim to summarize the latest insights into various forms of MC death in vitiligo and discuss the corresponding mechanisms.

Autophagy is a process involving the self-digestion of components that participates in anti-oxidative stress responses and protects cells against oxidative damage. However, the role of autophagy in the anti-oxidative stress responses of melanocytes remains unclear. To investigate the role of autophagy in human epidermal melanocytes, we knocked down and overexpressed ATG7, the critical gene of autophagy, in normal human epidermal melanocytes. We demonstrated that ATG7-dependent autophagy could affect melanin content of melanocytes by regulating melanogenesis. Moreover, suppression of ATG7-dependent autophagy inhibits proliferation and promotes oxidative stress-induced apoptosis of melanocytes, whereas enhancement of ATG7-dependent autophagy protects melanocytes from oxidative stress-induced apoptosis. Meanwhile, deficiency of ATG7-dependent autophagy results in premature senescence of melanocytes under oxidative stress. Notably, we verified that ATG7-dependent autophagy could alter oxidative stress homeostasis by regulating reactive oxygen species (ROS) production, nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, and the activity of several antioxidant enzymes in melanocytes. In conclusion, our study suggested that ATG7-dependent autophagy is indispensable for redox homeostasis and the biological functions of melanocytes, such as melanogenesis, proliferation, apoptosis, and senescence, especially under oxidative stress.

Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand‐cleaning‐ and medical‐glove‐related hand protection, mask‐ and goggles‐related face protection, UV‐related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.

Background Fractional radiofrequency (FRF) has been widely used in skin rejuvenation. To explore optimal settings, it is important to compare different treatment parameters. Objective This study was designed to compare the effect of moderate-energy and high-energy FRF treatment on a hairless mice model. Methods Fifteen photoaged hairless mice were assigned to 3 groups: control, moderate energy, and high energy. Two treatment sessions (T × 1 and T × 2) were performed at 1-month interval. Transepidermal water loss was measured at baseline, immediately, 1, 2, and 4 weeks after T × 1. Skin samples were harvested before each treatment, 1 and 2 months after T × 2. Neocollagenesis was evaluated by hematoxylin and eosin staining, Masson staining, and immunohistochemistry analysis. Results Transepidermal water loss of high-energy group was significantly higher than the moderate-energy group (p = .008) immediately after T × 1. Remarkable fibroblast proliferation was observed at 1 month after T × 1, followed by significant dermal thickening, and increase of Type I collagen and Type III collagen. There was no significant difference between 2 energy groups in fibroblast proliferation, dermal thickness, and collagen density. Conclusion The effect of moderate-energy treatment was comparable with that of high energy in neocollagenesis, whereas moderate energy yielded less damage to skin barrier function.

Background Melasma is a common hyperpigmentation skin disease on face. Light-emitting diode (LED) photomodulation (585 nm) is reported to be effective for the treatment of melasma. However, whether and how LED photomodulation would influence melanogenesis of human epidermal melanocytes (HEMs) is unknown. Objective To evaluate the effects of LED photomodulation (585 nm) on melanogenesis in HEMs. Methods HEMs were irradiated with fluences of 0, 5, 10 and 20 J/cm2 585 nm LED light. After 5-day treatment, cell viability was analyzed by CCK-8 assay, and apoptosis was assessed by Annexin V APC assay. Melanin content and tyrosinase activity were measured by spectrophotometer. Melanosome stage and autophagosomes were determined under transmission electron microscope (TEM). The formation of autophagic punctate structures was observed under confocal microscope. RT-PCR and western blotting were used to assess the expression of relative mRNA and protein levels. Results Yellow light LED 585 nm had no effects on HEMs cell viability and apoptosis. Treatment with LED 585 nm from 5 J/cm2 to 20 J/cm2 inhibited melanosome maturation, decreased melanin content and tyrosinase activity. Inhibition was accompanied by the decreased expression of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1) and microphthalmia-associated transcription factor (MITF) on both mRNA and protein levels. Autophagosomes were observed under TEM. Autophagic punctate structures of microtubule-associated protein light chain 3 (LC3) proteins were induced by LED 585 nm light. The configuration change of LC3 from LC3-I to LC3-II, and the degradation of p62 protein were observed after LED 585 nm. Furthermore, we also revealed that the anti-melanogenic effect of LED 585 nm photomodulation was reversed by 3-Methyladenine (3-MA), which inhibits autophagy by blocking autophagosome formation via the inhibition of type III Phosphatidylinositol 3-kinases (PI-3K). Conclusions Our finding demonstrated that LED photomodulation with 585 nm wavelength suppressed melanin content in HEMs, and the effect was caused by its dose-dependent inhibition on melanogenesis and the induction of HEMs autophagy. This may provide new insights into the efficacy of LED photomodulation in the treatment of hyperpigmentation disorders.

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

This study aimed to evaluate the effect of IPL treatment on Asian skin by reflectance confocal microscopy (RCM) analysis. Ten Asian female volunteers (39~54 years old, Fitzpatrick skin type III~IV) received five monthly IPL treatments. RCM skin images were evaluated, and several skin physiological parameters including thickness of stratum corneum, minimal thickness of epidermis, thickness of basal layer, density of dermal papillae, and mean diameter of papillae capillaries were measured both at baseline and 1 month after the last treatment. Transepidermal water loss (TEWL) was evaluated, as well. Thickness of stratum corneum was 4.80 ± 1.48 μm before IPL treatment and 5.50 ± 1.35 μm after treatment (p = 0.322). Both minimal thickness of epidermis and thickness of basal layer were significantly increased (p = 0.002 and 0.018, respectively) after IPL treatment. Dermal papillae density was significantly increased (p = 0.035), whereas mean capillary diameter was reduced significantly (p = 0.035). TEWL was slightly increased after treatment, while the difference was not significant on either T-zone or U-zone (p = 0.085 on T-zone and p = 0.114 on U-zone). RCM imaging is a feasible method to evaluate the effect of IPL effect on human skin. Moreover, IPL treatment serves to be highly safe in skin rejuvenation.

SummaryBackground Pimecrolimus 1% cream has already been proved to be an effective and safe alternative to treat seborrheic dermatitis. However, the treatment periods were inconstant in previous studies. Objective To evaluate the comparative efficacy of pimecrolimus 1% cream with different regimens for the treatment of facial seborrheic dermatitis. Method Thirty patients with facial seborrheic dermatitis were enrolled and randomly distributed to three groups. Patients of Group 1 were treated with topical pimecrolimus cream 1% twice daily for 2 weeks and then a moisturizer cream twice daily for 2 weeks. Patients of Group 2 were treated with pimecrolimus cream 1% twice daily for 2 weeks and then once daily for another 2 weeks. Patients of Group 3 had a consecutive course of pimecrolimus cream 1% twice daily for 4 weeks. Objective symptoms, subjective symptoms, and dermatology life quality index (DLQI) were measured at weeks 0, 2, 4, and 6. Results At week 4, the clinical severity scores of all three regimens significantly decreased (P

Background 5-Aminolevulinic acid mediated −photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, the therapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate the effects and mechanisms of ALA-PDT on the cell growth and lipogenesis of human SZ95 sebocytes. Material and methods Human SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6 K/p70 S6 K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells. Results ALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6 K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cells in suppressing the cell growth and reducing the secretion of lipids. Conclusion ALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγ signaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes.

IMPORTANCE: It is necessary to determine whether established clinical markers of vitiligo are associated with disease progression, severity, and patient prognosis. OBJECTIVE: To evaluate the utility of trichrome sign, confetti-like depigmentation, and Koebner phenomenon in assessing disease progression, severity, and prognosis in patients with vitiligo. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, 425 patients with vitiligo were recruited from the outpatient department of Huashan Hospital, Fudan University in Shanghai, China, from September 1, 2016, to May 13, 2019. MAIN OUTCOMES AND MEASURES: Disease progression, severity, and prognosis during a 12-month period. The active stage of vitiligo was defined as Vitiligo European Task Force spreading score of at least 1 or more lesions appearing as hypomelanotic with poorly defined borders using a Wood light. Progression was assessed using the Vitiligo Area Scoring Index (VASI) and serum CXCL10 level measurement. RESULTS: Of the 458 enrolled patients, 425 (235 female [55.3%]; mean [SD] age, 30.9 [10.2] years) completed the 12-month follow-up. Of the 425 patients (224 with no clinical marker and 201 with at least 1 clinical marker) included in this analysis, the proportion in the active stage of the disease was significantly higher in the cohort with at least 1 clinical marker compared with the cohort without any clinical marker at the first visit (196 of 201 [97.5%] vs 159 of 224 [71.0%]; P

Background : Melanoma is one of the most aggressive, therapy-resistant skin cancers in the world. Hydrogen sulfide (H2S), a newly discovered gasotransmitter, plays a crucial role in the progression and development of many types of cancers. However, the effect of H2S on human skin melanoma remains to be elucidated. Objective : We aimed to explore the effect of exogenous H2S on melanoma cells and its underlying mechanisms. Methods : In this study, human skin melanoma cell lines, including A375 and SK-MEL-28, were treated with a donor of H2S (NaHS). CCK-8, scratch assay, flow cytometric analysis, western blotting and transmission electron microscopy (TEM) were performed to explore the effects of H2S on cell behaviors. Results : Treatment with NaHS inhibited cell proliferation, migration and division, while it could induce cell apoptosis and autophagy in melanoma cell lines. Moreover, NaHS significantly decreased the expression of p-PI3K, p-Akt and mTOR proteins. Furthermore, insulin-like growth factor-1 (IGF-1), the activator of PI3K/AKT/mTOR pathway, could reverse the cell behaviors caused by NaHS. Conclusion : Our results demonstrated that exogenous hydrogen sulfide could inhibit human melanoma cell development via suppression of the PI3K/AKT/mTOR pathway. Hydrogen sulfide might serve as a potential therapeutic option for melanoma.

Objective The aim of this study was to evaluate the efficacy and safety of home and outpatient narrowband ultraviolet B light (NB-UVB) for the treatment of non-segmental vitiligo. Methods A total of 94 patients with non-segmental vitiligo were enrolled. Forty-eight patients were treated with home NB-UVB, and the other 46 patients were treated with outpatient NB-UVB over a period of 6 months. The efficacy, patient quality of life, and adverse events were assessed at month 3 and month 6 after treatment. Results There was no significant difference in repigmentation and VASI-reverse (VR) rates between outpatient NB-UVB and home NB-UVB groups. VR was higher in outpatient NB-UVB group at month 3, and similar at month 6. For long-standing vitiligo, VR was higher in the outpatient NB-UVB group compared with home NB-UVB group after 6 months of treatment. In recent vitiligo, the VR was similar between the two groups. Additionally, vitiligo-specific health-related quality-of-life instrument (VitiQoL) score was similar, and the adverse effects were minimal among the two groups. Conclusions The efficacy and safety of home NB-UVB and outpatient NB-UVB phototherapy for non-segmental vitiligo were comparable. According to our results, those with long-standing vitiligo may be recommended to receive outpatient NB-UVB phototherapy.

To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the expression of Toll like receptors (TLRs) in human keratinocytes and its role in acne treatment.TLR2 and TLR4 expression in acne lesions before and after ALA-PDT were examined by immunohistochemical assay. Primary keratinocytes were obtained from acne lesions, co-cultured with P. acnes and then treated with ALA-PDT using red or blue LED. Cytokines production were examined by ELISA, TLR2 and TLR4 gene expression by real-time PCR, and TLR2 and TLR4 protein expression by Western-blot assay.The overexpression of TLR2 and TLR4 in acne lesion were detected, which became negative or weaker after ALA-PDT. The infection of P. acnes in keratinocytes could significantly increase the levels of early inflammatory cytokines (e.g. IL-1α, TNF-α and IL-8) (P0.05). Such responses could be inhibited by ALA-PDT. P. acnes infection could also significantly increase TLR2 and TLR4 expressions in keratinocytes (P0.05), which could be down-regulated by ALA-PDT.ALA-PDT could inhibit innate immune responses in keratinocytes treated with P. acnes via TLRs pathways.

The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.

With the world's largest population at 1.3 billion and a rising number of foreigners, China requires physicians and a healthcare system that meets the needs of a large and diverse population. Along with rapid economic and technological advancements, the Medical Administration Division of the National Health and Family Planning Commission remarked that medical services through online appointments and payments have improved its efficacy over the past 2 years. According to the official report from the National Health and Family Planning Commission of the People's Republic of China website, China has so far established a total of 25,000 hospitals and 981,000 community health centers, that includes 17,100 dermatologists and 190,000 residents in training.

Background Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear. Objective To investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo. Methods One hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry. Results The serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells. Conclusion CCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo.

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.

To the EditorVitiligo is an acquired chronic depigmenting skin disorder caused by the autoimmune destruction of melanocytes, and it has a prevalence rate of 0.5–2% worldwide [1]. Vitiligo has a rem...

Background Impaired dendrite outgrowth of melanocytes is one of the reasons triggering vitiligo. RNASET2 was identified as one of the risk genes for vitiligo in a GWAS study conducted in the Chinese Han population. However, the role of Rnaset2 in the outgrowth of melanocytes is rarely studied. Objective This study is to investigate the effects of Rnaset2 in regulating the outgrowth of melanocytes and its interacting proteins. Methods Stress conditions (UV irradiation, hydrogen peroxide, and lipopolysaccharides) were applied to primary human epidermal melanocytes (HEMs) and epidermal keratinocytes (HEKs). HEKs with Rnaset2 overexpression were co-cultured with HEMs. Rnaset2 expression levels were detected by ELISA. HEMs, HEKs and A375 cells were treated with recombinant Rnaset2 protein and actin network was observed with fluorescence microscope. Cell migration assay was performed using nuclepore filters after incubating A375 cells with recombinant Rnaset2 protein. Human proteome microarray was performed to identify proteins interacting with Rnaset2. Co-immunoprecipitation was conducted to verify the results. Results Our results showed that after exposing to stress conditions, Rnaset2 expression and secretion by HEKs and HEMs were increased. Co-culture of HEKs and HEMs showed that outgrowth of HEMs was inhibited by Rnaset2 overexpression in HEKs. Additionally, human recombinant Rnaset2 protein treatment altered the actin network of HEMs, HEKs and A375 cells. The migration of A375 cells was also inhibited by human recombinant Rnaset2 protein treatment. Human proteome microarray identified shootin1, an important protein involved in axon outgrowth, as one of the interacting proteins of Rnaset2. Co-immunoprecipitation confirmed that Rnaset2 interacted with shootin1 in vitro. Conclusion Rnaset2 inhibits melanocyte outgrowth through interacting with shootin1 and this effect may be associated with vitiligo pathogenesis. Rnaset2 may be a potential therapeutic target for vitiligo.

Ablative skin rejuvenation therapies have limitations for Asian people, including post-inflammatory hyperpigmentation and long down time. Non-ablative lasers are safer but have limited efficacy. This study is to investigate the safety and efficacy of a combination therapy consisting of intense pulsed light (IPL), near infrared (NIR) light, and fractional erbium YAG (Er:YAG) laser for skin rejuvenation in Asian people. This study recruited 113 subjects from six sites in China. Subjects were randomly assigned to a full-face group, who received combination therapy, and split-face groups, in which one half of the face received combination therapy and the other half received IPL monotherapy. Each subject received five treatment sessions during a period of 90 days. Subjects were followed up at 1 and 3 months post last treatment. Three months after last treatment, the full-face group (n = 57) had a global improvement rate of 29 % and 29 % for wrinkles, 32 % for skin texture, 33 % for pigment spots, 28 % for pore size, respectively. For patients in the split-face groups (n = 54), monotherapy side had a global improvement rate of 23 % and 20 % for wrinkles, 27 % for skin texture, 25 % for pigment spots, 25 % for pore size, respectively. Both combination therapy and monotherapy resulted in significant improvements at the follow-up visits compared to baseline (P 0.001). Combination therapy showed significantly greater improvements compared to monotherapy at two follow-up visits (P 0.05). Combination therapy is a safe and more effective strategy than IPL monotherapy for skin rejuvenation in Asian people.

Acne vulgaris is one of the most common skin diseases in adolescents. In the present study, we aimed to evaluate the effectiveness and safety of topical 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) for the treatment of severe acne in Chinese adolescent patients. Twenty-one Chinese adolescent patients aged 12-18 years with Pillsbury III-IV severe facial acne were treated with three courses of ALA-PDT. A 5% ALA lotion was applied topically for 60 min followed by irradiation with light-emitting diode light at 633 nm with a light intensity of 75-80 mW/cm(2) and a light dose of 90-96 J/cm(2) . Clinical assessment was conducted before and after each treatment, and at each follow-up session. The total effective rates were 85.71%, 90.48%, and 95.23% after the three PDT sessions, and at the 4- and 8-week follow ups, respectively. ALA-PDT is an effective treatment for severe adolescent acne vulgaris, and is associated with mild and reversible side-effects.

Reflectance confocal microscopy (RCM) is a noninvasive technique for evaluating cutaneous lesions with cellular level resolution close to conventional histopathology. The aim of this study is to observe the vascular changes in Port-wine (PWS) lesions and assess the clinical efficacy of Pulsed Dye Laser (PDL) treatment by examining vessel diameter and density with RCM.Eleven adult patients with PWS, each had four test patches carried out with different pulse durations (1.5, 3, 6, and 10 ms), respectively; fluences of 9-12 J/cm²; and a spot size of 7 mm. The PDL treatment was repeated 3-5 times at a 2-month interval. Photographs and measurements with RCM were taken before each treatment and 2 months after the last treatment.The PDL treatment exhibited increasing clearance with reducing pulse durations. Vessel diameters and densities were significantly decreased in the same pulse-duration groups after treatment. There was significant difference between 1.5 ms pulse-duration group and other pulse-duration groups in reducing blood vessel diameter at the depth of 150 μm.RCM can be used to assess the clinical efficacy of PDL treatment.

Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of functional melanocytes from the epidermis and follicular reservoir. Among multiple hypotheses which have been proposed in the pathogenesis of vitiligo, autoimmunity and oxidative stress-mediated toxicity in melanocytes remain most widely accepted. Macroautophagy is a lysosome-dependent degradation pathway which widely exists in eukaryotic cells. Autophagy participates in the oxidative stress response in many cells, which plays a protective role in preventing damage caused by oxidative stress. Recent studies have enrolled autophagy as an important regulator in limiting damage caused by UV light and lipid oxidation, keeping oxidative stress in a steady state in epidermal keratinocytes and maintaining normal proliferation and aging of melanocytes. Impairment of autophagy might disrupt the antioxidant defense system which renders melanocytes to oxidative insults. These findings provide supportive evidence to explore new ideas of the pathogenesis of vitiligo and other pigmentation disorders.

Epidermal melanocytes play an important role in protecting skin from ultraviolet (UV) rays, and are implicated in a variety of skin diseases. Here, we developed an efficient method for differentiating induced pluripotent stem cells (iPSCs) into melanocytes. We first generated iPSCs from adult mouse tail-tip fibroblasts (TTFs) using retroviral vectors or virus-free piggyBac transposon vectors carrying murine Sox2, Oct3/4, cMyc and Klf4. The TTF-derived iPSC clones exhibited similar morphology and growth properties as mouse embryonic stem (ES) cells. The iPSCs expressed ES cell markers, displayed characteristic epigenetic changes and formed teratomas with all three germ layers. The iPSCs were used to generate embryoid bodies (EBs) and were then successfully differentiated into melanocytes by treatment with growth factors. The iPSC-derived melanocytes expressed characteristic melanocyte markers and produced melanin pigment. Electron microscopy showed that the melanocytes contained mature melanosomes. We manipulated the conditions used to differentiate iPSCs to melanocytes and discovered that Wnt3a is not required for mouse melanocyte differentiation. This report shows that melanocytes can be readily generated from iPSCs, providing a powerful resource for the in vitro study of melanocyte developmental biology and diseases. By inducing iPSCs without viruses, the possibility of integration mutagenesis is alleviated, providing iPSCs are more compatible for cell replacement therapies.

Objectives To analyze associations between the patterns of global DNA hypomethylation and expression of DNA methyltransferase (DNMT1, DNMT3A, and DNMT3B) in patients with systemic lupus erythematosus (SLE) and to obtain a deeper understanding of the role that epigenetic mechanism may have on SLE. Methods The global DNA methylation profile in T cells from 34 patients with SLE and 23 healthy controls was assessed by the specific monoclonal antibodies to 5-methylcytosine and was analyzed quantitatively by flow cytometry. Real-time reverse transcription–polymerase chain reaction was applied to analyze DNMTs (DNMT1, DNMT3A, and DNMT3B) mRNA levels in T cells from patients and controls. Results Patients with SLE had significantly global DNA hypomethylation than that in controls (P = 0.004), and the global DNA methylation was inverse correlated with the SLE Disease Activity Index (P