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Background. Granuloma annulare (GA) and sarcoidosis are granulomatous inflammatory diseases that share similarities. Objective. To identify the histological and immunohistochemical (IHC) features of GA and sarcoidosis. Methods. A retrospective review of 36 patients with GA and 26 with sarcoidosis was performed. Results from hematoxylin and eosin (H&E) staining and IHC staining of MMP-9 and pSTAT1 within the skin lesions of GA and sarcoidosis were analyzed, and random forest was applied for developing a predictive model. Results. Significantly greater expressions of MMP-9 (especially in elastic fibers, EFs, P < 0.0001) and pSTAT1 (P = 0.0003) were observed in lesion samples of GA versus sarcoidosis patients. In GA patients, MMP-9 was significantly upregulated in the interstitial type (P = 0.0222), while staining of pSTAT1 was positively correlated with the area of mucinous collagen in palisading GA (R = 0.5356 , P = 0.0484). In sarcoidosis patients, MMP-9 (R = − 0.7127 , P = 0.0009) and pSTAT1 (R = − 0.5604 , P = 0.0067) were found to show stronger expressions in lesions with less lymphocyte infiltration. The predictive model demonstrated an AUC of 0.9675. Conclusion. These results indicate that MMP-9 and pSTAT1 might exert roles in granulomatous inflammation in different modes, and the presence of more robust MMP-9 staining in EFs appears to be more suggestive of GA. [ABSTRACT FROM AUTHOR]

This study aimed to assess and compare the clinical efficacy and safety of a triple combination treatment using 2940 nm Er:YAG laser, triamcinolone acetonide solution combined with either 308 nm excimer laser or 0.1% tacrolimus for the treatment of stable segmental vitiligo. Patients with stable segmental vitiligo were randomly divided into two groups and received a 5‐month treatment with 2940 nm Er:YAG laser followed by triamcinolone acetonide and, either 308 nm excimer laser (Group A, N = 8) or 0.1% tacrolimus (Group B, N = 13). General information and imaging data were collected before and at 1 month after treatments. Marked repigmentation and overall repigmentation rates were analyzed and any adverse skin reactions were recorded. Both treatments significantly reduced the percent of skin lesions per total body surface area (p < 0.05) and no significant differences in repigmentation were observed between the two groups (p > 0.05). The marked repigmentation rate of Group A was 42.11% and overall repigmentation rate was 94.74%, while for Group B these rates were 51.16% and 100%, respectively. There were no significant differences in the number of fingertip units at each time point (p > 0.05). While there was a significant effect for time on the number of fingertip units without considering other factors (p < 0.05), the time x treatment interaction was not significant (p > 0.05). One Group A patient developed adverse reactions consisting of erythema, burning sensation and blisters and one Group B patient developed mild erythema and burning sensations. Both treatments demonstrated a high level of efficacy and safety in the treatment of stable segmental vitiligo. [ABSTRACT FROM AUTHOR]

Aim: Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence‐based guidelines to guide clinical practice are urgently needed. Methods: We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%. Results: Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained. Conclusions: It is a comprehensive and systematic evidence‐based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services. [ABSTRACT FROM AUTHOR]

Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2‐like type of gene expression in BMDMs with the inhibited Il‐6, Il1‐β and Arg‐1 and induced Tnf‐α, Il‐10 and Mgl‐1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c‐JUN. We also identified c‐JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis‐induced skin lesions were accompanied with an upregulation of c‐JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c‐JUN pathway, effects that can then control the expression of inflammatory factors. [ABSTRACT FROM AUTHOR]

The distinction between Keratoacanthoma (KA) and Cutaneous Squamous Cell Carcinoma (cSCC) is critical yet usually challenging to discriminate clinically and histopathologically. One approach to differentiate KA from cSCC is through assessing the immunohistochemical staining patterns of the three indicators, β-catenin, C-Myc, and CyclinD1, which are critical molecules that play important roles in the Wnt/β-catenin signaling pathway. Ki-67, as a proliferation biomarker for human tumor cells, was also assessed as an additional potential marker for differentiating KA from cSCC. In this report, these four indicators were analyzed in 42 KA and 30 cSCC cases with the use of the computer automated image analysis system. Computer automated image analysis is a time-based and cost-effective method of determining IHC staining in KA and cSCC samples. We found that C-Myc staining was predominantly localized in the nuclei of basal cells within KA patients, whereas cSCC staining was predominantly localized in the nuclei of diffuse cells. This C-Myc staining pattern has a sensitivity of 78.6% and a specificity of 66.7% for identifying KA. Moreover, positive rates of distinct expression patterns of C-Myc and Ki-67 may also serve as a means to clinically distinguish KA from cSCC. Taken together, our results suggest that these markers, in particular C-Myc, may be useful in differentiating KA from cSCC. [ABSTRACT FROM AUTHOR]

Background: Actinic keratosis (AK) is a precancerous disease, caused by ultraviolet radiation (UV). Objective: To analyze the clinical and pathological characteristics of AK in four areas with different ultraviolet radiation intensities. Methods: 1188 diagnosed AK patients, from January 2000 to July 2015, in dermatology department of four hospitals were collected. The UV intensity of hospital located cities from high to low is Kunming, Yinchuan, Shenyang and Nanjing. The information comes from medical records, and the pathological types and Keratinocyte Intraepithelial Neoplasia (KIN) grades were checked by two experienced pathologists. All information was conducted a retrospective multicenter research. Results: The patients were mainly middle‐aged and elderly female, which was in direct contrast to the majority of men in European. The age of onset in Kunming group was lower than that in Yinchuan Group (p = 0.013) and Nanjing Group (p < 0.01). The course of disease in Kunming group was significantly shorter than that in Nanjing Group (p < 0.001). The lesions were almost located in the exposed area. The proportion of unexposed areas in Shenyang group was significantly higher than that in other groups (p < 0.001). There were statistical differences in pathological morphological classification among the four groups. These differences were not affected by age and gender. The number of KIN III grade patients in Shenyang group was significantly higher than that in other three groups (p < 0.05). Conclusion: The Asian patients were mainly female. The clinical characteristics of AK are closely related to UV intensity, and environmental pollution, lifestyle, religious beliefs and other factors are also related. [ABSTRACT FROM AUTHOR]

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of resveratrol combined with ablative fractional CO2 laser system (AFL) treating skin photoaging. Methods: Thirty‐two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period. Results: All subjects in TG achieved improvements of their photoaging signs compared to pre‐treatment both the laser side and the non‐laser side at 6 months (p < 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p < 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p < 0.05). On the non‐laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p < 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG. Conclusion: The resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease characterized by well-defined scaly papules and plaques. Interleukin (IL)-17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 (STAT3) activation. Shikonin, a natural naphthoquinone isolated from Lithospermum erythrorhizon, possesses anti-inflammatory and immunosuppressive properties and can suppress IL-17-induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway. In the present study, MTS, iCELLigence and RT-qPCR were used to determine the optimal concentration and duration of IL-17 or shikonin acting on HaCaT cells. The changes in the expression levels of genes associated with the IL-6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array. Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer-binding protein δ (CEBPD). Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod-induced psoriasis in mice and the expression levels of CEBPD. Shikonin reversed IL-17-mediated downregulation of the tumor suppressor CEBPD in HaCaT cells. Moreover, low levels of CEBPD in the imiquimod-induced mouse model of psoriasis were restored by shikonin treatment, which ameliorated excessive keratinocyte proliferation. Taken together, these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Photodamages caused by UVA radiation induced oxidative injuries are closely related to photoaging and skin cancer. Paeoniflorin (PF), extracted from the root of Paeonia lactiflora, has been reported to be an effective antioxidant. PLIN2, known as adipose differentiation-related protein, has been previously involved in the regulation of oxidative stress. In this study, we were sought to investigate the photo-protective property of PF and PLIN2 in UVA-radiated human dermal fibroblasts (HDFs). HDFs were pre-treated with PF (800 μM) followed by UVA radiation (22.5 J/cm2). MTS activity, cell apoptosis, ROS, MDA, and SOD were detected, respectively. The expressions of Nrf2, HO-1, NQ-O1, and PLIN2 were determined using RT-qPCR or western blot. Nrf2 was silenced by siRNA, and PLIN2 was overexpressed via lentiviral transduction. Comparing to the UVA radiation, PF pre-treatment could prominently increase the MTS activity, decrease cell apoptosis, reduce the generations of ROS and MDA, increase the activity of SOD and increase the expression of Nrf2 and its target genes HO-1 and NQ-O1. When Nrf2 was knocked down, PF lost above protective properties. In addition, UVA induced oxidative stress led to upregulation of PLIN2 and the latter could be decreased by PF. Overexpression of PLIN2 improved MTS activity and reduced MDA level in HDFs. The combination of PLIN2 overexpression and PF pre-treatment corporately inhibited UVA-induced injury. Besides, we also found that PF and PLIN2 had a compensatory protection against UVA induced oxidative stress. In conclusion, our study demonstrated that UVA induced photodamages could be inhibited by PF via Nrf2/HO-1/NQ-O1 signaling pathway or by PLIN2, and the combination of PLIN2 overexpression and PF played additive effects against UVA-related oxidative stress. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune-mediated cutaneous disorder with a high incidence and prevalence. Patients with psoriasis may experience irritation, pain and psychological problems. The cause and underlying molecular etiology of psoriasis remains unknown. In an attempt to achieve a more comprehensive understanding of the molecular pathogenesis of psoriasis, the gene expression profiles of 175 pairs of lesional and corresponding non-lesional skin samples were downloaded from 5 data sets in the Gene Expression Omnibus (GEO) database. Integrated differentially expressed genes (DEGs) were obtained with the use of R software. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using the DAVID online analysis tool. The protein-protein interaction (PPI) network was constructed on the STRING platform and hub genes were calculated with the use of Cytoscape software. Finally, GEO2R was used to determine the expression of the hub genes in scalp psoriasis. A total of 373 genes from the 5 data sets were identified as DEGs, including 277 upregulated and 96 downregulated genes. GO analysis revealed that immune responses and epidermal differentiation/development were the most enriched terms in biological processes, extracellular space/matrix was the most enriched term in cellular components, and endopeptidase inhibitor activity was the most enriched term in molecular functions. In the KEGG pathway enrichment, DEGs were mainly enriched in the metabolic and viral infection-associated pathways. A total of 17 hub genes were calculated, including CSK2, CDC45, MCM10, SPC25, NDC80, NUF2, AURKA, CENPE, RRM2, DLGP5, HMMR, TTK, IFIT1, RSAD2, IFI6, IFI27 and ISG20, among which interferon-α-inducible genes were revealed to display a similar expression pattern as that obtained in scalp psoriasis. This comprehensive bioinformatic re-analysis of GEO data provides new insights on the molecular pathogenesis of psoriasis and the identification of potential therapeutic targets for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Previous studies on the correlation between positive autologous serum skin test (ASST) responses and the clinical features of patients with chronic spontaneous urticaria (CSU) have provided conflicting results. To evaluate the significance of ASST responses in CSU, a variety of databases were searched from inception to March 2018 to identify relevant studies on CSU. Data were analyzed with use of the Cochrane Collaboration's Review Manager 5.2. Multiple relevant factors of CSU were evaluated by calculating the weighted mean difference, odds ratio and 95% confidence interval. The results indicated that CSU cases with positive ASST responses had higher urticaria activity scores and higher levels of total serum immunoglobulin E than CSU cases with negative responses in the ASST. In addition, a positive ASST response was more likely to be accompanied with the presence of thyroid autoantibodies and angioedema. An increased prevalence of CSU was identified in females, who were more likely to have a positive response in the ASST. It was also indicated that a greater incidence of positive ASST responses was present in CSU patients as compared with that in healthy controls. No statistically significant differences were obtained between positive and negative ASST responses with regard to age and duration of disease. Based on these results, it was concluded that the ASST provides an effective means of predicting urticaria activity and recurrence in CSU patients. [ABSTRACT FROM AUTHOR]

Flat warts (FWs) usually result from human papillomavirus (HPV) types 3, 10, 28 or 41. Induction therapy was conducted on days 1, 2, 3, 11 and 12, followed by five consecutive weekly sections of maintenance therapy. Treatment of high risk human papillomavirus infection in low grade cervical squamous intraepithelial lesion with mild local thermotherapy: three case reports. [Extracted from the article]

In the clinic, vitiligo is characterized by two stages: Stable and progressive. The pathogenesis of vitiligo is still not clear. Here, we identified serum markers of vitiligo by screening for differentially expressed proteins in patients with vitiligo compared to healthy individuals. Serum samples were collected from patients with vitiligo (n=10 for both the stable and progressive stages) and healthy individuals (n=10). Two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and western blotting were used to validate the differential expression of the proteins in the serum (n=20 each, at both stages for patients and healthy individuals). A total of 48 differentially expressed proteins were identified by gel image analysis. There were 28 differentially expressed proteins in patients with progressive vitiligo (PV) and 13 differentially expressed proteins in patients with stable vitiligo (SV) compared with that in healthy individuals. Additionally, 7 differentially expressed proteins were identified in patients with PV compared with those in patients with SV. The western blotting results showed that Peroxiredoxin-6, apolipoprotein L1, apolipoprotein E and mannose-binding protein were differentially expressed in patients with different stages of vitiligo. Our results showed that change serum levels of several proteins might be useful as biomarkers or in understanding the pathogenesis of vitiligo. [ABSTRACT FROM AUTHOR]

Background and Objectives: The objective of this study was to evaluate the topical effects of sea buckthorn (SBT) oil on atopic dermatitis (AD)-like lesions in a mouse model generated by repeated topical administration of DNCB in BALB/c mice. Methods: DNCB was applied repeatedly on the dorsal skin of mice to induce AD-like lesions. Following AD induction, SBT oil was applied daily on the dorsal skin for 4 weeks. The severity of skin lesions was examined macroscopically and histologically. We further measured the production of MDC/CCL22 and TARC/CCL17 in IFN-γ/TNF-α activated HaCaT cells. Results : Topically applied SBT oil in DNCB-treated mice ameliorated the severity score of dermatitis, decreased epidermal thickness, reduced spleen and lymph node weights, and prevented mast cell infiltration. In addition, SBT oil suppressed the Th2 chemokines TARC and MDC via dose-dependent inhibition of NF-κB, JAK2/STAT1, and p38-MAPK signaling pathways in IFN-γ/TNF-α-activated HaCaT cells. Conclusion: These results suggest that SBT oil had a beneficial effect on AD-like skin lesions, partially via inhibition of the Th2 chemokines TARC and MDC in inflamed skin. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small-molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first-generation ADC. Since then, at least 100 ADC-related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization strategies for the next generation of drugs. Subsequently, experts have improved the first-generation ADCs and have developed second-generation ADCs such as ado-trastuzumab emtansine. Second-generation ADCs have higher specific antigen levels, more stable linkers and longer half-lives and show great potential to transform cancer treatment models. Since the first two generations of ADCs have served as a good foundation, the development of ADCs is accelerating, and third-generation ADCs, represented by trastuzumab deruxtecan, are ready for wide application. Third-generation ADCs are characterized by strong pharmacokinetics and high pharmaceutical activity, and their drug-to-antibody ratio mainly ranges from 2 to 4. In the past decade, the research prospects of ADCs have broadened, and an increasing number of specific antigen targets and mechanisms of cytotoxic drug release have been discovered and studied. To date, seven ADCs have been approved by the FDA for lymphoma, and three have been approved to treat breast cancer. The present review explores the function and development of ADCs and their clinical use in cancer treatment. [ABSTRACT FROM AUTHOR]

GLO:K8E/01jul21:jocd13835-fig-0001.jpg PHOTO (COLOR): 1 (A-B) Clinical appearance of the skin lesions; A, left upper limb; B, right upper limb; (C-D) histopathological findings gl One of the lesions was selected for biopsy. Lymphoid cells, tissue-like cells, and fibroblast-like cells of various morphologies may all be present within the connective tissue. Polymorphonuclear giant cells, granulocytes, and plasma cells can also exist in some of the lesions. [Extracted from the article]

Background: Genital warts are more extensive and difficult to treat in patients with diabetes mellitus due to defective immune responses. Purpose: Our aim was to confirm the suitability of local hyperthermia for the treatment of genital warts in patients with diabetes mellitus and to investigate the immune cells in lesional areas at different time intervals after treatment. Methods: We treated three diabetic patients with extensive genital warts by local hyperthermia at 44 °C for 30 min a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical clearance. Immunohistochemical profile was described on serial biopsies from a patient with confluent plaques. Results: The warty lesions in the patients resolved in 6, 4 and 9 weeks, respectively. Immunohistochemical staining in the regressing warts revealed abundant infiltrating CD4+ T and CD8+ T lymphocytes (P < 0.01), as well as macrophages and CD1a+ dendritic cells. Conclusions: This preliminary study suggested that local hyperthermia was a safe and effective single modality in the treatment of genital warts in diabetic patients and could induce a rapid immune response in lesional skin. [ABSTRACT FROM AUTHOR]

Purpose: A variety of medications and procedures are available for the treatment of warts, but it appeared the treatment response in systemic lupus erythematosus (SLE) patients is poor. It is necessary to investigate the feasibility, safety and efficacy of local thermotherapy for extensive viral warts. Materials and methods: A SLE patient on systemic steroid developed extensive viral warts on both her hands and feet for months. She had a high score of SLE Disease Activity Index (SLEDAI), up to 30, and was extensively treated with high and prolonged dosage of corticosteroid and intermittent use of cyclophosphamide. We applied local hyperthermia at 44 °C on a target lesion for 30 min on days 1, 2, 3, 17, 18, a protocol which has been successfully used in treating viral warts. There was no sign of clinical response in a 3-month follow-up. Then we treated the patient on a once-a-week protocol. Result: All the lesions cleared in ten weeks and there was no sign of recurrence. Conclusion: This observation suggests that more intensive local hyperthermia is required for clearing viral warts in SLE. [ABSTRACT FROM AUTHOR]