Vulvar lichen sclerosus in girls and adult females: A single-center retrospective study of 744 patients in China.

Vulvar lichen sclerosus (VLS) is a chronic, inflammatory disease which is accompanied by itching and pain, affecting the patient's daily life and sexual activity. However, the disease characteristics of children and adults are not completely the same. Currently, there are few studies in China that compare the characteristics of VLS between girls and adult female patients. The aim of this study was to compare the epidemiology, clinical features, and combined autoimmune diseases of VLS patients between girls and adult females, and to help clinicians better understand VLS in different age groups. We enrolled 744 female patients for analysis, divided by age into a child group (<18 years) and an adult group (≥18 years). Among girl patients, 94.6% had preadolescent onset, while among adult female patients, only 4.6% had preadolescent onset, which was a statistically significant difference. The highest percentage of adult female patients had onset during their child-bearing period (75.4%), while 20% had postmenopausal onset, with a significant difference when the three onset states were compared. White patches were equally common in both girl and adult female patients' external genital area, while mossy lesions and labia minora atrophy were more common in adult female patients. Involvement of the clitoris, labia minora, and vaginal opening area were more common in adult patients. The perianal area was more commonly involved in girl patients. We found eight cases (1.2%) of secondary squamous cell carcinoma in adult female patients. We also found that 13 patients had concurrent lichen sclerosus lesions on the vulva and extragenital region, including two girls and 11 adult females. Extragenital lichen sclerosus (EGLS) occurred mostly in the torso. Clinicians should be aware of these differences so that early diagnosis and treatment of the disease can be achieved, to avoid irreversible anatomical alterations and the risk of cancer.

Role of hippo pathway and cuproptosis-related genes in immune infiltration and prognosis of skin cutaneous melanoma.

Melanoma is the most lethal type of skin cancer with an increasing incidence. Cuproptosis is the most recently identified copper-dependent form of cell death that relies on mitochondrial respiration. The hippocampal (Hippo) pathway functions as a tumor suppressor by regulating Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) activity. However, its role in cuproptosis remains unknown. In addition, the correlation of cuproptosis-related genes and Hippo pathway-related genes with tumor prognosis warrants further investigation. In the present study, we explored the correlation of cuproptosis-related genes and Hippo pathway-related genes with the prognosis of melanoma through analysis of data from a public database and experimental verification. We found eight Hippo pathway-related genes that were downregulated in melanoma and exhibited predictive value for prognosis. There was a significant positive correlation between cuproptosis-related genes and Hippo pathway-related genes in skin cutaneous melanoma. YAP1 expression was positively correlated with ferredoxin 1 (FDX1) expression in the GSE68599 dataset and A2058 cells. Moreover, YAP1 was positively and negatively correlated with M2 macrophages and regulatory T cell infiltration, respectively. In conclusion, the present study demonstrated the prognostic value of Hippo pathway-related genes (particularly YAP1) in melanoma, revealing the correlation between the expression of Hippo pathway-related genes and immune infiltration. Thus, the present findings may provide new clues on the prognostic assessment of patients with melanoma and a new target for the immunotherapy of this disease.

Quality of life and burden of disease of vulvar lichen sclerosus: A single-center retrospective study in China.

OBJECTIVE: This study examined the quality of life and burden of disease of vulvar lichen sclerosus (VLS) patients in three states of menstruation to better understand VLS. METHODS: A total of 607 VLS patients were enrolled into this retrospective study. According to the ages of onset, menarche and menopause, the patients were divided into three groups: prepubertal group (n = 96), reproductive group (n = 400) and postmenopausal group (n = 111). Data were collected by direct interview and clinical examination. RESULTS: A total of 93% of patients had itching, with a median numerical rating scale score of five. In the prepubertal group, the median score was three. Nocturnal itching occurred in 49.6% patients. Nearly half of the patients (45.9%) thought the itching affected their sleep. However, this ratio was very different in the prepubertal group (20.7%). Some patients (12.8%) cleaned their vulva more than seven times per week. Only 17.2% of patients experienced no effect on their sex life. The median dermatology life quality index score in all patients was six, but it was only three in the prepubertal group. The median number of hospital visits was two times, and the number of clinic visits was three times. Previous expenses, in median, were 2000 RMB. For 84.3% patients, the gynecologic clinic was their first choice. CONCLUSION: VLS places great physical, mental and economic burdens on patients. Patients in the prepubertal group had milder symptoms and dermatology life quality index score. VLS should arouse the attention of patients and specialists.

A Case of Granuloma Faciale Successfully Treated with Minocycline.

Granuloma faciale (GF) is a rare chronic inflammatory dermatosis in clinical practice. The etiology is not yet clear, and it often occurs on the face. The progression of skin lesions is slow and persistent, with almost no self regression and a risk of recurrence, which may lead to disfigurement. We reported a 61-year-old male with GF who had poor reaction with topical corticosteroids and calcineurin inhibitors, but the lesions were significantly improved after systematic application of minocycline. This report describes the good clinical effect of minocycline on GF.

Efficacy of photodynamic therapy in cutaneous leishmaniasis: A systematic review.

OBJECTIVE: To systematically review the efficacy of photodynamic therapy (PDT) in the treatment of cutaneous leishmaniasis (CL). METHODS: PubMed, Embase and Cochrane Library databases were searched for articles published by November 16, 2022, with no time restrictions. 'Cutaneous leishmaniasis' and 'photodynamic therapy' were searched using predefined search strings. INCLUSION CRITERIA: (i) Randomized control trials; (ii) controlled clinical trials; (iii) case series; (iv) case reports; (v) participants were humans; (vi) clinical diagnosis was CL; (vii) treatment method used was PDT; and (viii) articles published in English. RESULTS: In total, 303 articles were identified, including 14 papers meeting the criteria. The number of patients in each study ranged from 1 to 60 and the age ranged from 1 to 82 years. Aminolevulinic acid and methyl aminolevulinate were used as photosensitizers. Red light and sunlight were used as light sources. All reported satisfactory clinical effects. Side effects of treatment included burning sensation, pain and pigmentation after treatment. However, they were tolerable and temporary. The follow-up time ranged between 9 weeks and 24 months. A total of two patients recurred, but one did not recur after another round of PDT during the follow-up period. CONCLUSIONS: The present study suggests that PDT is a safe and effective method for the treatment of CL, with tolerable side effects and good efficacy. As an alternative treatment method of CL, PDT has great potential. However, to verify the efficacy and specific mechanism of PDT for the optimal treatment strategy of CL, further research with larger sample sizes and longer follow-up times are needed.

SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors.

The interaction of SIRPα with CD47 represents a major mechanism for preventing macrophage phagocytosis. However, CD47-independent mechanisms are poorly defined. Here, we report a critical role of SLAM family receptors (SFRs), ubiquitously expressed on hematopoietic cells and forming homotypic interactions, in constraining macrophage phagocytosis. We found that SFR deficiency triggered macrophage phagocytosis of hematopoietic cells, leading to severe rejection of donor hematopoietic graft in recipient mice. Specific SFR members, mainly SLAMF3 and SLAMF4, were identified as "don't eat me" receptors on macrophages. These receptors inhibited "eat me" signals, such as LRP1-mediated activation of mTOR and Syk, through SH2 domain-containing phosphatases. SFRs combined with, but were independent of, CD47 to mitigate macrophage phagocytosis, and the combined deletion of SFRs and CD47 resulted in hematopoietic cytopenia in mice. This SFR-mediated tolerance was compromised in patients with hemophagocytic lymphohistiocytosis, a syndrome characterized by inappropriate phagocytosis toward hematopoietic cells. Loss of SFRs potently elicited macrophage rejection of hematopoietic tumors. Deletion of SFRs also significantly enhanced the phagocytosis of CD19-positive hematopoietic targets by the macrophages expressing the chimeric CD19 antigen receptor. Therefore, SFR-mediated inhibition of macrophage phagocytosis is critical to hematopoietic homeostasis, and SFRs may represent previously unknown targets for tumor immunotherapy.

The lncRNA H19/miR-766-3p/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT/mTOR Pathway.

BACKGROUND: The pathogenesis of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are well studied in psoriasis. However, little is known about how specific lncRNAs and miRNAs affect the mechanism of psoriasis development and which pathways are involved. OBJECTIVES: To explore the role of the lncRNA H19/miR-766-3p/S1PR3 axis in psoriasis. METHODS: miRNA and lncRNA microarrays were performed using IL-22-induced HaCaT cells and psoriatic lesions, respectively. Fluorescence in situ hybridization and quantitative reverse-transcriptase polymerase chain reaction were used to detect the expression of miR-766-3p and lncRNA H19. Luciferase reporter assays were used to identify miR-766-3p/lncRNA H19 and miR-766-3p/S1PR3 combinations. CCK-8 and ELISA were performed to evaluate the proliferation of keratinocytes and the secretion of pro-inflammatory cytokines. Western blot analysis was used to detect the expression of S1PR3 and its downstream effector proteins. RESULTS: MiR-766-3p was upregulated in both HaCaT cells treated with the psoriasis-related cytokine pool (IL-17A, IL-22, IL-1 alpha, oncostatin M, and TNF-alpha) and tissues. Overexpression of miR-766-3p promoted keratinocyte proliferation and IL-17A and IL-22 secretion. LncRNA H19 and S1PR3 were demonstrably combined with miR-766-3p by luciferase reporter assay. lncRNA H19 repressed proliferation and inflammation, which were reduced by the miR-766-3p. AKT/mTOR pathway effected proliferation and inflammation by the lncRNA H19/miR-766-3p/S1PR3 axis. CONCLUSIONS: We established that downregulation of lncRNA H19 promoted the proliferation of keratinocytes and skin inflammation by up-regulating miR-766-3p expression levels and inhibiting activation of S1PR3 through the AKT/mTOR pathway in psoriasis.

Myeloid deletion of phosphoinositide-dependent kinase-1 enhances NK cell-mediated antitumor immunity by mediating macrophage polarization.

A large number of heterogeneous macrophages can be observed in solid tumor lesions. Classically activated M1 macrophages are a powerful killer of cancer cells. In contrast, tumor-associated macrophages (TAMs) are often referred to as M2 phenotype and usually impair tumor immunity mediated by cytotoxic lymphocytes, natural killer (NK) cells and CD8+ T cells. Therefore, orchestrating M2 to M1 reprogramming will provide a promising approach to tumor immunotherapy. Here we used a PyMT-induced spontaneous breast cancer model in which M2-polarized macrophages were abundant. This M2 phenotype was closely related to tumor progression and immune dysfunction of NK cells and CD8+ T cells. We then found that these TAMs showed increased energy expenditure and over-activation of two kinases, Akt and mammalian target of rapamycin (mTOR). Myeloid inactivation of phosphoinositide-dependent kinase-1 (PDK1), the upstream regulator for Akt and mTOR signaling, significantly reduced excessive metabolic activation of macrophages. Notably, the loss of PDK1 significantly led to regression of breast cancer and prevented lung metastasis. Mechanistically, PDK1 deficiency mainly inhibited the activation of mTOR complex 1 (mTORC1), transforming TAMs into M1 phenotype, thereby reversing tumor-related dysfunction of T cells and NK cells. Therefore, targeting PDK1 may be a new approach for M2 macrophage-enriched solid tumor immunotherapy.

NOTCH1 Signaling Regulates Self-Renewal and Platinum Chemoresistance of Cancer Stem-like Cells in Human Non-Small Cell Lung Cancer.

Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse, and therapeutic resistance, but their specific pathogenic characters in many cancers, including non-small cell lung cancer (NSCLC), have yet to be well defined. Here, we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166+CD49fhiCD104-Lin- LCSC present in all human specimens of NSCLC examined, regardless of their histologic subtypes or genetic driver mutations. This specific cell population was tumorigenic and capable of self-renewal, giving rise to tumor spheres in vitro and orthotopic lung tumors in immune-compromised mice. Mechanistic investigations established that NOTCH1 was preferentially expressed in this cell subpopulation and required for self-renewal via the transcription factor HES1. Through a distinct HES1-independent pathway, NOTCH1 also protected LCSCs from cisplatin-induced cell death. Notably, treatment with a γ-secretase inhibitor that blunts NOTCH1 function ablated self-renewing LCSC activity and restored platinum sensitivity in vitro and in vivo Overall, our results define the pathogenic characters of a cancer stem-like subpopulation in lung cancer, the targeting of which may relieve platinum resistance in this disease. Cancer Res; 77(11); 3082-91. ©2017 AACR.