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Rapamycin is a mammalian target of rapamycin(mTOR) receptor inhibitor. Advances in the understanding of the mTOR signaling pathway and its downstream effects on tumorigenesis and vascular proliferation have broadened the clinical applications of mTOR receptor inhibitors in treating many challenging diseases. Rapamycin is used orally for the treatment of kidney transplantation, lymphatic leiomyomatosis of lung, tuberous sclerosis complex(TSC), and etc. But systemic therapy using the rapamycin has significant side effects. To mitigate the side effects of systemic rapamycin for dermatologic applications, clinicians have used topical therapy. In recent years, research publications on the topical rapamycin in the treatment of a variety of diseases have increased, as on such diseases of facial angiofibroma of tuberous sclerosis complex, lymphatic malformation, Kaposi hemangioendothelioma, tufted angiomas, and etc. Topical rapamycin can be used as an effective long-term therapy while avoiding systemic side effects, providing a new treatment method for dermatologists. This paper discusses the progress in the treatment of topical rapamycin preparations.

A 6-year-old girl presented with recurrent skin rash at the initial stage, recent joint pain, and neutrophilia was found during a routine blood test. After a multidisciplinary case discussion, she was diagnosed with chronic neutrophil leukemia, and the symptoms were relieved after hydroxyurea and luxolitinib treatment. She received the allogeneic hematopoietic stem cell transplantation subsequently. At present, she is in stable condition and under follow-up. Chronic neutrophil leukemia is a rare disease, which rarely occurs in children. It is more difficult to diagnose in patients with skin rash as the first manifestation. The diagnosis and treatment of this case reflects the important role of multidisciplinary cooperation in the diagnosis and treatment of difficult and rare diseases.

Objective To summarize the clinical and genetic features of children with autosomal dominant and recessive hyperimmunoglobulin E syndrome (HIES). Methods HIES patients were studied at the dermatology department of Beijing Children's Hospital, Capital Medical University were collected, from January 2013 to December 2021, diagnosed by both clinical manifestation and genetic assessment. The general data were summarized, the clinical and genetic characteristics were analyzed, and the similarities and differences between autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES) were compared. Results A total of 7 children with HIES were studied, including 3 cases of AD-HIES and 4 cases of AR-HIES. There were 4 males and 3 females. All children had recurrent eczema-like lesions, recurrent skin and pulmonary infections, and elevated serum IgE and eosinophil levels. The differences between AD-HIES and AR-HIES mainly include: the main cutaneous infection in 3 children with AD-HIES were bacterial infections (such as abscess and impetigo), while in 4 children with AR-HIES, cutaneous infections were mostly severe viral infection (such as verruca vulgaris and molluscum contagiosum). There were pulmonary parenchymal changes (such as pneumatoceles, cyst and atelectasis) in 3 children with AD-HIES, whilst there were no similar changes in the lungs of 4 children with AR-HIES; 75% of children with AR-HIES had allergic diseases (including asthma and food allergy), while there were no reports of allergic diseases in children with AD-HIES. As for manifestations outside of immune system, AD-HIES was more likely to appear facial dysmorphism(such a broad nasal bridge and a high-arched palate). Furthermore, the incidence of tumor in AR-HIES was higher than that in AD-HIES. AD-HIES was mainly caused by the mutation of STAT3 gene, and AR-HIES was mainly caused by the mutation of DOCK8 gene. We reported two new mutation sites of DOCK8 gene c.1798-2A > T and c.874G > A in two cases, respectively. Conclusions For children with clinical manifestations of recurrent eczema-like lesions, repeated infection and significant increase in serum IgE levels, HIES should be suspected, and genetic screening should be carried out to make definite diagnosis and classification, to achieve better long-term management and improve prognosis.

Background: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory cutaneous disease. IL-36 is a key treatment target in GPP. Spesolimab, a humanized monoclonal antibody of the IL-36 receptor, has demonstrated a good efficacy and a favorable safety profile in adults with GPP. However, data on its use in children are scarce. Methods: We treated patients aged 4– 12 years with GPP with a single dose of spesolimab. The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score, GPPGA pustulation sub-score, Generalized Pustular Psoriasis Area and Severity Index (GPPASI), and the Japanese Dermatological Association severity index for GPP were evaluated. The levels of IL-36α, IL-36β, and IL-36γ were detected by the magnetic bead-based immunoassays, and the levels of IL-17A, IL-17C, IFN-γ, TNF, IL-6, and IL-8 were measured by the Olink proximity extension assay technology. Results: We included five patients (four boys and one girl) with a median age was 6.9 years old (range: 4.8 to 10.6 years), and a median age of onset of 1.7 years (range: 3 months– 10 years and 5 months). After 1 week of spesolimab administration, all patients had a total GPPGA score of 0/1 and pustulation subscore of 0, all patients had a GPPASI of 50, and four patients had a GPPASI of 75. Meanwhile, plasma levels of IL-36α, IL-36β, IL-36γ, IL-17A, IL-17C, IFN-γ, TNF, IL-6, IL-8 all decreased, and those of IL-36α, IL-36β, IL-17A, IL-17C, and IL-6 were statistically significant. There was no recurrence after 2 to 8 months of treatment. No other adverse event was recorded apart from one patient who experienced an upper respiratory infection in the first week. Conclusion: Spesolimab might be a prospective option for children aged 4 to 12 years. [ABSTRACT FROM AUTHOR]

To assess the clinical efficacy and adverse reactions of 595nm PDL for treating pediatric PWS and to identify factors influencing treatment outcomes. Methods: This retrospective study included 974 pediatric patients with PWS treated at Beijing Children's Hospital from 2003 to 2021. Inclusion criteria required patients to be under 18, with solitary PWS and Fitzpatrick skin types II–IV. Treatment efficacy was evaluated using standardized photographs taken before and after treatment, with outcomes categorized by Achauer's clearance criteria. Ridit analysis assessed the impact of variables such as gender, age, lesion location, and treatment frequency on outcomes. Results: The overall efficacy rate was 65.3%, higher in females (69.7%) than males (59.7%). Adolescents had the highest efficacy (100%) due to better compliance. Limb lesions responded best (87.5%), followed by neck (75.0%), trunk (66.7%), and head/face (63.0%). Smaller lesions (≤ 3 cm²) achieved 76.8% efficacy. Efficacy rose with sessions, reaching 84.0% after three. The mandibular branch (V3) had the highest trigeminal efficacy (68.5%). Adverse reactions (4.31%) included pigmentation changes (2.87%), hypopigmentation (1.03%), and minimal scarring (0.41%). Conclusion: The efficacy of 595nm PDL for treating PWS in children is influenced by gender, age, lesion location, size, and the number of treatment sessions. PDL is an effective treatment for pediatric PWS with minimal adverse reactions. [ABSTRACT FROM AUTHOR]

Background Lipid metabolism has essential roles in skin barrier formation and the regulation of skin inflammation. Lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization. Objectives To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant. Methods Whole-exome sequencing was performed to identify underlying genetic variants. Quantitative polymerase chain reaction, Western blot and immunofluorescence staining were used to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of mutant SREBP-1 was determined by a luciferase reporter assay. A transgenic zebrafish model was constructed. Results Two unrelated patients presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C>A (p.Ser430*) in SREBF1 in both patients. The variant encoded a truncated protein that showed preferential nucleus localization, in contrast to wild-type SREBP-1 which – in sterol-sufficient conditions – is mainly localized in the cytoplasm. The luciferase reporter assay revealed that the p.Ser430* mutant exhibited enhanced transcriptional activity. Cultured patient primary melanocytes showed increased melanin synthesis vs. those from healthy controls. At 35 days postfertilization, the p.Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes. Conclusions We demonstrated that a gain-of-function variant of SREBF1 causes a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development, and paves the way for the development of novel therapeutic targets for skin dyspigmentation or cataracts. [ABSTRACT FROM AUTHOR]

Mupirocin, an antibiotic produced by Pseudomonas fluorescens, is mainly used for the topical treatment of various skin and soft tissue infections caused by Staphylococcus (including methicillin-resistant Staphylococcus aureus) and Streptococcus around the world for decades. Nevertheless, the clinical application scope of mupirocin varies in different countries due to differences in their medical policies, prescription types, and drug resistance. According to the experience of Chinese doctors in the past few years, mupirocin presented low drug resistance rates, and could be used as a treatment option for various primary infections and secondary infections, with antibacterial effects in a broad application. In this review, we summarized the experience of mupirocin used in the Chinese population and discussed its clinical value to provide novel insights and inspiration for physicians. [ABSTRACT FROM AUTHOR]

Challenges related to seismic performance and seismic mitigation are more pronounced in the presence of weak interlayers compared to typical layered soil conditions. This study focuses on a double-layer double-span rectangular frame subway station structure. A coupled static–dynamic finite element analysis model of the soil-structure system is established by using the finite element software ABAQUS/CAE V 6.14. The research investigates the influence of factors such as interlayer thickness, location, and strength on the seismic response of subway station structures. Furthermore, in order to evaluate the effectiveness of FPB in mitigating seismic effects in the weak interlayer ground, two different schemes are proposed in this paper. One is the structure without FPB and the other is the structure with FPB on the top of the central column. The findings reveal that weak interlayers exert a significant influence on the seismic response of subway station structures, especially when these lower-strength weak interlayers are located within the central portion of the subway station structure and exhibit considerable thickness. The FPB on the top of the central column can reduce the overall lateral stiffness of the subway station structure. This, in turn, results in a slight increase in the deformation of sidewall and inter-story displacement angles, accompanied by a marginal exacerbation of sidewall damage. However, the implementation of FPB effectively reduces the deformation of the central column and substantially mitigates the extent of damage to the central column. [ABSTRACT FROM AUTHOR]

Background Inherited hyperpigmented skin disorders comprise a group of entities with considerable clinical and genetic heterogenicity. The genetic basis of a majority of these disorders remains to be elucidated. Objectives This study aimed to identify the underlying gene for an unclarified disorder of autosomal-dominant generalized skin hyperpigmentation with or without glomuvenous malformation. Methods Whole-exome sequencing was performed in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. Variants were confirmed using Sanger sequencing and a minigene assay was employed to evaluate the splicing alteration. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the quantity of melanocytes and melanosomes in hyperpigmented skin lesions. GLMN knockdown by small interfering RNA assays was performed in human MNT-1 cells to examine melanin concentration and the underlying molecular mechanism. Results We identified five variants in GLMN in five unrelated families, including c.995_996insAACA(p.Ser333Thrfs*11), c.632 + 4delA, c.1470_1473dup(p.Thr492fs*12), c.1319G > A(p.Trp440*) and c.1613_1614insTA(Thr540*). The minigene assay confirmed that the c.632 + 4delA mutant resulted in abolishment of the canonical donor splice site. Although the number of melanocytes remained unchanged in skin lesions, as demonstrated by immunofluorescent staining of tyrosinase and premelanosome protein, TEM revealed an increased number of melanosomes in the skin lesion of a patient. The GLMN knockdown MNT-1 cells demonstrated a higher melanin concentration, a higher proportion of stage III and IV melanosomes, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6 K vs. mock-transfected cells. Conclusions We found that loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. Our study implicates a potential role of glomulin in human skin melanogenesis, in addition to vascular morphogenesis. [ABSTRACT FROM AUTHOR]

Importance: Postzygotic mutations in the GNAQ/GNA11 genes, which encode the G‐protein nucleotide binding protein alpha subunits, have been identified in patients with phakomatosis pigmentovascularis (PPV). However, little is known about the Chinese population. Objective: To identify pathogenic mutations in pediatric patients with PPV within the Chinese population. Methods: We performed whole‐exome sequencing (WES) using skin lesion tissues from pediatric patients diagnosed with PPV. Additionally, ultradeep‐targeted sequencing was conducted to validate the somatic mutations. A genotype‐phenotype correlation was analyzed by integrating data from previous reports with the findings of the present study. Results: Thirteen patients were enrolled, all diagnosed with the cesioflammea type of PPV, except for one patient with an unclassifiable type. We identified somatic GNA11 c.547C>T (p.R183C) variant in seven patients and GNAQ c.548G>A (p.R183Q) in four patients, with low allelic fractions ranging from 2.1% to 8.6% through ultradeep sequencing. Besides, a GNAQ c.548G>A (p.R183Q) variant was detected through targeted sequencing in one of two patients who did not exhibit detectable variants via WES. The genotype‐phenotype correlation analysis, involving 15 patients with a GNA11 variant and 10 with a GNAQ variant, revealed that facial capillary malformation (87% vs. 50%, P = 0.075) and ocular melanocytosis (80% vs. 40%, P = 0.087) appeared to be more frequent in patients with GNA11 mutation compared to those with GNAQ mutations. All four patients diagnosed with cesiomarmorata type or overlapping cesioflammea and cesiomarmorata type PPV carried the GNA11 variant. Interpretation: Our study demonstrated that the majority of PPV patients in the Chinese population carried a postzygotic variant of GNAQ/GNA11, thus further confirming the pathogenic role of GNAQ/GNA11 mosaicism in the development of PPV cesioflammea type. [ABSTRACT FROM AUTHOR]

Two new species, Macropelopia (Macropelopia) excavata Xu & Fu, sp. nov. and Macropelopia (Macropelopia) quadrimacula Xu & Fu, sp. nov., are described as male adults. A key to identify the males of Macropelopia from China is provided. Furthermore, in order to ascertain the genetic distance between these species and their morphological characteristics, mitochondrial cytochrome c oxidase subunit I gene sequences were uploaded to the National Center for Biotechnology Information. These COI sequences were then utilized to infer the relationships between the species, employing the neighbor-joining method. [ABSTRACT FROM AUTHOR]

The article discusses a rare case of Lipodystrophia centrifugalis abdominalis infantilis (LCAI) in a 4-year-old boy with a giant ulceration on his lower abdomen. Traditional treatments failed, but a combination of hydroxychloroquine (HCQ) and baricitinib led to significant improvement and complete healing of the ulcer. The authors suggest that this treatment approach may be effective for severe ulcerations in LCAI cases, highlighting the potential benefits of these medications in managing such conditions. [Extracted from the article]

Background: Stratum corneum (SC) plays a critical role in skin barrier function for protection and defense in nature. The acidic skin pH, which is also known as the acid mantle, is very important in fighting against outer environmental threats, especially, bacteria. Furthermore, recent research has shown that the transient bacteria could potentially penetrate into deeper layer of the SC down to a few micrometers while posing an additional threat to the deeper layers of the skin. Aim: To develop a sequential tape stripping method for assessing the impact of personal cleansing product on the SC surface layers' acid mantle properties and antimicrobial defense against transient bacteria. Methods: Fifty‐five subjects were recruited. High pH soap‐based Product 1 and low pH synthetic surfactant‐based Product 2 were applied on the left and right forearms of each subject. Sequential tape stripping was performed on the same spots to access multiple layers of the skin SC. Both antimicrobial defense property and skin pH of different skin layers were evaluated at baseline and 12 h after treatment. Results: The skin's antimicrobial defense was significantly higher 12 h after treatment of the low pH Product 2 as compared to the treatment of high pH Product 1. In fact, this trend was consistent across all three skin layers (Layer 1 to Layer 3) as measured in this study (p < 0.01). Furthermore, the skin surface pH of Layer 1 and Layer 3 were also lower 12 h after the treatment of low pH Product 2 as compared to that of the high pH Product 1 (p < 0.01). Conclusion: The results of this investigation demonstrated the benefits of 12‐h long lasting and deeper protection of SC acid mantle properties and antimicrobial defense using a low pH skin cleansing product as compared to a high pH product. [ABSTRACT FROM AUTHOR]

This article discusses a rare genetic disorder called Hypotrichosis with juvenile macular dystrophy (HJMD). HJMD is characterized by short and sparse hair at birth and progressive visual impairment due to mutations in the CDH3 gene. The article presents two families with HJMD and describes the specific mutations found in each family. Ophthalmic examinations revealed retinal abnormalities in the patients. The article also mentions the importance of the extracellular domains of the P-cadherin protein encoded by CDH3 and the potential for retinal gene therapy as a treatment option. [Extracted from the article]

This article discusses the case of a 6-year-old girl with inflammatory linear verrucous epidermal naevus (ILVEN), a rare skin disorder characterized by pruritic erythematous hyperkeratotic papules. The patient was found to have a somatic mutation in the CARD14 gene and was successfully treated with secukinumab. ILVEN is a heterogeneous group of Blaschko-linear inflammatory conditions, and genetic analysis is important for accurate diagnosis. The article also provides a table summarizing other diseases with genetic mutations that can manifest as ILVEN. The study was supported by the Beijing Natural Science Foundation. [Extracted from the article]

Introduction: Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. Materials and Methods: The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. Results: Forty‐five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. Conclusions: The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH. [ABSTRACT FROM AUTHOR]

This article discusses a retrospective case series conducted in China on lipodystrophia centrifugalis abdominalis infantilis (LCAI), a localized atrophic disease. The study analyzed the clinicopathological characteristics, treatment outcomes, and prognosis of 127 patients with LCAI. The patients were divided into two groups based on the stage of their condition. Treatment options included topical agents, hydroxychloroquine, and glucocorticoids. The study found that hydroxychloroquine or glucocorticoids were more effective than topical agents in treating LCAI. The maximum follow-up period was 17 years, and some patients showed complete recovery or partial improvement. The study also noted a possible relationship between LCAI and lupus erythematosus panniculitis. This research provides valuable insights into the treatment and management of LCAI. [Extracted from the article]