Objective:To analyze the clinical manifestations, laboratory results and treatment outcomes of juvenile localized scleroderma(JLS).Methods:This was a retrospective case series study.Epidemiological and clinical data of patients with JLS treated in the Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from January 2019 to August 2021 were analyzed.Results:Among the 228 children, there were 95 males and 133 females, with a male-to-female ratio of 1.0∶1.4.The median age of onset was 67 months(5.6 years), and the time from onset to diagnosis was 1 month to 106 months.Eight patients(3.5%) had suspected predisposing factors before onset, 25 patients(11.0%) had other diseases at the same time, and 3 patients(1.3%) had a family history of autoimmune diseases.The most common clinical type of JLS was circumscribed morphea(101 cases, 44.3%), followed by linear scleroderma(91 cases, 39.9%), generalized morphea(31 cases, 13.6%), mixed scleroderma(23 cases, 10.1%) and pansclerotic morphea(2 cases, 0.9%).Among them, 76 patients(46.3%) were antinuclear antibody(ANA) positive, and 14 patients(15.0%) were extractable nuclear antigen antibody(ENA) positive.Ninety-one of patients with circumscribed morphea were treated with medium and strong corticosteroids, vitamin D3 derivatives or calcineurin inhibitors.Patients of other types received systemic corticosteroid treatment, with an initial dose range of 1-2 mg/kg and a maximum dose of 60 mg/d.Among them, 72 patients were additionally treated with Methotrexate, with an initial dose range of 10-15 mg/m 2, once a week, and 9 patients were additionally treated with biological agents.The follow-up results showed that the skin symptoms of the patients who were followed up in the dermatology outpatient department had improved to a certain extent and could remain inactive. Conclusions:Children with JLS in the dermatology department are mainly preschool- and school-age.Circumscribed morphea is the most common type, mainly treated with glucocorticoids, vitamin D3 derivatives or calcineurin inhibitors.No specific laboratory test index is found.Corticosteroids combined with Methotrexate are recommended for systematic treatment of other types of JLS.

Objective:To compare the efficacy and safety of biologics versus methotrexate in the treatment of severe pediatric plaque psoriasis.Methods:A retrospective matched case-control study was carried out. Twenty children with severe plaque psoriasis from Beijing Children′s Hospital, Capital Medical University from June 2016 to November 2021 were included in this study, and the patients treated with biologics (adalimumab or secukinumab) were matched with those treated with methotrexate at a ratio of 1∶1 according to the psoriasis area and severity index (PASI) score and age. PASI, physician′s global assessment (PGA) , and body surface area (BSA) scores were assessed at weeks 4, 8 and 12 after the start of treatment, and adverse drug reactions were recorded. Statistical analysis was mainly carried out by using Mann-Whitney U test, Fisher′s exact test and generalized estimating equations. Results:At weeks 4 and 8, the proportions of patients achieving PASI75 and PASI90 were significantly higher in the biologics group (PASI75: 7/10, 10/10, PASI90: 5/10, 9/10, respectively) than in the methotrexate group (PASI75: 1/10, 5/10, PASI90: 0, 1/10, respectively; all P < 0.05) , while there was no significant difference between the biologics group and methotrexate group at week 12 (PASI75: 10/10 vs. 8/10, PASI90: 9/10 vs. 4/10, both P > 0.05) . There were no significant differences in the PASI, BSA or PGA scores between the two groups at baseline (all P > 0.05) , while the biologics group showed significantly decreased PASI and BSA scores at weeks 4, 8 and 12, and significantly decreased PGA score at week 8 compared with the methotrexate group (PASI: Z = 2.50, 3.56, 2.63, respectively; BSA: Z = 2.87, 3.57, 2.40, respectively; PGA: Z = 2.81; all P<0.05) . Analysis of changes over time showed that the PASI, PGA and BSA scores in the biologics group significantly decreased at weeks 4, 8 and 12 compared with those at baseline (all P<0.01) ; the PASI and PGA scores significantly decreased at weeks 8 and 12 compared with the corresponding scores at week 4 (all P<0.05) ; however, there were no significant differences in the PASI, PGA or BSA scores between week 12 and 8 (all P>0.05) . In the methotrexate group, the PASI, PGA and BSA scores at weeks 4, 8 and 12 were all significantly lower than the corresponding scores at the previous adjacent time points (all P<0.05) . There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.650) , and no serious adverse reactions occurred in either group. The main adverse reaction was infection in the biologics group, while infection and elevation of transaminase levels were common in the methotrexate group. Conclusion:Biologics and methotrexate were both effective and safe for the treatment of severe pediatricplaque psoriasis, and biologics facilitated rapider achievement of PASI75 and PASI90 compared with methotrexate.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

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.

Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.

Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration, and apoptosis. Fibroblast growth factor receptor 1 (FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However, the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATP-dependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48 inhibited cell proliferation in CRC cells (HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft (PDX) murine tumor models, we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1 kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC.

Objective:To investigate efficacy and safety of topical sirolimus cream in the treatment of superficial vascular malformation in children.Methods:A single-center prospective study was carried out. Children with superficial vascular malformation were enrolled into this study from Vascular Anomalies Clinic, Beijing Children′s Hospital, Capital Medical University from September 2019 to September 2020, and treated with 0.1% sirolimus cream. The efficacy was evaluated according to an international four-level classification system through imaging examination, dermoscopy and subjective evaluation, and adverse reactions during the treatment were monitored. Statistical analysis was carried out by t test, univariate analysis of variance or Fisher′s exact test. Results:A total of 19 children with superficial vascular malformations were enrolled, including 12 males and 7 females, aged 1 - 11.5 years. Fourteen children were diagnosed with vascular and lymphatic malformations, 3 with lymphatic malformations, and 2 with venous malformations. Sixteen children presented with lesions on the lower extremities, 8 were accompanied by pain, 2 presented with ulceration, and 6 had previous treatment history. After 6-month treatment, 3 patients achieved improvement of level Ⅰ, 4 of level Ⅱ, 4 of level Ⅲ, and 8 of level Ⅳ; 16 achieved improvement, and 12 achieved marked improvement. Six patients showed significantly decreased length, thickness and width of lesions after 6 months of treatment (1.83 ± 0.84 cm, 1.00 ± 0.55 cm, 2.25 ± 1.25 cm, respectively) compared with those before treatment (2.40 ± 0.95 cm, 1.35 ± 0.61 cm, 2.50 ± 1.34 cm, t = 5.22, 10.25, 3.73, respectively, all P < 0.05) . Gender, age, medical history and pain sensation did not significantly affect the therapeutic effect (all P > 0.05) , while diagnostic classification of vascular malformations significantly affected the therapeutic effect ( P = 0.008) . Among the 19 children, 2 had mild local burning sensation after the treatment. After 1- and 6-month treatment, the blood concentrations of sirolimus were both below 1.0 ng/ml. Conclusion:Topical sirolimus is effective and safe in the treatment of superficial vascular malformation in children.

Objective:To investigate clinical characteristics of pediatric psoriasis based on the information systems from two children′s hospitals.Methods:Clinical data on outpatients confirmly diagnosed with pediatric psoriasis were collected from information systems of Beijing Children′s Hospital affiliated to Capital Medical University and Children′s Hospital of Chongqing Medical University from January 1, 2015 to December 31, 2019, and a clinical and epidemiological investigation was conducted. Statistical analysis was carried out by using t test and chi-square test. Results:A total of 5 235 children with psoriasis were included, with the ratio of male to female being 1∶1.08. Their age at the clinic visit ( M [ Q1, Q3]) was 8.37 (6.48, 10.50) years, and the school-age children were the most common population; their age at onset was 7.57 (5.37, 9.82) years. Among the 5 235 children with psoriasis, there were 3 195 (60.82%) with psoriasis vulgaris, 281 (5.37%) with pustular psoriasis, 19 (0.36%) with erythrodermic psoriasis, and 1 (0.02%) with psoriatic arthritis. The trunk (87.76%, 1 097/1 250) was most frequently affected, followed by the limbs (87.68%, 1 096/1 250) , the scalp (62.56%, 782/1 250) , and the face and neck (35.76%, 477/1 250) . Among the 5 235 patients, 4 319 (82.50%) received topical treatments, 177 (3.38%) received systemic treatments, and 832 (15.89%) were treated with antibiotics. Among 3 497 children who received initial treatment regimens, the disease could be controlled in 3 423 (97.88%) without change in treatment regimens, while treatment regimens needed to be adjusted in 2.12%. Conclusions:In the two children′s hospitals, most children with psoriasis developed this condition and visited the clinic at school age, and the predominant clinical type was psoriasis vulgaris. Most skin lesions were extensive, and commonly occurred on the trunk and limbs. Scalp involvement was not uncommon. The condition could be controlled by topical treatments in most children with psoriasis, while a few patients needed systemic treatments.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

  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.