Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent lipid-peroxide-accumulation-induced membrane lipid peroxidation and mitochondrial atrophy.It differs from other programmed cell deaths in its morphological and biochemical properties.Ferroptosis is regulated by a variety of metabolic pathways that are involved in the acute lung injury induced by hemorrhagic shock,ischemia-reperfusion,sepsis,and radiation.This article reviews the main regulatory mechanisms of ferroptosis and its role in the pathogenesis of acute lung injury in various animal models with the aim of providing new strategies for the prevention and treatment of acute lung injury.

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.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

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 explore the method of intraperitoneal injection of allogenic fecal filtrate to establish the rat model of moderate and severe sepsis． Methods: The preparation method of allogeneic fecal filtrate was determined．Allogeneic fecal filtrate of different concentrations (0. 5，1，2 g / kg) was injected intraperitoneally to observe the general situation，survival time and severe degree of sepsis of rats. After determining the optimal concentration，the success rate of the model，serum inflammatory factors，serum concentration of D-lactic acid ( D-LA) and serum intestinal fatty acid binding protein (I-FABP) ，lung function changes，lung，liver and kidney tissue injury were further observed. Results: After intraperitoneal injection of allogenic fecal filtrate for 24 h，the rats of 1 g / kg group presented fever，tachypnea and hypotension，the survival rate was 83. 3% at 24 h and 16. 7% at 48 h， 2 g / kg group rats all died within 24 h，the dose of 1 g / kg was determined for subsequent experiments．Injected fecal filtrate for 24 h，the success rate of the sepsis model was 77. 8% . The levels of interleukin-6 ( IL-6) ，tumor necrosis factor-α ( TNF-α) ，D-LA and I-FABP in serum significantly increased． There were severe edema and bleeding in lung tissue，Pulmonary function appeared respiratory dysfunction，included functional residual capacity (FRC) ，quasi static compliance ( Cdyn) ，forced expiratory volume for the first 100 milliseconds(FEV100) ，peak expiratory flow (PEF) decreased，airway resistance (RI) ，inspiratory capacity (IC) increased．Liver and kidney tissues also showed varying degrees of edema and inflammatory cell infiltration，the levels of alanine aminotransferase (ALT) ，aspartate aminotransferase (AST) ，blood urea nitrogen (BUN) and creatinine ( Cr) in serum significantly increased． Conclusion Intraperitoneal injection of allogenic fecal filtrate ( 1 g / kg) can produce a relative typical septic model in rats.

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.

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [⁶⁴Cu]DPA and investigated the tumor engagement of [⁶⁴Cu/⁶⁸Ga]DPA in mouse models. Our results revealed that intact [⁶⁴Cu/⁶⁸Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [⁶⁴Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.