ObjectiveTo investigate the metabolic alterations of serum short chain fatty acids （SCFAs） in pediatric patients with atopic dermatitis （AD） and their correlation with different clinical phenotypes using targeted metabolomics. MethodsThis study enrolled 87 AD patients and 67 healthy controls （HC）. Serum levels of eight SCFAs were quantified by ultra-high-performance liquid chromatography-mass spectrometry. The associations between SCFAs and AD were assessed using various statistical methods. ResultsCompared with the HC group， levels of acetic acid （AA）， propionic acid （PA）， and caproic acid （CA） （P=0.002，P=0.002，P=0.043） decreased in the AD group. Logistic regression analysis identified AA （OR=0.449， 95% CI： 0.289–0.698） and PA （OR = 0.487， 95% CI： 0.324–0.732） as protective factors against AD. The combination of AA and PA yielded an area under the curve （AUC） greater than 0.7， indicating good diagnostic efficacy. Age-stratified analysis revealed that AA reduction was predominant in childhood， whereas PA reduction was predominant in adolescence. Pathway enrichment analysis showed significant enrichment of fatty acid biosynthesis （FDR=0.341， P=0.003） and vitamin K metabolism （FDR=1， P=0.039） pathways. Furthermore， subgroup analyses based on disease severity， personal/family history of atopy， and sex revealed no significant differences in SCFAs levels among the groups. ConclusionDifferential serum SCFAs and their enriched metabolic pathways may be implicated in the pathogenesis of AD.

Objective:To investigate differences in serum lipid profiles between patients with dermatomyositis (DM) and healthy controls.Methods:A retrospective analysis was conducted on the clinical data and serum samples collected from 51 patients with DM who visited the First Affiliated Hospital, Anhui Medical University from September 2020 to January 2022. Serum samples were also collected from 66 healthy controls during the same period. Serum lipid profiles were analyzed using ultra-performance liquid chromatography-mass spectrometry in both groups. Differential lipids were screened using principal component analysis and orthogonal partial least squares-discriminant analysis. The predictive value of these differential lipids for DM was evaluated by receiver operating characteristic (ROC) curve analysis, and their correlations with clinical indicators were also evaluated.Results:A total of 51 patients with DM were enrolled, including 27 males and 24 females, with ages ( M[ Q1, Q3]) of 55.00 (47.00, 66.00) years and body mass index (BMI) values of 22.64 (19.79, 24.75) . The control group included 66 healthy individuals (33 males and 33 females) , with ages of 51.00 (43.75, 56.00) years and BMI values of 23.60 (21.18, 25.19) . No significant differences were observed between the two groups in terms of sex, age, or BMI (all P > 0.05) . A total of 341 lipid metabolites were identified, and 16 lipid metabolites such as ceramides (Cer) , sphingomyelins, phosphatidylcholines (PC) , phosphatidylethanolamines, lysophosphatidylcholines (LPC) , and triglycerides (TG) significantly differed between the DM group and the control group, of which 8 were upregulated and 8 were downregulated in the DM group. ROC curve analysis identified 7 differential lipids with area under the curve (AUC) values of > 0.9, of which 2 were Cer, 3 were TG, 1 was phosphatidylethanolamine, and 1 was LPC. In the DM patients, serum LPC (22∶1) levels were negatively correlated with creatine kinase isoenzyme MB levels ( r = -0.276, P < 0.05) , serum PC (15∶1/16∶0) levels were negatively correlated with aspartate aminotransferase levels ( r = -0.305, P < 0.05) , and serum Cer (d18∶1/18∶0) levels were positively correlated with C-reactive protein levels ( r = 0.283, P < 0.05) . Significant differences in serum lipid levels were observed between some DM subgroups (all P < 0.05) : sphingomyelin (d24∶0) levels significantly differed between anti-Sj?gren syndrome type A/Ro52 antibody-positive and -negative DM patients; LPC (17∶1) levels significantly differed between anti-PM-SCL75 antibody-positive and -negative DM patients; LPC (20∶0) and PC (32∶1p) levels significantly differed between anti-Mi-2 antibody-positive and -negative DM patients; LPC (22∶1) and TG (9∶0/9∶0/9∶0) levels significantly differed between anti-TIF1-γ antibody-positive and -negative DM patients; Cer (d18∶1/18∶0) levels significantly differed between DM patients with and without Heliotrope's sign. Conclusion:Lipid profiles were significantly altered in DM patients compared with healthy controls, and some lipids showed potential diagnostic value for DM.

Objective : To investigate the mechanism of action of benvitimod (BVM) in the treatment of atopic der- matitis (AD) . Methods : HaCaT cells were stimulated by TNF-α and IFN-γ , and the cells were grouped into NC group , TNF-α/IFN-γ group , TNF-α/IFN-γ BVM group , and TNF-α/IFN-γ BVM ML385 group. The AD model of DNCB-induced Balb/c mice was divided into CON group , DNCB group , DNCB + BVM group , and DNCB + TAC group. The efficacy of BVM and its roles in antioxidant and pyroptosis regulation were evaluated. Results: Compared with the control group , BVM inhibited the inflammatory response of HaCaT cells stimulated by TNF-α and IFN-γ , and ameliorated the skin lesions and inflammation in the DNCB-induced AD mouse model ; at the same time , it significantly increased the expression of nuclearfactorerythroid-2-relatedfactor2 (NRF2)-related anti-oxida- tive stress proteins , and significantly reduced the expression of cellular reactive oxygen species (ROS) levels and pyroptosis proteins. At the same time , the levels of NRF2-related antioxidative stress proteins significantly in- creased , and the levels of ROS and pyroptosis proteins significantly decreased. Conclusion BVM activates the NRF2/ROS/NLRP3 pathway to inhibit pyroptosis , thereby reducing the inflammatory response in AD.

Objective:To investigate differences in serum lipid profiles between patients with dermatomyositis (DM) and healthy controls.Methods:A retrospective analysis was conducted on the clinical data and serum samples collected from 51 patients with DM who visited the First Affiliated Hospital, Anhui Medical University from September 2020 to January 2022. Serum samples were also collected from 66 healthy controls during the same period. Serum lipid profiles were analyzed using ultra-performance liquid chromatography-mass spectrometry in both groups. Differential lipids were screened using principal component analysis and orthogonal partial least squares-discriminant analysis. The predictive value of these differential lipids for DM was evaluated by receiver operating characteristic (ROC) curve analysis, and their correlations with clinical indicators were also evaluated.Results:A total of 51 patients with DM were enrolled, including 27 males and 24 females, with ages ( M[ Q1, Q3]) of 55.00 (47.00, 66.00) years and body mass index (BMI) values of 22.64 (19.79, 24.75) . The control group included 66 healthy individuals (33 males and 33 females) , with ages of 51.00 (43.75, 56.00) years and BMI values of 23.60 (21.18, 25.19) . No significant differences were observed between the two groups in terms of sex, age, or BMI (all P > 0.05) . A total of 341 lipid metabolites were identified, and 16 lipid metabolites such as ceramides (Cer) , sphingomyelins, phosphatidylcholines (PC) , phosphatidylethanolamines, lysophosphatidylcholines (LPC) , and triglycerides (TG) significantly differed between the DM group and the control group, of which 8 were upregulated and 8 were downregulated in the DM group. ROC curve analysis identified 7 differential lipids with area under the curve (AUC) values of > 0.9, of which 2 were Cer, 3 were TG, 1 was phosphatidylethanolamine, and 1 was LPC. In the DM patients, serum LPC (22∶1) levels were negatively correlated with creatine kinase isoenzyme MB levels ( r = -0.276, P < 0.05) , serum PC (15∶1/16∶0) levels were negatively correlated with aspartate aminotransferase levels ( r = -0.305, P < 0.05) , and serum Cer (d18∶1/18∶0) levels were positively correlated with C-reactive protein levels ( r = 0.283, P < 0.05) . Significant differences in serum lipid levels were observed between some DM subgroups (all P < 0.05) : sphingomyelin (d24∶0) levels significantly differed between anti-Sj?gren syndrome type A/Ro52 antibody-positive and -negative DM patients; LPC (17∶1) levels significantly differed between anti-PM-SCL75 antibody-positive and -negative DM patients; LPC (20∶0) and PC (32∶1p) levels significantly differed between anti-Mi-2 antibody-positive and -negative DM patients; LPC (22∶1) and TG (9∶0/9∶0/9∶0) levels significantly differed between anti-TIF1-γ antibody-positive and -negative DM patients; Cer (d18∶1/18∶0) levels significantly differed between DM patients with and without Heliotrope's sign. Conclusion:Lipid profiles were significantly altered in DM patients compared with healthy controls, and some lipids showed potential diagnostic value for DM.

OBJECTIVE: To explore the genetic basis for a child with café-au-lait macules and juvenile xanthogranuloma. METHODS: Clinical data and peripheral blood samples of the patient and her family members were collected and subjected to targeted capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: A deletional variant in exon 23 of the NF1 gene was detected in the proband. Sanger sequencing has verified it as a de novo variant, which was highly correlated with the clinical manifestations of the patient and her mother. The diagnosis of neurofibromatosis 1 (NF1) was established. The variant was unreported previously. CONCLUSION Targeted capture and next-generation sequencing combined with Sanger sequencing can facilitate early diagnosis of NF1 and provide a basis for the clinical treatment, genetic counseling and prenatal diagnosis.
Child ; Female ; Humans ; Cafe-au-Lait Spots/genetics* ; Genes, Neurofibromatosis 1 ; Neurofibromatosis 1/genetics* ; Xanthogranuloma, Juvenile/genetics*

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

A pedigree with familial acanthosis nigricans presenting with atypical clinical symptoms was reported. The 4-year-old female proband began to develop black patches on the neck and abdomen since the age of 1 year, which had gradually spread to the lips and front of the trunk in recent years. Reflectance confocal microscopy of the abdominal skin showed downward extension and twisting of dermal papillary rings with formation of gully-like structures, and moderately to highly refractive particles in the dermal papillary rings. The proband′s father and grandmother had similar medical history, but the pigmentation spontaneously subsided with age, leaving only local thickened skin lines. Peripheral blood samples were collected from the proband, her parents and grandmother, and panel-based targeted sequencing of peripheral blood DNA was performed for the proband. Sequencing showed a missense mutation c.1949A>C (p.Lys650Thr) in exon 14 of the FGFR3 gene in the proband, and Sanger sequencing confirmed the presence of this mutation in the proband and her father and grandmother. A diagnosis of familial acanthosis nigricans was made.

With the development of transcriptomic technologies such as gene chip technology and RNA sequencing technology, important related factors in the pathogenesis of atopic dermatitis (AD) have been gradually identified, such as different T helper (Th) cell subtypes and other immune-related cells (macrophages and Langerhans cells) ; abnormal changes in active substances such as interleukin-4, interleukin-13, fillagrin and loricrin released by immune-related cells such as Th2 cells and keratinocytes have been found to play major roles in pruritus and skin barrier damage in AD. In recent years, transcriptomic technologies have been applied to the analysis of changes in transcriptomic profiles of patients before and after treatment to evaluate patients′ condition and therapeutic effect. This review summarizes research progress in transcriptomics in AD in recent years.

Epidermal barrier defects and immune abnormalities are the main pathophysiological changes in the development of atopic dermatitis (AD) . Skin keratinocytes can release a variety of inflammatory factors and mediators under the treatment with various harmful factors. Three epithelium-derived cytokines interleukin (IL) -33, IL-25 and thymic stromal lymphopoietin are considered to be effective inducers of Th2 immune response in skin or mucosal barrier, which can activate immune cells, cause the secretion of Th2 cytokines, enhance the Th2 immune response, and participate in the occurrence and development of AD. This review focuses on the role of the above 3 epithelium-derived cytokines in the pathogenesis of AD.

Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway plays an important role in immune pathways in atopic dermatitis (AD) . Drugs that block the JAK-STAT signaling pathway, such as classic JAK inhibitors tofacitinib, ruxolitinib, etc., have been gradually applied to the treatment of AD in clinical trials, and good clinical efficacy has been achieved. In addition, other inhibitors of the JAK-STAT signaling pathway, such as apamin and dupilumab, also show some efficacy in the treatment of AD. This review summarizes recent studies on the JAK-STAT signaling pathway and its inhibitors.