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.

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.

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.

Objective: To investigate factors influencing disease severity in children of Han nationality with atopic dermatitis (AD) in China, and to provide scientific evidences for prevention and treatment of AD in children. Methods: From November 2005 to May 2015, data were collected from AD children aged 0-12 years in Department of Dermatology, The First Affiliated Hospital of Anhui Medical University and AD sample collection collaboration network in China. Statistical analysis was carried out with SPSS16.0 software by using univariate and multivariate ordinal logistic regression analysis to investigate factors influencing the severity of AD. Results: A total of 2 620 children with AD were enrolled into the study, including 230 (8.8%) with mild AD, 1 379 (52.6%) with moderate AD and 1 011 (38.6%) with severe AD. As univariate analysis showed, factors influencing the severity of AD included region, early onset, itching during sweating, xeroderma, ichthyosis, palmar hyperlinearity, lichen pilaris, orbital darkening, scalp dermatitis and infra-auricular fissure (all P<0.01) . There were no significant differences in the severity of AD between different genders, patients with and without personal or family atopic history, or between patients with and without a high serum IgE level (all P > 0.05) . Multivariate ordinal logistic regression analysis showed that southern region (OR = 2.10, 95% CI: 1.76 - 2.51) , early onset (OR = 1.32, 95% CI: 1.01 - 1.71) , itching during sweating (OR = 1.70, 95% CI: 1.42 - 2.02) , xeroderma (OR = 2.57, 95% CI: 2.10 - 3.15) , ichthyosis (OR = 1.49, 95% CI: 1.19 - 1.87) , palmar hyperlinearity (OR = 2.03, 95% CI: 1.61 - 2.57) , lichen pilaris (OR = 1.44, 95% CI: 1.17 - 1.78) , orbital darkening (OR = 1.53, 95% CI: 1.24 - 1.89) , scalp dermatitis (OR = 2.38, 95% CI: 2.01 - 2.82) and infra-auricular fissure (OR = 1.55, 95% CI: 1.31 - 1.85) were positively correlated with the severity of AD (all P<0.05) . Conclusion The severity of AD is associated with patients′ region, early onset, itching during sweating, xeroderma, and other concomitant symptoms.

Objective To summarize clinical nursing and management experience of patients with severe influenza viral pneumonia, and to further improve ICU nurses' clinical nursing and management ability in patients with this disease. Methods Retrospective analysis was applied. Clinical nursing and infection prevention and control experience of 36 patients with severe influenza viral pneumonia and acute respiratory distress syndrome in Beijing Chaoyang Hospital between December 2017 and March 2018 were summarized. The main points of nursing included mechanical ventilation nursing, extracorporeal membrane oxygenation nursing, prone position ventilation nursing, infection prevention and control, etc. Results Among the 36 severe influenza viral pneumonia patients, 11 cases died; 22 cases were transferred out/discharged; and the other 3 were still in ICU treatment. The mortality rate was 30.6%, and no cross-infection occurred. Conclusions Comprehensive, overall respiratory support and strict infection prevention and control are the key to the treatment of patients with severe influenza viral pneumonia.

Objective To compare the efficacies of 4 risk models (THRIVE[Totaled Health Risks in Vascular Events],MSS[Multicenter Stroke Survey],HIAT[Houston Intra-Arterial Therapy],and GRASPS[Glucose at presentation,Race,Age,Sex,Systolic blood pressure,Severity of stroke at presentation]) in predicting intracranial hemorrhage and poor outcomes in acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods From May 2013 to March 2016,153 consecutive patients with acute anterior circulation vascular occlusion conducted mechanical thrombectomy within 6 hours after onset and admitted to the Departments of Neurology,Jinling Hospital,Nanjing University School of Medicine and Zhongshan Hospital,Xiamen University were enrolled prospectively.Logistic regression analysis and the area under the receiver operating characteristic (ROC) curve (AUC) were used to investigate the efficacies of 4 risk models (the THRIVE,MSS,HIAT,and GRASPS scores) for predicting intracerebral hemorrhage (including any intracranial hemorrhage events and symptomatic intracranial hemorrhage) and poor outcomes (including 90 d all-cause death and modified Rankin Scale[mRS] score≥3) in acute anterior circulation ischemic stroke after mechanical thrombectomy.Results The MSS score (AUC 0.639,95%CI 0.548-0.730,P=0.004) and GRASPS score (AUC 0.616,95%CI 0.525-0.706,P=0.017) could predict any intracranial hemorrhage events,but the predictive accuracy was low.They had the predictive value for death within 90 d after mechanical thrombectomy,and the GRASPS score (AUC 0.783,95%CI 0.706-0.860,P<0.001) had the moderate predictive accuracy,and the AUC of the other 3 models was all<0.7,the predictive accuracy was low.The models could predict the poor prognosis at 90 d (90 d mRS≥3).The AUCs of both the GRASPS score and THRIVE score were >0.7.The AUC of GRASPS score was the largest (AUC 0.782,95%CI 0.708-0.885,P<0.01).Both had moderate predictive accuracy.Conclusion The GRASPS score had a better clinical predictive value for all-cause death and poor prognosis within 90 d after mechanical thrombectomy.The THRIVE score had a better clinical predictive value for poor prognosis at 90 d.The 4 models predictive value for intracranial hemorrhage events after mechanical thrombectomy should be further examined.

Aim To investigate the effect of sphingo-sine kinase 1 (SphK1 )on unilateral ureteral obstruc-tion(UUO)-induced tubulointerstitial fibrosis and ex-plore the possible mechanism.Methods The CD-1 mice were randomly divided into four groups:sham-op-eration group(Sham),PF-543 treatment control group (Sham +PF-543),model group(UUO)and PF-543 treatment group(UUO +PF-543).On 1 ,3,7 and 1 4 d after operation,eight mice were selected randomly from each group and sacrificed.The protein expressions of SphK1 ,mature TGF-β1 ,FN,ColⅠ,LC3,Beclin1 ,Atg5 and Atg1 2 were observed by Western blot.The histo-logical changes were examined by Masson′s trichrome stain.Immunhistochemistry was performed to measure the levels of expression of SphK1 ,FN and Col Ⅰ. Transmission electron microscope was used to observe the autophagic body.Results SphK1 expression and autophagy were both upregulated in a mouse model of kidney fibrosis induced by UUO. Meanwhile, in-creased mature TGF-β1 and deposition of extracellular matrix(ECM)were observed in tubulointerstitial areas compared with sham-operated mice.After intraperito-neal injection with the SphK1 specific inhibitor PF-543 in UUO mice,enhanced expression of SphK1 and acti-vated autophagy were significantly abrogated.Howev-er,aggravation of renal fibrosis was detected when SphK1 inhibitor PF-543 was applied to suppress SphK1 expression in UUO mice.Conclusion SphK1 activa-tion is renoprotective through the induction of autoph-agy in the pathogenesis of kidney fibrosis.