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.

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 investigate the prevalence of skin diseases in pre-school children aged 0-7 years in cities of China.Methods From November 2014 to April 2015,12 cities were chosen as survey spots,and pre-school children aged 0-7 years served as respondents.A population-based study was conducted,and 40 vaccination clinics and 80 kindergartens were selected by stratified random sampling.A questionnaire survey and dermatological examination were performed by trained dermatologists.Results A total of 20 033 pre-school children received questionnaires,whose age was 2.41 ± 1.82 years (range,0.08-6.83 years).Among these respondents,7 823 children were found to have skin diseases,with the total prevalence of skin diseases being 39.05％ (7 823/20 033).Additionally,the prevalence of skin diseases reported in the 12 cities from high to low was as follows:66.96％ (612/914,Dalian),56.73％ (2 310/4 072,Shanghai),55.49％ (556/1 002,Wuhan),49.18％ (390/793,Taiyuan),47.16％ (316/670,Chengdu),41.93 ％ (566/1 350,Nanjing),41.03％ (318/775,Chongqing),35.98％ (240/667,Hefei),33.87％ (677/1999,Shenzhen),31.37％ (554/1 766,Changsha),23.52％ (1 107/4 706,Beijing),13.42％ (177/1 319,Shenyang).Totally,40 kinds of skin diseases were investigated,and the 10 most common skin diseases were eczema/infantile eczema/atopic dermatitis (18.71％,3 749/20 033),ichthyosis vulgaris(6.25％,1 253/20 033),lichen pilaris (5.73％,1 148/20 033),diaper dermatitis (5.29％,1 059/20 033),papular urticaria(5.25％,1 052/20 033),hemangioma/vascular malformation (3.86％,774/20 033),pityriasis alba (3.45％,691/20 033),infectious skin diseases (2.59％,519/20 033),urticaria(1.71％,344/20 033)and contact dermatitis (0.5％,100/20 033).Conclusion The total prevalence of skin diseases among pre-school children in cities of China is 39.05％,and eczema/atopic dermatitis is the most common skin disease.

ObjectiveTo investigate the difference in the outcomes in patients with acute anterior circulation stroke having achieved the Thrombolysis in Cerebral Infarction (TICI) 2b and TICI 3 recanalization after mechanical thrombectomy.MethodsThe patients with acute anterior circulation stroke having achieved successful recanalization after mechanical thrombectomy were enrolled retrospectively.They were divided into TICI 2b (almost complete recanalization) group and TICI 3 (complete recanalization) group.The good outcome was defined as the modified Rankin Scale score 0-2 at 3 months after onset.ResultsA total of 83 patients were enrolled in the study, including 38 patients (45.8%) with TICI 2b and 45 (54.2%) with TICI 3;49 (59.0%) had good outcome, and 34 (40.9%) had poor outcome.The good outcome rate in the TICI 3 group was significantly higher than that in the TICI 2b group (68.9% vs.47.4%;χ2=3.946, P=0.047).After adjusting for age, hypertension, diabetes, baseline systolic blood pressure, triglyceride, intravenous thrombolysis, and ASITN/SIR collateral grades, TICI 3 was an independent predictor for good outcome at 3 months after onset (odds ratio [OR] 3.759, 95% confidence interval [CI] 1.098-12.871;P=0.035), while the higher baseline National Institutes of Health Stroke Scale score (OR 0.820, 95% CI 0.715-0.941;P=0.005) and higher fasting glucose (OR 0.610, 95% CI 0.410-0.906;P=0.014) were the independent predictors for poor outcome at 3 months after onset.ConclusionsThere are difference in the outcomes in patients with successful recanalization in anterior circulation stroke treated with mechanical thrombectomy.The outcome is substantially better in TICI 3 than TICI 2b patients.