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Atopic diseases used to be considered as complex polygenic diseases with the interaction of environmental factors and genetic susceptibility.In recent years, primary atopic diseases caused by single-gene mutations have been well concerned.This study aims to review the pathogenesis and clinical characteristics of atopic diseases, thus strengthening the understanding.
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Atopic dermatitis is a complex chronic, relapsing inflammatory skin disease.Atopic dermatitis in children is usually less severe than in adults, but it is with a high incidence and is susceptible to relapse.Therefore, the physical and mental health of children and their family maybe seriously affected.In the past, the treatments of atopic dermatitis have been limited to glucocorticoids and immunosuppressants.It is unsafe for children because of their toxicities.With the in-depth understanding of pathogenesis, more and more new therapies that focus on intervening in the inflammatory pathway by targeting specific cytokines or their receptors have been found and applied.This article reviews the progress of treatment of the disease to provide new insights for the optimal treatment of atopic dermatitis.
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Objective@#To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.@*Methods@#Forty-five healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 3 groups by a random number table method: sham operation group (Sham group, n=5), bupivacaine group (B group, n=20), and lipid emulsion group (L group, n=20). Cardiac arrest was induced by intravenously injecting 0.4% bupivacaine 30 mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L, and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B, followed by a 3-min infusion of 1 ml·kg-1·min-1in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure, heart rate, mean arterial pressure, rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0), time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC, and left ventricular tissues were obtained for determination of the expression of Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3, cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.@*Results@#Compared with Sham group, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated, and the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P<0.05). Compared with B group, the rate of successful resuscitation and survival rate were significantly increased, Tr was shortened, systolic blood pressure, heart rate, RPP and RPPh were increased after ROSC, the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated, the expression of Bax protein and mRNA, cleaved caspase-9, cleaved caspase-3 and cytoplasmic Cyt c was down-regulated (P<0.05), no significant change was found in To or Ts (P>0.05), and the pathological changes of myocardium were significantly attenuated in L group.@*Conclusion@#The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.
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Objective@#To study the application of copy number variation (CNV) analysis based on the raw data of next-generation sequencing (NGS) in diagnosing primary immunodeficiency disease (PID).@*Methods@#One hundred sixty-five patients with suspicious PID were tested by NGS in the Department of Rheumatology and Immunology, Shenzhen Children′s Hospital during September 2014 and Mary 2017. The raw data of the patients who got negative result were further analyzed for the CNV with CNVkit software. The pathogenic CNV were identified in the databases including Resource of Asian Primary Immunodeficiency Diseases (RAPID), Human Gene Mutation Database (HGMD) and ClinVar with the known 344 pathogenic genes of PID. The associated literature from January 2010 to May 2019 were searched in Pubmed, Weip, Wanfang and CNKI database with key words as "primary immunodeficiency disease" "copy number variation" and "next generation sequencing" .@*Results@#Ninety-five out of 165 patients (57.6%) had negative result of the NGS test, among whom the patients with immune dysregulation had the highest negative rate (68.6%, 24/35). CNV analysis found large fragment deletion in 12 patients, within which 7 was X-linked inheritance, 3 was autosomal recessive inheritance, 2 was autosomal dominant inheritance. Partial exon deletion was found in 4 patients while whole gene deletion in 8 patients. According to the review of literature, CNV was reported in 51 pathogenic genes of PID (14.8%, 51/344) , mainly intern deletion (70.6%, 36/51), while autosomal recessive inheritance (56.9%, 29/51) was the most common pattern.@*Conclusions@#CNV is not rare in PID. When the phenotype is clear in the patients who have negative NGS test, CNV should be considered.
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Copy number variation (CNV) is an important part of genomic structural variation.Studies have shown that CNV is closely related to the occurrence of diseases,such as neuro-developmental diseases,congenital metabolic diseases and viral infections.Primary immunodeficiency diseases (PIDs) are inheritary disorders in which part of the immune system is missing or has not function normally.With the development of sequencing technology,more and more attention has been paid in the CNV research of immune diseases.This article reviewed the progress between CNV and PIDs,as well as the important role of CNV in the diagnosis of PIDs.
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Objective To evaluate the role of mitochondrion-dependent apoptosis in reduction of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.Methods Forty-five healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 3 groups by a random number table method:sham operation group (Sham group,n =5),bupivacaine group (B group,n =20),and lipid emulsion group (L group,n =20).Cardiac arrest was induced by intravenously injecting 0.4％ bupivacaine 30mg/kg over 20 s to establish the cardiotoxicity model.Twenty percent lipid emulsion was intravenously injected in a dose of 5 ml/kg during resuscitation in group L,and normal saline was intravenously injected in a loading dose of 5 ml/kg during resuscitation in group B,followed by a 3-min infusion of 1 ml · kg-1 · min-1 in two groups.The successful resuscitation and survival rate at 120 min of return of spontaneous circulation (ROSC) were recorded.Systolic blood pressure,heart rate,mean arterial pressure,rate-pressure product (RPP) and ratio of RPP at each time point after recovery of spontaneous heart beat to baseline value (RPPh) were recorded every 10 min after ROSC.The time from administration to cardiac arrest (T0),time from beginning of cardiopulmonary resuscitation to appearance of the first spontaneous heart beat (Ts) and time from beginning of cardiopulmonary resuscitation to appearance of ROSC (Tr) were recorded.Rats were sacrificed at 120 min of ROSC,and left ventricular tissues were obtained for determination of the expression of Bax,Bcl-2,cleaved caspase-9,cleaved caspase-3,cytochrome C (Cyt c) in cytoplasm and mitochondria (by Western blot) and expression of Bax and Bcl-2 mRNA (by real-time polymerase chain reaction) and for examination of myocardial ultrastructure.Results Compared with Sham group,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was significantly down-regulated,and the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was up-regulated in B group (P＜0.05).Compared with B group,the rate of successful resuscitation and survival rate were signif-icantly increased,Tr was shortened,systolic blood pressure,heart rate,RPP and RPPh were increased after ROSC,the expression of Bcl-2 protein and mRNA and mitochondrial Cyt c was up-regulated,the expression of Bax protein and mRNA,cleaved caspase-9,cleaved caspase-3 and cytoplasmic Cyt c was downregulated (P＜0.05),no significant change was found in To or Ts (P＞0.05),and the pathological changes of myocardium were significantly attenuated in L group.Conclusion The mechanism by which lipid emulsion reduces bupivacaine-induced cardiotoxicity may be related to inhibiting mitochondrion-dependent apoptosis in rats.
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OBJECTIVE To study the change and significance of TNF-? and IL-18 in the Acinetobacter baumannii sepsis. METHODS Sixty male SD rats were divided into 6 groups. The first group was normal control group. The second to sixth groups were sepsis groups which were killed at 4h,16h,24h,48h,72h after injecting A. baumannii through intraperitoneal injection to make sepsis model. The level of TNF-? and IL-18 in the serum of rats was measured by enzyme linked immunosorbent assay (ELISA). RESULTS The level of TNF-? in the serum increased markedly in the sepsis groups (P
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OBJECTIVE To investigate the resistance of Acinetobacter baumannii(ABA),and the mechanism of imipenem resistance in A.baumannii.METHODS All specimens were identified by VITEK-60 and the drug resistance was detected by Kirby-Bauer test.Three dimensional test was used to detect ESBLs and AmpC.PCR and DNA sequencing were performed to determine VIM,IMP,OXA-23 and OXA-24 ?-lactamases.Outer membrane protein was analyzed by SDS-PAGE,Reserpine synergistic inhibition test was used to study the active efflux mechanism.RESULTS Totally 120 strains were isolated from sputum(76.9%),and 16 strains from secretion(10.3%).ICU was the main infected department(51 strains,32.7%).The resistance to sulperazone was the lowest(20.5%),and to imipenem accounted for 38.5%,Of the 20 imipenem resistant strains,10 strains were ESBLs positive(50%),and 20 strains were AmpC positive(100%).VIM,IMP and OXA-24 ?-lactamases were not detected out,19 strains(95%) produced OXA-23.Compared to the imipenem-sensitive strains,the resistant strains lacked the outer membrane protein of 22?103,29?103 and 33?103.The MICs of A.baumannii to imipenem were not decreased by reserpine which demonstrated that excretive mechanism was negative.CONCLUSIONS ICU is the main infected department for ABA.The resistance rate is increasing for longer-term usage of carbopenem;OXA-23 production is the important resistance mechanism in ABA,AmpC production and outer membrane protein lacking show close relation to the drug-resistance in A.baumannii.
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OBJECTIVE To investigate the distribution and drug resistance of pathogenic bacteria in septicemia in order to provide the reference for clinical antimicrobial agents usage.METHODS The blood samples of inpatients were cultured with blood culture apparatus,VITEK-AMS was used to identify the bacteria and conduct drug resistance test and ESBLs produced by Escherichia coli,and Klebsiella were detected by disc diffusion confirmatory test.RESULTS The 221 strains of pathogens that caused septicemia were mainly distributed in ICU,blood department and infection department.The 61 strains of E.coli were isolated,among which ESBLs were detected and accounted for 39.3%(24),26 strains of Klebsiella were isolated,among which ESBLs were detected and accounted for 26.9%(7),ESBLs strains were more resistant than ESBLs negative strains.Thirty two strains of Staphylococcus were isolated,among which MRS were detected and accounted for 62.5%(20).The pathogens showed highly multiple drug-resistance.Vancomycin and imipenem were the highest susceptible for Gram-positive and Gram-negative bacteria,respectively.CONCLUSIONS The pathogens that caused septicemia are mainly distributed in ICU,blood department and infection department.The situation of antibiotic resistance of pathogens is very serious now.Therefore,it is important to prevent the septicemia and to detect enzyme producing strains regularly for reference of reasonable antibiotic use.