1.Susceptibility gene research of coronary artery lesions in Kawasaki disease
International Journal of Pediatrics 2017;44(5):297-300
Kawasaki disease is an acute and systemic vasculitis of small and medium-sized arteries,which often occurs in children under 5 years old.The etiology and pathogenesis of Kawasaki disease remain unclear.Epidemiological data have shown the incidence in Asian population is higer than that in non-Asian population.Coronary artery lesions are the most serious complications in children with Kawasaki disease,which can result in ischemic cardiomyopathy,myocardial infarction or sudden death.Coronary artery lesions occur in about 25% untreated children and in 5% treated children.In recent years,replacing rheumatic fever,it has been the leading cause of acquired heart disease in children in developed countries.Current research on coronary artery lesions is a hotspot of Kawasaki disease,and genetic factors play an important role in the development of the lesions.Studies show that genes such as ITPCK,CASP3,TNF-α,CD40,IL-10,PELI1,GRIN3A,CTLA-4,SNX24,LRP1B are closely related to coronary artery lesions.In this article,we review some susceptibility genes on coronary arterial lesions in Kawasaki disease.
2. Identification of mutations associated with coronary artery lesion susceptibility in Kawasaki disease by targeted enrichment of genomic region sequencing technique
Danying ZHU ; Sirui SONG ; Lijian XIE ; Feng QIU ; Jing YANG ; Tingting XIAO ; Min HUANG
Chinese Journal of Pediatrics 2017;55(7):529-533
Objective:
To screen and identify the mutations in Kawasaki disease by targeted enrichment of genomic region sequencing technique and investigate susceptibility genes associated with coronary artery lesion.
Method:
This was a case-control study.A total of 114 patients diagnosed as Kawasaki disease treated in Shanghai Children′s Hospital between December 2015 and November 2016 were studied and another 45 healthy children who were physically examined in outpatient department were enrolled as control group. Patients were divided into two groups based on the results of echocardiogram. Peripheral venous blood was obtained from patients and controls. Genomic DNA was extracted. SeqCap EZ Choice libraries were prepared by targeted enrichment of genomic region technology. Then the libraries were sequenced to identify susceptibility genes associated with coronary artery lesion in patients diagnosed as Kawasaki disease.Susceptible genes were identified by Burden test, Pearson chi-square test or Fisher′s exact probability test.
Result:
There was statistically significant difference in TNFRSF11B(rs2073618)G>C(p.N3K)mutation and GG/GC/CC genotype between Kawasaki disease group and control group(χ2=15.52,
3.Establishment of a new scoring model for IVIG non-response of Kawasaki disease
Danying ZHU ; Sirui SONG ; Han ZHANG ; Jian ZHAO ; Bei JIANG ; Lijian XIE ; Tingting XIAO ; Min HUANG
International Journal of Pediatrics 2018;45(7):532-536,542
Objective To analyze the possible risk factors of IVIG non-response of Kawasaki disease (KD),Shanghai Children's Hospital and Shanghai Junze Software develop an research platform,which is based on E-Science model.Through the mathematical model by integrating the risk factors to explore the method of effective prediction for IVIG non-response,and to provide the clinical basis for timely and effective treatment and prognosis of the disease.Methods The data of KD children who were hospitalized in Shanghai Children's Hospital from January 2013 to November 2016 were included.The indexes included gender,age,time of IVIG treatment,and laboratory examinations.The multivariate logistic regression was used to analyze the influencing factors of IVIG non-response.The indexes in the model were deduced according to the independent variables of the logistic regression equation.The ROC curve and the area under the curve were calculated for the new prediction model.The sensitivity and specificity of the new prediction model were calculated according to the cutoff value.Finally,the new model was compared with the Kobayashi and Egami scoring model.Results The levels of CRP,NLR,LDH,ALB and FDP in children with KD were influencing factors for IVIG nonresponse (P < 0.05).According to the logistic regression equation,the sensitivity and specificity of the model used to predict IVIG non-response were 69.7% and 80.4%,respectively,and the area under the ROC curve was 0.825 (95% CI:0.769-0.882).Kobayashi and Egami scoring models were tested,the sensitivity and specificity of the new scoring system were better than previous ones.Condusion The scoring model established in this study has a good effect in predicting IVIG non-response in KD patients and could be used in clinical practice,and it is worthy to be validated and adjusted by large-scale data.
4.Effects of long-term high-fat diet on bone mineral density and intestinal flora
Kan XU ; Nan WU ; Lihong GAO ; Lin ZHU ; Danying ZHANG ; Yu HU
Chinese Journal of Endocrinology and Metabolism 2022;38(8):665-673
Objective:To investigate the effects of long-term high-fat diet on bone mineral density and intestinal flora in mice.Methods:Sixteen male C57BL/6 mice were randomly divided into control group (NC group) and high-fat group (HF group). After 24 weeks of high-fat feeding, biochemical indicators such as blood glucose and blood lipids were detected, bilateral femurs were taken and bone microstructure was analyzed with micro-computered tomography (micro-CT), and changes of intestinal microbial composition and proportion were revealed using 16S rDNA sequencing technology.Results:Compared with the control group, the serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in HF group were significantly increased. Micro-CT uncovered that the bone mineral density (Tb.BMD), bone volume fraction (BV/TV) and the number of trabecular bone (Tb.N) decreased, yet structural model index (SMI) and the trabecular fraction (Tb.Sp) increased in the HF group mice. The gut microbiota 16S rDNA sequence analysis showed that the proportion of Proteobacter was significantly increased and the proportions of pachycete, warty microbacterius, and actinomycete were reduced in HF group at the phyla level. The proportion of Bacteroidetes S24-7_norank in the NC group was significantly higher than that in the HF group, and the multilevel discriminant analysis of species differences (LEfSe) identified that the difference was significant, yet the proportion of Bacteroides, Pseudo-Prevotella, Desulfovibrio, Altobacter, and Helicobacter in the HF group were higher than those in the NC group, which were significant differences in Altobacter and Helicobacter at genus level.Conclusion:Long-term high-fat feeding can cause the destruction of femoral trabecular structure, decrease in the number of trabeculus bones, and bone mineral density in C57BL/6 mice. It also leads to significant changes in the composition and proportion of the intestinal flora.
5.Serum IL-17A, IL-18, and SCD25 (IL-2R) in early diagnosis of Kawasaki disease
Sirui SONG ; Danying ZHU ; Liqin CHEN ; Lijian XIE ; Tingting XIAO ; Min HUANG
Journal of Clinical Pediatrics 2018;36(5):367-371
Objective To investigate the acute phase expression of serum cytokines in children with Kawasaki disease (KD) and its association with coronary artery lesions (CALs). Methods Expression of 13 cytokines in serum of 104 KD patients including 11 cases with CALs and 74 febrile control cases admitted to the hospital from October 2016 to March 2017 were retrospectively analyzed. Results Interleukin (IL)-8, IL-1, IL-2, IL-6, IL-10, IL-17A, IL-18, tumor necrotic factor-α and SCD25 (IL-2R) were declined significantly after intravenous immunoglobulin administration (IVIG) in KD patients (all P<0.05). Compared with the fever control group, Pre-IVIG, an IL-17A level ≥ 0.155 pg/mL had a sensitivity of 50% and 93.2% specificity for predicting KD; IL-18 level ≤ 15.43 pg/mL had a sensitivity of 71.2%, and the specificity was 54.1%; SCD25 (IL-2R) ≥ 29475.29 pg/mL had a 65.4% sensitivity and 81.1% specificity for predicting KD. Before IVIG treatment, the level of IL-10 was significantly lower in KD patients with CALs than in those without CALs. Conclusions Determination of various cytokines profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.
6.Overexpression of p21 Has Inhibitory Effect on Human Hematopoiesis by Blocking Generation of CD43+ Cells via Cell-Cycle Regulation
Jiahui ZENG ; Huifang ZHANG ; Yuanling LIU ; Wencui SUN ; Danying YI ; Lijiao ZHU ; Yonggang ZHANG ; Xu PAN ; Yijing CHEN ; Ya ZHOU ; Guohui BIAN ; Mowen LAI ; Qiongxiu ZHOU ; Jiaxin LIU ; Bo CHEN ; Feng MA
International Journal of Stem Cells 2020;13(2):202-211
Background and Objectives:
p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis.
Methods:
and Results: We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34+ cells, but it significantly decreased the production of CD43+ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis.
Conclusions
In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43+ cells, but not CD34+ cells. The mechanisms via which CD34+ cells are blocked by RUNX1b overexpression remain to be elucidated.
7. Effects of hand-transmitted vibration on subjective symptoms in mine drilling workers
Maosheng YAN ; Anji ZHU ; Danying ZHANG ; Zhipeng HE ; Hansheng LIN ; Peng CAI ; Changke TAN ; Qingsong CHEN
China Occupational Medicine 2020;47(02):168-171
OBJECTIVE: To investigate the effect of hand-transmitted vibration on the subjective symptoms of mine drilling workers. METHODS: A total of 117 mine drilling workers exposed to hand-transmitted vibration were selected as the exposure group, and 46 workers without hand-transmitted vibration exposure were selected as control group by judgment sampling method. The Occupational Epidemiology Questionnaire of Mine Drilling Workers was used to investigate their subjective symptoms. RESULTS: The prevalence of tinnitus, hearing loss, cough and sputum in the exposure group was higher than that in the control group(P<0.05). The occurrence rate of numbness, tingling, self-reported white fingers and cold hands in the exposure group was higher than that in the control group(P<0.05). The total rate of symptoms of hand in the exposure group was higher than that in the control group(38.5% vs 21.7%, P<0.05). The multivariate logistic regression analysis results indicated that hand-transmitted vibration exposure and service length were risk factors of abnormal hand symptoms(P<0.05). CONCLUSION: Occupational hand-transmitted vibration exposure can affect the hand subjective symptoms of mine drilling workers, and the length of service is a synergistic influencing factor.
8.Research progress on laboratory examination index of clinical prognosis in individualization of cyclosporine A
Jinwei HU ; Huaijun ZHU ; Qianying LAO ; Danying LI
China Pharmacy 2022;33(18):2285-2289
Cyclosporine A is widely used in organ transplantation and autoimmune diseases . Due to the obvious differences in metabolism between individuals ,the dosage should be adjusted according to the patient ’s blood concentration during clinical use . But the blood concentration does not reflect accurately its clinical prognosis . This article focuses on the four laboratory examination indexes following aspects :the cyclosporine A concentration of peripheral blood mononuclear cells ,calcineurin activity ,T cell function and metabolite concentration of cyclosporine A . The relationship between them and the pharmacokinetics of cyclosporine and clinical prognosis were reviewed . It’s found that the above indicators have a certain predictive effect on the clinical prognosis of patients receiving cyclosporine A ,which can make up for the insufficiency of blood drug concentration monitoring ,and the clinical practicability needs to be further improved .