1.Bivariate heritability estimation of resting heart rate and common chronic disease based on extended pedigrees.
Hong Chen ZHENG ; En Ci XUE ; Xue Heng WANG ; Xi CHEN ; Si Yue WANG ; Hui HUANG ; Jin JIANG ; Ying YE ; Chun Lan HUANG ; Yun ZHOU ; Wen Jing GAO ; Can Qing YU ; Jun LV ; Xiao Ling WU ; Xiao Ming HUANG ; Wei Hua CAO ; Yan Sheng YAN ; Tao WU ; Li Ming LI
Journal of Peking University(Health Sciences) 2020;52(3):432-437
OBJECTIVE:
To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes.
METHODS:
The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables.
RESULTS:
The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120-0.407), 0.404 (95%CI: 0.135-0.673), and 0.799 (95%CI: 0.590-1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120-1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181-0.788, P<0.05).
CONCLUSION
Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure
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Chronic Disease
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Female
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Heart Rate
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Humans
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Hypertension
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Male
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Middle Aged
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Pedigree
2.Study on application of next-generation sequencing technology in diagnosis of cardio-facio-cutaneous syndrome
Hai XIAO ; Zhaojing ZHANG ; Xue LV ; Tao LI ; Qiannan GUO ; Qiaofang HOU ; Hongdan WANG ; Hongyan LIU ; Xiaodong HUO ; Shixiu LIAO
Chongqing Medicine 2018;47(8):1074-1076
Objective To explore the role of next-generation sequencing(NGS)technology in the assisted diagnosis of RA-Sopathies.Methods Peripheral blood was extracted from 1 child patient with suspected Noonan syndrome and her parents,and the gene mutations were detected by adopting the aCGH and NGS.The results were verified by Sanger sequencing.Results The NGS results revealed that the heterozygous mutation of c.1406G>A existed in BRAF gene,and the results of Sanger sequencing in this child case was consistent with the NGS results.The Sanger sequencing results in her parents showed the locus was G/G wild type. Conclusion This child case was diagnosed as CFC.NGS plays a good auxiliary role in the differentiation diagnosis of RASopathies.
3.GW4869 inhibits the release of exosomes from bone marrow mesenchymal stem cells
Shu-Li SUN ; Pei-Xin XIAO ; Hui DING ; Jing WANG ; Zi-Quan LIU ; Jin-Yang LIU ; Xue WANG ; Sha SHI ; Qi LV ; Hao-Jun FAN
Chinese Journal of Tissue Engineering Research 2018;22(1):26-31
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and BMSCs-derived exosomes have similar functions, but the regulatory mechanism underlying the release of exosomes is still unclear. OBJECTIVE: To investigate the role of GW4869, an inhibition of neutral sphingomyelinase 2, in the release of exosomes in BMSCs and the influence of GW4869 on BMSCs proliferation. METHODS: Rat BMSCs were divided into three groups: normal control group, 24-hour GW4869 treatment group and withdrawal of GW4869 for 24 hours group (24-hour GW4869 treatment followed by 24-hour successive culture with drug withdrawal). Cultured cells were collected to extract exosomes by ultracentrifugation. Western blot was used to detect exosome-associated proteins CD63 and tumor susceptibility gene 101 (TSG101). The concentration and size distribution of exosomes were measured using nanoparticle tracking analysis. BCA was used to test the level of total proteins in exosomes. Live cell imaging system was used to observe the influence of GW4869 on BMSCs proliferation. RESULTS AND CONCLUSION: (1) Western blot results showed that exosomes expressed marker proteins such as CD63, TSG101. (2) Findings from the nanoparticle tracking analysis confirmed that the size of released exosomes was about 114 nm. (3) Significantly reduced release of exosomes was found in the two treatment groups compared with the normal control group (P < 0.01), but there was no significant difference between 24-hour GW4869 treatment group and withdrawal of GW4869 for 24 hours group (P > 0.05). (4) No significant difference in the proliferation of BMSCs was found among the three groups (P > 0.05). To conclude, 24-hour W4869 can inhibit the release of exosomes by BMSCs and this inhibitory effect is still sustained within 24 hours after drug withdrawal. However, GW4869 has no influence on the proliferation of BMSCs.
4.HyaIuronic acid scaffoIds: appIication research and product prospects
Xiao-Ou ZHANG ; Yang LV ; Hua MAO ; Xin-Yi FAN ; Si-Ling HUANG ; Xue-Ping GUO
Chinese Journal of Tissue Engineering Research 2018;22(2):294-302
BACKGROUND: Hyaluronic acid is an important component of extracellular matrix, has good biocompatibility, unique rheological properties and a variety of physiological functions. Therefore, it has wide application prospect in the tissue engineering. OBJECTIVE: To review the latest research progress in hyaluronic acid scaffold materials in different directions of tissue engineering. METHODS: Using the keywords of "hyaluronic acid, tissue engineering, regeneration, scaffold" in English and Chinese, we retrieved relevant articles published from January 2013 to September 2016 in the databases of PubMed, ScienceDirect and CNKI. RESULTS AND CONCLUSION: The application of hyaluronic acid tissue engineering scaffold materials mainly focuses on the regeneration of bone, cartilage, cardiovascular and nerve. The researchers optimize the composition, ratio of different materials, and modification or cross-linking methods to obtain the ideal scaffold materials to match the mechanical properties and physiological activity of the target tissue. However, there are not enough data on the influence of the molecular weight of hyaluronic acid and the original source of other raw materials on the scaffold properties. Further investigations are needed on the clinical transformation of hyaluronic acid tissue engineering products.
5.The current situation of the drug supply and determinants of drug shortage in primary health centers:A case study of Anhui Province
Ri-Xiang XU ; Xue-Feng XIE ; Shu-Ting LI ; Xiao-Yu CHEN ; Ting-Yu MU ; Xiong-Wen LV
Chinese Journal of Health Policy 2018;11(3):78-82
Objective: To investigate the current situation of drug supply and determinants of drug shortage in primary health institutions in Anhui province. Methods:Primary health institutions in Anhui province were selected as the main research subjects. One hundred and six (106) primary health institutions from three areas/districts in Anhui province namely northern Anhui,Central Anhui,and Southern Anhui were selected with stratified random sampling as the first sample,and 54 pharmaceutical producing enterprises and 62 pharmaceutical trading enterprises were selected with convenience sampling method as the second sample. The survey was conducted by issuing questionnaires to record views of the respondents to help understand the current situation of drug supply from the first sample and the main de-terminants and solutions of drug shortage from two samples. Results:13% of the primary health institutions still suffer from serious shortage of drug supply; the drug distribution rate varies greatly between units, and 19% of the primary health institutions have a drug distribution rate below 70%,and all primary health institution within the scope of inves-tigation experienced drug shortages. The frequency of choices of determinants of drug shortage were in sequence of or-der:drug demand instability (19.20%), drugs have a new and higher profit alternative (15.94%), etc.; The fre-quency of choices of solutions of drug shortage of primary health institution were in sequence of order:to improve the national list of essential medicines(12.78%),appropriate improvement in efficacy the low-priced varieties(with cura-tive effect) (12.03%),etc. Conclusions:Primary health institutions suffer from drug shortage issue widely,and the reasons for the shortage of drugs are more complicated;the government should continue to implement relevant policies, comprehensively improving the primary health institution drug supply mechanisms in all to prevent drug shortages.
6.Textual research of chu, huo, huo, and hua.
China Journal of Chinese Materia Medica 2018;43(2):401-403
Origin of Chinese Characters (Shuowen Jiezi) records a large number of drug names, providing rich materials for the study of the history of pharmacy. But in the aftertime circulating process, errors were inevitable, making the ancient scholars disagree on the relationship between some drug names and their referents. This paper would give a textual research on medication names about chu, huo, huo, and hua. Relevant content was analyzed by using Shuowen Jiezi, Er Ya,Yu Pian and previous annotations of these exegesis books, as well as herbal literature. The relationship between the names and referents, as well as their lexical meanings were clarified by comparing textual content in specialized book about Chinese exegetics and previous herbal literature. Their medicinal efficacy was explained, and the value of herbalism in these exegesis books was explored.
Books
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Herbal Medicine
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Medicine, Chinese Traditional
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Research
7.The role of poloxamer 188 for cord blood mononuclear cells into megakaryocytes cultivation and induction in three-dimensional WAVE Bioreactor.
Lin CHEN ; Wen YUE ; Xiao Yan XIE ; Xiu Yuan ZHANG ; Yang LV ; Da Qing LIU ; Jia Fei XI ; Ming Yi QU ; Zeng FAN ; Fang FANG ; Xue Tao PEI
Chinese Journal of Hematology 2018;39(1):28-31
Objective: To observe the effect of poloxamer 188 (P188) on megakaryocyte cultivation and induction from cord blood mononuclear cells in order to obtain more megakaryocyte progenitor cells (MPC). Methods: The cord blood mononuclear cells were isolated and inoculated in cell culture bag or cell culture flask respectively. The WIGGENS shaker and cell culture bags were used to mimick WAVE Bioreactor for three-dimensional (3D) cell culture, and the P188 was added to induction medium, The cells were detected for morphology, surface marker, viability, and number on day 14. Results: In the two-dimensional (2D) culture, CD41(+), CD41(+)/CD61(+), CD61(+) megakaryocytic numbers increased significantly after adding P188 (all P<0.01). And in the 3D culture of adding P188, the cell volume became larger and the nuclear shape was irregular, the cytoplasm appeared magenta granules, and the megakaryocyte cells became more mature. By 3D culture, the expression of CD41/CD61 was (36.30±1.27)% vs (23.95±1.34)%, hence the differentiation for MPC was significantly higher than that in the 2D group (P<0.01). Furthermore, adding P188 in 3D culture resulted in highest differentiation efficiency for MPC [(59.45±1.20)%]. There were no significantly differences in terms of cell viability and cell number among 3D culture containing P188, 2D and 3D culture groups (all P>0.05). Conclusion: 3D culture was beneficial for the differentiation of MPC, but the cell viability was lower than 2D group; However, the satisfied cell growth and better induction efficiency were obtained by adding of P188, which might provide a new method of megakaryocytes production for clinical application.
Bioreactors
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Cell Differentiation
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Cells, Cultured
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Fetal Blood
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Megakaryocytes
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Poloxamer
8.Changes of Peripheral Blood Marrow-Derived Suppressor Cell Level after Chemotherapy Induction Remission by VDLP Regimen and Their Relationship with Immune System in B-ALL Children.
Xue-Mei GUO ; Yong-Jun FANG ; Cheng-Lan LV ; Yong-Ren WANG ; Xiao-Yan SUN
Journal of Experimental Hematology 2017;25(6):1611-1614
OBJECTIVETo investigate the changes of peripheral blood marrow-derived suppressor cell level after chemotherapy induction remission by regimen consisting of vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) and to analyze their relationship with immume system in B-ALL children.
METHODSThirty B-ALL children after induction remission by VDLP regimen from August 2015 to August 2016 were selected as B-ALL group and 30 normal healthy children were selected as control group. The peripheral blood in 2 groups was collected and detected by flow cytometry, then the ratios of CD30cells and CD33HLA-DRmarrow-derived suppressor cells, CD14CD33HLA-DRmarrow-derived suppressor cells and CD15CD33HLA-DRmarrow-derived suppressor cells were calculated, and their changes after induction remission by VDLP regimen and the relationship with immune system were analyzed.
RESULTSAfter treatment the ratio of CD33cells in peripheral blood of B-ALL group and control group was not significantly different (P> 0.05), moreover, the ratio of CD33cells in B-ALL group was significantly higher than that before treatment (P<0.05), while the ratios of CD33HLA-DRmarrow-derived suppressor cells, CD14CD33HLA-DRmarrow-derived suppressor cells and CD15CD33HLA-DRmarrow-derived suppressor cells in B-ALL group were significantly lower than those in control group (all P<0.05), but the ratios of these cells in B-ALL group were higher than those before treatment, and yet there was no statistical significance (P>0.05).
CONCLUSIONThe ratios of marrow-derived suppressor cells in peripheral blood of B-ALL children in complete remission after treatment with VDLP regimen are higher than those before treatment, but are significantly lower than normal value, which may be related with non-complese recovery of immune system in B-ALL children after treatment.
9.Long-term Prognosis of Revascularization in Patients With Ostial/shaft Lesions of Unprotected Left Main Coronary Artery (ULMCA)
peng Xian YU ; zheng Shu LV ; Fei YUAN ; ling Xiao ZHANG ; chun Yue GAO ; qiang Ji HE ; Yu LI ; jun Xue REN
Chinese Circulation Journal 2017;32(9):869-873
Objective:To compare the long-term prognosis of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with ostial/shaft lesions of unprotected left main coronary artery (ULMCA).Methods:A total of 259 patients with isolated ostial/midshaft lesions of ULMCA who received PCI or CABG in our hospital from 2003-01 to 2009-07 were enrolled.The patients were divided into 2 groups:PCI group,n=149 patients who received drug-eluting stents (DES) implantation and CABG group,n=110.The end points were all cause death,myocardial infarction (MI) and major adverse cardiac and cerebrovascular events (MACCE) which included cardiac death,non-fetal MI,stroke,repeated revascularization and the composite events death.Results:The median follow-up period was 7.1 years (inter quartile range 5.3-8.2 years) in all patients.Before multivariate adjusting,the following parameters were similar between PCI group and CABG group:all cause death (12.7% vs 29.7%),P=-0.096;non-fatal MI (14.8% vs 8.5%),P=0.844;stroke (9.3% vs 6.3%),P=0.904;repeated revascularization (26.8% vs 19.0%),P=0.234;composite events of cardiac death/stroke/MI (18.9% vs 20.3%),P=0.224 and MACCE occurrence (37.5% vs 34.2%),P=0.946.With adjusted variations,the trend was similar to pre-adjustment.Conclusion:During the maximum 8.2 years follow-up period,PCI and CABG had the similar efficacy and safety in patients with ostial/shaft lesions of ULMCA.
10.Explore pharmacological mechanism of glycyrrhizin based on systems pharmacology.
Yu-Kun ZHAO ; Li LI ; Xue LIU ; Shi-Ping CHENG ; Qing-Qing GUO ; Dan-Ping FAN ; Kang ZHENG ; Xiao-Juan HE ; Ai-Ping LV
China Journal of Chinese Materia Medica 2016;41(10):1916-1920
To explore the pharmacological mechanism of glycyrrhizin with series methods of systems pharmacology, main diseases related to glycyrrhizin were obtained by text mining tool; and the target proteins of glycyrrhizin were obtained via the database of Polysearch and PubChem. Then, the target proteins interaction network of glycyrrhizin was built using the software called Cytoscape. Next, the protein groups related to glycyrrhizin were analyzed by using Gene Ontology (GO) tool, and the action pathway of its target proteins was analyzed by using enrichment method. Text mining results showed that the related diseases of glycyrrhizin included chronic hepatitis C, chronic hepatitis, hepatitis, HIV virus, liver cancer and so on. Gene ontology analysis indicated that glycyrrhizin played a role mainly through modification of proteins and chromatin. The signaling pathway enrichment results showed that the main action proteins of glycyrrhizin were related to MAPK signaling pathway, toll-like receptor signaling pathway, neurotrophic factor signaling pathway, cancer and apoptosis pathways. So we can conclude that glycyrrhizin may exert its biological functions primarily by regulating multiple pathways such as MAPK signaling pathway and Toll-like receptors signaling pathway. The pharmacological action of a drug can be rapidly and comprehensively analyzed by the ways of systems pharmacology.

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