1.Association of BHMT and BHMT2 gene polymorphisms with non-syndromic congenital heart disease: a case-control study
Jiapeng TANG ; Jun OU ; Yige CHEN ; Mengting SUN ; Manjun LUO ; Qian CHEN ; Taowei ZHONG ; Jianhui WEI ; Tingting WANG ; Jiabi QIN
Chinese Journal of Preventive Medicine 2024;58(4):497-507
Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.
2.Association of BHMT and BHMT2 gene polymorphisms with non-syndromic congenital heart disease: a case-control study
Jiapeng TANG ; Jun OU ; Yige CHEN ; Mengting SUN ; Manjun LUO ; Qian CHEN ; Taowei ZHONG ; Jianhui WEI ; Tingting WANG ; Jiabi QIN
Chinese Journal of Preventive Medicine 2024;58(4):497-507
Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.
3.Effects of Serum Containing Wenjing Tongluo Decoction on Mouse Chondrocyte Injury and IκB-ζ/HIF-1α/LDHA Axis
Wei WEI ; Chenjian PENG ; Renjun GU ; Xiwu YAN ; Jiapeng YE ; Guicheng HUANG ; Luning SUN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(5):469-478
OBJECTIVE To study the effects and mechanisms of serum containing Wenjing Tongluo Decoction on interleukin-1β(IL-1β)-induced mouse primary chondrocyte injury.METHODS The IL-1β-induced primary chondrocyte injury model was estab-lished,and the mRNA expression of inflammatory factors IL-1β,IL-6,TNF-α,cartilage degradation-related proteases matrix metal-loproteinase 3(MMP3),MMP9,MMP13,ADAM metallopeptidase containing thrombospondin 1 motif 4(ADAMTS4),and glycoly-sis-related enzymes lactate dehydrogenase A(LDHA),M2 pyruvate kinase(PKM2),reduced coenzyme Ⅱ oxidase 2(NOX2)and re-duced coenzyme Ⅱ oxidase 4(NOX4)in the cells was detected;the intracellular MMP3,MMP13,P65,IκB-ζ,hypoxia-inducible factor 1α(HIF-1α)and LDHA protein expression levels were determined;the concentrations of nitric oxide(NO),malondialdehyde(MDA)and lactic acid in the cell supernatant were further detected,and the ratio of the reduced state(NADH)and oxidized state(NAD+)of intracellular coenzyme Ⅰ(NAD),as well as intracellular reactive oxygen species(ROS)levels were assayed.RESULTS Serum containing Wenjing Tongluo Decoction significantly inhibited the mRNA expression of IL-1β,IL-6,and TNF-α in IL-1β chondrocytes(P<0.01),reduced the NO concentration in the cell supernatant(P<0.05,P<0.01),and downregulated the protein ex-pression of IκB-ζ(P<0.05)and P65(P<0.05,P<0.01).Serum containing Wenjing Tongluo Decoction significantly downregulated the mRNA expression of MMP3,MMP9,MMP13 and ADAMTS4(P<0.01),and inhibited the protein expression of MMP13(P<0.05,P<0.01)and MMP3(P<0.05).In terms of oxidative stress,it significantly suppressed the production of ROS in chondrocytes,increased the NADH/NAD+ratio,reduced the MDA concentration in the supernatant,and downregulated the expression of HIF-1α protein(P<0.01).The serum containing Wenjing Tongluo Decoction significantly reduced the lactic acid concentration,downregulated the expression of LDHA,PKM2,NOX2 and NOX4,and reduced the level of intracellular glycolysis(P<0.05,P<0.01).CONCLU-SION The serum containing Wenjing Tongluo Decoction can alleviate IL-1β-induced mouse primary chondrocyte injury by inhibiting inflammation,cartilage degradation,oxidative stress and glycolysis,which may be related to the regulation of IκB-ζ/HIF-1α/LDHA axis.
4.Clinical significance of group A streptococcal infection in pediatric patients with enthesitis related arthritis
Jing MA ; Junmei ZHANG ; Xiaohua TAN ; Yan LI ; Chao LI ; Yurong PIAO ; Shipeng LI ; Jiapeng SUN ; Tongxin HAN ; Weiying KUANG ; Caifeng LI
Chinese Journal of Rheumatology 2022;26(7):456-460
Objective:To demonstrate the clinical significance of group A streptococcal infection (GAS) in patients with enthesitis related arthritis (ERA).Methods:A retrospective study was conducted on ERA (136) and PolyRF-/Oligo juvenile idiopathic arthritis (JIA) (272) patients in Beijing Children's Hospital from 2016 to 2018. Anti-streptococcal hemolysin "O" (ASO) was tested and documented in all patients. The infection rate of GAS was compared between patients with ERA and PolyRF-/Oligo JIA. Patients with ERA were divided to two groups according to the result of ASO (ASO positive and ASO negative). All the clinical data were documented and compared within the two groups. The statistical methods used mainly include t test, rank sum test, chi-square test, and Spearman correlation analysis.Results:The GAS infection rate of patients with ERA was higher than patients with PolyRF-/Oligo JIA (17.6% vs 9.5%, χ2=5.52, P=0.019). In ERA patients, clinical data were analyzed, and a statistical significant difference was observed in the presence of human leukocyte antigen (HLA)-B27 between ASO positive and ASO negative group [75.0%(18/24) vs 49.1%(55/112), χ2=5.329, P=0.021]. Statistical differences were found in Patrick's sign positive rate between the two groups [100%(24/24) vs 67.0%(75/112), χ2=10.61, P=0.001]. There was statistically significant difference between the two groups regarding the radiogr-aphic grading at the sacroiliac joint. More patients with positive ASO had grade Ⅲ damage at the sacroiliac joint compare to patients with negative ASO [68.2%(15/22) vs 28.4%(29/102), χ2=12.49, P<0.001]. The logarithmic of the ASO was slightly correlated with the radiographic grade of sacroiliac joint ( r=0.26, P=0.005). Conclusion:Patients with ERA are prone to be infected by GAS. It's probably related to HLA-B27 postivity for antigen presentation. Patients who were infected by GAS fre-quently have sacroiliac joint involvement, and tend to be more sever. This indicates that GAS may play an important role in the pathogenesis of sacroiliac joint destruction.
5.Development of Cardiac Output Monitoring Technology.
Yang SUN ; Xu ZHANG ; Jilun YE ; Jiapeng PENG ; Pengfei LYU
Chinese Journal of Medical Instrumentation 2018;42(4):268-271
Cardiovascular disease has become a serious disease that threatens the health of human beings, cardiac output is an important indicator of cardiovascular function, monitoring cardiac output and related hemodynamic parameters have significant clinical value. This article summarizes the development history, principle, method, advantages and disadvantages of various monitoring technologies from three aspects:invasive, minimally invasive and noninvasive, the development and application of cardiac output monitoring technology are prospected.
Cardiac Output
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Hemodynamics
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Humans
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Monitoring, Physiologic
;
instrumentation
6.Research Progress of External Defibrillation Technique and Its Application.
Pengfei LYU ; Jilun YE ; Xu ZHANG ; Yang SUN ; Jiapeng PENG
Chinese Journal of Medical Instrumentation 2018;42(3):188-192
Defibrillator is an important first aid equipment with people attach importance to life and health in today, people pay more attention to the development of defibrillator. This paper reviews the development history of the defibrillator, gives a brief introduction to the structure and working principle of the defibrillator, and then analyzes the key technology of defibrillator, compares the mainstream products on the market and prospects the development trend of defibrillator.
Defibrillators
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Electric Countershock
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First Aid
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Humans
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Technology
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Ventricular Fibrillation
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therapy
7.Observations on the Efficacy of Acupuncture plus TDP in Treating StageⅡ-Ⅲ Pressure sore
Jiapeng YANG ; Qingshuang WEI ; Zhiyan XU ; Jia LI ; Hengrui GUO ; Zhongren SUN
Shanghai Journal of Acupuncture and Moxibustion 2017;36(5):568-572
Objective To investigate the clinical efficacy of acupuncture plus TDP in treating stageⅡ-Ⅲ pressure sore.Methods Thirty-three patients with pressure sore meeting the inclusion criteria were randomly allocated to treatment and control groups, 17 cases each. Both groups were first given routine clean care. The control group received routine surgical asepsis dressing change and the treatment group, fire needling, surrounding electroacupuncture and TDP irradiation to the affected part. The pressure sore area was observed and the PUSH score was recorded in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups of patients. Results The total efficacy rate was 88.0% in the treatment group and 71.0% in the control group; there was no statistically significant difference between the two groups (P>0.05). The total efficacy rate was 88.0% in the treatment group and 71.0% in the control group; there was no statistically significant difference between the two groups (P>0.05). The cure and marked efficacy rate was 58.8% in the treatment group and 23.5% in the control group; there was a statistically significant difference between the two groups (P<0.05). There was a statistically significant pre-/post- treatment difference in the pressure sore area in the two groups at one, two and three weeks after treatment (allP<0.05). There was a statistically significant difference in the pressure sore area between the two groups at two and three weeksafter treatment (bothP<0.05). There was a statistically significant pre-/post-treatment difference in the PUSH score in the two groups at two and three weeks after treatment (bothP<0.05). There was a statistically significant difference in the PUSH score between the two groups at three weeks after treatment (P<0.01).Conclusions Acupuncture plus TDP can markedly relieve the clinical symptoms and accelerate the sore healing in treating stageⅡ-Ⅲ pressure sore.
8.Relationship between hyperhomocysteinemia and chronic kidney disease in children
Jiapeng SUN ; Huijie XIAO ; Jie DING ; Fang WANG ; Jing LIU
Chinese Journal of Applied Clinical Pediatrics 2017;32(11):852-855
Objective To investigate the detection rate and possible factors of hyperhomocysteinemia(HHcy) in children with chronic kidney disease(CKD).Methods The clinical data of children with CKD between July 2012 and September 2016 in the Department of Pediatrics,Peking University First Hospital were retrospectively collected.The homocysteine(Hcy) level of patients were measured.The other data included the general information,diagnosis and laboratory test results.Results Seventy-six pediatric patients with CKD were enrolled including 49 boys and 27 girls.The average age of the patients was (9.9±3.4) years old.The main cause of the patients in the study was primary glomerulopathy(48.7%,37/76 cases),and the rest were congenital and inherited glomerular diseases(36.8%,28/76 cases),secondary glomerular diseases(9.2%,7/76 cases)and renal tubular diseases(5.3%,4/76 cases).Fifty patients (65.8%,50/76 cases) had normal level of Hcy which was 10.40(7.30,11.62) μmol/L.Twenty-six patients(34.2%,26/76) were detected with HHcy whose Hcy level was 17.93(16.76,24.11) μmol/L.The detection rate of HHcy in CKD stage 1,stage 2,stage 3,stage 4 and stage 5 was 13.9%(5/36 cases),22.2%(2/9 cases),50.0%(4/8 cases),57.1%(4/7 cases) and 68.8%(11/16 cases) respectively,and the detection rate increased with CKD stages and the difference was statistically significant (χ2=17.574,P<0.001).The level of Hcy was 10.05(7.04,12.47) μmol/L,11.75(10.78,16.44) μmol/L,13.73(10.09,18.23) μmol/L,15.81(11.12,20.71) μmol/L and 17.39(11.86,24.76) μmol/L in CKD stage 1,stage 2,stage 3,stage 4 and stage 5,respectively.The Kruskal-Wallis test revealed that the distribution of homocysteine in CKD stages had statistically significant difference(P=0.001).Multiple linear regression model showed that creatinine clearance was an independent predicator of HHcy.Conclusions In this study of the CKD patients,the detection rate of HHcy was high and increased with the progression of CKD.HHcy is mainly influenced by creatinine clearance in CKD.The level of Hcy should be monitored regularly in children with CKD and HHcy should be treated with proper measures.
9.Effects of co-administration with morin and acetyl-resveratrolon pharmacokinetics of saquinavir in rats
Jingru ZHANG ; Xiaotong YU ; Ning SUN ; Jiapeng LI ; Yi QIN ; Jian GU ; Libo ZHAO
Chinese Pharmacological Bulletin 2017;33(10):1414-1420
Aim To assess the impact of morin and acetyl-resveratrol on the oral bioavailability and pharmacokinetics of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats.Methods Twenty rats were randomized into four groups of equal size, including a control group, two intervention groups and a positive control group, and administered orally 30 mg·kg-1 SQV with or without 40 mg·kg-1 morin or acetyl-resveratrol or verapamil (as positive control).The plasma concentrations of saquinavir were determined using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the PK of SQV was assessed using non-compartmental analysis.Results The PK parameters values of SQV, SQV+morin, SQV+acetyl-resveratrol, SQV+verapamil were as follows: AUC0-t, 381.53 μg·h·L-1,185.53 μg·h·L-1, 360.43 μg·h·L-1, 529.95 μg·h·L-1;AUC0-∞, 409.48 μg·h·L-1, 228.52 μg·h·L-1,446.67 μg·h·L-1, 552.41 μg·h·L-1;Cmax, 110.80 μg·L-1, 86.44 μg·L-1, 139.84 μg·L-1, 423.60 μg·L-1;Tmax, 0.25 h, 0.25 h, 0.25 h, 0.50 h;T1/2, 5.72 h, 5.94 h, 6.78 h, 3.78 h;MRT0-∞, 10.30 h, 9.61 h, 12.30 h, 4.89 h;CL/F, 7.59 mL·kg-1·h-1, 13.88 mL·kg-1·h-1, 7.28 mL·kg-1·h-1, 5.52 mL·kg-1·h-1.Conclusions Multiple peak phenomenon can be observed in the plasma SQV profiles.Morin can significantly reduce the SQV oral bioavailability and affect SQV PK profiles while acetyl-resveratrol cannot significantly affect the SQV oral bioavailability and SQV PK profiles in rats.
10.Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication.
Jiaying HAN ; Yinjing SUN ; Jiapeng HOU ; Yuyan WANG ; Yu LIU ; Cao XIE ; Weiyue LU ; Jun PAN ;
Acta Pharmaceutica Sinica B 2015;5(6):577-582
This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles (SMINs) designed to adhere to Helicobacter pylori (H. pylori). Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method. A fraction of Lpp20, an outer membrane protein of H. pylori known as NQA, was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles. The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance (SPR), change in zeta potential and fluorescence polarization (FP). The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles. In vitro experiments also indicate that such SMINs are able to adhere to H. pylori and may be useful for H. pylori eradication.

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