1.Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response.
Lin Juan GUO ; Xing Hua JIANG ; Wen Feng HE ; Peng YU ; Rong WAN ; Qi Ling KONG ; Chuan LIU ; Jian Hua YU ; Zhi Gang YOU ; Qi CHEN ; Bo ZHU ; Yan Qing WU ; Jin Song XU ; Kui HONG
Chinese Journal of Cardiology 2021;49(1):43-48
Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.
2.Historical Evolution and Modern Research on Shaoyao Gancaotang
Yuan-zhang QU ; Sheng-jun MA ; Guang-wei ZHU ; Lin-chun WAN ; Bo SUN ; Ya-jing LI ; Jie GUO ; Teng-teng XU ; A-qian CHANG ; Gang LI ; Lin-yong YANG ; Bao-guo LI
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(6):216-225
Shaoyao Gancaotang, first seen in
3.Effect of Tongxie Yaofang on p38 MAPK Pathway Associated Protein and Its Target Gene Expression in Colon Tissues of D-IBS Rats with Liver-stagnation and Spleen-deficiency
Jun-xiong GUO ; Li MA ; Wan-rong KANG ; Xiao-min XU ; Bin WANG ; Sheng-gang XU ; Yu-juan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(4):1-8
Objective::To explore the effect of Tongxie Yaofang on p38 mitogen activated protease(p38 MAPK), mitogen and stress protein kinase 1(MSK1), cyclic adenosine effector response element binding protein(CREB)mRNA and protein expression in colon tissue of diarrhea type irritable bowel syndrome (D-IBS) rat model with liver depression and spleen deficiency(GYPX), and interleukin-1
4.Preliminary application of CPC/PMMA composite bone cement in kyphoplasty for the elderly.
Xuan-Geng DENG ; Xiao-Ming XIONG ; Wei CUI ; Tao GU ; Dun WAN ; Hua-Gang SHI ; Xing CHEN ; Si-Mao SONG ; Wei HOU ; Guo-Long MEI ; Wen-Bing JIANG
China Journal of Orthopaedics and Traumatology 2020;33(9):831-836
OBJECTIVE:
From the perspective of clinical application to analyze the effectiveness and reliability of CPC/PMMA bone cement in percutaneous kyphoplasty (PKP) for the treatment of elderly patients with osteoporotic thoracolumbar fractures.
METHODS:
A retrospective analysis was performed on 62 patients with osteoporotic compression fracture of single-vertebral thoracic or lumbar segment who underwent PKP surgery and had a bone density less than or equal to -3.0 SD from February 2016 to December 2016. Among them, 23 patients were in CPC/PMMA group, with an average age of (77.6±2.2) years old, 39 patients in PMMA group, with an average age of (77.1±1.1) years old. The indexes between two groups were compared, including the visual analogue scale (VAS), height ratio of anterior vertebra (AVHR), local Cobb angle, cement leakage, new adjacent vertebral fracture(NAVF).
RESULTS:
There were no significant difference in gender, age, follow-up time and preoperative VAS, AVHR, local Cobb angle between two groups (>0.05), at the 1 day after operation, VAS, AVHR, local Cobb angle in all patients got obvious improvement (<0.05), which was no significant difference at 1 day after operation and final follow-up (>0.05). At the same time, there was no statistically significant difference in the incidence of new adjacent vertebral fracture and cement leakage (>0.05). The pain in both groups continued to improve at follow up after operation (<0.05), the local Cobb angle increased (<0.05) and AVHR decreased slightly (<0.05). However, the images of conventional methods (X-ray or CT) could not find signs about CPC degeneration and new bone ingrowth.
CONCLUSION
CPC/PMMA composite bone cement is safe and reliablein PKP for treatment of elderly patients with osteoporotic thoracolumbar fractures, which can effectively relieve pain and maintain vertebral body stability. It has the same curative effect as PMMA bone cement. It was worthy to research more in future, although no direct evidences support the CPC/PMMA composite bone cement can reduce the incidence of adjacent vertebral fracture, CPC degeneration or new bone ingrowth.
Aged
;
Bone Cements
;
Dinucleoside Phosphates
;
Fractures, Compression
;
Humans
;
Kyphoplasty
;
Osteoporotic Fractures
;
Polymethyl Methacrylate
;
Reproducibility of Results
;
Retrospective Studies
;
Spinal Fractures
;
Treatment Outcome
;
Vertebroplasty
5.Clinical comparative study of short-segment and long-segment fixation for single-segment thoracic and lumbar spine III stage Kümmell disease.
Xuan-Geng DENG ; Xiao-Ming XIONG ; Dun WAN ; Hua-Gang SHI ; Wei CUI ; Xing CHEN ; Guo-Long MEI ; Si-Mao SONG ; Wei HOU
China Journal of Orthopaedics and Traumatology 2019;32(7):598-603
OBJECTIVE:
By comparing the clinical efficacy of short-segment and long-segment fixation for single-segment thoracic and lumbar spine III stage Kümmell disease to explore a more suitable fixed segment for the disease.
METHODS:
The clinical data of 46 patients with single-segment thoracic and lumbar spine III stage Kümmell disease treated from July 2013 to December 2016 were retrospectively analyzed. Forty-six patients were divided into short-segment fixation group(one vertebra above and below the diseased vertebra) and long-segment fixation group(two vertebrae on the upper and lower of the diseased vertebra) according to different methods of cement stick fixation. There were 25 patients in the short-segment fixation group, including 9 males and 16 females, with an average age of (75.3±4.5) years old, lumbar spine bone mineral density T-value of (-3.1±0.3) g/cm³, follow-up time of (13.0±2.3) months; there were 21 patients in long-segment fixation group, 6 males and 15 females, with an average age of (74.5±3.9) years old, lumbar spine bone mineral density T-value of (-3.2±0.3) g/cm³, follow-up time of (14.7±3.6) months.The gender, age, follow-up time, operation time, intraoperative blood loss, cement leakage, and the rate of adjacent vertebrae fractures were compared between two groups, as well as pain VAS score, ODI, and kyphosis angle before and after surgery.
RESULTS:
There were no significant differences in age, gender, bone density, pain VAS score, ODI, and kyphosis between two groups before surgery. The operation time and intraoperative blood loss of short-segment fixation group were less than that of long-segment fixation group. The pain VAS score, ODI and kyphosis of the two groups were significantly improved at 7 days after the operation and at the latest follow-up, there was no significant difference between two groups. There were no significant differences in bone cement leakage(9/25 vs 11/21) and adjacent vertebrae fractures(4/25 vs 3/21).
CONCLUSIONS
Both long-segment fixation and short-segment fixation can effectively relieve pain, correct kyphosis, improve functional index, and achieve better clinical results, but short-segment fixation has less operation time and less intraoperative blood. So single-segment thoracic and lumbar spine III stage Kümmell disease does not need to extend the fixed segment, short-segment fixation is more in line with clinical needs and worthy of further study.
Aged
;
Female
;
Fracture Fixation, Internal
;
Humans
;
Kyphosis
;
Lumbar Vertebrae
;
Male
;
Retrospective Studies
;
Spinal Fractures
;
Thoracic Vertebrae
;
Treatment Outcome
6.Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy.
Dong-Fei WANG ; Jia-Lan LYU ; Juan FANG ; Jian CHEN ; Wan-Wan CHEN ; Jia-Qi HUANG ; Shu-Dong XIA ; Jian-Mei JIN ; Fang-Hong DONG ; Hong-Qiang CHENG ; Ying-Ke XU ; Xiao-Gang GUO
Journal of Zhejiang University. Science. B 2019;20(9):766-775
OBJECTIVE:
Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation.
METHODS:
We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype-phenotype correlation analysis.
RESULTS:
The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters.
CONCLUSIONS
The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.
Adaptor Proteins, Signal Transducing/genetics*
;
Adult
;
Aged
;
Alleles
;
Asian People
;
Cardiomyopathy, Dilated/surgery*
;
China/epidemiology*
;
Defibrillators, Implantable
;
Exons
;
Female
;
Genetic Association Studies
;
Genetic Predisposition to Disease
;
Genotype
;
Humans
;
LIM Domain Proteins/genetics*
;
Linkage Disequilibrium
;
Male
;
Middle Aged
;
Mutation
;
Polymorphism, Genetic
;
Sequence Analysis, DNA
7.Application of bronchoalveolar lavage fluid in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation.
Shu LI ; Li Ping WAN ; Guo Gang XIE ; Ai Hua BAO ; Yi SUN ; Wen SHU ; Jie Ling JIANG ; Jun YANG ; Xian Min SONG ; Chun WANG
Chinese Journal of Hematology 2019;40(10):822-826
Objective: To evaluate the diagnostic value of bronchoalveolar lavage (BAL) for pulmonary complications in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its safety. Methods: Patients with pulmonary complications after allo-HSCT underwent BAL. Microbiological smears, culture, PCR of CMV-DNA, EBV-DNA and TB-DNA, macro genomes new generation sequencing (mNGS) techniques were performed to detect pathogens in BAL fluid (BALF) . Results: A total of 73 allo-HSCT patients with 86 times of pulmonary complications enrolled this prospective study. They underwent 132 times of BAL procedures. The clinical diagnoses of 88.4% cases were made based on BALF analysis. Of them, 67 cases (77.9%) had infectious pulmonary complications, including 29 cases (33.7%) of fungal infection, 18 cases (20.9%) of mixed infection, 11 cases (12.8%) of viral infection and 9 cases (10.5%) of bacterial infection. The other 9 cases (10.5%) of non-infectious pulmonary complications included 8 cases (9.3%) of idiopathic pneumonia syndrome (IPS) and 1 case (1.2%) of pulmonary infiltration of lymphoma. The diagnoses of the remaining 10 cases (11.6%) were not determined. The platelet counts of 33 patients were less than 50×10(9)/L before BAL. None of them developed severe bleeding complications during or after BAL. Transient fever occurred in 10 patients after BAL. Blood cultures showed staphylococcal bacteremia in them and anti-infection therapies were effective. No life-threatening complications occurred in all of the patients during or after BAL. Conclusion: BALF analysis was informative for the diagnosis of pulmonary complication and safe for patients with pulmonary complications after allo-HSCT.
Bronchoalveolar Lavage
;
Bronchoalveolar Lavage Fluid
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Humans
;
Pneumonia/etiology*
;
Prospective Studies
8.Combination of electronic bronchoscope and narrow band imaging (NBI) in diagnosis of carcinomatous hydrothorax
Gang QING ; Wan-Xiu HUANG ; Xian JIANG ; Tang-Ling YANG ; Qing-Ping FU ; Xin-Fang MEI ; Guo-Hua XU ; Ting LIU
China Journal of Endoscopy 2018;24(2):52-56
Objective To evaluate the value of the electron bronchoscopy in diagnosis of carcinothoracic fluid in the case of replacing medical thoracoscopy and combining narrow-band imaging (NBI). Methods 89 cases of suspected cancerous pleural effusion patients, used electronic bronchoscope Olympus BF-1T 260 in place of medical thoracoscopy to enter pleural cavity in the usual way. First observed by white light bronchoscopy (WLB), then by narrow-band imaging (NBI) and take 5 pieces of tissue out respectively on the pleura of the lesion for pathological examination. Then compare the sensitivity and specificity of WLB and NBI methods, and the bleeding after biopsy. Result Among 89 cases of suspected cancerous pleural effusion patients, 85 cases found positive by white light bronchoscopy (WLB) , negative in 4 cases, 6 cases bleeding after biopsy (6.70%). Compared with the pathological results, WLB sensitivity 97.50%, specificity 22.22%. 68 cases found positive by NBI, negative 21 cases, no active bleeding after biopsy. Compared with the pathological results, the sensitivity of the NBI 86.67%, specificity 78.57%. Compared WLB with NBI, the former's sensitivity is superior to the latter, the latter's specificity is superior to the former. Both comparisons about sensitivity diagnosis of the and specificity are statistically significant (P < 0.05). Conclusion Electronic bronchial in place of medical thoracoscopy has high diagnostic rate in the carcinothoracic fluid, and the combination of NBI can improve the accuracy and security of the biopsy.
9.Quality assurance of computerized system for GLP laboratory
Hong LI ; Chunqi WU ; Gang HAN ; Yansheng DONG ; Qiaozhen GUO ; Jianjing WANG ; Shufang WAN ; Huazhi MA ; Quanjun WANG
Drug Evaluation Research 2017;40(4):433-436,491
In view of the characteristics of the computerized system,the key points in the quality assurance (QA) of the computerized system was discussed and summarized combined with the requirements of the GLP laboratory in Europe and America.The validation of computerized system,the control during the use of computerized system,period maintenance and safety protection of computerized system,archives of electronic data was discussed,expecting to provide reference for the management of computerized system in Chinese GLP laboratory which is generally not high currently.The experiences were obtained as follow:Through repeated inspection and review,the problem was found and set as the risk point;a targeted QA inspection plan was made focusing on the risk-based inspection and the QA inspection plan was timely adjusted according to the problems,which ensures the pertinence and validity of the QA inspection.
10.Preliminary report of using cardiopulmonary exercise testing guide exercise rehabilitation in patients with chronic heart failure.
Yan-ling LIU ; Xing-guo SUN ; Hua GAO ; Zhen-ying ZHANG ; Jing FENG ; Li-qing JIANG ; Jian ZHANG ; Jia-ning XI ; Jing-min ZHOU ; Wan-gang GE
Chinese Journal of Applied Physiology 2015;31(4):374-377
OBJECTIVEThe exercise rehabilitation in patient with chronic heart failure (CHF) is standard clinical practice, but it is rare using CardioPulmonary Exercise Testing (CPET) guide to prescribe exercise rehabilitation in China.
METHODSWe performed symptom limited maximal CPET in 10 patients with CHF, randomly divided into two groups: 5 patients as control without exercise and 5 exercise patients used Δ50%W intensity to exercise 30 min/d, 5 d/w, x12 w. Before and after 12 w rehabilitation, we evaluated functions.
RESULTSThere were no significant difference between two groups patients (P > 0.05). The exercise duration was increased from 8 min to 23 min after rehabilitation (P < 0.001); distance 6 minutes walking was increased from 394 m to 470 m (P < 0.05); score of Minnesota quality of life was decreased from 25 to 3 in exercise group (P < 0.01). However, there were nosignificant changes in control group (P>0.05) and their changes were smaller than those in exercise group (P < 0.01).
CONCLUSIONThe CPET guiding exercise rehabilitation is safe and effective for patients with CHF.
China ; Chronic Disease ; Exercise Test ; Exercise Therapy ; Heart Failure ; therapy ; Humans ; Quality of Life ; Walking

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