1.Three-dimensional finite element analyses of bone surface stress of two kinds of conjunction implant.
Jing LAN ; Xin XU ; Guang-shui JIANG ; Yan-jin GUAN ; Hai-yun HUANG ; Jing LAN
West China Journal of Stomatology 2008;26(4):443-447
OBJECTIVETo establish a three-dimension finite element model of mandible with two kinds of dental implant and to study the stress of implant-bone interface.
METHODSMeasuring the data of the components of the dental implant and using spiral CT image reconstruction technique to scan the cross section of the mandible. Three-dimension finite element analysis software Unigraphics and MSC. Marc/Mentat were used to build the conjunction model and bone model of two implant systems. Loading 200 N axially and 100 N 30 degrees obliquely on the models respectively, the stress distribution patterns of the bone interface of two implant systems were analyzed.
RESULTSThe stress distribution on the bone interface of two implant systems was similar. The peak stress of oblique loading was higher than that of axial loading. The peak stress district of the bone was concentrated on the stricture of the implant cervix, which was more obviously displayed on the Replace Select implant. The peak stresses on the bone interface of Replace Select implant were higher than that of Replace implant in all loadings.
CONCLUSIONTo Replace Select especially, oblique force should be avoided in clinical practice in case of the bone absorption.
Computer Simulation ; Dental Implants ; Finite Element Analysis ; Humans ; Mandible ; Stress, Mechanical
2.Design and activity verification of human parathyroid hormone (1-34) mutant protein.
Shuang QIU ; Yue-Shui JIANG ; Zhi-Qin LI ; Jian-Yong LEI ; Yun CHEN ; Jian JIN
Acta Pharmaceutica Sinica 2012;47(7):909-915
Through protein-protein BLAST of homologous sequences in different species in NCBI database and preliminary simulating molecular docking and molecular dynamics by computer software discovery studio 3.1, three amino acids R25K26K27 of natural human parathyroid hormone (1-34) with Q25E26L27 were mutated and the biological activity of the mutant peptide was evaluated. Result showed that: root mean superposition deviation RMSD value between PTH (1-34)-(RKK-QEL) and PTH (1-34) peptide main chain was 2.509 3, indicating that the differences between the two main chain structural conformation was relatively small; the interaction energy between PTH (1-34)-(RKK-QEL) and its receptor protein PTH1R had been enhanced by 7.5% compared to nature PTH (1-34), from -554.083 kcal x mol(-1) to -599.253 kcal x mol(-1); the number of hydrogen bonds was increased from 32 to 38; PTH (1-34)-(RKK-QEL) can significantly stimulate the RANKL gene expression (P < 0.01) while inhibiting the OPG gene expression (P < 0.01) in UAMS-32P cells; in the co-culture system of UAMS-32P cells and mouse primary femur bone marrow cells, PTH (1-34)-(RKK-QEL) stimulated the formation of osteoclasts (P < 0.01) and had a higher biological activity than PTH (1-34) standard reagents.
Animals
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Bone Marrow Cells
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cytology
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metabolism
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Coculture Techniques
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Mice
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Mutant Proteins
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genetics
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pharmacology
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Mutation
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Osteoclasts
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cytology
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drug effects
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Osteogenesis
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drug effects
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Osteoprotegerin
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genetics
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metabolism
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RANK Ligand
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genetics
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metabolism
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RNA, Messenger
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metabolism
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Receptor, Parathyroid Hormone, Type 1
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metabolism
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Teriparatide
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pharmacology
3.Effect of electroacupuncture on expressions of acetylcholine and mucin 5AC in the lungs of rats with chronic obstructive pulmonary disease
Wen-Juan CONG ; Jing LI ; Yu-Jing LIAO ; Xin-Fang ZHANG ; Chuan-Wei JIANG ; Shui-Ying XIANG ; Wen-Biao HUANG ; Xiao-Yun LIU ; Zi-Bing LIU
Journal of Acupuncture and Tuina Science 2018;16(3):133-139
Objective:To observe the effect of electroacupuncture (EA) on the expressions of acetylcholine (ACh) and mucin 5AC (MUC5AC) in the lungs of rats with chronic obstructive pulmonary disease (COPD),and explore the mechanism of EA in treating COPD.Methods:Thirty Sprague-Dawley (SD) rats were randomly divided into a control group,a COPD group,and an EA group,with 10 rats in each group.The control group was a group of normal rats.The COPD rat model was induced by cigarette smoke combined with lipopolysaccharide (LPS).The COPD rats were treated with EA at bilateral Feishu (BL 13) and Zusanli (ST 36) in the EA group,30 min each time,once a day,successively for 14 d.The lung function was tested.The contents of ACh and MUC5AC in lungs and bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA).Pearson method was used to analyze the correlation between pulmonary function and the content of MUC5AC in lungs.The mRNA and protein expressions of MUC5AC in lung tissues were detected by real-time polymerase chain reaction (RT-PCR) and Western blot (WB),respectively.The immune response of MUC5AC was observed by immunohistochemistry.Results:Eight rats were left in each group,and the other two died.Compared with the control group,the total airway resistance (Raw) increased significantly and dynamic compliance (Cdyn) decreased significantly in the COPD group (P<0.01);compared with the COPD group,the Raw level declined significantly and Cdyn increased significantly in the EA group (P<0.01).The contents of ACh and MUC5AC in the lungs and BALF were remarkably higher in the COPD group compared with those in the control group (P<0.01,P<0.001);compared with the COPD group,the contents of ACh and MUC5AC were significantly lower in the EA group (P<0.05,P<0.001).There was a negative correlation between MUC5AC content and lung function (P<0.001).The mRNA and protein expressions of MUC5AC in the lungs were significantly higher in the COPD group than in the control group (P<0.001);compared with the COPD group,the expressions were significantly lower in the EA group (P<0.01).Compared with the control group,the immune response of MUC5AC in the airway epithelium significantly increased in the COPD group (P<0.001);the immune response of MUC5AC was significantly lower in the EA group compared with that in the COPD group (P<0.001).Conclusion:EA treatment can improve the lung function of COPD rats,which may be related to its effect in the down-regulation of ACh and MUC5AC contents in the lungs as well as the inhibition of mucus hypersecretion.
4.The optimization of culture conditions of MRC -5 human diploid cell
Chun-Yan GU ; Cai-Hua TANG ; Jian-Bo LI ; Jia-Yuan BAO ; Yun-Shui JIANG
Journal of Preventive Medicine 2015;(3):257-261
Objective To optimize the culture conditions of MRC -5 human diploid cell.Methods To compare the growth status of MRC -5 cells,three kinds of culture medium with T25 bottles and Spinner cultivation system Cytodex1 micro carrier were used.Morphology,cell counting,growth curve,glucose -lactic acid value were observed and detected daily for screening a kind of suitable medium.Cell proliferation was compared with different levels of the bovine serum.Results There were no significant differences among the three kinds of culture medium.There were significant differences among MEM((43.25 ±0.60)×104 cells/mL,(12.98 ±1.27)×105 cells /mL),M199 ((35.40 ±1.41 )×104 cells/mL, (10.76 ±1.31)×105 cells /mL)and DMEM/F12 ((36.75 ±1.59)×104 cells/mL,(11.22 ±1.42)×105 cells /mL)(P<0.01).The cell proliferation of MEM cultures was 5.17 and 6.49 times better than those of M199 and DMEM/F12 cultures.Imported fetal bovine serum cell proliferation ((4.55 ±0.51)×105 cells /mL)was better than the other three bovine serum ((4.12 ±1.03,3.59 ±0.48,3.53 ±0.52)×105 cells /mL).Conclusion Tree kinds of culture medium can be used to culture MRC -5 human diploid cell.The MEMculture is better.Imported fetal bovine serum is better than other kinds of serum.
5.Clinical study on Zhuyu Tongfu serial recipe combined with acupuncture and massotherapy in treating hypertensive cerebral hemorrhage.
Hua LIU ; Guo-ping ZHANG ; Shui-jiang SONG ; Mei-ping DING ; Jun-fu ZHOU ; Xiao-dong BIE ; Jian-ren LIU ; Yun ZHANG ; Zhuo-hua LI ; Hai-feng GAO ; Guang-guo LIU ; Lai-ting FEI
Chinese journal of integrative medicine 2005;11(3):167-172
OBJECTIVETo observe the clinical efficacy and mechanism of Zhuyu Tongfu (ZYTF) Serial Recipe combined with acupuncture and massotherapy in treating hypertensive cerebral hemorrhage (HCH).
METHODSOne hundred and eighteen patients with hypertensive cerebral hemorrhage, on the basis of conventional Western medicine treatment, were randomly divided into ZYTF combined with acupuncture and massotherapy group (treated group) and simple Western medicine group (control group); the clinical efficacy, neurofunction deficit scoring (NDS) alterations and hematoma absorption rate of both groups were observed, and also the plasma superoxide dismutase (SOD) activity, plasma lipid peroxidase (LPO) content, erythrocyte glutathion peroxidase (GSH-Px) activity, hematocrit (Ht) and the whole blood viscosity (Va) change were also observed.
RESULTSIn the treated group, the clinical efficacy, NDS improvement and hematoma absorption rate were superior to that of the control group; comparison between the two groups after treatment showed that plasma SOD activity and GSH-Px activity got more elevated and plasma LPO content, Ht and Va more lowered in the the treated group than those in the control group.
CONCLUSIONZYTF combined with acupuncture and massotherapy has better effect, its therapeutic mechanism was possibly correlated to the elevation of plasma SOD activity, GSH-Px activity and lowering of plasma LPO content, Ht and Va.
Acupuncture Therapy ; methods ; Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Intracranial Hemorrhage, Hypertensive ; therapy ; Male ; Massage ; methods ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Treatment Outcome
6.Research on rules of distribution and development of traditional Chinese medicine syndromes of 2,237 HIV/AIDS cases.
Jian WANG ; Ying LIU ; Wen ZOU ; Hong-Juan LI ; Li-Yun HE ; Ji-Peng DONG ; Yu-Wen CEN ; Xin DENG ; Li WANG ; Guo-Liang ZHANG ; Jian-Hua HU ; Shi-Ping XIE ; Jiang-Rong WANG ; Xiao-Jing WANG ; Yan-Ping MA ; Xiao-Ping YANG ; Yong LI ; Shui-Qing LIU ; Xia LI
China Journal of Chinese Materia Medica 2013;38(15):2472-2475
HIV/AIDS patients in high prevalence areas with different routes of infection (sexually transmitted 878 cases, 527 cases of intravenous drug user, paid blood donor 652 cases) were choosen for traditional Chinese medicine (TCM) syndrome investigation for one-year clinical follow-up. This paper primarily concluded the nature, location and pathogenesis of AIDS diseases. Deficiency of Yang and Yin, combining deficiency of Qi are the basic deficiency syndromes, while stagnation of dampness, toxic fire are the excess syndromes; the disease location of HIV infector is spleen, main syndrome is deficiency of spleen Qi; the disease location of AIDS patient is kidney, main syndrome is deficiency of spleen and kidney Yang. The pathogenic development tendency is from deficiency of Qi to combining stagnation of dampness and toxic fire, finally to deficiency of Qi and Yin, deficiency of Yang.
Adolescent
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Adult
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Aged
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Female
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Follow-Up Studies
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HIV Infections
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diagnosis
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etiology
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transmission
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Humans
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Male
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Medicine, Chinese Traditional
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methods
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Middle Aged
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Young Adult
7.Chemical investigation of the roots of Polygala sibirica L.
Yu-Hong ZHOU ; Shui-Ying ZHANG ; Qiang GUO ; Xing-Yun CHAI ; Yong JIANG ; Peng-Fei TU
Chinese Journal of Natural Medicines (English Ed.) 2014;12(3):225-228
AIM:
To investigate the chemical constituents of the roots of Polygala sibirica L. (Polygalaceae)
METHOD:
The isolation was performed by solvent extraction and various chromatographic techniques, including silica gel, Sephadex LH-20, ODS, semi-preparative HPLC, and preparative TLC. The chemical structures were elucidated based on extensive spectroscopic analysis, including HR-ESI-MS and 1D- and 2D-NMR spectroscopic data.
RESULTS:
A total of sixteen compounds, including five xanthones (5, 7-10), five saccharide esters (1, 3, 4, 12, 13), two flavonoids (14, 16), two triterpenoids (11, 15), one phenylpropanoid (6), and one benzophenone glycoside (2) were isolated. Their structures were determined as sibiricose A7 (1), sibiriphenone A (2), polygalatenoside A (3), polygalatenoside C (4), lancerin (5), 3, 4, 5-trimethoxycinnamic acid (6), 6-hydroxy-1, 2, 3, 7-tetramethoxyxanthone (7), 1, 3, 7-trihydroxy-2-methoxyxanthone (8), onjixanthone II (9), 1, 2, 3, 6, 7-pentamethoxyxanthone (10), presenegenin (11), 3'-O-3, 4, 5-trimethoxycinnamoyl-6-O-4-methoxy benzoyl sucrose (12), tenuifoliside C (13), 5, 3'-dihydroxy-7, 4'-dimethoxyflavonol-3-O-β-D-glucopyranoside (14), tenuifolin (15), and rhamnetin 3-O-β-D-glucopyranoside (16).
CONCLUSION
Compounds 1 and 2 are two new compounds from P. sibirica.
Benzophenones
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chemistry
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isolation & purification
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Coumaric Acids
;
chemistry
;
isolation & purification
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Glucosides
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chemistry
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isolation & purification
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Molecular Structure
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Plant Extracts
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chemistry
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Plant Roots
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chemistry
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Polygala
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chemistry
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Triterpenes
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chemistry
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isolation & purification
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Xanthones
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chemistry
;
isolation & purification
8.Multi-Omics and Its Clinical Application in Hepatocellular Carcinoma: Current Progress and Future Opportunities.
Wan-Shui YANG ; Han-Yu JIANG ; Chao LIU ; Jing-Wei WEI ; Yu ZHOU ; Peng-Yun GONG ; Bin SONG ; Jie TIAN
Chinese Medical Sciences Journal 2021;36(3):173-186
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the fourth leading cause of cancer related death worldwide. China covers over half of cases, leading HCC to be a vital threaten to public health. Despite advances in diagnosis and treatments, high recurrence rate remains a major obstacle in HCC management. Multi-omics currently facilitates surveillance, precise diagnosis, and personalized treatment decision making in clinical setting. Non-invasive radiomics utilizes preoperative radiological imaging to reflect subtle pixel-level pattern changes that correlate to specific clinical outcomes. Radiomics has been widely used in histopathological diagnosis prediction, treatment response evaluation, and prognosis prediction. High-throughput sequencing and gene expression profiling enabled genomics and proteomics to identify distinct transcriptomic subclasses and recurrent genetic alterations in HCC, which would reveal the complex multistep process of the pathophysiology. The accumulation of big medical data and the development of artificial intelligence techniques are providing new insights for our better understanding of the mechanism of HCC via multi-omics, and show potential to convert surgical/intervention treatment into an antitumorigenic one, which would greatly advance precision medicine in HCC management.
Artificial Intelligence
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Carcinoma, Hepatocellular/therapy*
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Gene Expression Profiling
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Humans
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Liver Neoplasms/genetics*
;
Prognosis
9.HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems.
Ping LI ; Ying WU ; Yan XIE ; Feng CHEN ; Shao qiang CHEN ; Yun Hao LI ; Qing Qing LU ; Jing LI ; Yong Wei LI ; Dong Xu PEI ; Ya Jun CHEN ; Hui CHEN ; Yan LI ; Wei WANG ; Hai WANG ; He Tao YU ; Zhu BA ; De CHENG ; Le Ping NING ; Chang Liang LUO ; Xiao Song QIN ; Jin ZHANG ; Ning WU ; Hui Jun XIE ; Jina Hua PAN ; Jian SHUI ; Jian WANG ; Jun Ping YANG ; Xing Hui LIU ; Feng Xia XU ; Lei YANG ; Li Yi HU ; Qun ZHANG ; Biao LI ; Qing Lin LIU ; Man ZHANG ; Shou Jun SHEN ; Min Min JIANG ; Yong WU ; Jin Wei HU ; Shuang Quan LIU ; Da Yong GU ; Xiao Bing XIE
Chinese Journal of Preventive Medicine 2023;57(7):1047-1058
Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy
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Child
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Humans
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Female
;
Glycated Hemoglobin
;
Cohort Studies
;
Diabetes Mellitus/diagnosis*
;
Sensitivity and Specificity
;
ROC Curve
10.To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia.
Xiao Shuai ZHANG ; Bing Cheng LIU ; Xin DU ; Yan Li ZHANG ; Na XU ; Xiao Li LIU ; Wei Ming LI ; Hai LIN ; Rong LIANG ; Chun Yan CHEN ; Jian HUANG ; Yun Fan YANG ; Huan Ling ZHU ; Ling PAN ; Xiao Dong WANG ; Gui Hui LI ; Zhuo Gang LIU ; Yan Qing ZHANG ; Zhen Fang LIU ; Jian Da HU ; Chun Shui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yan Qiu HAN ; Li E LIN ; Zhen Yu ZHAO ; Chuan Qing TU ; Cai Feng ZHENG ; Yan Liang BAI ; Ze Ping ZHOU ; Su Ning CHEN ; Hui Ying QIU ; Li Jie YANG ; Xiu Li SUN ; Hui SUN ; Li ZHOU ; Ze Lin LIU ; Dan Yu WANG ; Jian Xin GUO ; Li Ping PANG ; Qing Shu ZENG ; Xiao Hui SUO ; Wei Hua ZHANG ; Yuan Jun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2023;44(9):728-736
Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult
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Humans
;
Adolescent
;
Imatinib Mesylate/adverse effects*
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Incidence
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Antineoplastic Agents/adverse effects*
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Retrospective Studies
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Pyrimidines/adverse effects*
;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
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Treatment Outcome
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Benzamides/adverse effects*
;
Leukemia, Myeloid, Chronic-Phase/drug therapy*
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Aminopyridines/therapeutic use*
;
Protein Kinase Inhibitors/therapeutic use*