1.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
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Adolescent
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Imatinib Mesylate/adverse effects*
;
Incidence
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Antineoplastic Agents/adverse effects*
;
Retrospective Studies
;
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*
;
Aminopyridines/therapeutic use*
;
Protein Kinase Inhibitors/therapeutic use*
2.Birth weight curves of twin neonates with a gestational age of 25-40 weeks and their regional differences in 11 cities of China: an analysis of 17 256 cases.
Xiao-Yun HUANG ; Yuan-Fang ZHU ; Hui-Long LIU ; Guang-Wu WU ; Chuan-Yong LIU ; Ding-Yuan ZENG ; Jun HE ; Qing-Xi SHI ; Chang-Shui CHEN ; Bin ZHU ; Gao-Xiong WANG ; Hao SHI ; Hao-Hua LU
Chinese Journal of Contemporary Pediatrics 2022;24(8):899-907
OBJECTIVES:
To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve.
METHODS:
A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves.
RESULTS:
A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities.
CONCLUSIONS
The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.
Birth Weight
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Child
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China
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Cities
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Gestational Age
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Humans
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Infant
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Infant, Newborn
;
Twins
3.Birth weights of singleton neonates of 14 Chinese ethnic groups in 11 cities of China.
Xiao-Yun HUANG ; Yuan-Fang ZHU ; Hui-Long LIU ; Mian-Ai FU ; Chuan-Yong LIU ; Ding-Yuan ZENG ; Jun HE ; Qing-Xi SHI ; Chang-Shui CHEN ; Bin ZHU ; Gao-Xiong WANG ; Hao SHI ; Hao-Hua LU
Chinese Journal of Contemporary Pediatrics 2022;24(11):1219-1225
OBJECTIVES:
To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups.
METHODS:
The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages.
RESULTS:
A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups.
CONCLUSIONS
The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.
Infant, Newborn
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Male
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Child
;
Humans
;
Infant
;
Birth Weight
;
Ethnicity
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Cities
;
Gestational Age
;
China
4.Effect of Danggui Buxuetang on Functional Activity of Endothelial Progenitor Cells Exposed to Shear Stress
Zhen QIN ; Shui-qing HUANG ; Zheng-xin WEI ; Ming NI ; Xiao-kang CHAI
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(2):1-7
Objective:To investigate the effect of Danggui Buxuetang(DGBX)on the functional activity of rat endothelial progenitor cells(EPCs)exposed to different luminar shear stress (SS). Method:EPCs isolated from rat bone marrow were incubated on a parallel plate flow chamber at a steady SS of 0, 0.12, 1.2, 2.4 Pa for 6 h,then the cells exposed to different SS were randomly divided into 8 groups: control group (perfused with serum free medium),simvastatin group(0.1 μmol·L-1 simvastatin),3 DGBX groups(low,medium,high-dose DGBX)and 3 inhibitor groups(3 DGBX groups with LY294002). After 12 h,the samples were collected for the detection of cell proliferation ,migration,tubule formation ,the secretion of nitric oxide (NO) ,and the expressions of endothelial nitric oxide synthase(eNOS) mRNA and protein kinase B(Akt),respectively. Result:Compared with the control group,simvastatin and DGBX(high-dose)could both promote the functional activities and NO secretion,and up-regulate the expressions of eNOS mRNA and Akt protein in EPCs exposed to different SS(
5.Protective Effect of Danggui Buxuetang on Endothelial Progenitor Cells Against Oxidative Stress Injury Induced by H2O2
Jing GUO ; You-sheng MO ; Qi WANG ; Shui-qing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(20):39-45
Objective:To observe protective effect of Danggui Buxuetang (DBT) on oxidative stress injury of mouse bone marrow-derived endothelial progenitor cells (EPCs) against induced by hydrogen peroxide (H2O2). Method:Monocytes from bone marrow of mice were obtained by density gradient centrifugation, and EPCs were obtained by specific culture medium. The experiment was divided into blank group,model group,DBT group (100,200,400 mg·L-1). Methyl thiazolyl tetrazolium(MTT) assay was used to determine the survival rate of EPCs and establish the cell injury model induced by H2O2. MTT,transwell chamber,matrigel and superoxide fluorescent anion probe (DHE) were used to detect the proliferation,migration,
6.Screening of long non-coding RNA related to CYP450s involved in biosynthesis of tanshinones.
Yuan CAI ; Ying MA ; Juan GUO ; Yong-Qing WANG ; Qing DU ; Tong CHEN ; Shui-Han ZHANG ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2019;44(12):2480-2485
Tanshinones are abietane-type norditerpenoid quinones that make up the main bioactive ingredients of traditional Chinese medicine Salvia miltiorrhiza. Cytochrome CYP450 plays an important role in the post-structural modification of tanshinone biosynthesis pathway. Long non-coding RNA( lncRNA) have been defined as transcripts longer than 200 nucleotides,which have been functionally characterized in regulating the growth and development,secondary metabolism and stress of medicinal plants. In this study,we perform a comprehensive identification of lncRNAs in response to tanshinone metabolism induced by yeast extract( YE) and Ag~+ S. miltiorrhiza hairy roots. Deep RNA sequencing was used to identify a set of different 8 942 lncRNAs,of which 6 755 were intergenic lncRNAs. We predicted a total of 1 115 814 lncRNA-coding gene pairs,including 122 lncRNA-coding gene as cis pairs. The correlation analysis between lncRNA and CYP450 related to tanshinone biosynthesis was carried out and a total of 16 249 lncRNA-CYP450 target gene pairs were identified. Further analysis with functional known CYP76 AH1,CYP76 AH3 and CYP76 AK1 involved in tanshinone biosynthesis,we also identified a set of 216 target genes. These candidate genes will be the important target in the downstream regulation mechanism analysis of the tanshinone biosynthesis pathway.
Cytochrome P-450 Enzyme System
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genetics
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Diterpenes, Abietane
;
biosynthesis
;
Gene Expression Regulation, Plant
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Plant Roots
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RNA, Long Noncoding
;
genetics
;
RNA, Plant
;
genetics
;
Salvia miltiorrhiza
;
genetics
7. Protective Effect of Danggui Buxue Tang on Impaired Functional Activity of Endothelial Cells Exposed to Low Flow Shear Stress
Zhen QIN ; Zheng-xin WEI ; Shui-qing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(16):12-16
Objective: To investigate the protective effect of Danggui Buxue Tang(DGBX)with Angelicae Sinensis Radix(AS) and Astragali Radix(AR)at different radios on impaired functional activity of endothelial cells(ECs)exposed to low-fluid shear stress (FSS). Method: Low FSS was loaded by a parallel plate flow chamber,and ECs were divided into normal FSS group,low FSS group(each preincubated with M199 medium for 2 h),simvastatin group(preincubated with 0.1 μmol·L-1 simvastatin for 2 h),and 3 DGBX groups(preincubated with 3 g·L-1 AS and AR at 1:1,1:3,1:5 for 2 h,respectively). Then,the normal group was exposed to 1.2 Pa FSS,while the rest groups were all exposed to low FSS. At time points of 30,60, 360 min,the proliferation was detected by methyl thiazoly tetrazolium(MTT),the secretion of nitric oxide(NO) was detected by nitrase reduction test,and the mRNA and protein expressions of endothelial nitric oxide synthase(eNOS) were detected by Real-time fluorescence guantitative polymerase chain reaction(Real-time PCR) and Western blot,respectively. Result: Compared with the normal group, the secretion of NO and the expression of eNOS in ECs were both increased significantly at 60 min (P<0.01),then decreased at 360 min. Compared with the model group,there was no significant change in proliferation in DGBX groups,but DGBX could promote the NO secretion and the expression of eNOS in ECs exposed to low FSS at 360 min respectively, whereas the function of DGBX(AS and AR at 1:3,1:5) was obviously observed. Conclusion: DGBX could protect the functional activity of ECs exposed to low FSS.
8.Subacute toxicity metabonomics of Jinlingzi powder based on LC-MS.
Shu-Jie SHEN ; Su-Fang SHUI ; Bing-Kun XIAO ; Jian-Yun YANG ; Rong-Qing HUANG
China Journal of Chinese Materia Medica 2017;42(4):777-782
To further understand the metabolic characteristics of Jinlingzi powder toxicity effect in rats and explore the effect of Jinlingzi powder on unknown biological pathways in the treatment process. In this experiment, the effect of three doses of Jinlingzi powder decoction on rat liver and kidney was investigated to explore the characteristics and rules of Jinlingzi powder on in vivo metabonomic changes in rats. First, urine and serum samples of the rats were used for LC-MS analysis. Under the XCMS online analysis, 44 differential substances were found in the identification of metabolites. Finally, Metpa was used for metabolic pathways enrichment and analysis, and five related metabolic pathways were obtained: steroid hormone biosynthesis, tryptophan metabolism, pentose and glucuronate interconversions, ascorbate and aldarate metabolism, as well as glutathione metabolism. Metabolic network diagram showed that the toxicity-related pathways were mainly associated with lysine metabolism in living organisms, glucuronic acid conversion, and hormone metabolism, especially the metabolism imbalance of lysine and glutathione would result in the disorder of energy metabolism or oxidative stress regulation, and thus inducing the damage in rats. Subacute toxicity test results for three doses groups (low, middle and high doses) showed that, Jinlingzi powder with doses of 19.7 g•kg⁻¹ and 39.4 g•kg⁻¹ caused obvious toxic effect, indicating Jinlingzi powder could produce toxic effect in vivo in a dose-dependent manner, and cause irreversible damage to the body.
9.Anti-inflammation effect of Jinlingzi San in rat metabonomics based on 1H-NMR and LC-MS technology.
Shu-Jie SHEN ; Su-Fang SHUI ; Bing-Kun XIAO ; Jian-Yun YANG ; Rong-Qing HUANG
China Journal of Chinese Materia Medica 2017;42(2):363-369
To further explore the regulatory effect of Jinlingzi San on in vivo inflammatory mechanism during inflammatory treatment, this study adopted 1H-NMR and LC-MS technology to analyze differences in in vivo metabolites of carrageen-induce rat foot swelling model. Besides, biomarkers related to inflammation models of Jinlingzi San in SD rats were discovered to speculate the regulatory mechanism of Jinlingzi San in resisting carrageen-induce inflammation. Through the analysis of detection spectrum, we found 18 biomarkers of metabolites(citrate, pyruvate, malic acid, succinate, glutamate, lysine, tartrate, 2-oxobutyric acid, glycine, guanosine, 9-cis-retinoic acid, triphosphate, inosine 5'-diphosphate, inosine diphosphate, tripolyphosphate, inorganic triphosphate, glycerophosphocholine, 21-deoxycortisol). Relevant pathway analysis results were TCA cycle, pyruvate metabolism, glycine, serine and threonine metabolism, and dicarboxylic acid metabolism. From the metabolic network, we can see that the anti-inflammatory effect of Jinlingzi San can regulate citric acid, succinic acid and glycine content to resist oxygen free radical and reduce body damage by ROS, so as to down-regulate inflammatory factors generated from body tissues and resist inflammation.
10.L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes.
Xiang-Zhu XIE ; Xin HUANG ; Shui-Ping ZHAO ; Bi-Lian YU ; Qiao-Qing ZHONG ; Jian CAO
Chinese Medical Journal 2016;129(9):1108-1112
BACKGROUNDAdipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein-1 (MCP-1). Oxidized low-density lipoprotein (oxLDL) participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinflammatory function of oxLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L1 adipocytes induced by oxLDL and to elucidate the possible mechanisms.
METHODSFully differentiated 3T3-L1 adipocytes were incubated in the medium containing various concentration of L-4F (0-50 μg/ml) with oxLDL (50 μg/ml) stimulated, with/without protein kinase A (PKA) inhibitor H-89 (10 μmol/L) preincubated. The concentrations of MCP-1 in the supernatant, the mRNA expression of MCP-1, the levels of CCAAT/enhancer binding protein α (C/EBPα), and CCAAT/enhancer binding protein β (C/EBPβ) were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber.
RESULTSOxLDL stimulation induced a significant increase of MCP-1 expression and secretion in 3T3-L1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F (50 μg/ml) (P > 0.05). OxLDL stimulation showed no significant effect on C/EBPα protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPβ protein level in oxLDL-induced 3T3-L1 adipocytes.
CONCLUSIONSOxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.
3T3-L1 Cells ; Animals ; CCAAT-Enhancer-Binding Protein-beta ; analysis ; physiology ; Chemokine CCL2 ; genetics ; secretion ; Cyclic AMP ; physiology ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Humans ; Lipoproteins, LDL ; antagonists & inhibitors ; pharmacology ; Mice ; Peptides ; pharmacology ; Signal Transduction ; physiology

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