1.Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia
Xiao-Lan LIU ; Wen-Zhong LI ; Qian ZHANG ; Xue-Mei WANG ; Yu-Ru ZHOU ; Cheng-Gao WU ; Si-Min XIONG ; Ai-Ping LE ; Zhang-Lin ZHANG
Journal of Experimental Hematology 2024;32(2):525-531
Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P<0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P>0.05).Compared with the control group,190 differential metabolites(VIP>1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.
2.Urinary Metabolomics Aanlysis of Differences in Effect of Aconiti Coreani Radix and Typhonii Rhizoma on Gerbils with Stroke
Liting ZHOU ; Wanting ZENG ; Ru JIA ; Huiying XU ; Yihui DING ; Hao DONG ; Haowen MA ; Yang QU ; Qian CAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):157-166
ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique, and then to clarify the mechanism of the two, as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group(CG), model group(MG), Aconiti Coreani Radix group(RA) and Typhonii Rhizoma group(RT). Except for the CG, ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG, rats in the other groups received whole powder suspension(0.586 mg·g-1) was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0, 3, 7 and 14. After the end of administration, the serum, brain tissue and urine of gerbils in each group were collected, and the rate of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC), and the levels of interleukin(IL)-6, tumor necrosis factor(TNF)-α, malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and nitric oxide(NO) in serum and brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), and the data were processed by multivariate statistical analysis, and differential metabolites were screened based on value of variable importance in the projection(VIP) of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG) database and Metaboanalyst 5.0. ResultCompared with the CG, the neurological deficit score was significantly increased in the MG(P<0.05), compared with the MG, the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d(P<0.05). Compared with the CG, the rate of cerebral infarction was significantly increased in the MG(P<0.05), compared with the MG, the rates of cerebral infarction in the RA and RT were significantly reduced(P<0.05). Compared with the CG, the levels of IL-6, TNF-α, and MDA in the serum and brain tissue of gerbils from the MG were significantly increased(P<0.05), and the levels of SOD, GSH and NO were significantly reduced(P<0.05). Compared with the MG, Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6, TNF-α and MDA, and up-regulated the levels of SOD, GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics, of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma, and could be used as potential biomarkers for both treatments in stroke gerbils, respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism, pyrimidine metabolism, and aminoacyl-tRNA biosynthesis. In addition, Aconiti Coreani Radix could also regulate riboflavin metabolism, Typhonii Rhizoma could also regulate purine metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism, biosynthesis of pantothenate and coenzyme A, and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke, with Aconiti Coreani Radix having stronger effects. From the metabolomics results, the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism, oxidative stress and so on, while Typhonii Rhizoma mainly involve amino acid metabolism, lipid metabolism, energy metabolism, etc.
3.A case-control study of the association between anti-Müllerian hormone and ischemic stroke
Xinyu CHEN ; Zhengyuan ZHOU ; Shujun GU ; Chengcheng DUAN ; Qiyu QIAN ; Ru LI ; Huan ZHANG
Chinese Journal of Geriatrics 2024;43(2):175-179
Objective:To investigate the association between plasma anti-Müllerian hormone(AMH) levels and ischemic stroke.Methods:In this case-control study, 93 ischemic stroke patients were randomly selected as the case group from a study on the prevention and treatment of metabolic syndrome, which was conducted in 2018-2019 in Changshu, Jiangsu Province, while 372 nonischemic stroke patients were selected as the control group according to the principle of 1∶4 matching.An enzyme-linked immunosorbent assay was used to measure plasma AMH levels.The conditional logistic regression model and restricted cubic spline were used to analyze the relationship between AMH levels and ischemic stroke.Results:A total of 465 subjects with an average age of (68.7±7.4)years were included in this study, of whom 215(46.2%)were men and 250(53.8%)were women.According to our conditional Logistic regression analysis, the risk of ischemic stroke was reduced by 44% for every unit increase in the log-AMH level( OR=0.56, 95% CI: 0.37-0.85)in the overall population after multivariate adjustment.Compared with the tertile with the lowest AMH level, the risk of ischemic stroke in the tertile with the highest AMH level decreased significantly( OR=0.37, 95% CI: 0.19-0.69). When subgrouped by sex, the tertiles with the highest AMH levels were associated with a 66% lower risk of ischemic stroke in men( OR=0.34, 95% CI: 0.13-0.88)and a 64% lower risk of ischemic stroke in women( OR=0.36, 95% CI: 0.15-0.87), compared with the tertiles with the lowest AMH levels.The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between plasma AMH levels and ischemic stroke both in the general population and in male or female population( Pvalues for linear trends were 0.0002, 0.008 and 0.007, respectively). Conclusions:Higher plasma AMH levels decrease the risk of ischemic stroke with a dose-response pattern.
4.Diabetes Promotes Myocardial Fibrosis via AMPK/EZH2/PPAR-γ Signaling Pathway
Shan-Shan LI ; Lu PAN ; Zhen-Ye ZHANG ; Meng-Dan ZHOU ; Xu-Fei CHEN ; Ling-Ling QIAN ; Min DAI ; Juan LU ; Zhi-Ming YU ; Shipeng DANG ; Ru-Xing WANG
Diabetes & Metabolism Journal 2024;48(4):716-729
Background:
Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified.
Methods:
In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed.
Results:
In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation.
Conclusion
Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.
5. Betulinic Acid Improves Cardiac Function in Septic Rats Through AKT / mTOR and AKT / AMPK -modulated Autophagy
Xiang-Fei MENG ; Xin-Ru ZHOU ; Jing HUANG ; Meng-Yuan CHEN ; Li-Juan LIU ; Lu-Jia SHI ; Ci-Ai CHEN ; Ling-Bo QIAN
Chinese Journal of Biochemistry and Molecular Biology 2023;39(6):840-847
Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.
6.Effects of Dayuanyin decoction on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome
Ru ZHANG ; Haitao DU ; Xiaoxue WANG ; Yi WANG ; Qian ZHOU ; Shanxin LIU ; Ping WANG
China Pharmacy 2023;34(24):3000-3005
OBJECTIVE To study the effects of Dayuanyin decoction (DYY) on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome. METHODS Thirty-six BALB/c mice were divided into the normal group (NC group), model group (MC group), positive control group (LBM group, 57.59 mg/kg ribavirin), DYY low-dose, medium-dose and high-dose groups (LDYY,MDYY,HDYY groups,1.67,3.34,6.68 g/kg,calculated by crude drug), with 6 mice in each group. Except for NC group, RSV-Hanshi yufei syndrome model was induced by “Hanshi modeling+RSV infection”; after the second cold and wet stimulation, RSV solution was dripped into the nasal cavity at 50% tissue culture infectious dose, once a day, for 3 consecutive days; each administration group was given corresponding solution intragastrically 4 hours after each nasal drip, once a day, for 5 consecutive days. The levels of motilin (MTL) and gastrin (GAS) in serum, the levels of IL-6 and IL-1β in supernatant of lung tissue, and the percentage of peripheral blood lymphocytes were all determined. The pathological changes of lungs were observed, and the changes of gut microbiota were analyzed. RESULTS Compared with MC group, the levels of MTL in serum (except for HDYY group), and the levels of IL-6 and IL-1β in supernatant of lung tissue were all decreased significantly in DYY groups, while the level of GAS (except for HDYY group) in serum was increased significantly (P<0.05 or P<0.01). The pathology of lung tissue was improved, the percentage of T lymphocytes in LDYY group and the percentages of T lymphocyte and B lymphocyte in MDYY group were all increased significantly (P<0.05 or P<0.01). Compared with the NC group, Bacteroidetes, Actinobacteria, Bacteroides, Alistipes, Bacteroidota, Bacteroides acidfaciens and Alloprevotella were expressed in high abundance, while Firmicutes, Proteobacteria, Lachnospiraceae NK4A136 group, Kineothrix and Clostridiales unclassified were expressed in low abundance. After the intervention of medium-dose DYY, the relative abundance of each microbiota tended to be adjusted back, with different species including Lachnospiraceae_UCG-Ruminococcus, etc. CONCLUSIONS Dayuanyin decoctioncan reduce the lung injury caused by RSV, the mechanism of which may be associated with relieving inflammation, regulating gastrointestinal hormone levels, the percentage of lymphocytes and the abundance of beneficial and harmful bacteria in the intestinal tract.
7.Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing.
Fang Ming WANG ; Chuan Yu YANG ; Yuan QIAN ; Fang LI ; Li GU ; Dong Mei CHEN ; Yu SUN ; Ru Nan ZHU ; Fang WANG ; Qi GUO ; Yu Tong ZHOU ; Ri DE ; Ling CAO ; Dong QU ; Lin Qing ZHAO
Chinese Journal of Pediatrics 2022;60(1):30-35
Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.
Adenovirus Infections, Human/epidemiology*
;
Adenoviruses, Human/genetics*
;
Beijing/epidemiology*
;
Child
;
Child, Hospitalized
;
Cross-Sectional Studies
;
Female
;
Humans
;
Infant
;
Male
;
Phylogeny
;
Respiratory Tract Infections/epidemiology*
8.Analysis of factors influencing high frequency hearing loss among noise-exposed workers in an air conditioner manufacturing industry
QIU Cong xi CHEN Lin ZHOU Hao ZHANG Jin wei LIN Qiu yue XIAO Lü ; wu LI Yan ru HUANG Pei - , - , FENG Qian li LIU Yi min WANG Zhi
China Occupational Medicine 2022;49(06):652-656
Objective ( )
To explore the feasibility of using generalized estimating equation GEE to analyze the influencing
- ( )
factors of high frequency hearing loss HFHL among noise exposed workers in an air conditioner manufacturing enterprise.
Methods -
The noise exposed workers in an air conditioner manufacturing industry who had been tested for pure tone hearing
threshold twice or more from 2015 to 2019 were selected as the research subjects using the judgment sampling method. Data
, , , , , ( )
such as age length of service gender smoking alcohol consumption body mass index BMI and HFHL were collected. The
Results
influencing factors of HFHL were analyzed using the GEE. The detection rates of HFHL from 2015 to 2019 were
, , , , ,
22.2% 23.8% 24.2% 24.1% and 20.9% respectively. Among them the detection rate of HFHL in 2019 was lower than that
( P ) , ,
in 2017 and 2018 all <0.001 . The GEE analysis results showed that the risks of HFHL in 2015 2016 2017 and 2018 were
( P ),
higher than that in 2019 all <0.01 regardless of interaction effects and after adjusting for confounding factors such as
, [OR( CI)] ( -
duration of noise exposure smoking and BMI. The odds ratios and 95% confidence intervals 95% were 1.19 1.07
), ( - ), ( - ) ( - ),
1.33 1.26 1.13 1.39 1.30 1.18 1.43 and 1.27 1.15 1.39 respectively. The risk of HFHL was higher in males than in
(P ), OR( CI) ( - ) , (P ), OR
females <0.01 and 95% was 3.78 3.00 4.77 . The older the age the higher the risk of HFHL <0.01 and
( CI) ( - ) Conclusion -
95% was 1.07 1.05 1.09 . The influencing factors of HFHL among noise exposed workers in the air conditioner industry are age and gender. GEE can be used to analyze the factors influencing the longitudinal data of HFHL in
workers with noise exposure.
9.Clinical Characteristics of Old Patients with Spinal Cord Injury
Hai-qiong KANG ; Hong-jun ZHOU ; Bo WEI ; Gen-lin LIU ; Ying ZHENG ; Ying ZHANG ; Chun- xia HAO ; Yi-ji WANG ; Xiao-lei LU ; Yuan YUAN ; Qian-ru MENG
Chinese Journal of Rehabilitation Theory and Practice 2021;27(8):943-950
Objective:To investigate the clinical characteristics of old patients with spinal cord injury. Methods:From January 1, 2013 to December 31, 2019, totally 386 old (≥ 60 years) patients with spinal cord injury were enrolled. Their gender, age, etiology, American Spinal Injury Association Impairment Scale (AIS) and complications were analyzed. Results:In the old patients with spinal cord injury, traumatic spinal cord injury was more common in males (71.17%) and non-traumatic spinal cord injury was more common in females (56.19%). Fall on level surface was the most important cause of spinal cord injury both in old men (28.83%) and women (24.76%). Tumor (19.05%) was the most common non-traumatic cause of spinal cord injury in old female patients. Cervical segment (78.46%) was the most common site of injury in old traumatic spinal cord injury, while thoracic segment (52.14%) was the most common site of injury in non-traumatic spinal cord injury. Grade D (38.08%) was the most common AIS grade, followed by grades C (28.76%), A (21.50%), and B (11.66%). Spinal canal stenosis (23.31%) played an important role in the etiology of old spinal cord injury. Neuralgia, venous thrombosis of lower extremities and urinary tract infection were the most common complications in old patients with spinal cord injury. Conclusion:Fall on level surface is the leading cause of spinal cord injury in old patients, and the proportion of fall in the etiology of old spinal cord injury tends to increase with age. It is important to take effective measures to avoid falling in the old adults to prevent spinal cord injury.
10.Survey of Neurological Function and Complications of Pediatric Spinal Cord Injury
Ying ZHANG ; Hong-jun ZHOU ; Gen-lin LIU ; Ying ZHENG ; Xiao-lei LU ; Hai-qiong KANG ; Chun-xia HAO ; Bo WEI ; Yi-ji WANG ; Yuan YUAN ; Qian-ru MENG ; Jian-jun LI
Chinese Journal of Rehabilitation Theory and Practice 2021;27(6):706-711
Objective:To investigate the outcome of neurological function and the clinical characteristics of complications in children with spinal cord injury. Methods:From 2011 to 2019, children under 15 years old with spinal cord injury were selected in our hospital. Their level of injury and American Spinal Injury Association Impairment Scale (AIS) at one month, three months and one year were recorded. And the complications such as pressure ulcers/scald, urinary tract infection, hydronephrosis/vesicoureteral reflux, constipation, osteoporosis/fracture, deep vein thrombosis, neurodynia, heterotopic ossification, scoliosis and hip dysplasia were analyzed. Results:Of 159 individuals, 41 were boys and 118 were girls, the average age at injury was (6.08±2.57) years. The main cause of spinal cord injury was sports accidents (47.8%), and the main injury sites were thoracic spinal cord injury (89.3%). The cause of spinal cord injury was correlated with age at injury (

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