1.Changes and significance of granulocyte-like myeloid-derived suppressor cells during acute phase of Kawasaki disease
Pengqiang WEN ; Guobing WANG ; Jiehua MEI ; Zhongxiang QI ; Li YANG ; Mingguo XU ; Cong LIU ; Chengrong LI
Chinese Journal of Microbiology and Immunology 2022;42(7):540-548
Objective:To investigate the changes and significance of granulocyte-like myeloid-derived suppressor cells (G-MDSC) in the acute phage of Kawasaki disease (KD).Methods:Forty-two children with acute KD were enrolled in the present study and 32 age-matched healthy children were selected as control group. The proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC, the concentration of reactive oxygen species (ROS) and the expression of arginase-1 (Arg-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4), glycoprotein 130 (gp130) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) at protein level were detected by flow cytometry. Quantitative real-time PCR was used to measure the expression of inducible nitric oxide synthase (iNOS), interferon regulatory factor 8 (IRF-8), IL-6 receptor α subunit (IL-6Rα), granulocyte colony-stimulating factor receptor (G-CSFR), CCAAT/enhancer binding protein β (C/EBPβ), suppressor of cytokine signaling 1 (SOCS1) and SOCS3 at mRNA level in G-MDSC. Chromatin immunoprecipitation was performed to detect the acetylation of histone H3 at the promoters of SOCS1 and SOCS3 genes. Plasma concentrations of IL-6 and granulocyte colony-stimulating factor (G-CSF) and protein levels of IL-10, transforming growth factor-β (TGF-β) and nitric oxide (NO) in the culture supernatant of G-MDSC stimulated with LPS were measured by ELISA. Results:(1) Compared with the control group, the proportion of HLA-DR -CD11b + CD33 + CD14 -CD15 + G-MDSC as well as the concentration of ROS and the expression of inhibitory molecules (Arg-1, PD-L1 and CTLA4) in G-MDSC increased significantly in patients with acute KD ( P<0.05). Moreover, the concentrations of IL-10 and TGF-β in culture supernatant of G-MDSC were also higher than those of the control group after stimulation with lipopolysaccharide for 48 h ( P<0.05). All of the seven afore-mentioned indexes in KD patients with coronary artery lesion (CAL group ) were lower than those in patients without coronary artery lesion (NCAL group) ( P<0.05), and restored to some extent after IVIG therapy ( P<0.05). There were no statistical differences in iNOS expression or NO concentration in culture supernatant of G-MDSC among different groups ( P<0.05). (2) Plasma concentrations of IL-6 and G-CSF, and the expression of IL-6Rα, gp130, G-CSFR, pSTAT3 and C/EBPβ increased remarkably during acute phase of KD ( P<0.05). The expression of IRF-8 at transcription level in patients with acute KD was found to be lower than that of healthy controls ( P<0.05), and restored significantly after IVIG therapy ( P<0.05). Moreover, the plasma concentrations of IL-6 and G-CSF and the expression of IL-6Rα, gp130, G-CSFR and IRF-8 in the CAL group were higher than those in the NCAL group ( P<0.05), while the expression of pSTAT3 and C/EBPβ was lower in the CAL group ( P<0.05), which were restored by IVIG therapy ( P<0.05). (3) In patients with acute KD, the expression of SOCS1 and SOCS3 at mRNA level and histone acetylation at the promoters of SOCS1 and SOCS3 genes were reduced significantly in comparison with those in healthy controls ( P<0.05) , but were increased remarkably after IVIG treatment( P<0.05). The four indexes were higher in the CAL group than in the NCAL group ( P<0.05). Pearson correlation analysis showed the expression of SOCS1 and SOCS3 was negatively correlated with the protein level of pSTAT3 in G-MDSC of patients with acute KD ( r=-0.46 and -0.32, P<0.05). Conclusions:Changes in the number and function of G-MDSC caused by aberrant histone acetylation at SOCS1 and SOCS3 genes might contribute to the immune dysfunction and vascular damage in patients with KD.
2.Present practice of patients and their family as advisors overseas and its enlightenments to China
Jie CHEN ; Jiehua SHENG ; Huafang ZHANG ; Suxiang LIU ; Lili YANG
Chinese Journal of Hospital Administration 2022;38(2):156-160
Invitation of patients and their families as advisors in medical activities is conducive to enhancing patient safety and medical quality, as an innovative way for hospital reform and development. By analysis of such practice of overseas hospitals, the authors recommended on introducing this practice into China. The specific recommendations included creating a social support atmosphere for patient and family as advisors, promoting patient and family engagement by hospitals, establishing a management evaluation system for the patient and family engagement, improving the comprehensive literacy level of patient and family advisors, and building an internet platform for patient and family engagement.
3.Effects of hyperbaric oxygen combined with gemcitabine on the apoptosis of PANC-1 cells and tumor markers in nude mice with pancreatic cancer
Mei WU ; Jiehua XUE ; Haidong MA ; Junping YANG
Chinese journal of nautical medicine and hyperbaric medicine 2022;29(3):312-316
Objective:To explore the effect of the combination of hyperbaric oxygen(HBO)and gemcitabine(GEM)on the apoptosis of PANC-1 cells and tumor markers in the serum of nude mice with pancreatic cancer.Methods:Fifteen nude mouse models of transplanted tumors of pancreatic cancer were established and randomly divided into control group,GEM group,and HBO+GEM group according to the experimental design,with five mice in each group. The control group was reared normally after successful modeling. The GEM group was treated with 10 mg/kg of GEM by gavage,and the HBO+GEM group was treated with 10 mg/kg of GEM by gavage followed by oxygen inhalation at 0.2 MPa for 60 min. All the three groups were treated every other day for 21 days. The volume and weight of transplanted tumors were measured,the apoptosis of PANC-1 cells was detected by TUNEL staining,and the levels of serum tumor markers were measured using an automated chemiluminescence immunoassay analyzer. The expression levels of apoptosis-related proteins in tumor tissues were measured by western blotting.Results:The tumor volume of the nude mice in the HBO+GEM group was significantly lower than those of the control group and the GEM group on the 6th,9th,10th,15th,18th,and 21st days,with statistically significant differences( P<0.05). The tumor weight[(0.54±0.08)g]in the HBO+GEM group was significantly lower than those in the control group[(1.23±0.17)g]and the GEM group[(0.89±0.11)g],and the differences were statistically significant( P<0.05). The apoptosis rate of PANC-1 cells in the HBO+GEM group[(47.26±7.22)%]was significantly higher than those in the control group[(6.83±0.89)%]and the GEM group[(26.84±3.29)%],and the differences were statistically significant( P<0.05 or P<0.01). Compared with the control group and the GEM group,the serum levels of carcinoembryonic antigen(CEA)of the nude mice in the HBO+GEM group were significantly reduced,while the levels of carbohydrate antigen 19-9(CA19-9)and tumor-specific growth factors(TSGF)in the HBO+GEM group were significantly increased,and the differences were statistically significant( P<0.05). Compared with the control group and the GEM group,the expression levels of Bax,Caspase-3,and Cytochrome C protein in the transplanted tumor tissues of the nude mice in the HBO+GEM group were significantly higher,while the expression level of Bcl-2 protein was significantly lower,all with statistically significant differences( P<0.05). Conclusion:The combination of HBO+GEM can enhance the inhibitory effect of GEM on transplanted tumors of pancreatic cancer in nude mice,and its mechanism may be related to inducing the apoptosis of PANC-1 cells and regulating CEA,CA19-9,and TSGF.
4.Effects of hyperbaric oxygen combined with gemcitabine on the apoptosis of PANC-1 cells and tumor markers in nude mice with pancreatic cancer
Mei WU ; Jiehua XUE ; Haidong MA ; Junping YANG
Chinese journal of nautical medicine and hyperbaric medicine 2022;29(3):312-316
Objective:To explore the effect of the combination of hyperbaric oxygen(HBO)and gemcitabine(GEM)on the apoptosis of PANC-1 cells and tumor markers in the serum of nude mice with pancreatic cancer.Methods:Fifteen nude mouse models of transplanted tumors of pancreatic cancer were established and randomly divided into control group,GEM group,and HBO+GEM group according to the experimental design,with five mice in each group. The control group was reared normally after successful modeling. The GEM group was treated with 10 mg/kg of GEM by gavage,and the HBO+GEM group was treated with 10 mg/kg of GEM by gavage followed by oxygen inhalation at 0.2 MPa for 60 min. All the three groups were treated every other day for 21 days. The volume and weight of transplanted tumors were measured,the apoptosis of PANC-1 cells was detected by TUNEL staining,and the levels of serum tumor markers were measured using an automated chemiluminescence immunoassay analyzer. The expression levels of apoptosis-related proteins in tumor tissues were measured by western blotting.Results:The tumor volume of the nude mice in the HBO+GEM group was significantly lower than those of the control group and the GEM group on the 6th,9th,10th,15th,18th,and 21st days,with statistically significant differences( P<0.05). The tumor weight[(0.54±0.08)g]in the HBO+GEM group was significantly lower than those in the control group[(1.23±0.17)g]and the GEM group[(0.89±0.11)g],and the differences were statistically significant( P<0.05). The apoptosis rate of PANC-1 cells in the HBO+GEM group[(47.26±7.22)%]was significantly higher than those in the control group[(6.83±0.89)%]and the GEM group[(26.84±3.29)%],and the differences were statistically significant( P<0.05 or P<0.01). Compared with the control group and the GEM group,the serum levels of carcinoembryonic antigen(CEA)of the nude mice in the HBO+GEM group were significantly reduced,while the levels of carbohydrate antigen 19-9(CA19-9)and tumor-specific growth factors(TSGF)in the HBO+GEM group were significantly increased,and the differences were statistically significant( P<0.05). Compared with the control group and the GEM group,the expression levels of Bax,Caspase-3,and Cytochrome C protein in the transplanted tumor tissues of the nude mice in the HBO+GEM group were significantly higher,while the expression level of Bcl-2 protein was significantly lower,all with statistically significant differences( P<0.05). Conclusion:The combination of HBO+GEM can enhance the inhibitory effect of GEM on transplanted tumors of pancreatic cancer in nude mice,and its mechanism may be related to inducing the apoptosis of PANC-1 cells and regulating CEA,CA19-9,and TSGF.
5.Correlation between hemolysis degree and antibody IgG subtypes contained in infant serum and erythrocyte eluates
Jin YANG ; Jiehua CHU ; Mingpeng CAO ; Lingbo LI ; Jing ZHONG
Chinese Journal of Blood Transfusion 2021;34(6):624-627
【Objective】 To analyze the effects of IgG subtypes(IgG 1 and IgG3) of antibodies contained in infant serum and erythrocyte eluates on hemolytic disease of the newborn(HDN), so as to provide reference for its early clinical diagnosis and treatment. 【Methods】 49 newborns with HDN in our hospital from June 2019 to March 2020 were detected for three hemolytic tests(direct antiglobulin test, elution test and indirect antiglobulin test), as well as the components of IgG1 and IgG3 in eluates. The correlation analysis was conducted by combining birth hours (physiological jaundice) and hemolytic degrees (total bilirubin, indirect bilirubin, and hemoglobin). 【Results】 In the 44 cases of IgG1 and IgG3 subtype detection of infant RBC eluates, regression equations could be established between total bilirubin, indirect bilirubin and birth hours, and between hemoglobin and elution test, and linear regression relationships were found (P<0.05). In the 28 cases of IgG1 and IgG3 subtype detection of infant serum, regression equations could be established between total bilirubin, indirect bilirubin, birth time and IgG3 subtype, and between hemoglobin and IgG1 subtype (P<0.05), and linear regression relationships were found (all P<0.05). Three infants, presenting IgG1 and IgG2 subtypes(+ ) and three hemolysis tests(-), were all second pregnancy, constituted by Rh-HDN of 2 case and other-system-HDN 1. 【Conclusion】 The degree of HDN is directly related to IgG1 and IgG3 antibodies in infant blood plasma. In addition to the total bilirubin and indirect bilirubin, the changes of IgG3 antibodies in infant plasma and IgG1 antibody in anemic infants should be monitored. If IgG1 and IgG3 antibodies are yielded even with all negative ABO-HDN hemolysis tests, non-ABO-HDN should be considered in time to achieve accurate diagnosis and treatment.
6.Evaluation of microstructural changes of brain parenchyma in patients with essential hypertension by diffuse kurtosis imaging and enhanced T2 star weighted angiography
Jiehua YANG ; Zhongxian YANG ; Chunjuan CHEN ; Huanze WU ; Pingyi XU ; Wei CHEN
Chinese Journal of Neuromedicine 2021;20(9):907-914
Objective:To evaluate the microstructural changes of brain parenchyma in patients with essential hypertension by diffuse kurtosis imaging (DKI) and enhanced T2 star weighted angiography (ESWAN).Methods:A prospective study was performed; 27 patients with essential hypertension, admitted to our hospital from April 2019 to September 2019, and 16 healthy subjects matched with gender, age and education level were enrolled in our study. According to the presence or absence of cerebral microbleeds (CMBs), patients with essential hypertension were divided into essential hypertension with CMBs group ( n=8) and essential hypertension without CMBs group ( n=19). MRI, DKI and ESWAN were performed on all subjects. The mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) of bilateral hippocampal gyrus, centrum semiovale, caudate head, posterior limb of internal capsule, thalamus, red nucleus, substantia nigra, pons, and cerebellum were measured. Results:As compared with the healthy subjects, the patients with essential hypertension had significantly lower MK values in the left semioval center, bilateral caudate head, left posterior limb of internal capsule, and bilateral thalamus, significantly higher MD value in the right thalamus, and statistically lower FA value in the left posterior limb of internal capsule ( P<0.05). The essential hypertension with CMBs group had significantly lower MK values in left hippocampus gyrus, left centrum semiovale, bilateral caudate head, left posterior limb of internal capsule, bilateral thalamus, and left substantia nigra, significantly higher MD value in right thalamus, and significantly lower FA value in left posterior limb of internal capsule as compared with essential hypertension without CMBs group and healthy control group ( P<0.05). Conclusion:In patients with essential hypertension, the brain microstructural changes are found in the hippocampus, centrum semiovale, caudate head, posterior limb of internal capsule, thalamus and substantia nigra; these changes are more obvious in essential hypertension patients with CMBs; DKI and ESWAN can effectively assess the early brain microstructure changes in patients with essential hypertension.
7.Application study of non-motor functional area in patients with Parkinson disease by magnetic resonance spectroscopy
Jiehua YANG ; Huanze WU ; Jitian GUAN ; Qincheng ZHANG ; Wei CHEN
Chinese Journal of Postgraduates of Medicine 2017;40(4):333-337
Objective To detect the metabolites of non-motor functional area in patients with Parkinson disease (PD) by proton magnetic resonance spectroscopy (1H-MRS).Methods Forty-two PD patients (PD group) tested with unified PD rating scale (UPDRS) and 20 healthy controls(normal control group) were enrolled in this study.MRI and 1H-MRS using a GE signa excite1.5T MR was obtained,and the ratios of metabolites such as N-acetylaspartate(NAA)/creatin(Cr),NAA/cholinecompounds(Cho) in the prefrontal lobe,hippocampus,cuneus gyrus and dorsal thalamus were compared.Correlations between brain metabolites and UPDRS were analyzed.Results The levels of NAA/Cr,and NAA/Cho in bilateral dorsal thalamus,cuneus gyrus,hippocampus,prefrontal lobe in PD group were significantly lower than those in normal control group (P < 0.01).The level of Cho/Cr in right hippocampus,right cuneus gyms,and right dorsal thalamus in PD group was significantly higher than that in normal control group (P < 0.05).The NAA/Cho in the left hippocampus (r =-0.388,P =0.011) and left cuneus gyrus (r =-0.325,P =0.036) was negatively correlated with UPDRS scores (P < 0.05).Conclusions There is extensive neuronal damage and some glial proliferation in the non-motor functional areas including prefrontal lobe,hippocampus,cuneus gyrus,anddorsal thalamus in the PD patients.The degree of damage in left hippocampus and left cuneus gyms is positively correlated with the severity of the disease clinically.
8.Clinical Observation of Urokinase and Alteplase Each Combined with Enoxaparin Sodium in the Treat-ment of Acute ST Segment Elevation Myocardial Infarction
Jiehua LI ; Hong JIN ; Haixia YANG
China Pharmacy 2016;27(20):2830-2832,2833
OBJECTIVE:To compare clinical efficacy,safety and economy of urokinase and alteplase each combined with Enoxaparin sodium in the treatment of acute ST segment elevation myocardial infarction (STEMI). METHODS:80 STEMI pa-tients were randomly divided into control group and observation group,with 40 cases in each group. Both groups received Aspirin enteric-coated tablet for antiplatelet aggregation,and Clopidogrel hydrogen sulfate tablet for anticoagulation before thrombolysis. Control group were given urokinase 1 500 000 U added into 0.9% Sodium chloride injection 100 ml,ivgtt,within 30 min;given Enoxaparin sodium injection 7 500 U intramuscularly 12 h after thrombolysis,for 3-5 d. Observation group was given Enoxaparin sodium 60 U/kg,ivgtt,1 mg/ml Alteplase for injection 8 ml with intravenous push,other 42 ml ivgtt within 90 min;continued to receive Enoxaparin sodium with 12 U/(kg·h)micro-pump for 48 h,followed by Low molecular weight heparin calcium injection 5 000 U intramuscularly,bid,for consecutive 5 d. Clinical efficacy of 2 groups were observed,and thrombolytic recanalization situa-tion were observed 30,60,90 and 120 min after thrombolysis. ECG,cost-effectiveness and ADR were also observed. RESULTS:The effective rate of observation group(92.50%)was significantly higher than that of control group(85.00%). The rates of throm-bolytic recanalization in observation group 60,90 and 120 min after thrombolysis were significantly higher than in control group, with statistical significance(P<0.05). Q wave time,Qwave/Rwave and ST segment deviation of observation group after treatment were significantly lower than those of control group,with statistical significance(P<0.05). The total hospitalization cost of obser-vation group was significantly higher than that of control group,with statistical significance(P<0.05);there was no statistical sig-nificance in effective rate and the per unit cost of thrombolytic recanalization rate (P>0.05). The incidence of ventricular aneu-rysm,pericardial effusion,heart failure or cardiac shock,angina pectoris after infarction,severe arrhythmia,death and other as-pects in observation group were significantly lower than in control group,with statistical significance(P<0.05). CONCLUSIONS:Alteplase and enoxaparin thrombolysis therapy is better than urokinase and enoxaparin for STMEI in respects of clinical efficacy, and thrombolytic recanalization with less ADR and better safety;urokinase is cheaper and better than alteplase in cost-effectiveness ratio. Both of them can be used after careful consideration.
9.Effects of hyperbaric oxygen on learning, memory and the expression of brain-derived growth factor and acetylcholine
Jiehua YANG ; Xiaoqi XIAN ; Daming OU ; Jing SUN
Chinese Journal of Physical Medicine and Rehabilitation 2014;36(7):508-511
Objective To observe the effects of hyperbaric oxygen (HBO) on cerebral small vessel disease (CSVD) and on learning,memory and the expression of brain-derived neurotrophic factor (BDNF) and acetylcholine (Ach) in the cerebral cortex and hippocampus.Methods Sixty healthy,male Wistar rats were studied.Allograft thrombosis particles 48 to 74 μm in diameter were injected into the rats' external carotid arteries to create a CSVD model.The rats were then divided randomly into a hyperbaric oxygen group,a nimotop group and a control group.The hyperbaric oxygen group rats were given hyperbaric oxygen therapy 12 hours after the modeling.The nimotop group rats were given nimodipine by intragastric perfusion 12h after the modeling.The rats in the control group had no special intervention.At 7,14 and 28 days after the modeling,any changes in learning and memory were assessed with a Morris water maze test.Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of BDNF in the cerebral cortex and of Ach in the hippocampus at 28 days.Results At both 14 and 28 days the average escape latency of the rats in the hyperbaric oxygen group was significantly shorter than those of the nimotop and control groups.The average platform crossing time had increased significantly more than in the nimotop and control groups.At both 14 and 28 days the escape latency and platform crossing times of the nimotop group were significantly better than in the control group.Ach content and BDNF content were significantly higher in the HBO group than in the nimotop and control groups.Conclusions Hyperbaric oxygen treatment can promote BDNF release in CSVD,which is helpful to protect and repair neural mitochondria,to maintain the cortex and hippocampal neurotransmitters on a stable level,and to improve learning and memory.Its effect is better than that of nimotop.
10.Effect of duloxetine on the levels of cytokines in patients with first-episode depression
Suhua ZHAO ; Jiehua KONG ; Chanjuan YANG ; Yuhua LIN ; Lingzhi WANG
Chinese Journal of Behavioral Medicine and Brain Science 2012;21(2):158-160
ObjectiveTo explore the changes of the levels of cytokines in patients with first-episode depression and the effect on the levels of cytokines after the treatment with duloxetine.MethodsThe serum levels of interleukin 1 ( IL-1 ),interleukin 6 ( IL-6 ),tumor necrosis factor-alpha ( TNF-αt ),interleukin4 ( IL-4 ),interleukin10(IL-10) were measured in 38 patients with depression before and after duloxetine treatment by enzyme linked immunosorbent assay(ELISA).HAMD score were assessed at pre- treatment and post-treatment to assess curative effect.The control group was 30 healthy individuals.All data were statisticaly analyzed by SPSS.ResultsBefore treatment,the HAMD score and the levels of serum IL-6,TNF-α,IL-1 in first-episode depressant patients were remarkablely higher than those in the control group( IL-6:( 10.66 ± 3.12 ) pg/ml vs (2.72 ± 0.91 ) pg/ml ;TNF-α:(77.49 ±3.12) pg/ml vs (37.48 ±5.87) pg/ml; IL-1:(39.09 ± 3.77 ) pg/ml vs ( 10.31 ± 1.05 ) pg/ml ),the levels of serum IL-4 and IL-10 in first-episode depressant patients were remarkablely lower than those in the control group(P<0.05,P<0.01 ).The HAMD score and the levels of serum IL-6,TNF-α,IL-1 in post-treatment were remarkablely lower than pre-treatment (P < 0.05 ),but which were still higher than the control group(P< 0.05 ).The levels of serum IL-4 and IL-10 in post-treatment were remarkablely increased than pre-treatment(P<0.05).The levels of serum IL-6,TNF-α,IL-1 were positively correlated with the HAMD score( r =0.667,0.486,0.727,P <0.01 ),but the levels of serum IL-4 and IL-10 were negatively correlated with the HAMD scorae ( r=-0.433,-0.269,P<0.05,P< 0.01 ).ConclusionsThe first-episode depressant patients show immune disorder induced by cytokines.Anti-depressant activity of duloxetine may participate in the regulation of cytokines and Th1/Th2 unbalance.

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