1.Evaluation of brain glymphatic system function in patients with bipolar disorder based on diffusion tensor imaging along the perivascular space
Liqian CUI ; Huixing ZENG ; Yixin CHEN ; Yizhi ZHANG ; Jinbiao LI ; Wenhao DENG ; Liping CAO
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(5):400-405
Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.
2.Expression of Serum FABP4 and FGF19 Levels in Patients with β-Thalassemia and Their Relationship with Prognosis
Yixin CHEN ; Feng PAN ; Ya XU ; Xin PENG ; Lu LIANG ; Rujing LI ; Cong LI ; Hongxin ZENG
Journal of Modern Laboratory Medicine 2024;39(5):96-101
Objective To explore the expression of serum fatty acid-binding protein 4(FABP4)and fibroblast growth factor 19(FGF19)in patients with β-thalassemia and their relationship with clinical prognosis.Methods A total of 112 cases ofβ-thalassemia patients diagnosed and treated in Qianjiang Hospital Affiliated to Chongqing University from January 2018 to August 2020 were selected as the case group,and 60 healthy individuals who underwent physical examinations during the same period were taken as the control group.Enzyme-linked immunosorbent assay was used to detect levels of serum FABP4 and FGF19 expression.Multivariate logistic regression analysis was used to analyze factors affecting the prognosis of patients with β-thalassemia.Receiver operating characteristic curve was used to analyze the prognostic value of FABP4 and FGF19 in patients with β-thalassemia.Results The serum FABP4 level(67.13±11.35 μg/L)in the case group was higher than that in the control group(22.01±4.16μg/L),while the serum FGF19 level(104.24±21.46 ng/L)was lower than that in the control group(218.01±36.79 ng/L),with significant differences(t=29.708,25.620,all P<0.05).The serum FABP4 levels(54.20±12.63 μ g/L,66.83±10.5 μ g/L,79.72±11.05 μ g/L)in the mild group,intermediate group,and severe group were increased sequentially,while FGF19 levels(122.53±22.36 ng/L,103.16±20.37 ng/L,86.53±18.14 ng/L)were decreased sequentially,and the differences were significant(F=39.701,24.231,all P<0.05).Compared to the survival group,serum FGF19 level(62.80±22.09 ng/L vs 110.16±20.69 ng/L),Hb and the proportion of heterozygous genotypes in the death group patients(β CD17/β N,β CD41-42/β N)was lower,while serum FABP4(116.69±12.30 ng/L vs 60.05±10.17 ng/L),ferritin and the proportion of cardiac enlargement were higher,with significant differences(t/x2=4.436~18.981,all P<0.05).FGF19(OR=0.634,95%CI:0.451~0.891)was an independent protective factor for β-thalassemia patients(P<0.001),and serum FABP4(OR=1.840,95%CI:1.193~2.838)was an independent risk factor for prognosis(P<0.001).The area under the curve(95%CI)of serum FABP4 and FGF19 combination in prognosis evaluation for β-thalassemia patients was 0.897(0.853~0.951),which was greater than the single serum indicator detection of 0.842(0.801~0.879)and 0.814(0.762~0.858),with significant differences(Z=4.864,5.270,P=0.002,0.001).Conclusion The serum FABP4 expression is increased,but serum FGF19 expression is decreased in patients with β-thalassemia.The combination of serum FABP4 and FGF19 may have a high predictive value for the prognosis of patients with β-thalassemia.
3.Gastric cancer cell-derived exosome miR-382-5p induced by Helicobacter pylori inhibits macrophage autophagy and promotes M2 polarization by targeting PTEN
Wenjing LI ; Kaiyun GUO ; Junzi LUO ; Yunxing HE ; Jie DUAN ; Na WANG ; Kunning WANG ; Yixin ZENG ; Xinyi LUO ; Yan ZHANG
Chinese Journal of Immunology 2024;40(6):1153-1159
Objective:To investigate the effect and mechanism of the gastric cancer cells-derived exosome miR-382-5p in-duced by Helicobacter pylori(H.pylori)on the autophagy and polarization of macrophages,providing new clues for further elucidating the carcinogenic mechanism of H.pylori.Methods:Ultracentrifugation and exosome extraction kit were used to extract the exosomes re-leased by the H.pylori stimulated group and the blank control group AGS cells cells,then transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA)and Western blot were employed to identify exosomes.qRT-PCR was used to detect the expres-sion of miR-382-5p in H.pylori induced AGS-derived exosomes.miR-382-5p mimic was transfected into THP-1 macrophages,then the expressions of autophagy markers(LC3Ⅱ,p62,and Beclin-1)were evaluated by Western blot,the number of autophagosomes was detected by immunofluorescence.The expression levels of PTEN protein,downstream proteins PI3K,AKT,mTOR and its phosphory-lated proteins p-PI3K,p-AKT,p-mTOR were detected by Western blot.Flow cytometry was used to detect the expression levels of macrophage phenotypic molecules CD206 and HLA-DR.ELISA was used to detect the secretion of cytokines TNF-α,IL-6,IL-10 and Arginase1 in macrophage supernatants.Results:The extracted exosomes were consistent with exosome morphology and highly ex-pressed the surface marker proteins CD9,CD63 and TSG101.Compared with the blank control group,the expression level of exosom-al miR-382-5p in H.pylori-infected group was significantly increased.miR-382-5p mimic transfection resulted in decreased expression of LC3 Ⅱ and Beclin-1 in macrophages,increased expression of P62 and decreased number of autophagosomes.Moreover,the protein expression level of PTEN was significantly decreased in the miR-382-5p mimic transfection group,while the expression levels of p-PI3K,p-AKT and p-mTOR were significantly increased.miR-382-5p mimic transfection also resulted in increased expression of mac-rophage M2 type marker protein CD206 and decreased expression of M1 type marker protein HLA-DR,as well as increased expres-sions of IL-10 and Arginine1,whereas decreased expression of IL-6 and TNF-α.Pretreatment with the pathway inhibitor BEZ235 par-tially reverses the effects of miR-382-5p on macrophage autophagy and polarization.Conclusion:H.pylori-induced gastric cancer cells-derived exosomal miR-382-5p suppresses macrophage autophagy and induces M2 polarization through down-regulation of PTEN ex-pression and activation of the PI3K/AKT/mTOR signaling pathway.
4.Andrographolide regulates SLC7A11/GPX4 axis in ferroptosis to attenuate intestinal injury in sepsis
Ming HUANG ; Yixin ZHANG ; Guodong CAO ; Youcheng ZENG ; Liang LIN ; Xiaoyue WANG ; Qinghong CHENG
Acta Universitatis Medicinalis Anhui 2023;58(12):2094-2100
Objective To investigate whether Andrographolide(AG)can alleviate intestinal injury in sepsis by ac-tivating the SLC7A11/GPX4 axis in ferroptosis.Methods Forty rats were randomly divided into sham group(sham group),sepsis group(CLP group),AG low,medium and high dose groups(5,10 and 20 mg/kg).HE staining was used to observe the pathological changes of Intestinal tract.ELISA method was used to determine Inter-leukin 6(IL-6),tumour necrosis factor α(TNF-α),intestinal fatty acid binding protein(I-FABP),D-lactate content.The mechanism of ferroptosis was explored with AG high dose group(AG20 group),forty rats were ran-domly divided into sham group,CLP group,ferroptosis inhibitor(Fer-1)group,AG20+Fer-1 group.HE staining and transmission electron microscopy were used to observe the pathological changes of Intestinal tract.The kits were used to determine oxidative stress MDA,GSH levels and Fe3+content.Western blot was used to detect the protein levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy poly-peptide 1(FTH-1).Results Compared with the sham group,the CLP group showed severe morphological damage to the small intestine,with significantly higher levels of inflammation,I-FABP and D-lactate(all P<0.05),the AG group reversed these changes in a concentration-dependent manner(all P<0.05).Compared with the CLP group,the AG20 and Fer-1 groups showed improved pathological damage to the small intestine,with lower levels of MDA and Fe3+and higher levels of GSH,SLC7A11,GPX4 and FTH-1 protein expression increased(all P<0.05),and pathological injury and oxidative stress were reduced in the AG20+Fer-1 group,and SLC7A11,GPX4 and FTH-1 protein expression increased more significantly(all P<0.05).Conclusion The mechanism by which AG attenuates intestinal injury in sepsis may be related to SLC7A11/GPX4 axis activation in ferroptosis.
5.H2S attenuates sepsis-induced cardiomyopathy by regulating the Xc -/ GPX4 pathway in ferroptosis
Guodong Cao ; Feifei Deng ; Yuhan Zhao ; Youcheng Zeng ; Liang Lin ; Lichun Guo ; Xiqing Luo ; Yixin Zhang ; Ming Huang ; Qinghong Cheng
Acta Universitatis Medicinalis Anhui 2022;57(12):1959-1964
Objective :
To investigate whether NaHS,a hydrogen sulfide donor,can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc -/ GPX4 signaling pathway in ferroptosis.
Methods :
Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis,which was divided into Control group,LPS group and LPS + NaHS group.The kits were applied to detect the changes of cardiomyocyte viability,Fe2 + ,LDH and CK-MB,determine the levels of oxidative stress indexes GSH and MDA,detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes, and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot.
Results:
Compared with the Control group,H9c2 cell viability decreased,Fe2 + concentration increased ,GSH ,MDA and ROS levels increased,mitochondrial JC-1 monomer increased ,expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased,and cell damage increased after LPS stimulation (P<0. 05) .Compared with the LPS group,NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration,decreased the level of LPS-induced oxidative stress in H9c2 cells ,and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P<0. 05 ) .
Conclusion
The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc -/ GPX4 signaling pathway in fer- roptosis.
6.Chest CT comparison of ground glass opacity-like 2019 novel coronavirus pneumonia and early-stage lung carcinoma
LIU Changyu ; CAI Yixin ; HAO Zhipeng ; GAO Yi ; ZENG Zhilin ; ZHANG Ni ; FU Xiangning
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(04):376-380
Objective To investigate CT image features of ground glass opacity (GGO)-like 2019 novel coronavirus (2019-nCoV, SARS-CoV-2) pneumonia (COVID-19) and early-stage lung carcinoma for control and therapy of this acute severe respiratory disease. Methods We retrospectively analyzed the clinical data of 71 GGO-like COVID-19 patients who received therapy in Tongji Hospital of Huazhong University of Science and Technology between January 17th and February 13th, 2020. These 71 GGO-like COVID-19 patients were as a COVID-19 group. And 80 GGO-like early-stage lung carcinoma patients who underwent resection were as a lung carcinoma group. Clinical features such as sex, age, symptoms including fever, cough, fatigue, myalgia and dyspnea, detailed exposure history, confirmatory test (SARS-CoV-2 quantitative RT-PCR) and pathologic diagnosis were analyzed. Results Significantly different symptoms and exposure history between the two groups were detected (P<0.001). More lesions (61 patients at percentage of 85.92%, P<0.001), relative peripheral locations (69 patients at percentage of 97.18%, P<0.001) and larger opacities (65 patients at percentage of 91.55%, P<0.001) were found in chest radiographs of GGO-like COVID-19 compared with GGO-like early-stage lung carcinoma. Similar features appeared in early-stage of COVID-19 and lung carcinoma, while pneumonia developed into more extensive and basal predominant lung consolidation. Coexistence of GGO-like COVID-19 and early-stage lung carcinoma might occur. Conclusion Considering these similar and unique features of GGO-like COVID-19 and early-stage lung carcinoma, it is necessary to understand short time re-examination of chest radiographs and other diagnostic methods of these two diseases. We believe that the findings reported here are important for diagnosis and control of COVID-19 in China.
7.Comparison of Recovery Phase CT Features between Mild/moderate and Severe/critical Coronavirus Disease 2019 Patients.
Wenbin ZOU ; Changyu LIU ; Yixin CAI ; Zhilin ZENG ; Ni ZHANG ; Xiangning FU
Acta Academiae Medicinae Sinicae 2020;42(3):370-375
To investigate the computed tomographc(CT)features of mild/moderate and severe/critical cases of coronavirus disease 2019(COVID-19)in the recovery phase. Totally 63 discharged patients in Wuhan,China,who underwent both chest CT and reverse transcription-polymerase chain reaction(RT-PCR)from February 1 to February 29,2020,were included.With RT-PCR as a gold standard,the performance of chest CT in diagnosing COVID-19 was assessed.Patients were divided into mild/moderate and severe/critical groups according to the disease conditions,and clinical features such as sex,age,symptoms,hospital stay,comorbidities,and oxygen therapy were collected.CT images in the recovery phase were reviewed in terms of time from onset,CT features,location of lesions,lobe score,and total CT score. There were 37 patients in the mild/moderate group and 26 in the severe/critical group. Compared with the mild/moderate patients,the severe/critical patients had older age [(43±16) years (52±16) years; =2.10, =0.040], longer hospital stay [(15±6)d (19±7)d; =2.70, =0.009], higher dyspnea ratio (5.41% 53.85%; =18.90, <0.001), lower nasal oxygen therapy ratio (81.08% 19.23%;=23.66, <0.001), and higher bi-level positive airway pressure ventilation ratio (0 57.69%; =25.62, <0.001). Time from onset was (23±6) days in severe/critical group, significantly longer than that in mild/moderate group [(18±7) days] (=3.40, <0.001). Severe/critical patients had significantly higher crazy-paving pattern ratio (46.15% 10.81%;=4.24, =0.039) and lower ground-glass opacities ratio (15.38% 67.57%; =16.74, <0.001) than the mild/moderate patients. The proportion of lesions in peripheral lung was significantly higher in mild/moderate group than in severe/critical group (78.38% 34.61%; =13.43, <0.001), and the proportion of diffusely distributed lesions was significantly higher in severe/critical group than in mild/moderate group (65.38% 10.81%; =20.47, <0.001). Total CT score in severe/critical group was also significantly higher in severe/critical group than in mild/moderate group [11 (8,17) points 7 (4,9) points; =3.81, <0.001]. The CT features in the recovery stage differ between mild/moderate and severe/critical COVID-19 patients.The lung infiltration is remarkably more severe in the latter.
Adult
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Aged
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Betacoronavirus
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China
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Coronavirus Infections
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diagnostic imaging
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Humans
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Middle Aged
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Pandemics
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Pneumonia, Viral
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diagnostic imaging
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Retrospective Studies
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Tomography, X-Ray Computed
8.Susceptibility genes and risk prediction model of cardiovascular toxicity related to antineoplastic therapy in tumor patients
Binliang LIU ; Fei MA ; Yixin ZENG
Chinese Journal of Oncology 2020;42(10):838-842
Cardiovascular toxicity of cancer patients in antineoplastic therapy is gradually paid widespread attention. Although many high-risk factors of cardiovascular toxicity associated with chemotherapy, targeted therapy or immunotherapy have been identified, it is still difficult to establish accurate risk prediction model. Traditional risk prediction model cannot adequately explain the differences in cardiovascular toxicity susceptibility among patients, makes it difficult to accurately screen high-risk groups, early diagnose and prevent cardiovascular toxicity. Finding susceptible genes of cardiovascular toxicity associated with antineoplastic therapy and incorporating single-nucleotide polymorphisms into risk prediction model can significantly improve the identification of high-risk population of cardiovascular toxicity.
9.Susceptibility genes and risk prediction model of cardiovascular toxicity related to antineoplastic therapy in tumor patients
Binliang LIU ; Fei MA ; Yixin ZENG
Chinese Journal of Oncology 2020;42(10):838-842
Cardiovascular toxicity of cancer patients in antineoplastic therapy is gradually paid widespread attention. Although many high-risk factors of cardiovascular toxicity associated with chemotherapy, targeted therapy or immunotherapy have been identified, it is still difficult to establish accurate risk prediction model. Traditional risk prediction model cannot adequately explain the differences in cardiovascular toxicity susceptibility among patients, makes it difficult to accurately screen high-risk groups, early diagnose and prevent cardiovascular toxicity. Finding susceptible genes of cardiovascular toxicity associated with antineoplastic therapy and incorporating single-nucleotide polymorphisms into risk prediction model can significantly improve the identification of high-risk population of cardiovascular toxicity.
10.FOLFOX/XELOX plus cetuximab administered weekly versus biweekly as a first-line treatment for patients with KRAS/RAS wild-type metastatic colorectal cancer: a retro-spective study
Yue YU ; Wen ZHANG ; Yongkun SUN ; Lin YANG ; Chengxu CUI ; Yixin ZENG ; Aiping ZHOU
Chinese Journal of Clinical Oncology 2018;45(23):1210-1214
To compare the efficacy and safety of cetuximab biweekly regimen with those of standard weekly regimen as a first-line therapy of KRAS/RAS wild-type metastatic colorectal cancer. Methods: Patients who received weekly or biweekly administra-tion of cetuximab plus FOLFOX/XELOX as a first-line therapy from July 2010 to December 2017 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively screened for eligibility. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and frequencies of adverse events (AEs) between the two groups were compared. Results: Of 152 eligible patients, 55 were in the biweekly group and 43 were in the weekly group. The biweekly group had significantly higher ORR than the weekly group (76.3% vs. 54.8%, P=0.025). Median PFS in the biweekly and weekly groups were 10.3 and 8.8 months, respectively (P=0.288), and the median OS were 33.5 and 27.4 months, respectively (P=0.563). The two groups showed no significant difference in PFS and OS. For overall AEs, the biweekly group presented significantly more stomatitis (32.7% vs. 14.0% , P=0.032) and tended to show substantially more acne-like rash (80.0% vs. 62.8%, P=0.058) and leukopenia and/or neutropenia (72.7% vs. 55.8%, P=0.081). The frequency of 3/4 grade acne-like rash in the biweekly and weekly groups were 18.2% and 7.0%, respectively (P=0.105). The frequency of all grade 3/4 AEs between the two groups showed no significant difference (P>0.05). Conclusions: Biweekly regimen of cetuximab plus FOLFOX/XE-LOX had similar efficacy and higher ORR compared with those of standard weekly regimen. Cetuximab administered biweekly may be an optional choice in clinical practice, with close attention paid to increased frequency of certain AEs.


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