1.Differential transcriptomic landscapes of multiple organs from SARS-CoV-2 early infected rhesus macaques.
Chun-Chun GAO ; Man LI ; Wei DENG ; Chun-Hui MA ; Yu-Sheng CHEN ; Yong-Qiao SUN ; Tingfu DU ; Qian-Lan LIU ; Wen-Jie LI ; Bing ZHANG ; Lihong SUN ; Si-Meng LIU ; Fengli LI ; Feifei QI ; Yajin QU ; Xinyang GE ; Jiangning LIU ; Peng WANG ; Yamei NIU ; Zhiyong LIANG ; Yong-Liang ZHAO ; Bo HUANG ; Xiao-Zhong PENG ; Ying YANG ; Chuan QIN ; Wei-Min TONG ; Yun-Gui YANG
Protein & Cell 2022;13(12):920-939
SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals
;
COVID-19/genetics*
;
Macaca mulatta
;
SARS-CoV-2/genetics*
;
Transcriptome
2.Based on PI3K/Akt/mTOR Signaling Pathway to Explore Mechanism of Zhigancao Tang Against MIRI-induced Ventricular Tachycardia and Ventricular Fibrillation in Rats
Xu-ying ZHENG ; Chun-jie MA ; Yong-zhen CHEN ; Cun-xia REN ; Ren-xiu NIU ; Hua LIAN ; Kun CHEN ; Xiao-hui TAN ; Qing-zhi YAN ; Xing ZHANG ; Hao WU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(17):1-8
Objective:Through phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway, explore the effect of Zhigancao Tang on myocardial ischemia-reperfusion injury(MIRI)The role and mechanism of arrhythmia(ventricular tachycardia and ventricular fibrillation). Method:The 72 SD rats were randomly divided into sham operation group,model group, Zhigancao Tang low,medium and high dose group(11.43,22.86,45.72 g·kg-1),Wenxin granule group(2.43 g·kg-1),continuous drug intervention for 10 days. Two hours after the last administration,the MIRI model of rat was prepared by ligating the left anterior descending coronary artery,and the changes of electrocardiogram were recorded. After successful modeling,blood and heart tissue were collected to detect the content of creatine creatine(CK),lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)in the serum, the enzyme-linked immunoassay(ELISA) method was used to detect cardiac troponin(CtnI)content, immunohistochemical detection of myocardial PI3K,Akt,mTOR expression. Western blot was used to detect the myocardial autophagy-related protein microtubule-associated protein 1 light chain 3(LC-3),autophagy markers Beclin1 and PI3K/Akt/mTOR signaling pathway related protein expression and phosphorylated p-PI3K,p-Akt,p-mTOR levels. Result:In model group, 100% of ventricular tachycardia and 91.67% of ventricular fibrillation occurred. Compared with sham operation group, the serum levels of CK,LDH,AST,and CtnI in the model group were significantly increased(
3.Primary Study of Henan Cerebral Palsy Register and Rehabilitation Management System
Jun-ying YUAN ; Yi-wen WANG ; Jun WANG ; Jie LIU ; Bo CUI ; Zhi-jun CAI ; Hai CHEN ; Yong-qiang GAO ; Feng-wei LIU ; Guo-hui NIU ; Chun-ya SU ; Jun-hui WANG ; Liang WANG ; Hua-chun XIONG ; Hong-yin ZHAI ; Deng-na ZHU
Chinese Journal of Rehabilitation Theory and Practice 2020;26(8):885-891
Objective:To introduce the construction of Henan Cerebral Palsy Register and Rehabilitation Management System (HCPRRMS) and to explore the construction project of regional register and surveillance of cerebral palsy. Methods:The construction process, registration content and preliminary results of HCPRRMS were systematically introduced. Results:HCPRRMS was independent developed in 2014. Since March, 2015, the system has been used to register information of patients with cerebral palsy in the Third Affiliated Hospital of Zhengzhou University. Until September, 2019, a total of 23 child rehabilitation institutions had used the registration management system. There were 1357 patients with cerebral palsy registered in this system, in which 936 cases (68.98%) were male, 501 cases (36.92%) were with gestational weeks < 37, 443 cases (32.65%) were with birth weight < 2500 g, and 430 cases (31.69%) were born with hypoxic-ischemic encephalopathy. Among them, the spastic cerebral palsy patients (1117 cases, 86.74%) accounted for the highest proportion. There was significant difference among types of cerebral palsy and the classification of GMFCS. A total of 1117 patients with cerebral palsy showed MRI-identified brain abnormalities, in which, periventricular leukomalacia accounted for the most (480 cases). For the complications, epilepsy accounted for 14.44% (196 cases), vision impairment accounted for 8.03% (109 cases), hearing impairment accounted for 11.64% (158 cases). Among 769 cases aged more than two years, language-speech dysfunction accounted for 52.66% (424 cases); and among 216 cases aged more than four years, mental retardation accounted for 37.96% (82 cases). Conclusion:HCPRRMS could help to understand the risk factors, clinical characteristics, and complications of cerebral palsy.
4.Research progress on neural mechanism of peripheral inflammation in Parkinson's disease.
Yong-Ting LIU ; Ming-Hao SUN ; Chun-Wei CAI ; Chao REN ; Hai-Chen NIU
Acta Physiologica Sinica 2019;71(5):732-740
Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by loss of dopaminergic (DA) neurons in the dense part of the substantia nigra (SNpc). Postmortem analysis of PD patients and experimental animal studies found that microglial cell activation and increased levels of pro-inflammatory factors were common features of PD brain tissue. At the same time, the invasion and accumulation of peripheric immune cells were detected in the brain of PD patients. In this paper, peripheral inflammation across the blood-brain barrier (BBB), the misfolded α-synuclein (α-syn)-induced microglial cell activation and intracerebral inflammation in PD are summarized, providing potential therapeutic measures for delaying the onset of PD.
Animals
;
Blood-Brain Barrier
;
Dopaminergic Neurons
;
pathology
;
Humans
;
Inflammation
;
pathology
;
Microglia
;
Parkinson Disease
;
pathology
;
Substantia Nigra
;
pathology
;
alpha-Synuclein
5.Astragalus polysaccharide attenuates liver injury in rats with chronic cadmium exposure
Fang-Yu AN ; Chun-Lu YAN ; Yong-Qi LIU ; Zhi-Wei WU ; Yun SU ; Yan-Qiang NIU ; Peng-Yao LIU
Basic & Clinical Medicine 2018;38(2):189-193
Objective To explore the effects of Astragalus polysaccharides on liver injury induced by cadmium chloride. Methods The cadmium chloride solution was administrated i.v. to develope rat model of liver injury. Rats were randomized divided into three groups;control group, model group, Astragalus polysaccharides intervention group. After the 5 weeks, the rats were sacrificed and the livers were weighted, alanine aminotrans ferase(ALT), aspartate aminotransferase (AST) and lactate dehydrogenase(LDH), the contents of cadmium(Cd) was checked by plasma mass spectrometerthe(ICP-MS), the contents of interleukin-2(IL-2) and transforming growth factor-β1(TGF-β1) was measured by ELISA, the the protein expression of Bcl-2 and Bax was observed by immunohisto-chemistry staining method. Results The liver weight was increased in model group, the level of ALT, AST and LDH were also ascended in model group, the contents of Cd, TGF-β1 and the protein expression of Bax all increased in mode group(P<0.05 or P<0.01). The content of IL-2 and the protein expression of Bcl-2 were decreased in mode group (P<0.05 or P<0.01). Compared with the model group, the liver index was decreased in Astragalus polysaccharides intervention group, the levels of ALT, AST and LDH were also reduced in Astragalus poly-saccharides intervention group, the contents of Cd, TGF-β1 and the protein expression of Bax were all dropped in Astragalus polysaccharides intervention group(P<0.05 or P<0.01).The content of IL-2 and the protein expression of Bcl-2 increased in Astragalus polysaccharides intervention group(P<0.05 or P<0.01). Conclusions Astragalus polysaccharides may reduce the oxidative stress injury of rats liver cells indued by cadmium chloride, and its mechanism may be explained by regulation of Bcl- 2/Bax protein expression.
6.Association of in-stent restenosis with serum Gal-3 and MMP-9 levels
Xiao-Ting NIU ; Yang XU ; Yang ZHENG ; Xiao-Huan LIU ; Hong GONG ; Ya-Jie FAN ; Chun-Yan ZHANG ; Yan ZHANG ; Yan-Chao HU ; Yong-Qin LI ; Cong-Xia WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2018;39(4):483-487,503
Objective To investigate the relationship of galectin-3 (Gal-3)and matrix metalloproteinase-9 (MMP-9)with in-stent restenosis (ISR).Methods We consecutively recruited 434 patients who had undergone successful drug eluting stent (DES)implantation.Then we divided them into ISR group (n=41)and NO-ISR group (n=393)according to the results of coronary angiography review.Independent risk factors for ISR were found out by multivariate analysis and the two groups were matched for these factors except for Gal-3 and MMP-9 .After elim-ination of the influence of confounders,serum Gal-3 and MMP-9 were compared between the groups and their rela-tions with the severity of ISR were analyzed.Patients were grouped based on Gal-3 and MMP-9 concentrations and major adverse cardiac events (MACEs)were compared between the two groups.Results After elimination of the influence of confounders,the results showed that serum levels of Gal-3 and MMP-9 were significantly higher in ISR group than in NO-ISR group (P<0.001).Serum levels of Gal-3 and MMP-9 increased with the increased grade of classification.Serum levels of Gal-3 and MMP-9 were obviously higher in classes Ⅲ and Ⅳ ISR than in class Ⅰ (P<0.05).Patients with higher levels of Gal-3 and MMP-9 had a higher incidence of MACEs (P<0.01).ISR group had a higher incidence of MACEs than NO-ISR group (P<0.05).Conclusion Serum levels of Gal-3 and MMP-9 are correlated with ISR and its severity,and they are independent risk factors for ISR.The rate of MACEs during follow-up period was increased with the increased levels of Gal-3 and MMP-9 .
7.Therapeutic effect of metoprolol combined trimetazidine on ischemic heart failure and its influence on inflammatory factors
Hai-Yan LI ; Yong-Chun WANG ; Hui NIU ; Chun-Ling ZHAO ; Li-Juan XIE ; Guo-Hua WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2018;27(1):42-46
Objective: To study therapeutic effect of metoprolol combined trimetazidine on ischemic heart failure (IHF) and its influence on inflammatory factors. Methods: A total of 172 IHF patients treated in our hospital were collected. They were randomly and equally divided into trimetazidine group and combined treatment group (received metoprolol combined trimetazidine), and both groups were treated for 30d. Cardiac function, levels of inflammatory factors, N terminal pro brain natriuretic peptide (NT-proBNP), heart type fatty acid-binding protein (H-FABP) and quality of life (QOL) before and after treatment, and cerebral infarction rate after one-year treatment were compared between two groups. Results: Compared with trimetazidine group after treatment, there were significant rise in left ventricular ejection fraction [(44. 68±4. 51) % vs. (49. 79±4. 99) %], significant reductions in left ventricular end-diastolic dimension [(50. 41± 5. 06) mm vs. (47. 28±4. 83) mm], left ventricular end-systolic dimension [(41. 57±4. 22) mm vs. (36. 72±3. 71) mm], levels of NT-proBNP [(3. 48±0. 35) ng/L vs. (3. 06±0. 32) ng/L], H-FABP [(11. 41±1. 26) μg/L vs. (8. 55±0. 86) μg/L], interleukin 6 [(53. 21±5. 36) ng/L vs. (43. 58±4. 44) ng/L], tumor necrosis factorα [(161. 97±16. 28) ng/L vs. (108. 27±10. 11) ng/L]and C reactive protein [(15. 72±1. 59) ng/L vs. (11. 10±1. 12) ng/L]and QOL score [(48. 75±4. 89) scores vs. (43. 15±4. 33) scores]in combined treatment group, P<0. 05 or<0. 01. Total effective rate of combined treatment group was significantly higher than that of trimetazidine group (90. 70% vs. 72. 09%, P=0. 002); after one-year treatment, incidence rate of cerebral infarction in combined treatment group was significantly lower than that of trimetazidine group (2. 33% vs. 10. 47%, P=0. 029). Conclusion: Metoprolol combined trimetazidine can significantly improve myocardial blood supply, correct immune imbalance, improve cardiac function and quality of life in IHF patients. The therapeutic effect is significant, and it can prevent cerebral infraction, which is worth extending.
8.The therapeutic effects of Yougui pill on knee osteoarthritis and the expression of Wnt signal pathway related factors in rats.
Chun-Lu YAN ; Sheng-Hua LI ; Fang-Yu AN ; Yong-Qi LIU ; Peng-Fei XIA ; Zheng-Min MA ; Yan-Qiang NIU ; Peng-Yao LIU
Chinese Journal of Applied Physiology 2018;34(2):177-181
OBJECTIVES:
To observe the effects of Yougui pill (Traditional Chinese Medicine) on the related factors of Wnt signal pathway of rats with knee osteoarthritis (KOA), and explore its protective mechanism.
METHODS:
Sixty SPF SD rats were randomly divided into the sham-operative group, model group, glucosamine sulfate group, high-dose, middle-dose, low-dose of Yougui pill treated group (=10). KOA model was established by modified Hulth method for six weeks. The rats in the high, middle and low-dose of Yougui pill group were treated with Yougui pills at the doses of 20,10 and 5 g/kg respectively by gastrogavage once a day for 8 weeks, while equal volume of normal saline was given to those in the sham and model control group and an equal volume of glucosamine sulfate (1.7 g/kg·d) was given to those in glucosamine sulfate group for 8 weeks. The knee joint was removed after the last dose of drug. The pathological changes of cartilaginous tissues were observed under a microscope. The mRNA levels of Dickkopf homolog 1(DKK1), Wnt induced secreted protein 1(WISP1), Wnt1, low density lipoprotein receptor related protein 5(LRP5) and beta -catenin in rats cartilaginous tissues were analyzed by using RT-PCR method, and the protein contents of DKK1, WISP1, Wnt1, LRP5 and beta-catenin in cartilaginous tissues were detected by Western blot.
RESULTS:
Compared with the sham group, the articular cartilage was severely damaged, the Mankin score was increased significantly (<0. 05), the mRNA and protein expression levels of DKK1 in cartilaginous tissue were markedly decreased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were increased significantly in model group(<0.05). Compared with model group, the articular cartilage lesions was light (<0.05), the Mankin Score was decreased significantly(<0.05), and the mRNA and protein levels of DKK1 in cartilaginous tissue were increased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were decreased in Yougui pill high-dose group and glucosamine sulfate group (<0.05).
CONCLUSIONS
Yougui pill has protective effects on the KOA by inhibiting the expressions of WISP, Wnt1, LRP5, beta-catenin and increasing the expression of DKK1 cytokine in the Wnt signaling pathway.
Animals
;
CCN Intercellular Signaling Proteins
;
metabolism
;
Drugs, Chinese Herbal
;
pharmacology
;
Glucosamine
;
pharmacology
;
Intercellular Signaling Peptides and Proteins
;
metabolism
;
Osteoarthritis, Knee
;
drug therapy
;
Proto-Oncogene Proteins
;
metabolism
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Wnt Signaling Pathway
;
Wnt1 Protein
;
metabolism
;
beta Catenin
;
metabolism
9.Protective effects of Astragalus polysaccharides in renal injury under cadmium in rats
Fang-Yu AN ; Chun-Lu YAN ; Yong-Qi LIU ; Hua JIN ; Zhi-Wei WU ; Yun SU ; Yan-Qiang NIU ; Peng-Yao LIU
The Chinese Journal of Clinical Pharmacology 2018;34(1):49-52
Objective To explore the role of Astragalus polysaccharidesin renal tissue under cadmium treatment in rats.Methods The SPFWistar rats were randomized divided into three groups:normal group,model group,experimental group.The normal group was intraperitoneallyinjected with 0.9% saline solution,while the model group and theexperimental group were intraperitoneally injected daily with cadmiumchloride (CdC12) in a single dose of 1.5 mg· kg-1 body weight.At thesame time,the experimental group was given Astragalus polysaccharide20 mg · kg-1 once a day for five consecutive weeks.The model group andthe experimental group were given 0.9% saline solution once a day for five consecutive weeks.After the last injection,all the rats were sacrificed by femoral artery sampling.The content of cadmium (Cd) was measured by atomic absorption spectrophotometry.The levels of superoxide dismutase (SOD),malondialdehyde (MDA),lactate dehydrogenase(LDH),glautathione peroxidase(GSH-Px) were checked by colorimetric analysis.The contents of interleukin -2(IL-2),transforming growth factor-3 (TGF-β) were determined by enzyme linked immunosorbent assay.The protein expressions of Bcl-2 and Bax were analyzed by immunohistochemical method.Results IL-2 level in normal group,model group,experimental group were (117.38 ± 10.89),(71.82 ± 14.56),(102.46 ±13.82)pg·mL-1,respectively;TGF-β1level in above groups were (4.88 ±0.38),(9.77 ±0.21),(6.35 ±0.41)pg·mL-1,respectively;GSH-Px level in above groups were (240.48 ± 18.24),(159.26 ± 21.06)(191.50 ± 23.82) U · g-1,respectively;LDH level in above groups were (1125.25 ± 37.91),(2089.46 ± 35.87)(1159.61 ± 28.86) U · g-1,respectively;Cd level in above groups were (0.02 ± 0.01),(19.68 ± 1.85)(12.99±2.11)mg · kg-1,respectively;SOD level in above groups were (71.55 ± 3.56),(39.30 ± 3.36)(67.25±2.68) U · mg-1,respectively;MDA level in above groups were (3.96 ± 0.79),(7.47 ± 0.78)(5.61 ±0.99) nmol · mg-1,respectively;Bcl-2 gray level in above groups were 37.54±3.23,68.43 ±5.2138.25 ± 6.17,respectively;Bax gray level in above groups were 57.87 ± 8.93,27.54 ± 5.45,48.23 ± 3.54.respectively.Compared with the normal group,all factors in the model group were significantly (all P < 0.01).Compared with the model group,all factors in the experimental group were significandy (P < 0.05 or P <0.01).Conclusion Astragalus polysaccharides pretreatment has a certain protective effect against cadmium-induced renal damage in rats and the protection is achieved by the regulation of Bcl-2/Bax protein expression.
10.Usefulness of lumen area parameters determined by intravascular ultrasound to predict functional significance of intermediate coronary artery stenosis.
Ming CUI ; Dan ZHU ; Li-jun GUO ; Li-ying SONG ; Yong-zhen ZHANG ; Fu-chun ZHANG ; Jie NIU ; Gui-song WANG ; Jiang-li HAN ; Wei GAO
Chinese Medical Journal 2013;126(9):1606-1611
BACKGROUNDCoronary artery disease is the leading cause of death in China. Percutaneous coronary intervention is a recent milestone technology for treatment coronary artery disease. However, clinical decision making for patients with intermediate coronary stenosis is still controversial. We designed this study to assess the optimal intravascular ultrasound (IVUS) criteria for predicting functional significance of intermediate coronary lesions.
METHODSWe enrolled 141 patients with 165 intermediate coronary lesions located in vessels with a diameter ≥ 2.50 mm. IVUS of intermediate coronary lesions were performed before intervention. Pressure-derived fractional flow reserve (FFR) was measured at maximal hyperemia induced by adenosine infusion. An FFR < 0.80 was considered as abnormal functional significance.
RESULTSFor the overall 165 lesions, the mean FFR value was 0.84 ± 0.09. The diameter of the stenosis by visual estimation on angiogram was (59.63 ± 11.29)%. Minimum lumen diameter (MLD), minimum lumen area (MLA) and plaque burden (PB) were (2.00 ± 0.36) mm, (3.88 ± 1.34) mm(2), (67.28 ± 9.89)% respectively by IVUS measurements. An FFR < 0.80 was seen in 43 lesions (30.5%). There was a moderate correlation between IVUS parameters and FFR, including MLD (r = 0.372, P < 0.001), MLA (r = 0.442, P < 0.001) and PB (r = -0.172, P < 0.05). MLA was a predictor for FFR as a continuous variable independent of possible confounding variables (P < 0.05), and MLA and PB, were predictors for FFR < 0.80 as binary variables (P < 0.05). The best cutoff value of MLA to predict FFR < 0.80 was < 3.15 mm(2), with a 73.6% diagnostic accuracy; sensitivity 71.4%, specificity 67.0%, AUC = 0.709, and P < 0.001. The cutoff value of the PB to predict FFR < 0.80 was 65.45%; sensitivity 82.6%, specificity 41.2%, AUC = 0.644, and P < 0.01. If both MLA and PB were taken into account, the negative predictive value and the positive predictive value were 88.7% and 64.8% respectively.
CONCLUSIONSAnatomic measurements of intermediate coronary lesions obtained by IVUS showed a moderate correlation to FFR values. IVUS-derived MLA ≥ 3.15 mm(2) may be useful to exclude FFR < 0.80, but poor specificity limits its applicability for physiological assessment of lesions < 3.15 mm(2). MLA was one of many factors affecting coronary flow hemodynamics. Both MLA and PB should be taken into account when determining functional ischemia.
Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Stenosis ; diagnostic imaging ; physiopathology ; Fractional Flow Reserve, Myocardial ; Humans ; Middle Aged ; Ultrasonography, Interventional ; methods

Result Analysis
Print
Save
E-mail