1. Effects of jiawei danshen yin combined with mir-21 on iri myocardial cells
Chinese Pharmacological Bulletin 2020;36(2):277-281
Objective To investigate the protective effect of Jiawei Danshen Yin combined with microRNA-21 on IRI myocardial cells,and to study its protective mechanism. Methods H9C2 cardiomyocytes were cultured and divided into four groups: Blank group, IRI model group of cardiomyocytes,miR-21 group,miR-21 combined with Jiawei Danshen Yin group (JWDSY group). Apoptotic rate, apoptosis-related protein and PTEN signaling pathway expression of cardiomyocytes were detected. Results Electron microscopy showed that mitochondria in model group were damaged significantly , and ultrastructural damage in JWDSY group was alleviated; ELISA demonstrated that cTnl was elevated in model group and decreased in JWDSY group with statistical significance (P < 0. 01); flow cytometry re vealed that the apoptotic rate was significantly increased in model group (36. 79 ±2. 12) ,but markedly decreased in JWDSY group (14. 65 ± 0. 94), and the difference was statistically significant ( P < 0. 05 ). Western blot results showed that PTEN expression was uP-regulated and P-Akt expression down-regulated in model group,while PTEN expression decreased and P-Akt expression increased in JWDSY group, and the difference was statistically significant ( P < 0. 05 ). Conclusions miR-21 combined with Jiawei Danshen Yin can inhibit cardiomyocyte apoptosis and protect IRI cardiomyocytes by reducing PTEN expression and activating PI3K/Akt signaling pathway,.
2.Pharmacokinetics of two recombinant humanized monoclonal antibodies against ricin in rhesus monkeys
Ya GAO ; Xiao-xia ZHU ; Zhi-yun MENG ; Hui GAN ; Ruo-lan GU ; Zhuo-na WU ; Wen-zhong SUN ; Gui-fang DOU
Acta Pharmaceutica Sinica 2022;57(2):480-483
Recombinant humanized anti-ricin monoclonal antibody (MIL50) is a recombinant humanized monoclonal antibody targeting ricin. In this study, an ELISA method was used to establish a method for the determination of MIL50 in macaque serum, and a cross design method was used. Twelve rhesus monkeys were intravenously injected 1 mg·kg-1 test preparation (MIL50 freeze-died powder injection) and reference preparation (MIL50 liquid preparation) to determine the plasma concentration of MIL50 at different time points, and the pharmacokinetic parameters were analyzed to compare the pharmacokinetic characteristics of MIL50 liquid preparation and freeze-died powder injection in rhesus monkeys. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Chinese Academy of Medical Sciences and Use of Laboratory Animals and the regulations derived by the Animal Care and Welfare Committee of the Institute of Radiation Medicine, Academy of Military Medical Sciences (IACUC-DWZX-2020-503). The results showed that there was no significant difference between
3.Inhibition of rho kinase attenuates high flow induced pulmonary hypertension in rats.
Fu-Hai LI ; Wei XIA ; Ai-Wu LI ; Cui-Fen ZHAO ; Ruo-Peng SUN
Chinese Medical Journal 2007;120(1):22-29
BACKGROUNDThe RhoA/Rho kinase pathway may participate in the pathogenesis of hypoxia and monocrotaline induced pulmonary hypertension. This study tested whether RhoA/Rho kinase pathway is involved in the pathogenesis of high flow induced pulmonary hypertension in rats.
METHODSMale Wistar rats (4 weeks) were randomly divided into 4 shunt groups, 4 treated groups and 4 control groups. Shunt and treated groups underwent left common carotid artery/external jugular vein shunt operation. Control groups underwent sham operation. Treated groups received fasudil treatment and the others received same dose of saline. At weeks 1, 2, 4 and 8 of the study, right ventricular systolic pressure was measured and blood gases were analysed to calculate Qp/Qs. The weight ratio of right ventricle to left ventricle plus septum and the mean percentage of medial wall thickness in moderate sized pulmonary arteries were obtained. RhoA activity in pulmonary arteries was detected using Rho activity assay reagent. Rho kinase activity was quantified by the extent of MYPT1 phosphorylation with Western blot. Proliferating cells were evaluated using proliferating cell nuclear antigen immunohistological staining.
RESULTSCarotid artery/jugular vein shunt resulted in high pulmonary blood flow, both an acute and a chronic elevation of right ventricular systolic pressure, significant medial wall thickening characterized by smooth muscle cells proliferation, right ventricular hypertrophy and increased activation of RhoA and Rho kinase. Fasudil treatment lowered pulmonary artery systolic pressure, suppressed pulmonary artery smooth muscle cells proliferation, attenuated pulmonary artery medial wall thickening and inhibited right ventricular hypertrophy together with significant suppression of Rho kinase activity but not Rho activity.
CONCLUSIONSActivated RhoA/Rho kinase pathway is associated with both the acute pulmonary vasoconstriction and the chronic pulmonary artery remodelling of high flow induced pulmonary hypertension. Fasudil treatment could improve pulmonary hypertension by inhibiting Rho kinase activity.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; therapeutic use ; Animals ; Cell Proliferation ; drug effects ; Enzyme Activation ; drug effects ; Hypertension, Pulmonary ; drug therapy ; etiology ; Hypertrophy, Right Ventricular ; prevention & control ; Intracellular Signaling Peptides and Proteins ; antagonists & inhibitors ; physiology ; Male ; Muscle, Smooth, Vascular ; drug effects ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Serine-Threonine Kinases ; antagonists & inhibitors ; physiology ; Pulmonary Artery ; pathology ; Pulmonary Circulation ; drug effects ; Rats ; Rats, Wistar ; Systole ; drug effects ; Vasoconstriction ; drug effects ; rho-Associated Kinases ; rhoA GTP-Binding Protein ; physiology
4.Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog.
Zi-Hua ZHENG ; Xiao-Xia ZHU ; Hui GAN ; Ruo-Lan GU ; Zhuo-Na WU ; Zhi-Yun MENG ; Gui-Fang DOU
Acta Pharmaceutica Sinica 2013;48(8):1307-1311
Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.
Animals
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Area Under Curve
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Batroxobin
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administration & dosage
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blood
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pharmacokinetics
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pharmacology
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Dogs
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Enzyme-Linked Immunosorbent Assay
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Fibrin Fibrinogen Degradation Products
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metabolism
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Fibrinogen
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metabolism
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Fibrinolytic Agents
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administration & dosage
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blood
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pharmacokinetics
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pharmacology
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Infusions, Intravenous
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Male
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Partial Thromboplastin Time
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Prothrombin Time
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Thrombin Time
5.MECP2 duplication syndrome: a clinical analysis of three cases and literature review.
Dan-Xia TANG ; Dong-Fang LI ; Ruo-Hao WU ; Li-Na ZHANG ; Xiang-Yang LUO
Chinese Journal of Contemporary Pediatrics 2017;19(5):489-493
MECP2 duplication syndrome (MDS) is a rare pediatric disease and mainly manifests as delayed motor development, language loss or delay, recurrent infection, severe intellectual disability, epilepsy, autistic symptoms, and early infantile hypotonia. In this article, the three children with this disease were all boys. Cases 1 and 2 had delayed motor development, and language loss or delay as initial manifestations, and case 3 had recurrent infection as initial manifestation. Physical examination showed hypotonia and negative pathological signs in each case. Case 1 had tonic-clonic seizures and electroencephalography showed focal seizures, for which he was given oxcarbazepine, levetiracetam, and clonazepam as the antiepileptic treatment to control seizures. Case 3 experienced one absence seizure and three head-nodding seizures with normal electroencephalographic findings during these seizures, and therefore, he was not given antiepileptic treatment. In each case, recurrent infection was improved with the increase in age, but there were no significant improvements in language or intelligence. Array-based comparative genomic hybridization (aCGH) showed MECP2 duplication in X chromosome in each case, and so they were diagnosed with MDS. MDS should be considered for children with delayed development complicated by recurrent infection and epileptic seizures, and early aCGH helps with the diagnosis of this disease.
Child
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Comparative Genomic Hybridization
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Humans
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Infant
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Male
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Mental Retardation, X-Linked
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complications
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genetics
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Methyl-CpG-Binding Protein 2
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genetics
6.Low molecular weight heparin microcapsule coated occluder for atrial-septal defects.
Yong SUN ; Jian WU ; Ruo-Xi ZHANG ; Xiu-Jie SHI ; Hai-Xia LIU ; Yang ZHAO ; Bo YU
Chinese Medical Journal 2009;122(12):1429-1434
BACKGROUNDWhether the low molecular weight heparin microcapsule coated occluder is helpful to endothelialization in atrial-septal defect models is uncertain. This study aimed to investigate the best conditions for low molecular weight heparin coated NiTi alloy occluder and provide the evidence of the efficacy and safety of atrial-septal defect occluders in vivo.
METHODSLow molecular weight heparin microcapsules were investigated using gelatin as microcapsule material. The prepared low molecular weight heparin gelatin particles were subjected to nickel and titanium alloy occluder coating by sodium hyaluronate. A dog model of atrial septal defects was established after treatment with low molecular weight heparin microcapsule coated occluder (n = 4) and uncoated occluder (n = 4). Endotheliocytes and fibroblastic cells in occluders were observed. And the rate of endothelialization was detected.
RESULTSWhen the concentration of gelatin was 1%, the diameters of particles were mostly about 100 microm, and the particle size was uniform. The envelope efficiency of low molecular weight heparin microcapsule was about 80%. The endothelialization of occluder in the model was more obvious in the coated group than in the uncoated group (P < 0.0001).
CONCLUSIONSLow molecular weight heparin can be prepared into microcapsules with their particle size in nanometric grade. The antithrombotic properties are kept in the nickel and titanium alloy occluder successfully coated with sodium hyaluronate. The endothelialization after the interventional occlusion in the coated group is obvious, indicating that low molecular weight heparin is helpful to the growth of endothelial cells in the occlude and the healing after the interventional occlusion.
Alloys ; chemistry ; Animals ; Anticoagulants ; pharmacology ; Capsules ; chemistry ; Disease Models, Animal ; Dogs ; Endothelial Cells ; drug effects ; ultrastructure ; Fibroblasts ; drug effects ; Gelatin ; chemistry ; Heart Septal Defects, Atrial ; drug therapy ; Heparin, Low-Molecular-Weight ; chemistry ; pharmacology ; Immunohistochemistry ; Microscopy, Electron, Transmission ; Particle Size ; Random Allocation
7.ClinicalValueofMRQuantitativeFatAnalysisinOrbitsofPatientswithGraves Ophthalmopath
Ruo-cheng LI ; Xia-hua HUANG ; Wen-hao FU ; Meng-sha ZOU ; Di-de WU ; Shu-bin HONG ; Hong-zhang ZHU ; Yan-hong YANG
Journal of Sun Yat-sen University(Medical Sciences) 2019;40(6):875-880
【Objective】To measure the orbital fat fraction(FF)of Graves ophthalmopathy(GO)patients and normal individuals with MR Water- fat separation(Dixon) technology ,and to explore the value of orbit MR quantitative fat analysis in diagnosis and treatment for GO patients.【Methods】Forty GO patients and 20 normal individuals who underwent orbital MR imaging were analyzed prospectively from February 2017 to February 2019 in the First Affiliated Hospital of Sun Yat- sen University. All participants received bilateral orbital MR examination with oblique coronary FSE T2- weighted imaging combined with two-point Dixon technique,and then the signal intensity values of ipsilateral extraocular muscles and lacrimal glands on water and fat phase images were measured to calculate FF. The differences of mean FF between the two groups were evaluated,and the correlation between FF of GO and TRAb,CAS score,and the course of GO were conducted by Spearman rank correlation analysis. 【Results】 The median FF of extraocular muscles in GO patients was higher than that of normal individuals,and the result showed a statistically significant difference(P < 0.05), while the FF of lacrimal glands in the two groups showed no statistical difference. The FF of extraocular muscles in the GO group were correlated with TRAb,CAS score and the course of GO(P < 0.05),especially the course was more correlative.【Conclusions】The fat content of extraocular muscles in GO patients were higher than that of normal individuals ,and there was a positive correlation in the fat content among TRAb,CAS score and the course of GO,suggesting that MR fat quantitative analysis may provide a new reference indexes for the evaluation of clinical staging ,curative effect assessment in GO patients.
8.Determination of biodistribution of 99mTc-3PRGD2 in mice bearing the lung carcinoma xenograft byγcounter
yun Li NIU ; 100850 北京,军事医学科学院野战输血研究所 ; Jian LI ; Bing JIA ; yun Zhi MENG ; yun Tao LIU ; lan Ruo GU ; xia Xiao ZHU ; Hui GAN ; na Zhuo WU ; Gui-fang BAI-PING ; DOU MA
Journal of International Pharmaceutical Research 2017;44(8):795-799
Objective To establish a quantitative analysis method for determining 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2,a radioactive tumor agent)byγcounter, and to investigate the distribution of 99mTc-3PRGD2 in mice bearing with lung carcinoma xenograft. Methods The mice were divided into 4 normal groups and one blocking peptide group(control group). The 99mTc-3PRGD2(8μg/kg)was injected to mice bearing with lung carcinoma xenograft through the tail intravenous administration. Tissues of the normal mice were taken at 0.5,1,2 and 4 h. The control group were treated by 3PRGD2 and 99mTc-3PRGD2. The control mice were injected with the 3PRGD2 saline solution(2.5 mg/ml,0.2 ml)at 0.5 h earlier before the injection of 99mTc-3PRGD2. The tu?mor and organ tissues of the control mice were taken at 2 h. The radioactivity was detected by Gamma Counter. Results The radioac?tivity of 99mTc-3PRGD2 detected was high in the tumor and very low in brain. In addition,high radioactivity in kidneys and bladder sug?gested that the drug excreted by renal. Conclusion The results proved that the blocking peptide can competitively inhibit the combi?nation of 99mTc-3PRGD2 and integrinαvβ3 receptors.
9.Scoping review of progress in cohort studies of autism spectrum disorder.
Yun Xiao WU ; Zhi Xia LI ; Xiao Zhen LYU ; Mai WANG ; Tian Yu HUANG ; Jian Hong CHENG ; Ruo gu MENG
Chinese Journal of Epidemiology 2023;44(5):837-844
Objective: To understand the status of autism spectrum disorder (ASD) cohort studies and explore the feasibility of constructing ASD disease-specific cohorts based on real-world data (RWD). Methods: ASD cohort studies published by December 2022 were collected by literature retrieval from major Chinese and English databases. And the characteristics of the cohort were summarized. Results: A total of 1 702 ASD cohort studies were included, and only 60 (3.53%) were from China. A total of 163 ASD-related cohorts were screened, of which 55.83% were birth cohorts, 28.22% were ASD-specific cohorts, and 4.91% were ASD high-risk cohorts. Most cohorts used RWD such as hospital registries or conducted community-based field surveys to obtain participant information and identified patients with ASD by scales or clinical diagnoses. The contents of the studies included ASD incidence and prognostic risk factors, ASD comorbidity patterns and the impact of ASD on self-health and their offspring's health. Conclusions: ASD cohort studies in developed countries have been in the advanced stage, while the Chinese studies are still in their infancy. RWD provides the data basis for ASD-specific cohort construction and offers new opportunities for research, but work such as case validation is still needed to ensure the scientific nature of cohort construction.
Humans
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Autism Spectrum Disorder
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Cohort Studies
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Databases, Factual
10.Triaging patients in the outbreak of COVID-2019
Guo-Qing HUANG ; Wei-Qian ZENG ; Wen-Bo WANG ; Yan-Min SONG ; Xiao-Ye MO ; Jia LI ; Ping WU ; Ruo-Long WANG ; Fang-Yi ZHOU ; Jing WU ; Bin YI ; Zeng XIONG ; Lu ZHOU ; Fan-Qi WANG ; Yang-Jing TIAN ; Wen-Bao HU ; Xia XU ; Kai YUAN ; Xiang-Min LI ; Xin-Jian QIU ; Jian QIU ; Ai-Min WANG
Chinese Journal of Infection Control 2023;22(3):295-303
In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50%of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.