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,.

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 C_max and AUC_0-5d in the two groups. The liquid preparation was the reference preparation, with C_max ratio of 101.6% and AUC_0-5d ratio of 101.9%, the 90% confidence interval of C_max was 79.42%-129.92%, and the 90% confidence interval of AUC_0-5d was 85.72%-121.18%. These results suggested that different dosage forms of MIL50 had certain differences in the changes of blood drug concentration in rhesus monkeys.

Objective:To analyze the main risk factors of recurrence after wound healing in patients with diabetic foot ulcer (DFU) , so as to provide a basis for clinical prevention of DFU recurrence.Methods:Cochrane Library, PubMed, Embase, Web of Science, CNKI, Wanfang Database, VIP Chinese Science and Technology Journal Full-text Database, and China Biomedical Literature Database were searched by computer, and the risk factors for recurrence of DFU patients were collected from the establishment of the databases to July 10, 2021. Meta-analysis was performed using RevMan 5.3 software.Results:Finally, 12 articles were included, with a total of 2 585 patients, including 982 cases in the recurrence group and 1 603 cases in the non-recurrence group. Meta-analysis results showed that Wagner grade (gradeⅢ, Ⅳ) ( OR=4.40, 95% CI: 2.21-8.78, P<0.01) , accompanied by peripheral neuropathy ( OR=5.69, 95% CI: 4.53-7.14, P<0.01) , accompanied by peripheral vascular disease ( OR=3.54, 95% CI: 3.05-4.11, P<0.01) , multidrug-resistant infection ( OR=3.61, 95% CI: 3.13-4.17, P<0.01) , history of amputation ( OR=19.18, 95% CI: 10.69-34.42, P <0.01) , duration of previous DFU greater than or equal to 60 days ( OR=1.02, 95% CI: 1.00-1.03, P<0.01) , poor blood glucose control ( OR=3.39, 95% CI: 2.67-4.31, P<0.01) , underlying osteomyelitis ( OR=2.86, 95% CI: 2.29-3.58, P<0.01) , initial ulcer on the sole of the foot ( OR=2.80, 95% CI: 2.10-3.73, P<0.01) , smoking ( OR=2.30, 95% CI: 1.18-4.48, P=0.01) were risk factors for DFU recurrence. Conclusions:Based on the available evidence, Wagner grade (gradeⅢ, Ⅳ) , accompanied by peripheral neuropathy, accompanied by peripheral vascular disease, multidrug-resistant infection, history of amputation, duration of previous DFU greater than or equal to 60 days, poor blood glucose control, underlying osteomyelitis, initial ulcer on the sole of the foot and smoking are risk factors for DFU recurrence. Medical staff should pay attention to these influencing factors and take corresponding measures for targeted prevention, so as to improve the quality of diabetic foot care services.

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 ; Area Under Curve ; Batroxobin ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Fibrin Fibrinogen Degradation Products ; metabolism ; Fibrinogen ; metabolism ; Fibrinolytic Agents ; administration & dosage ; blood ; pharmacokinetics ; pharmacology ; Infusions, Intravenous ; Male ; Partial Thromboplastin Time ; Prothrombin Time ; Thrombin Time

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

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

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 ; Comparative Genomic Hybridization ; Humans ; Infant ; Male ; Mental Retardation, X-Linked ; complications ; genetics ; Methyl-CpG-Binding Protein 2 ; genetics

【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.

Objective: To construct and identify lentiviral vector containing human ILK-shRNA and mda7 gene.Methods:Based on the human ILK gene sequences , RNAi target sequences were designed and cloned into the lentiviral vector pSicoR -eGFP by restriction endonuclease HpaⅠand XhoⅠdouble digestion and T 4 DNA ligase ligation . Based on the human mda7 gene sequences , PCR primers were designed to clone the full-length mda7, and were cloned into the lentiviral vector pLVX-Puro.After the candidate clones were identified by DNA sequencing , the recombinant plasmid and the three packaging plasmids were co-transfected into the human embryonic kidney 293T cells by lipofectamine 2000 to produce the lentiviral particles .Human prostate cancer PC-3 cells were infected with the constructed lentiviral vector .The ILK and mda7 expression levels in PC-3 cells were quantified by qPCR and Western blot , respectively .The effect of ILK and mda7 on proliferation and migration of PC-3 cells were assessed by MTT method and Transwell assay, respectively.Results: ILK-pSicoR-eGFP and mda7-pLVX-Puro lentiviral vectors were successfully constructed .Strong green fluorescence was observed in the 293T cells under the fluorescent microscope after co-transfection of 293T cells with 4 plasmids of lentiviral vector .The transfection efficiency of the collected virus exceeded 90%in the 293T cells and the PC-3 cells were infected with the lentiviral particles with high efficiency .The A and B lentiviral vector inhibited the expression of ILK at both the mRNA and protein levels in PC-3 cells significantly .The mda7-pLVX-Puro lentiviral vector increased the expression of mda 7 in PC-3 cells, and the ability was maintained for one month.Within 96 h, ILK and mad7 significantly inhibited the proliferation and migration of PC-3 cells ( Ps <0.05 ) . Conclusion: The lentiviral vectors of ILK knockdown and mda 7 over-expression have been successfully constructed and identified . The recombinant lentivirus can efficiently infect human prostate cancer PC -3 cells, in which ILK expression is inhibited and mda 7 is over-expressed .

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.