Background and purpose:Myelosuppression is the most common dose-limiting toxicity of tumor chemotherapy in which leukocytopenia and neutropenia are the most common conditions. Not only are up-titrations of the doses of chemotherapeutic drugs limited, but also normal process of the chemotherapy is affected. Filgrastim-Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) has the activity of stimulating the formation of granulocyte colony and promoting the growth, proliferation and differentiation of granulocytes which can be signiifcantly effective on leukocytopenia and neutropenia induced by chemotherapy. In this study, we observed the leukogenic effects, toxic and side effects of low, medium, and high doses of rhG-CSF used prophylactically after chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), to explore a rational application strategy for rhG-CSF..Methods:One hundred and twenty six patients with pathologically proved advanced non-small cell lung cancer (NSCLC) under chemotherapy were digitally randomized to A, B and C groups. Filgrastim was given to patients of the three groups 24h after the end of chemotherapy. The dosages are: Group A (low dose): 300 μg of Filgrastim, s.c., qd × 1 day; Group B (medium dose): 300 μg of Filgrastim, s.c., qd × 2 days; Group C (high dose): 300 μg of Filgrastim, s.c., qd × 3 days. Then the signs and symptoms as well as toxic and side effects of Filgrastim after medication were observed.Results:Prophylactic usage of medium and high dosages of rhG-CSF could maintain WBC count at no less than 4.0×109/L in nearly 60% of patients. In patients with Grade III leukopenia, more days were needed for recovery of white blood cell (WBC) count with the low dose, while signiifcantly (P<0.05) less days were needed with the high dose. In view of the dynamic changes of neutrophil(ANC), additioning of the high dose of rhG-CSF after chemotherapy could increase the average level ofANC, notably shortening the duration of lowANC caused by chemotherapy. The incidence of infections was 4.76% for the 126 patients as a whole, 9.52% for the low dose group, and 4.76% for the middle dose group. The patients could tolerate the slight side effects incurred during treatment with Filgrastim.Conclusion:All of the three doses (low, medium, and high) of prophylactic administration of Filgrastim after chemotherapy can promote recoveries of WBCs and neutrophil granulocytes and reduce opportunities of infections. High doses of rhG-CSF can be faster and safer in increasing WBCs and neutrophil granulocytes.

Objective To investigate the effects of α-asarone on acti-vation of astrocytes of rat hippocampus.Methods Rat status epilepticus ( SE) lasted for 1 hour.The activations of astrocyte in rat hippocampus of control group , model group and α-asarone treatment group were ob-served by Glial fibrillary acidic protein ( GFAP) immunohistochemistry.The astrocytes of rat hippocampus after passage were randomly assigned to control group , lipopolysaccharide ( LPS ) model group and α-asarone treatment group.Then the ability of cell proliferation were detected by CCK8.The GFAP were detected by Western -blotting .Results The most obvious activation of astrocyte in hippocampus of post -SE rats was observed at 1 d, then back to normal at 28 d after SE.Compared with model group , the activated levels of astrocyte in α-asarone treatment group were significantly decreased at 1,3,7 days after SE (P<0.05).Compared with model group , proliferation of astrocyte induced by LPS were significantly decreased in 50 μg· mL-1 and 100 μg· mL-1 ofα-asarone treatment groups and GFAP expression were significantly de-creased in 100 μg· mL-1α-asarone group (P<0.05).Conclusionα -Asarone could decreased the activation of astrocyte of rat hippocampus.

Stainless steel has been widely used in non-active surgical implantable medical device of cardiovascular, orthopedics, dental and ophthalmology. In this paper, we mainly focused on development of stainless steel, as well as the material-related standard evolution. We further summarized the recent advancement of stainless steel use in surgical implantable medical device. Insight and regulatory perspective has been further demonstrated.
Prostheses and Implants ; Stainless Steel

OBJECTIVETo study the effects of resvaratrol derivatives on spontaneous HR and CF of isolated guinea pig atrium.

METHODThe dose-effect curve of resvaratrol was observed. The possible mechanism of potassium channels responsible for changes of CF and HR after administering with resvaratrol was measured.

RESULTResvaratrol reduced the spontaneous HR and weakened the CF in a dose-dependent manner ranging from 10(-6) to 3 x 10(-4) mol x L(-1) (P < 0.05). As compared with Res group, the effects were partly blocked by Gli (P < 0.05) and TEA (P < 0.01), but not blocked by 4-AP, BaCl2, Atropine.

CONCLUSIONResvaratrol can induce negative chronotropic action and negative (inotropic action. The mechanism(s) may relate to the opening of K(ATP) and Kc(Ca).

Animals ; Barium Compounds ; pharmacology ; Cardiotonic Agents ; administration & dosage ; isolation & purification ; pharmacology ; Chlorides ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Glyburide ; pharmacology ; Guinea Pigs ; Heart Rate ; drug effects ; In Vitro Techniques ; KATP Channels ; antagonists & inhibitors ; Male ; Myocardial Contraction ; drug effects ; Plants, Medicinal ; chemistry ; Potassium Channel Blockers ; pharmacology ; Potassium Channels, Calcium-Activated ; antagonists & inhibitors ; Potassium Channels, Inwardly Rectifying ; antagonists & inhibitors ; Stilbenes ; administration & dosage ; isolation & purification ; pharmacology ; Tetraethylammonium ; pharmacology

OBJECTIVETo observe the protective effects of resveratrol (RES) on the heart function of the rats with adriamycin-induced heart failure.

METHODThirty adult male SD rats were randomly divided into 5 groups: normal control (NC) group, adriamycin (ADR) group, RESL + ADR group, RES(H) + ADR group and RES group. RES of 30, 120, 120 mg x kg(-1) x d(-1) was given intraperitoneally (ip) once a day for 3 days in RES(L) + ADR group, RES(H) + ADR group and RES group respectively. The other two groups were given the same amount of normal saline the same way. On the 4h day,ADR of 10 mg x kg(-1) was given intraperitoneally once to induce myocardium injury model. After twenty-four hours, the pathological and biochemical changes of the myocardium were examined.

RESULTAs compared with NC group, the MDA, NO and NOS of the ADR group were significantly higher (P < 0.05), and the SOD of the ADR group were markedly lower (P < 0.05). As compared with ADR group, the indexes in RES(L) + ADR group, RES(H) + ADR group were exactly opposing, and took on dose dependance (P < 0.05). Light microscopic morphometry of the heart samples of the rats in ADR + RES(L, H) groups revealed typical diminishing of damage.

CONCLUSIONRES can relieve the toxic effects of ADR on myocardium, and the cardioprotective effects may be correlated with its antioxidant activity and downregulation of NO.

Animals ; Doxorubicin ; Heart ; physiopathology ; Heart Failure ; chemically induced ; pathology ; physiopathology ; Male ; Malondialdehyde ; blood ; Myocardium ; pathology ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Superoxide Dismutase ; blood

Objective To explore the expression of miRLet-7 family members in breast cancer and its correlation with overall survivals (OS), and to find more effective molecular targets for breast cancer prevention and treatment.Methods Kaplan-Meier (KM) plotter online database was used to analyze the correlation among the expression of Let-7 family members (Let-7a, 7b, 7c, 7d, 7e, 7f, 7g, 7i, miR-98, miR-202) correlated with overall survival (OS) and the prognosis and clinical pathological parameters of breast cancer patients, and Hazard ratio (HR), 95％confidence interval (CI), and P value were determined.ResultsThe study showed that the high expression level of Let-7a, Let-7b, Let-7c, Let-7e, Let-7f, Let-7g, miR-98 and the low expression level of miR-202 was associated with better OS for breast cancer patients (P＜0.05).We further assessed the prognostic value of Let-7 in different subtypes and clinical stage.The expression of Let-7a, Let-7b, Let-7f, Let-7g, miR-98, miR-202 was related to clinical stage (P＜0.05).Let-7a, Let-7b, Let-7c, Let-7e, Let-7f, Let-7g, miR-98 and miR-202 was related to lymph node status (P＜0.05).In triple-negative breast cancers (TNBC), with breast cancer subtype, the expression of Let-7b, Let-7c, Let-7g and miR-202 was significantly correlated to overall survival (P＜0.05).Conclusion The Let-7 is significantly correlated with OS in breast cancer patients.The results suggested that members of the Let-7 have different values in predicting the prognosis of breast cancer.Among them, Let-7b, Let-7g and miR-202 are closely related with clinical stage and TNBC, and might promote development of Let-7 as targeted inhibitors for the treatment of breast cancer.

Objective To analyze the effects of S100A6 on Wnt/β-catenin signaling pathway and its molecular mechanism. Methods The expression of GST-hS10OA6 was induced with IPTG in Escherichia coli BL21, and the fusion protein was purified with glutathione-sepharose 4B beads. β-catenin level of human colon cancer cell line MG63 and human osteosarcoma cell line HCTl16 cells infected with AdS10OA6 was measured by Western blot. Luciferase activity assay was applied to analyze the effect of S100A6 on the β-catenin/TCF4 activity. The interactions between S100A6 and β-catenin/GSK-3β/Dvl/Axin were detected by GST-pulldown/Western blot. Results The β-catenin level in AdS100A6-infected MG63 and HCT116 cells was significantly increased in comparison with that in the AdGFP control group (P<0.01). The luciferase activity in human embryonic renal cell line 293 cells transfected with pTOP-Luc and followed by GST-hS100A6 treatment was increased by 20. 2-fold in comparison with that in the GST control group (P<0.01). The interaction between GST-hS100A6 and Axin was not found. Conclusion S100A6 up- regulates the Wnt/β-catenin signaling pathway, and this may be attributed to the interaction between S100A6 and β-catenin/GSK-3β/Dvl.

Heart failure (HF),a chronic progressive disease,is a global health problem and the leading cause of deaths in the global population.The pathophysiological abnormalities of HF mainly include abnormal cardiac structure (myocardium and valves),disturbance of electrophysiological activities,and weakened myocardial contractility.In addition to drug therapy and heart transplantation,interventional therapies can be employed for advanced-stage HF,including transcatheter interventions and mechanical circulatory assist devices.This article introduces the devices used for advanced HF that have been marketed or certified as innovative or breakthrough devices around the world and summarizes the research status and prospects the trend in this field.As diversified combinations of HF devices are used for the treatment of advanced HF,considerations regarding individualized HF therapy,risk-benefit evaluation on device design,medical insurance payment,post-market supervision system,and protection of intellectual property rights of high-end technology are needed,which will boost the development of the technology and industry and benefit the patients.
Humans ; Heart-Assist Devices ; Heart Failure/therapy* ; Heart Transplantation ; Myocardium ; Chronic Disease

Hematopoietic stem cells (HSC) are the source of all blood cells, which can differentiate into various hematopoietic hierarchy cells. Physiological level of reactive oxygen species (ROS) plays an important role in regulating functions of HSC as excessive ROS is harmful to HSC. Oxidative reductases and antioxidants can eliminate cellular ROS to maintain ROS homeostasis and thus avoid excessive ROS-caused damages. There are several types of oxidative reductases in cells such as catalase, manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1), thioredoxin reductase 1 (Txrnd1) and Nqo1 [NAD(P)H dehydrogenase quinone 1]. However, the functional roles of various oxidative reductases in regulating ROS level in hematopoietic cells remain unclear. This study was to investigate the expression patterns of these oxidative reductases in mouse hematopoietic cells that were sorted out via flow cytometry and to find out important oxidative reductases involving in HSC ROS regulation. The expression of various oxidative reductases was detected by semi-quantitative real-time PCR. The results showed that the expression level of catalase in T cell population was 0.14 times that in LT-HSC population (P < 0.05). The expression levels of MnSOD in CLP population and myeloid cells were 0.56 and 0.47 times that in LT-HSC population respectively (P < 0.05). The expression levels of GPX1 in ST-HSC, GMP, Myeloid cells, MEP, T lymphocytes and B lymphocytes were 1.79, 2.96, 2.07, 0.58, 0.10, 0.6 times that in LT-HSC population respectively (P < 0.05). The expression levels of Txrnd1 in ST-HSC, MPP, CMP, GMP, Myeloid cells, T lymphocytes and B lymphocytes were 3.36, 3.18, 4.19, 6.39, 4.27, 0.016, 0.56 time that in LT-HSC population, respectively (P < 0.05). The expression levels of Nqo1 in ST-HSC, MPP, CMP, GMP, CLP and B cell were 0.30, 0.17, 0.25, 0.10, 0.04, 0.01 times that in LT-HSC population, respectively (P < 0.05). It is concluded that the expression levels of oxidative reductases (catalase, MnSOD, GPX1, Txrnd1 and Nqo1) in hematopoietic hierarchy cells are cell-type specific. It suggests that reductases may play divergent roles in various hematopoietic cell populations. More importantly, the expression level of Nqo1 in LT-HSC population significantly increased as compared with other cell populations, thereby suggesting its unique regulatory role in HSC.
Animals ; Hematopoietic Stem Cells ; enzymology ; Mice ; Mice, Inbred C57BL ; Myeloid Cells ; enzymology ; Oxidation-Reduction ; Oxidative Stress ; Oxidoreductases ; metabolism ; Reactive Oxygen Species ; metabolism

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.