Objective To investigate the effects of LBL-007, a novel fully human lymphocyte activation gene 3 (LAG-3) monoclonal antibody, in combination with programmed cell death protein 1 (PD-1) antibody, on the invasion, migration and proliferation of tumor cells, and to elucidate the underlying mechanisms. Methods Human lymphocyte cells Jurkat were co-cultured with A549 and MGC803 tumor cell lines and treated with the isotype control antibody human IgG, LBL-007, anti-PD-1 antibody BE0188, or tumor necrosis factor-alpha (TNF-α, the NF-κB signaling pathway agonist). Tumor cell proliferation was assessed using a colony formation assay; invasion was measured by Transwell^TM assay; migration was evaluated using a wound healing assay. Western blotting was employed to determine the expression levels of NF-κB pathway-related proteins: IκB inhibitor kinase alpha (Ikkα), phosphorylated Ikkα (p-IKKα), NF-κB subunit p65, phosphorylated p65 (p-p65), NF-κB Inhibitor Alpha (IκBα), phosphorylated IκBα (p-IκBα), matrix metalloproteinase 9 (MMP9), and MMP2. Results Compared with the control and IgG isotype groups, LBL-007 and BE0188 significantly reduced tumor cell proliferation, invasion, and migration. They also decreased the phosphorylation of p-IKKα, p-p65 and p-IκBα, and the expression of MMP9 and MMP2 of tumor cells in the co-culture system. The combined treatment of LBL-007 and BE0188 enhanced inhibitory effects. Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway.
Humans ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Neoplasm Invasiveness ; Antibodies, Monoclonal/pharmacology* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Cell Line, Tumor ; Antigens, CD/immunology* ; Lymphocyte Activation Gene 3 Protein ; A549 Cells ; I-kappa B Kinase/metabolism* ; Jurkat Cells ; Matrix Metalloproteinase 9/metabolism*

Objective To investigate the role of silencing regulatory protein 1(Sirt1)in the regulation of Vibrio vulnificus sepsis-induced macrophage apoptosis and the molecular mechanisms.Methods Mouse RAW264.7 macrophages which stably overexpressed Sirt1 were constructed and screened by genistein G418.CCK-8 analysis was used to detect the proliferation of cells in the control group and Sirt1-Flag group.The changes of expression levels of apoptosis-associated protein poly ADP-ribose polymerase(PARP),cleaved-PARP,caspase3,cleaved-caspase3 and acetylated p53 in different treatment groups were detected via Western blotting.A Vibrio vulnificus sepsis model in mice was established,and the expression levels of apoptosis-associated protein cleaved-caspase3 in the lung,spleen and liver of mice of different treatment groups were detected by immunohistochemistry.Results Overexpression of Sirt1 reduced VVC-induced RAW264.7 cell damage.Overexpression of Sirt1 as well as RSV pretreatment lowered the expression of apoptosis-associated protein cleaved-PARP,cleaved-caspase3 and acetylated p53 in VVC-stimulated RAW264.7 cells and mouse peritoneal macrophages.In the mouse model of Vibrio vulnificus sepsis,therapeutic administration of RSV reduced the expression of apoptosis-associated protein marker cleaved-caspase3 in lung,spleen and liver tissues.Conclusion Sirt1 can inhibit p53 acetylation and reduces apoptosis in mouse macrophages,which helps protect against Vibrio vulnificus sepsis.

Lymphocyte-activation gene 3(LAG-3)is an inhibitory immune checkpoint receptor that negatively regulates the function of T cells to prevent over-activation of the immune system from damaging human body.In the existence of tumors and chronic infections,persistent antigenic stimulation induces upregulation of LAG-3 expression in effector T cells,leading to T cell exhaustion and tumor immune escape.Targeting LAG-3 drugs can reactivate the anti-tumor function of T cells by specifically blocking the signaling pathway of LAG-3,and have shown promising efficacy in a variety of solid tumors,hematologic tumors and autoimmune diseases.In this paper,we summarize the current research progress on the structure,ligand and regulatory function of LAG-3,review the current status of clinical trials of LAG-3-targeted drugs,and further discuss the clinical application strategy and development direction of LAG-3-targeted drugs,with a view to providing reference for further in-depth research on LAG-3.

As one of the important factors that impact the life of quality to the elderly,visual impairment has become a research highlight in developed countries.And some related results have been found out.It is in the primary stage of establishing the elderly community extending service system in China.Based on this background,literature about the impact of visual impairment on quality of life of the residential setting elderly and related interventions were reviewed.By drawing the experience from developed countries,we aim to innovate perfect interventions,improve the quality of life,avoid unexpected events such as fall and medication mistakes.

This paper points out the experimental animal ethics education in pharmacology teaching and the im-portance of the experiment,it is good to raises the student good humanity accomplishment and scientific research quality, and promote medical research and life ethics of benign interaction.It also expounds the basic content of ex-perimental animal ethics education,including:animal welfare, the 3R principle, AAALAC accreditation and analy-sis of the experimental animal welfare legislation status, raises questions about animal ethics education problems and thinking in the pharmacology experiment teaching in ourschool.The experimental animal ethics education should become an important part of pharmacology experimental teaching, which enhanced the students′s ethical awareness to better understand and respect for life, and contribute to the sustainable development of medical and pharmaceutical research.

Objective To evaluate and compare C5 palsy and closure of the opened lamina after expansive open-door Laminoplasty (EOLP) with miniplate or suture/anchor fixation.Methods Between January 2011 and January 2013,a total of 142 patients with cervical myelopathy who were treated by EOLP were divided into hinge-side fixation group (fixed with suture/anchor,78 cases)and open-side fixation group (fixed with miniplate,64 cases).The Japanese Orthopaedic Association (JOA) score was used for neurological assessment and recovery rate (RR) counting.Opening angles,cervical curvature index (CCI),posterior shifting of spinal cord (PSSC) and severity of cord compression were recorded and compared.Results All patients in both group were followed up for more than 12 months.All incisions healed by first intention.C5 palsy occurred in 9 patients (9/78,11.5％) of hingeside fixation group,and 1 patients (1/64,1.6％) of open-side fixation group,showing significant difference (P=0.047).Opening angles and PSSC in hinge-side fixation group were greater than that in open-side fixation group.PSSC of 10 patients with C5 palsy were 3.97±1.19 mm,and greater than that of other patients without C5 palsy 2.57± 1.01 mm.There was no significant difference in CCI before (12.23％±3.70％,11.38％±4.29％) and 1 week (12.12％±3.77％,11.31％±4.35％) after operation.No significant difference was found in JOA scores (12.35±1.09,13.55±0.91),JOA improvement rate (64.24％±9.49％,61.78％±11.48％) and cord compression (0.74±0.71,0.75±0.67) at 12 months after operation.In 6 months postoperatively,27％ of patients in hinge-side fixation group,none in open-side fixation group were identified with 10％ decrease or more in opening angles of lamina.Conclusion EOLP with miniplate fixation has the same clinical outcome as fixed with suture/anchor,but will reduce the incidence of C5 palsy and prevent further closure of the opened lamina.

OBJECTIVETo investigate the origin of a rare supernumerary chromosome in a patient with premature ovarian failure (POF), and to explore the relationship between this abnormal karyotype and pathogenesis of POF.

METHODSGTG banding karyotyping, Q-banding and fluorescence in situ hybridization (FISH) were employed for the investigation.

RESULTSThe extra chromosome was identified as i(Y)(q10) by FISH with a panel of sex chromosome probes. The patient's karyotype was described as: 47,XX,+ ish mar i(Y)(q10) (DXZ1-, SRY-, DYZ3+, DYZ1++, wcpY+).

CONCLUSIONCo-occurrence of the supernumerary i(Y)(q10) with a female kryotype is extremely rare. This supernumerary chromosome may cause failure of X chromosomes synapsis during pachytene of meiosis I, which may trigger apoptosis of many oocytes and result in POF of the patient. Q-banding, FISH and multiple probes have been critical for accurate diagnosis of the unknown chromosome.

A comprehensive analysis was carried out about the influencing factors of medication safety in the elderly with multiple chronic diseases,who lived in the community and stayed at their own homes.Applicable and simple preventive countermeasures should be established to ensure the medication safety outside medical agency.We should promote extending service of hospitals,cooperate with community and nursing facility in order to increase life quality of the elderly,and supply reference for professional continuous service model including rapid aging,empty nest with advanced age,disability and dementia and elderly people with chronic diseases.

Objective To evaluate the correlating clinical factors of coronary artery calcification score(CACS).Methods 141 patients suspected of coronary artery disease were included.They underwent multi-slice row computed tomography,pulse wave velocity ( PWV ),UCG and blood biochemistry within a period of 3 months.The subjects were divided into three groups according to CAC score:A(CACS =0-10),B ( CACS = 11-400),C ( CACS > 400).Results CACS was significantly associated with age,history of hypertension and diabetes mellitus.It was also associated with the presence of mitral annular calcification and aortic valve calcification,low ankel brachial pressure index(ABI) and high mean artery pressure(MAP) as well as high values of brachial ankel PWV (baPWV) and Upstroke time (UT).Muhifactorial logistic regression analysis showed that the presence of aortic valve calcification and mitral annular calcification,the history of diabetes mellitus and high value of UT were independently correlated with severe coronary artery calcification.Conclusions Aortic valve calcification,mitral annular calcification,history of diabetes mellitus,high value of UT were independently correlated with severe coronary artery calcification.Measurement of PWV and UCG should be performed before muhi-slicerow computed tomography,because the assessment of coronary artery lumen narrowing with multi-slice row computed tomography can not be carried out accurately in the presence of severe coronary artery calcification.

ObjectiveTo analyze hospitalized death related factors in elderly patients with nonST-segment elevation myocardial infarction (NSTEMI). MethodsThree hundred and two patients (≥65 years old) with NSTEMI were included. Thirty-two patients of them died in hospital (death group). Their clinical data were retrospectively analyzed and correlated factors for in-hospital death were evaluated. ResultsCompared with survival group, patients in death group were more likely to have 3 or more chronic diseases,heart function killip grades Ⅲ- Ⅳ, heart rate＞ 100/min and peripheral blood WBC count＞10X 10＜'9＞/L on admission (all P＜:0.05). There was no significant difference in fasting plasma glucose level and serum creatinine on admission between the two groups (both P:＞0.05). But after glomerular filtration rate(eGFR) were estimated by the modified abbreviated MDRD equations based on the Chinese CKD patients, patients in death group were more likely to be with renal dysfunction and pulmonary infection (both P＜0.01 ). Multiple logistic regression analysis showed that heart function killip grades Ⅲ-Ⅳ, renal dysfunction evaluated by eGFR, pulmonary infection on admission were the independent predictors for in-hospital death in elderly patients with NSTEMI. ConclusionsCoexistence of 3 or more chronic diseases is a related factor of death and heart function killip grades Ⅲ-Ⅳ, renal dysfunction evaluated by eGFR and pulmonary infection are the independent predictors for in-hospital death in elderly patients with NSTEMI.