全面实施课程思政教育是贯彻立德树人的重要举措,也是提高人才培养数量和质量的关键途径.基础医学教育阶段是现代医学教育的基石,培育德才兼备的拔尖创新型基础医学人才对于我国人民打好新时代攻坚战有着全局性、战略性的重要意义.我院总结了基础医学拔尖创新人才培养过程中课程思政教育的现状以及存在的问题,基于ADDIE模型挖掘课程思政要素,提高课程思政教学质量,完善课程思政评教程序,构建了基础医学拔尖创新型人才培养过程中的课程思政教育建设方案.该课程思政教学体系实现了集知识传授、能力培养、价值塑造为一体基础医学拔尖创新人才培养目标,具有重要的理论研究意义和实践应用价值.

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.

立德树人一直是我国高等教育发展的核心环节,随着我国基础医学教育水平的不断提升,培养德才兼备、高层次创新型人才已经成为现阶段我国高校基础医学教育的重中之重.基础医学作为一门重要的基础学科,在基础医学的教学过程中进行课程思政建设具有强烈的必要性和迫切性,更是当下基础医学拔尖创新人才培养的重点.目前基础医学课程中开展的课程思政还存在一定的问题,亟需寻找新的教学模式以提高教学质量和效率.ADDIE教学模式作为一种新型教学方式已在教育培训等多个领域取得了明显成果.文章提出基于ADDIE教学模式进行基础医学课程思政的教学改革,将基础医学专业课程与思政教育相互融合,设计开发"专业+思政"双向融合式课程思政教学模式,实践并评估双向融合式课程思政教学效果,最终实现专业教学与思政育人1+1>2的教学目标.

医学生理学是高等医学教育的基础学科,在医学教育的发展中起着重要作用.为了适应当代医学的发展速度,提高教学质量,医学生理学教学模式的改革成为一种趋势与必然.机能学数字人ESP在医学生理学教学中的应用是近年来医学生理学教学改革的一个重要尝试.机能学数字人ESP应用于医学生理学教学中具有传统课堂所无法比拟的趣味性以及灵活性,以其具有的独特优势在生理学教学展现出越来越强的应用价值并带来了实质性的教学进步.但是该系统仍存在一定的缺陷需要认识以及反思,教师应该在教学过程中充分利用其优势,将机能学数字人ESP作为教学的一种补充,而不是完全依赖于该系统.总之,机能学数字人ESP能够提高医学生理学的教学质量,但是目前也存在着一定的问题,应在后续医学发展中进一步完善.

Persistent injury and the following improper repair in bronchial epithelial cells are involved in the pathogenesis of airway inflammation and airway remodeling of asthma. E-cadherin (ECAD) has been shown to be involved in airway epithelium injury repair, but its underlying mechanisms to this process is poorly understood. Here, we describe a previously undetected function of ECAD in regulating the balance of EMT and MET during injury repair. Injury in mice and human bronchial epithelial cells (HBECs) was induced by successive ozone stress for 4 days at 30 min per day. ECAD overexpression in HBECs was induced by stable transfection. EMT features, transforming growth factor beta1 (TGF-β1) secretion, transcriptional repressor Snail expression, and β-catenin expression were assayed. Ozone exposure and then removal successfully induced airway epithelium injury repair during which EMT and MET occurred. The levels of TGF-β1 secretion and Snail expression increased in EMT process and decreased in MET process. While ECAD overexpression repressed EMT features; enhanced MET features; and decreased TGF-β1 secretion, Snail mRNA level, and β-catenin protein expression. Moreover, activating β-catenin blocked the effects of ECAD on EMT, MET and TGF-β1 signaling. Our results demonstrate that ECAD regulates the balance between EMT and MET, by preventing β-catenin to inhibit TGFβ1 and its target genes, and finally facilitates airway epithelia repair.

Lower respiratory tract infection (LRTI) induced by respiratory syncytial virus (RSV) is an important cause of hospitalization for infants. Compared with adults, infants are more likely to cause serious respiratory diseases after RSV infection due to the specific immature airway structure and immune system. The balance of immune resistance and immune tolerance of the host is critical to effective virus clearance and disease control. This paper reviews the relationship between RSV infection and respiratory diseases in infancy, the influence factors of the high pathogenicity of RSV infection in early life, as well as the research progress of anti-RSV therapy, and expands the specific molecular events regulating immune resistance and immune tolerance. We expect to present new ideas for the prevention and treatment of RSV-related respiratory diseases in clinical practice.

“双一流”建设的目标之一就是要培养具有国际视野、具备跨学科知识基础、富有创新精神和实践能力的创新型人才.基础医学研究是研究人类疾病的本质和规律的医学学科,它是针对临床问题而开展的前瞻性和独创性的研究工作.该文针对“双一流”建设背景下基础医学研究生在创新型人才培养过程的问题,分析影响基础医学研究生创新能力的因素,最后结合“双一流”的发展战略,从制定培养方案、建设师资队伍、优化课程设置、建立创新培养新平台等方面阐述“双一流”建设背景下提高基础医学研究生创新能力的培养策略.

To prepare anti-mouse uteroglobin binding protein (mUGBP) polyclonal antibody, two polypeptides were synthesized based on the bioinformatics analysis of mUGBP, and New Zealand white rabbits were immunized separately with each peptide coupled with keyhole limpet hemocyanin (KLH). The data indicate that a 13-amino acid polypeptide (positions 221st-233rd) was able to generate anti-peptide antibodies. The titer of the antisera detected with ELISA was 1:10(8). The antisera were then purified with immuno-affinity chromatography to obtain antibodies. Western blot analysis of mUGBP expressed as a fusion protein with a green fluorescent protein (GFP) was performed on the cell lysates of COS-1 cells with the purified antisera, suggesting that the antisera specifically recognized UGBP. By immunohistochemistry and indirect immunofluorescence analysis, we examined the expression of UGBP in the lung tissues from a patient undergoing surgical lung resection for a tumor and from normal mouse lung tissue, and found for the first time that UGBP protein was widely expressed in both mouse and human lung tissue with the most abundant expression in bronchial epithelial cells. These results suggest that the antigen epitopes of mUGBP are well predicted by using bioinformatics analysis. We have obtained anti-mUGBP polyclonal antibody, which will be useful for further investigation.

在生物学、微生物学、免疫学、化学血液学、生物物理学、细胞学、病理学等医学实验中,生物安全是一个十分重要的问题。实验室生物安全是保护被实验因子免受污染、保证实验研究可信性与科学性的必要条件。因此,生物安全建设已成为医学实验室发展不可缺少的环节。现针对医学实验室生物安全防护管理,进行初步研究和探讨。

目的 观察LPS诱导急性肺损伤时肺内是否存在谷氨酸(Glu)的释放.方法 腹腔注射内毒素制备小鼠急性肺损伤模型,于6h后采用生理盐水行支气管肺泡灌洗,用高效液相色谱法测量灌洗液中氨基酸的浓度.结果 与生理盐水对照组相比,LPS处理组支气管肺泡灌洗液中Glu的浓度增高(P<0.01);苏氨酸、蛋氨酸及精氨酸的浓度降低(P<0.05),其它氨基酸浓度无显著性变化.结论 在LPS诱导的肺损伤过程中肺组织中部分氨基酸代谢发生显著变化,肺内谷氨酸的释放增多,进一步提示Glu参与了内毒素诱导的肺损伤的病理生理过程.

Aim To investigate the potential role of desipramine(DP) on lipoplysaccharide(LPS)-induced acute lung injury(ALI)and the mechanism of its action. Methods Kunming mice were divided into four groups randomly: NS group (NS),DP control group (DP),LPS group(LPS)and DP treatment group(DP+LPS). The model of ALI in mice was induced by lipop-lysaccharidel(LPS,10 mg·kg-1,ip). Six hours after LPS challenged,the lung samples were taken for determination of lung wet-to-dry weight ratio( W/D),my-eloperoxidase ( MPO ) activity,and malondialdehyde ( MDA ) content. The bronchoalveolar lavage fluid (BALF) samples were analyzed for total protein concentrateion and white blood cell(WBC)count. The lev-els of tumor necrosis factor-α ( TNF-α) in lung were measured by ELISA. Results LPS could significantly increase the total protein concentration and WBC number in BALF. The lung W/D ration,MPO activity,MDA content and the levels of TNF-α in lungs all increased after ip injection of LPS. Pretreatment with DP decreased all the changes induced by the LPS. Conclusion Pretreatment with DP protects lung from LPS-induced lung injury in mice,which is,at least in part, through inhibiting the level of TNF-α and decreasing the sequestration of neutrophils and lipid peroxidation.

L-glutamate (Glu) is an excitatory neurotransmitter in the mammalian central nervous system. Relatively much attention has been paid to functional expression of Glu signaling molecules in peripheral tissues very recently. The present study tested the hypothesis that the activation of group I metabotropic glutamate receptor (mGluRI) in neutrophils stimulated neutrophils adherence to endothelial cells by increasing the surface expression of certain adhesion molecules. Peripheral blood was obtained by venipuncture from healthy donors, and the neutrophils were isolated by Ficoll-Hypaque gradient centrifugation. Neutrophils floating into DMEM/F12 culture medium containing 10% fetal bovine serum were then used immediately. Immunocytochemistry and real-time quantitative RT-PCR were used to detect the expression of mGluRI (mGluR1 and mGluR5) in neutrophils. The adherence of neutrophils to cultured human normal umbilical vein endothelial cells (HUVE-12) was measured by the colorimetric method. Cell surface expression of adhesion molecule CD11a in the neutrophils was determined by flow cytometry. Immunocytochemistry and real-time quantitative RT-PCR showed that mGluR1 and mGluR5 were constitutively expressed in neutrophils. Application of mGluRI agonist S-3,5-dihydroxyphenylglycine (S-DHPG) (1x10(-8)-1x10(-6) mol/L) showed a dose-dependent stimulatory effect on the adherence of neutrophils to HUVE-12 (P<0.05 or P<0.01), with a maximum effect at 1x10(-6) mol/L (P<0.01). Incubations as short as 30 min were sufficient to induce increased adherence after the beginning of S-DHPG treatment. Following time extension (0.5-5 h), S-DHPG (1x10(-6) mol/L) increased the rate of neutrophils adhesion to HUVE-12 with a maximum effect at 0.5 h (P<0.01). However, a time-dependent effect of S-DHPG on the rate of neutrophils adhesion to HUVE-12 was not observed during the experimental period. 1x10(-6) mol/L of S-DHPG also induced an increased surface expression of adhesion molecule CD11a (P<0.01) when neutrophils were preincubated with 1x10(-6) mol/L of S-DHPG for 1 h. Furthermore, the specific mGluRI antagonist (RS)-alpha-methyl-4-carboxyphenylglycine ((+/-)-MCPG, 0.5 mmol/L) significantly abolished the stimulatory effect of S-DHPG (1x10(-6) mol/L) on the adherence of neutrophils to HUVE-12 (P<0.01). These results suggest that the activation of mGluRI in neutrophils results in increased adhesion molecule CD11a expression and thereby promotes the adherence of neutrophils to endothelial cells.

Objective To determine the protective effect of Ginkgo biloba extract (Ginaton) on acute lung injury induced by lipopolysaccharide (LPS) and its protective mechnism in mice.Methods The Kunming mice were randomly allocated into sham,LPS,Ginaton,and Ginaton+LPS groups.LPS was intraperitoneally injected at a dose of 10 mg/kg body weight in the LPS group,along with equal volumes of saline in the sham group.Ginaton+LPS group and Ginaton group were treated with Ginaton (100 mg/kg,intraperitoneally) 2 h prior to the injection of LPS or saline,respectively.The mice were killed 8 h after LPS challenge The bronchoalveolar lavage fluid (BALF) samples were analyzed for the concentration of total protein,lactate dehydrogenase (LDH) activity.The lung samples were taken for histologic evaluation and for determination of wet-to-dry (W/D) lung weight,malondialdehyde (MDA) level,myeloperoxidase (MPO) activity,nitric oxide (NO) level,and inducible nitric oxide synthase (iNOS) activity,as well as immunohistochemistry analysis for iNOS and heme oxygenase-1 (HO-1) protein expression.Results All the indexes except HO-1 in the ginaton group were not significantly different to those in the control group.But lung tissue and BALF showed serious inflammatory changes in the LPS group.Compared with the LPS group,in addition to inflammatory reaction,the changes of protein content and LDH in BALF and W/D,level of MDA and NO,activity of MPO and iNOS in lung tissues were significantly reduced in the Ginaton+LPS group.(P0.05 or P0.01).The expression ofiNOS protein in lung tissues was obvious higher in the LPS group than that of the Ginaton+LPS group (P0.01);however expression of HO-1 in the Ginoton + LPS group was significantly higher than that of the Ginoton group.Conclusion Ginaton can play a protective role against LPS-induced acute lung injury and it may be associated with the up-regulation of HO-1 and the down-regulation ofiNOS expression and activity.

Standardization management is the trend of medical laboratory development.Laboratory Bio-safety(LBS) construction has become an imperative part of laboratory advancement.LBS is a series of approaches to ensure the scientific of experimental research and to protect the laboratory factors from pollution associated with laboratory pathogens contamination.It is necessary to guide our medical graduates performing experiments according to laboratory bio-safety rules.In this paper,we discussed what should be trained and how to train the medical graduates just before the beginning of their research work.

High-density lipoprotein (HDL), an abundant plasma lipoprotein, has been thought to be anti-inflammatory in both health and infectious diseases. It binds lipopolysaccharide (LPS) and neutralizes its bioactivity. The present study aimed to investigate the potential role of HDL, which was separated from human plasma, in LPS-induced acute lung injury in mice. Kunming mice (18-22 g) were treated with either HDL (70 mg/kg body weight, via tail vein) or saline 30 min after LPS administration (10 mg/kg body weight, intraperitoneally) and were decapitated 6 h after LPS challenge. The arterial blood was collected and analyzed for blood gas variables (PaO(2), pH, and PaCO(2)). The bronchoalveolar lavage fluid (BALF) samples were analyzed for total protein concentration, lactate dehydrogenase (LDH) activity, and white blood cell (WBC) count. The lung samples were taken for histopathological evaluation and for determination of lung wet-to-dry weight ratio (W/D), malondialdehyde (MDA) content, myeloperoxidase (MPO) activity and tumor necrosis factor α (TNF-α) content. Arterial blood gas analysis showed that after LPS challenge, HDL-treated mice exhibited a higher PaO(2), and pH, but a lower PaCO(2) than HDL-untreated ones (P<0.01). LPS-induced increases in total protein concentration, WBC number and LDH activity in BALF were significantly attenuated in HDL-treated mice (P<0.01). HDL treatment also resulted in a significant protection of lung tissues against LPS-induced acute lung injury via decreasing W/D ratio, MPO activity, MDA content, and the content of the pro-inflammatory cytokine TNF-α (P<0.05, P<0.01). Histological examination revealed that HDL treatment resulted in significantly lower scores of acute lung injury induced by LPS, with reduced hemorrhage, intra-alveolar edema and neutrophilic infiltration (P<0.01). It is suggested that HDL plays a protective role in attenuating LPS-induced acute lung injury in mice.

Antigen presenting is the initial step of the immune responses. In order to verify that human bronchial epithelial cells (HBECs) can express antigen presentation molecules, which can be modulated by intrapulmonary regulatory peptides, the present study was designed to examine the expressions of human leukocyte antigen DR (HLA-DR), CD80 and CD86 in resting or ozone-stressed HBECs by using immunocytochemistry and flow cytometry analysis. The results showed that HBECs expressed HLA-DR, CD80 and the expressions of HLA-DR and CD80 molecules were down-regulated under ozone stress. While VIP, P3513 and CGRP upregulated the expression of HLA-DR in resting or ozone-stressed HBECs, they had different effects on CD80 expression. VIP did not influence the expression of CD80 under resting state, but increased the expression of CD80 under ozone stress. CGRP decreased CD80 expression in resting HBECs, but increased CD80 expression in ozone-stressed HBECs. P3513 increased CD80 expression in resting HBECs, but decreased CD80 expression in ozone-stressed HBECs. The expression of CD86 was absent in resting or ozone-stressed HBECs. The results obtained demonstrate that HBECs have the capability to act as antigen presenting cells and the expression of HLA-DR and costimulatory molecules can be modulated by intrapulmonary regulatory peptides.

OBJECTIVE:To examine the expression of matrix metalloproteinase-9 (MMP-9) in human bronchial epithelial cells treated with calcitonin-gene-related peptide (CGRP).METHODS:RT-PCR and gelatin zymography were performed to examine the dynamic expression and activity of MMP-9 in human bronchial epithelial cells at different doses (10(-10), 10(-9), 10(-8), 10(-7), and 10(-6)mol/L) and different time points (6,12,18,24,36, and 48h) after the stimulation of CGRP.RESULTS:The unstimulated human bronchial epithelial cells only secreted a small amount of MMP-9. After the CGRP stimulation, the expression of MMP-9 presented in a concentration-dependent (10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L) and time-dependent (6,12,18,24,36, and 48 h) manners (P<0.01) in human bronchial epithelial cells. The effect of CGRP could be diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (P<0.05).CONCLUSION:CGRP can stimulate the secretion and expression of MMP-9 in human bronchial epithelial cells, and the signal transduction is partly via the PKC and CaM pathway.

AIM To explore the effects of calcitonin-gene-related peptide (CGRP) on LPS-induced MMP-9 secretion by alveolar macrophages (AM) in vitro. METHODS The supernatant of LPS-induced Wistar rat AM from different intervention groups were collected to measure the activity by gelatin zymography. RESULTS (Only secreting a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in a concentration-dependent manner (p < 0.01). (2) The activity of MMP-9 in CGRP intervention groups at different levels were significantly lower than those in non-intervention group (p < 0.01). (3) The inhibiting effects of CGRP were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (p < 0.05). CONCLUSION These data suggested that CGRP involved in the MMP-9 secretion by AM, partly, via PKC and CaM pathway.