Glioma is a prevalent form of primary malignant central nervous system tumor, characterized by its cellular invasiveness, rapid growth, and the presence of the blood-brain barrier (BBB)/blood-brain tumor barrier (BBTB). Current therapeutic approaches, such as chemotherapy and radiotherapy, have shown limited efficacy in achieving significant antitumor effects. Therefore, there is an urgent demand for new treatments. Therapeutic peptides represent an innovative class of pharmaceutical agents with lower immunogenicity and toxicity. They are easily modifiable via chemical means and possess deep tissue penetration capabilities which reduce side effects and drug resistance. These unique pharmacokinetic characteristics make peptides a rapidly growing class of new therapeutics that have demonstrated significant progress in glioma treatment. This review outlines the efforts and accomplishments in peptide-based therapeutic strategies for glioma. These therapeutic peptides can be classified into four types based on their anti-tumor function: tumor-homing peptides, inhibitor/antagonist peptides targeting cell surface receptors, interference peptides, and peptide vaccines. Furthermore, we briefly summarize the results from clinical trials of therapeutic peptides in glioma, which shows that peptide-based therapeutic strategies exhibit great potential as multifunctional players in glioma therapy.

Diabetic nephropathy is one of the most important chronic microvascular complications of diabetes, and its main feature is diabetic glomerulosclerosis. Endothelial sirtuin 1 (SIRT1) expression is related to aging, and reducing SIRT1 expression promotes endothelial cell aging. Plasminogen activator inhibitor-1 (PAI-1) can be synthesized in a variety of cells, such as endothelial cells. Dulaglutide is a glucagon-like peptide-1 (GLP-1) drug, and it can activate the GLP-1 receptor and promote the conversion of intracellular adenosine triphosphate to adenylate cyclase, thereby activating phosphokinase A, and regulating blood glucose levels effectively in the body. We analyzed the effects of Dulaglutide on inhibiting cell senescence by studying the effects of its different concentrations on telomerase activity and senescence-related gene expression. Our results suggest that Dulaglutide can alleviate high-glucose-induced oxidative stress in human retinal endothelial cells by restoring the expressions of SIRT1 and endothelial nitric oxide synthase (eNOS), thereby inhibiting the expression of PAI-1, and restoring telomerase activity. This suggests that the activity of retinal endothelial cells can be controlled by regulating the expression of SIRT1, so as to achieve the effect of treating diabetic retinopathy.

目的 探讨混合式教学在培养农村订单定向医学生"医学遗传学"课程中的应用效果.方法 研究时间为2021年2月至7月,依据随机数字表法将西安医学院2019级139名农村订单定向医学生分为混合式教学组(70名)和对照组(69名).对照组采用传统讲授法,混合式教学组采用案例教学、微课等多种教学方法.两组均采用考试成绩分析结合调查问卷的方法进行教学效果评价.结果 混合式教学组期中考试成绩、期末成绩和考试总成绩均高于对照组,差异有统计学意义(P<0.05).调查问卷结果显示,混合式教学组医患沟通能力,综合分析问题的能力、临床思维3个方面均优于对照组,差异有统计学意义(P<0.05).结论 混合式教学提升教学质量,增强了农村订单定向医学生岗位适应力,为进一步优化农村订单定向医学生培养模式提供参考.

创新教材建设,并与翻转课堂、线上线下混合式教学等新型教学模式相结合,使教学资源优质化,教学内容和形式多样化.目标和宗旨是将教学关注点由教师转向学生,提高学生自主学习能力,激发学习主动性,加强师生之间的交流与互动.

目的:探讨环状RNA 0000285(circ_0000285)是否靶向miR-127-5p调控阿尔茨海默病(AD)细胞模型损伤.方法:采用β淀粉样蛋白25-35多肽片段(Aβ25-35)诱导神经细胞瘤细胞SK-N-SH建立AD体外细胞模型.采用实时定量PCR(RT-qPCR)测定circ_0000285和miR-127-5p表达水平.试剂盒测定丙二醛(MDA)含量以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性.流式细胞术分析细胞凋亡,Western blot检测B细胞淋巴瘤(Bcl-2)和Bcl相关x蛋白(Bax)蛋白表达水平.采用上述方法测定干扰circ_0000285表达或过表达miR-127-5p对AD模型细胞凋亡、损伤的影响.双荧光素酶报告实验和RT-qPCR用于验证circ_0000285对miR-127-5p的靶向调控作用.结果:Aβ25-35处理显著上调circ_0000285表达及Bax蛋白水平,下调miR-127-5p及Bcl-2蛋白表达水平,增加MDA含量,降低SOD和GSH-Px活性,并提高细胞凋亡率.干扰circ_0000285表达或过表达miR-127-5p可显著下调Bax蛋白水平,上调Bcl-2蛋白表达水平,降低MDA含量,增加SOD和GSH-Px活性,并降低细胞凋亡率.circ_0000285靶向负调控miR-127-5p表达.抑制miR-127-5p表达显著减弱了干扰circ_0000285表达对模型细胞凋亡、损伤的影响.结论:干扰circ_0000285表达可通过靶向miR-127-5p减弱Aβ25-35诱导的SK-N-SH细胞损伤.因此,circ_0000285/miR-127-5p途径可能是AD的潜在治疗靶点.

《高等学校课程思政建设指导纲要》为"课程思政"的设计提供了依据和引领.近年来,本校医学遗传学教学团队深入挖掘医学遗传学课程中蕴含的思想政治教育资源,将价值塑造、知识传授和能力培养三者有机结合,开展了医学遗传学"课程思政"教学改革实践.本文根据医学遗传学的学科特点,探索了医学遗传学"课程思政"的育人目标及实施途径,采用教师评价和学生自我评价两者结合评估课程育人的成效,为相关课程"课程思政"建设提供了经验和参考.

亨廷顿舞蹈症(Huntington’s disease，HD)是一种罕见的神经退行性疾病，遗传方式为常染色体显性遗传。主要临床症状：不自主性舞蹈样动作、精神障碍和进行性认知障碍。主要发病机制：Huntingtin基因第一外显子，串联重复三核苷酸CAG的拷贝数异常增多，产生氨基端富含异常增多的谷氨酰胺的Huntingtin蛋白（mHtt），从而导致纹状体神经元发生选择性变性坏死。mHtt蛋白极易降解，进而聚集形成毒性的寡聚体。毒性蛋白可通过破坏线粒体膜电位，抑制氧化还原酶基因表达，最终导致氧化应激发生。近年来，靶向氧化损伤治疗成为缓解HD症状的新策略。此综述旨在对HD中氧化应激的发生机制及抗氧化治疗新进展进行归纳和总结，为临床治疗HD等多种神经退行性疾病提供依据。

目的 研究依那普利联合氢氯噻嗪治疗小儿急性肾小球肾炎(AGN)疗效及对血清白细胞介素18(IL-18)和血清可溶性自杀相关因子/可溶性配体(sFas/sFasL)的影响.方法 采用前瞻性随机对照试验,选取2017年4月-2019年4月于三家医院接受治疗的102例小儿AGN患者为受试对象,随机分为对照组(n=50)和观察组(n=52).两组均给予基础治疗,对照组给予加用氢氯噻嗪,观察组加用依那普利联合氢氯噻嗪,连续治疗14d,比较两组临床疗效、肾功能[血肌酐(SCr)、血尿素氮(BUN)、胱抑素C(CysC)、24h蛋白尿定量(24hU-pro)]、炎性因子[白细胞介素-6(IL-6)、IL-18、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子-α(TNF-α)]及细胞凋亡因子(sFas、sFasL)水平变化,并记录其不良反应发生情况.结果 观察组及对照组临床有效率分别为96.15％和84.00％,差异具有统计学意义(P<0.05);治疗后,两组患者SCr、BUN、CysC、24hU-pro、IL-6、IL-18、GM-CSF、TNF-α、sFas、sFasL水平较治疗前均存在显著下降的趋势(P<0.05),且组间比较差异明显(P<0.05);两组患者不良反应发生率均无统计学意义(P均>0.05).结论 依那普利联合氢氯噻嗪治疗小儿AGN疗效显著,其作用机制可能与改善肾功能、降低炎性因子及sFas、sFasL水平有关.

Diabetic retinopathy(DR),one of the common complications of diabetes,is the leading cause of visual loss in working-age individuals in many industrialized countries.It has been traditionally regarded as a purely microvascular disease in the retina.However,an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the retina.Deterioration of neural retina could precede microvascular abnormalities in the DR,leading to microvascular changes.Furthermore,disruption of interactions among neurons,vascular cells,glia and local immune cells,which collectively form the neurovascular unit,is considered to be associated with the progression of DR early on in the disease.Therefore,it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration,neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage DR.Here,we present current perspectives on the pathophysiology of DR as a neurovascular disease,especially at the early stage.Potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.

Nogo proteins, also known as Reticulon-4, have been identified as myelin-derived inhibitors of neurite outgrowth in the central nervous system (CNS). There are three Nogo variants, Nogo-A, Nogo-B and Nogo-C. Recent studies have shown that Nogo-A/B is abundant in macrophages and may have a wider effect on inflammation. In this review, we focus mainly on the possible roles of Nogo-A/B on polarization and recruitment of macrophages and their involvement in a variety of inflammatory diseases. We then discuss the Nogo receptor1 (NgR1), a common receptor for Nogo proteins that is also abundant in microglia/macrophage in the CNS. Interaction of Nogo and NgR1 in microglia/macrophage may affect the adhesion and polarization of macrophages that are involved in multiple neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Overall, this review provides insights into the roles of Nogo proteins in regulating macrophage functions and suggests that, potentially, Nogo proteins maybe a new target in the treatment of inflammatory diseases.

AIM: To study the histological and ultrastructural changes of mouse retina after exposure to e-cigarette and the potential mechanism.METHODS: Totally 18 male c57BL mice aged 8-week-old were divided into control group(n=6), 0mg nicotine group(n=6)and 12mg nicotine group(n=6). The histological and ultrastructural changes of retina were evaluated by hematoxylin and eosin(HE)staining and transmission electron microscope(TEM), respectively. Additionally, the expression of Tuj1 and 8-OHdG was examined using immunofluorescent staining. RESULTS: In comparison with control group, the thickness of whole retina, nerve fiber layer(NFL)and inner plexiform layer(IPL)was significantly decreased in experimental groups(0mg and 12mg nicotine group)(P&amp;amp;lt;0.01), but no significant difference was observed between 0mg and 12mg nicotine group(P&amp;amp;gt;0.05). The dramatically reduced microvilli of RPE cells were also observed in experimental groups using TEM. Furthermore, residual microvilli were shortened. The expression of Tuj1 was decreased in ganglion cell layer(GCL), NFL and IPL, but no significant changes in the number of retinal ganglion cells were shown among three groups(P&amp;amp;gt;0.05). In addition, the increased expression of 8-OHdG was observed in GCL and inner nuclear layer(INL)in experimental groups.CONCLUSION: E-cigarette can lead to the retinal damages in mice, which might be due to oxidative stress.

Cancer is a key cause of death worldwide. Despite the development of radiotherapy, chemotherapy and even immunotherapy, surgery remains the standard treatment for cancer patients. Recently, many studies have shown that propofol, a commonly used anesthetic drug, can affect the prognosis of cancer. In this review, we provide an overview of the molecular mechanisms of propofol in the development of cancer. Propofol not only affects epigenetic pathways, such as those involving miRNA, lncRNA and histone acetylation, but also modulates genetic signaling pathways, including the hypoxia, NF-κB, MAPK, SLUG and Nrf2 pathways. In addition, propofol influences the immune function of patients and impacts the degree of immunosuppression. Furthermore, we briefly summarize the clinical trials on the effect of propofol in cancer development. Ultimately, further studies distinguishing the types of tumors in clinical trials are needed to clarify the correlation between propofol and cancer.

Jellyfish, such as Chrysaora quinquecirrha, hold an important evolutionary position and have great ecological value. However, limited genomic resources are currently available for studying their basic genetic and development processes. Here, we de novo assembled the first high-quality reference genome of C. quinquecirrha, and successfully annotated 21,606 protein-coding genes. Codon usage analysis identified the frequent use of low-GC-content codons during protein-coding gene translation. Analysis of the relative evolution rate indicated that jellyfish had a faster evolution rate than sea anemones but slower rate than the species in Hydra. Phylogenetic analysis with two other species of jellyfish indicated that Aurelia aurita and Nemopilema nomurai have a closer relationship with each other than with C. quinquecirrha, with divergence from their common ancestor occurring ≈475.7 million years ago. Our study not only showed the genomic characteristics and molecular adaptive evolution of C. quinquecirrha, but also provides valuable genomic resources for further study on complex developmental processes and environmental adaptations.

Stress-induced premature senescence (SIPS) is characterized by the secretion of a variety of inflammatory cytokines, chemokines, and proteases, which are defined collectively as the senescence-associated secretory phenotype (SASP). AMP-activated protein kinase (AMPK) activation contributes to SIPS prevention, and the impact of AMPK on SASP may be included, but the mechanisms governing this phenomenon have not elucidated. In this study, we showed that SIPS is accompanied by a dynamic fluctuation of NF-κB activation, which induces SASP production, whilst reinforcing and amplifying local STAT3 signalling and subsequently enhancing downstream senescence. NF-κB and STAT3 inhibitors attenuate oxidative stress-induced senescence in a time-dependent manner. Conditioned medium (CM) from senescent cells rich in SASP factors can induce growth arrest and promote senescence in healthy cells; accordingly, a STAT3 inhibitor blunts the SASP-induced senescence, indicating a positive feedback mechanism via the NF-κB/STAT3 pathway that sustains SASP production and promotes senescence. In addition, we confirmed that AMPK negatively regulates SASP production and senescence development associated with NF-κB/STAT3 inhibition. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence development via inhibiting the NF-κB/SASP/STAT3 signalling mediated positive feedback loop.

目的 探讨尼莫地平对大鼠星形胶质细胞(Ast)β淀粉样蛋白(Aβ)转运功能的影响及可能机制.方法 利用Transwell装置共培养大鼠脑微血管内皮细胞与大鼠Ast建立体外血脑屏障模型,并分为Ast组(给予0μmol/L尼莫地平)、低浓度尼莫地平+Ast组(给予5μmol/L尼莫地平)、中浓度尼莫地平+Ast组(给予10μmol/L尼莫地平)、高浓度尼莫地平+Ast组(给予20μmol/L尼莫地平).给予相应干预48 h后,检测跨膜电阻及荧光素-葡聚糖4000(FD4)通透性以评价血脑屏障完整性,观察Aβ跨血脑屏障由脑侧向血管侧的转运情况,检测蛋白磷酸酶2A(PP2A)活性,以及低密度脂蛋白受体相关蛋白1(LRP-1)、晚期糖基化终产物受体(RAGE)、磷酸化Tau(p-Tau)蛋白、PP2A、成对免疫球蛋白样受体B(PirB)、糖原合酶激酶3β(GSK3β)蛋白表达水平.结果 4组细胞的跨膜电阻、FD4通透性差异无统计学意义(P>0.05).Ast组、低浓度尼莫地平+Ast组、中浓度尼莫地平+Ast组、高浓度尼莫地平+Ast组Aβ跨血脑屏障由脑侧向血管侧转运量依次增多,Ast中LRP-1蛋白表达、PP2A活性及蛋白表达依次升高,RAGE、p-Tau、PirB、GSK3β蛋白表达依次降低(均P<0.05).结论 尼莫地平可促进大鼠Ast中Aβ的外向转运,减少Tau蛋白磷酸化,这可能其与下调RAGE、PirB、GSK3β蛋白表达,上调LRP-1、PP2 A蛋白表达有关.

With the completion of the human genome project and the advancement of sequencing technology, the ethical issues involved in medical genetics have become increasingly prominent. This requires the integration of ethical and other ideological elements into classroom teaching of medical genetics, and cultivation of the ethical qualities of medical undergraduates. This paper systematically discusses the reform of medical genetics curriculum focusing on ethical issues from the aspects of syllabus construction, ethical issues, and classroom practice and effect. Strengthening the ethical literacy of medical undergraduates is an inevitable trend in the development of medical genetics, and it is a realistic need for comprehensive education. Besides, the teaching reform based on the ethical problems, is also possible to improve the curriculum construction as a pilot project with a step-by-step remodeling strategy, and comprehensively promote the reformation of education of medical genetics.

Astrocytes are the largest group of glial cells in the brain and participate in several essential functions of the central nervous system (CNS). Disruption of their normal physiological function can lead to metabolism disequilibrium and the pathology of CNS. As an important mechanism of aging, cellular senescence has been considered as a primary inducing factor of age-associated neurodegenerative disorders. Senescent astrocytes showed decreased normal physiological function and increased secretion of senescence-associated secretory phenotype (SASP) factors, which contribute to Aβ accumulation, tau hyperphosphorylation, and the deposition of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD). Astrocyte senescence also leads to a number of detrimental effects, including induced glutamate excitotoxicity, impaired synaptic plasticity, neural stem cell loss, and blood-brain barrier (BBB) dysfunction. In this review article, we have summarized the growing findings regarding astrocyte senescence and its putative role in the pathologic progress of AD. Additionally, we also focus on the significance of targeting astrocyte senescence as a novel and feasible therapeutic approach for AD.

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by brain function disorder and chronic cognitive function impairment. The onset of AD is complex and is mostly attributed to interactions between genetic factors and environmental factors. Lifestyle, dietary habits, and food consumption are likely to play indispensable functions in aged-related neurodegenerative diseases in elderly people. An increasing number of epidemiological studies have linked dietary fatty acid factors to AD, raising the point of view that fatty acid metabolism plays an important role in AD initiation and progression as well as in other central nervous system disorders. In this paper, we review the effects of the consumption of various dietary fatty acids on AD onset and progression and discuss the detrimental and beneficial effects of some typical fatty acids derived from dietary patterns on the pathology of AD. We outline these recent advances, and we recommend that healthy dietary lifestyles may contribute to preventing the occurrence and decreasing the pathology of AD.

Temozolomide (TMZ) is the first-line chemotherapy drug that has been used to treat glioma for over a decade, but the benefits are limited by half of the treated patients who acquired resistance. Studies have shown that glioma TMZ resistance is a complex process with multiple factors, which has not been fully elucidated. Ferroptosis, which is a new type of cell death discovered in recent years, has been reported to play an important role in tumor drug resistance. The present study reviews the relationship between ferroptosis and glioma TMZ resistance, and highlights the role of ferroptosis in glioma TMZ resistance. Finally, the investigators discussed the future orientation for ferroptosis in glioma TMZ resistance, in order to promote the clinical use of ferroptosis induction in glioma treatment.

该文介绍了具有口腔黏膜表面麻醉的单味中药主要有檐酥、草乌、细辛、九里香、两面针、胡椒、菊三七、丁香油酚、薄荷脑和花椒等,其有效成份分别是蟾蜍灵、古柯碱、丁香油酚、乌头碱、次乌头碱等,可选择性的作用于感觉神经末梢产生表面麻醉作用.同时回顾和分析了不同的中药复方表面麻醉剂分别用于口腔溃疡、黏膜炎性疼痛、拔牙、牙槽脓肿切开、口腔表浅手术及扁桃体切除术等临床应用效果.