Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in septic patients and is associated with high mortality and progression to chronic kidney disease (CKD). Previous studies have demonstrated that thymosin β4 (Tβ4) attenuates lipopolysaccharide (LPS)-induced liver injury and ischemic AKI via inhibiting inflammatory response. Here, we aimed to investigate the effects of Tβ4 on SA-AKI and elucidate its underlying mechanisms.Methods: In vivo and in vitro models of SA-AKI were established using LPS. Tβ4 was administered 30 min after LPS exposure. Transcriptome sequencing was performed to explore the underlying molecular mechanisms, which were further validated by western blotting in vitro. Results: In LPS-induced SA-AKI mice, serum Tβ4 levels were decreased markedly. After administering Tβ4, the renal dysfunction and morphologic damage were significantly mitigated in LPS-treated mice. Consistently, Tβ4 ameliorated renal inflammation and apoptosis in SA-AKI mice. Transcriptome-sequencing analysis indicated that MAPK signaling pathway was involved in both SA-AKI pathogenesis and the protective effect of Tβ4. Western blotting of the renal tissues confirmed that LPS remarkably increased the phosphorylation of JNK1/2, p38 MAPK and ERK1/2, while Tβ4 significantly suppressed their activation. Furthermore, pharmacological activation of the MAPK pathway with anisomycin abrogated the inhibitory effects of Tβ4 on MAPK signaling in an in vitro SA-AKI model.Conclusion: Tβ4 alleviate renal inflammation and apoptosis in SA-AKI by suppressing MAPK signaling pathway. Tβ4 has therapeutic potential as an early intervention strategy for SA-AKI.

AIMS:To investigate the role of the habenula (Hb)-centered brain network in regulating the cardiac autonomic nervous system (ANS) in subthreshold depression (StD), and to explore the brain-heart axis mechanisms underlying the antidepressant effects of heart rate variability biofeedback (HRV-BF) as a non-pharmacological intervention. METHODS:Thirty four StD participants and 32 healthy controls (HC) completed scale assessments (HAMD-17, PHQ-9, and PSQI) and cardiovascular measurements. StD participants received a 4-week HRV-BF with pre- and post-rs-BOLD fMRI. Bilateral Hb was used as the seed for ROI- and voxel-wise functional connectivity (FC) analyses. To minimize potential confounding effects of sex imbalance, only female participants were included in voxel-wise FC analysis (StD group, n = 8; HC group, n = 11) and pre-post intervention comparisons in ROI-wise FC analysis(StD group, n = 8). RESULTS:StD participants exhibited elevated heart rate, reduced HRV indices (lnRMSSD, HF power, lnSDNN), and increased LF power. ROI-wise FC analysis revealed that with increasing depression scores, z-transformed functional connectivity (zFC) value between the Hb and the nucleus accumbens (NAc), ventral pallidum (VeP), amygdala, globus pallidus internus (GPi), and substantia nigra (SN) shifted from positive to negative, indicating a transition from functional connectivity coupling to anti-coupling. Among these, Hb-NAc and Hb-VeP showed high discriminatory power (AUC = 0.876, p < 0.001). Voxel-wise FC analysis demonstrated weakened Hb functional connectivity with several key regions within the default mode network, salience network, central executive network, visual network, and sensorimotor network, including precuneus, right posterior cingulate cortex, left middle cingulate cortex, right superior parietal lobule, cuneus, right calcarine cortex, left superior occipital gyrus, right paracentral lobule, and right postcentral gyrus. A 4-week HRV-BF intervention improved HRV indices and partially restored the functional connectivity of Hb-centered networks, accompanied by significant improvements in depressive symptoms and sleep quality. CONCLUSION:Aberrant Hb-centered functional connectivity may contribute to cardiac autonomic dysfunction in StD. Specifically, Hb-NAc and Hb-VeP functional connectivity may serve as neuroimaging biomarkers for StD. HRV-BF enhances vagal tone, rebalances cardiac ANS function, and partly restores Hb-centered brain network functional connectivity, thereby alleviating depressive symptoms and improving sleep quality. These findings highlight that Hb may be a key hub within the brain-heart axis and suggest this pathway as a promising early non-pharmacological intervention target.

虚拟现实(VR)是用户利用视、听、嗅、触等各种感觉通路完成对实际的模拟.VR科技能够给生物反馈系统带来更真实的生物反应现场环境与反馈信息,并且二者的融合比传统的生物反馈科技有着更巨大的优越性.本文简要介绍广州新华学院VR的生物反馈实验室的建设及应用情况,为其他高校基于VR的生物反馈实验室建设及设备研制提供思路.

（2016年7月27日）2016年7月27日上午，在贵阳参加中国高等教育学会高校科研与教学深度融合报告会，下午有半日余暇，与同行造访阳明洞，有感而发。早先向往的龙场悟道/霎时间突现眼前/仿佛伯安先生/仍坐在肃穆的阳明洞间洞徒四壁刻着无数崇拜者的叹赞/却没有留下先生你的半语片言

目的 探讨线上教学采用"激越四段式"教学法的效果.方法 对2020年5—6月线上学习的医学本科生在5月采用"激越四段式"教学法,在6月采用常规授课,比较这两种教学法的效果.结果 采用"激越四段式"教学法,平均每次课点赞数和互动的消息数较多,学生的见习资格考试成绩较高,从期末到见习之前成绩下降较少(P<0.05).结论?"激越四段式"教学法能够增加师生互动,活跃课堂气氛,有助于学生更牢固地掌握所学的知识.

以广州新华学院为例,结合生命周期理论各阶段特征,从建立健全风险识别机制及舆情机制;制定科学合理的应急预案;成立疫情防控专班组,完善决策机制;完善应急物资储备机制;完善身心健康评估制度5个方面探讨高校突发公共卫生事件处理机制的实施路径,为高校应对突发公共卫生事件提供理论支持.

Endothelial cell activation plays a critical role in leukocyte recruitment during inflammation and infection. We previously found that cholinergic stimulation (via vagus nerve stimulation) attenuates vascular endothelial impairment and reduces the inflammatory profile in ovariectomized rats. However, the specific molecular mechanism is unclear. This study was designed to explore the effects and molecular mechanisms of cholinergic agonists (acetylcholine [ACh]) on lipopolysaccharide (LPS)-induced endothelial cell activation in vitro. Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of LPS (10/100/1000 ng/mL) to activate endothelial cells. HUVECs were untreated, treated with ACh (10−5 M) alone, treated with 100 ng/mL LPS alone, or treated with different concentrations of ACh (10−9/10−8/10−7/10−6/10−5 M) before LPS stimulation. HUVECs were also pre-treated with 10−6 M ACh with or without mecamylamine (an nAChR blocker) (10 µM) and methyllycaconitine (a specific α7 nAChR blocker) (10 µM) and incubated with or without LPS. ELISA, western blotting, cell immunofluorescence, and cell adhesion assays were used to examine inflammatory cytokine production, adhesion molecule expression, monocyte-endothelial cell adhesion and activation of the MAPK/NF-κB pathways. LPS (at 10 ng/mL, 100 ng/mL and 1,000 ng/mL) increased VCAM-1 expression in HUVECs in a dose-dependent manner (with no significant difference between LPS at 100 ng/mL and 1,000 ng/mL). ACh (10−9 M–10−5 M) blocked adhesion molecule expression (VCAM-1, ICAM-1, and E-selectin) and inflammatory cytokine production (TNF-α, IL-6, MCP-1, IL-8) in response to LPS in a dose-dependent manner (with no significant difference between 10−5 and 10−6 M Ach). LPS was also shown to significantly enhance monocyte-endothelial cell adhesion, which was largely abrogated by treatment with ACh (10−6 M). VCAM-1 expression was blocked by mecamylamine rather than methyllycaconitine. Lastly, ACh (10−6 M) significantly reduced LPS-induced phosphorylation of NF-κB/p65, IκBα, ERK, JNK and p38 MAPK in HUVECs, which was blocked by mecamylamine. ACh protects against LPS-induced endothelial cell activation by inhibiting the MAPK and NF-κB pathways, which are mediated by nAChR, rather than α7 nAChR. Our results may provide novel insight into the anti-inflammatory effects and mechanisms of ACh.

Background Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with poor prognosis. The aberrant expression of circadian genes contributes to the origin and progression of breast cancer. The present study was designed to explore the potential function and prognosis value of circadian genes in TNBC. Methods The transcriptome data of circadian genes were downloaded from The Cancer Genomic Atlas (TCGA), GSE25066 and GSE31448 datasets. The differential expressed circadian genes between non-TNBC and TNBC patients were analysed by Wilcoxon test. Univariate and multivariate Cox regression analyses were employed to identify the prognostic circadian genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to study the biological functions of ARNTL2. The composition of 22 immune cells in the tumour samples was estimated with CIBERSORT algorithm. The correlations between ARNTL2 expression and tumour-infiltrating immune cells were evaluated by Spearman correlation coefficient. Results A total of 8 circadian genes were found to be differentially expressed between non-TNBC and TNBC, but only ARNTL2 has prognostic value. Multivariate Cox analysis identified that ARNTL2 was an independent prognosis factor for overall survival and relapse-free survival in TNBC patients. Functionally, ARNTL2 was mainly involved in immune response processes such as positive regulation of cytokine production, regulation of innate immune response, and cellular responses to molecules of bacterial origin. High expression of ARNTL2 was positively correlated with activated CD4 memory T cells, activated mast cells, and neutrophil infiltration and the expression of markers of neutrophils (ITGAM), dendritic cells (HLA-DRA, HLA-DPA1, ITGAM), Th1 (IL1B, STAT1), Th2 (IL13), Th17 (STAT3) and mast cells (TPSB2, TPSAB1). Conclusion ARNTL2 may be linked with the functional modulation of the tumour immune microenvironment and serve as a potential biomarker for predicting the prognosis of TNBC patients.

G protein-coupled oestrogen receptor 1 (GPER1), predicted to be a novel oestrogen receptor, has been linked to the development and progression of breast cancer. However, the molecular mechanisms underlying its functions remain elusive. Here, we show that the protein levels of GPER1 are negatively associated with those of ERα and that higher expression of GPER1 correlated with a better clinical outcome in oestrogen receptor-positive (ER+) breast cancer patients. Activation of GPER1 decreases ERα protein levels, which subsequently suppresses ERα-mediated transcription and target gene expression but does not affect its mRNA expression in ER + breast cancer cells. A mechanistic study revealed that GPER1 mediates ubiquitin (Ub)-proteasome-dependent degradation of ERα via upregulation of the Cullin3-based E3 ubiquitin ligase adaptor protein speckle-type POZ protein (SPOP), and depletion of SPOP abrogates GPER1-induced ERα ubiquitination and degradation. Functionally, GPER1 activation inhibits 17β-oestradiol (E2)-induced ER + breast cancer cell proliferation, migration, and invasion in vitro and tumour growth in vivo. Our findings reveal a novel mechanism by which GPER1 negatively modulates the ERα signalling pathway via promoting its ubiquitin-proteasome-dependent degradation, which may contribute to its inhibition of breast cancer progression.

The qualitative analysis results of teachers' abilities are difficult to quantify, and ability problems in the teaching process are difficult to be effectively measured. In order to study methods to improve teachers' teaching abilities, this paper builds a corresponding teacher competence evaluation model based on machine learning and digital twin technology, establishes a data collection model for teachers' professional competence, and establishes a data fusion model. It includes data cleaning model based on XML information template, data integration model, multi-index screening mechanism and clustering strategy based on perturbation attributes. On this basis, this paper uses decision tree algorithm, random forest algorithm and neural network algorithm to construct three scheduling rule mining models aiming at teachers' professional ability. In addition, this paper establishes a digital twin-driven multi-knowledge model scheduling optimization architecture that uses the three scheduling rules mined. The research results show that the model constructed in this paper has good performance.

将理念运用于高校办公,有统领全局、理清工作步骤、突出工作目标、提高工作效率和质量的作用,本文从办公实践出发,探讨利用思维导图提升高校办公效率的具体做法.

背景与目的 近年来,研究已证实在包括乳腺癌在内的多种肿瘤的进展中,RNA的N6-甲基腺苷(N6-methyladenosine,m6A)修饰是一个重要的调节过程.脂肪量与肥胖相关(fat mass and obesity-associated,FTO)酶,最初被称为肥胖相关蛋白,是第一个被发现的m6A去甲基化酶.然而,FTO与乳腺癌之间的关系目前还存在争议.本研究旨在阐明FTO在乳腺癌中的作用及其临床意义,并探讨其作用机制.方法 我们首先用定量逆转录–PCR(quantitative reverse transcription-PCR,qRT-PCR)、Western blotting和免疫组织化学法检测了乳腺癌细胞系和组织中FTO的表达.用划痕实验和Transwell实验检测了FTO过表达或表达敲降的SKBR3和MDA-MB453细胞的迁移和侵袭能力.采用RNA测序(RNA sequencing,RNA-seq)分析FTO的下游靶分子.采用qRT-PCR、荧光素酶报告基因分析和Western blotting证实FTO/miR-181b-p/ARL5B轴.用划痕实验和Transwell侵袭实验检测了ADP核糖基化因子样蛋白GTP酶5B(ADP ribosylation factor like GTPase 5B,ARL5B)在乳腺癌细胞中的生物学功能.结果 人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)表达阳性的乳腺癌中FTO高表达,其高表达与肿瘤进展[(肿瘤大小(P<0.001)、核分级(P=0.001)、癌旁淋巴及血管浸润(P<0.001)、淋巴结转移(P=0.002)及TNM分期(P=0.001)]及不良预后相关.另外,体外实验证实FTO可增强乳腺癌细胞的迁移及侵袭.在机制方面,RNA测序和进一步的验证实验均表明,FTO可通过抑制miR-181b-3p上调ARL5B的表达.我们进一步证实了ARL5B在乳腺癌细胞中发挥了致癌活性.结论 本研究证实了FTO可通过FTO/miR181b-3p/ARL5B通路促进乳腺癌细胞的迁移及侵袭.

*These authors contributed equally to this work. Purpose: The present study aims to demonstrate the correlation between estrogen-related receptor α (ERRα) and G protein-coupled estrogen receptor (GPER) expression and its predictive role in the prognosis of patients with triple-negative breast cancer (TNBC). Methods: A retrospective review of 199 cases of TNBC was conducted to assess the GPER and ERRα expression, and its clinicopathologic and prognostic implications. Subsequently, the effects of ERRα and GPER on cell viability, migration, and invasion induced by estrogen were also investigated in vitro. Results: Compared to TNBCs with ERRα low expression, ERRα-high patients exhibited higher nuclear grade, more frequent lymph nodal metastasis, a higher rate of local recurrence, and distant metastasis. Survival analyses revealed that ERRα-high patients had decreased overall survival (OS), local recurrence-free survival (LRFS), and distant diseasefree survival (DDFS) than ERRα-low patients. The GPER expression level positively correlated with ERRα (R=0.167, P=0.18), and TNBCs with ERRα-low/GPER-low demonstrated the best survival outcomes among groups. In vitro, E2 significantly enhanced cell viability, migration, and invasion in BT-549 and MDA-MB-231 cell lines, which was associated with the increased expression of ERRα. Moreover, the overexpression of ERRα induced by estrogen and G1 (GPER agonist) was reversed by knocking down of GPER and blocking the MAPK signaling with PD98059 in both cell lines. Conclusion: Our findings suggest that ERRα and GPER synergistically predict unfavorable prognosis in TNBCs. Mechanically, GPER mediates the upregulation expression of ERRα induced by estrogen and promotes cell viability, migration, and invasion.

PURPOSE:The present study aims to demonstrate the correlation between estrogen-related receptor α (ERRα) and G protein-coupled estrogen receptor (GPER) expression and its predictive role in the prognosis of patients with triple-negative breast cancer (TNBC).METHODS:A retrospective review of 199 cases of TNBC was conducted to assess the GPER and ERRα expression, and its clinicopathologic and prognostic implications. Subsequently, the effects of ERRα and GPER on cell viability, migration, and invasion induced by estrogen were also investigated in vitro.RESULTS:Compared to TNBCs with ERRα low expression, ERRα-high patients exhibited higher nuclear grade, more frequent lymph nodal metastasis, a higher rate of local recurrence, and distant metastasis. Survival analyses revealed that ERRα-high patients had decreased overall survival (OS), local recurrence-free survival (LRFS), and distant disease-free survival (DDFS) than ERRα-low patients. The GPER expression level positively correlated with ERRα (R=0.167, P=0.18), and TNBCs with ERRα-low/GPER-low demonstrated the best survival outcomes among groups. In vitro, E2 significantly enhanced cell viability, migration, and invasion in BT-549 and MDA-MB-231 cell lines, which was associated with the increased expression of ERRα. Moreover, the overexpression of ERRα induced by estrogen and G1 (GPER agonist) was reversed by knocking down of GPER and blocking the MAPK signaling with PD98059 in both cell lines.CONCLUSION:Our findings suggest that ERRα and GPER synergistically predict unfavorable prognosis in TNBCs. Mechanically, GPER mediates the upregulation expression of ERRα induced by estrogen and promotes cell viability, migration, and invasion.

目的:在新型冠状病毒肺炎疫情下,探讨"线上激越四段式"教学在生物医学信号处理课程中的应用效果.方法:以中山大学新华学院2017级生物医学工程专业的81名学生作为研究对象,在生物医学信号处理课程中选取随机信号基础这一章采用"线上激越四段式"教学,分为线上精讲导学、线上自主学习、线上小组讨论和线上分享超越4个阶段.教学过程结束后,对学生发放满意度调查问卷并进行实验作业考核和电话随访,对线上教学的效果进行评价.结果:问卷调查显示,77.2％的学生对"线上激越四段式"教学满意,91.1％的学生认为该教学方法可推广;实验考核结果显示,94.5％的学生在规定的时间内完成上交,72.9％的学生高质量地完成了实验任务;电话采访结果表明,大部分的学生认为"线上激越四段式"教学起到了激励和超越的效果.结论:"线上激越四段式"教学有利于提高学生自主学习的能力,应用于生物医学信号处理课程中取得了较好的效果.

The COVID-19 outbreak can be seen as a 'big test' for China; a summative assessment of its preparedness on multiple fronts, including medical education. Being intimately involved in the coordinated response, the First Affiliated Hospital of Sun Yat-sen University has been a first-hand witness to the strengths and weaknesses of the current medical education system in China. On the one hand, we believe that the distinguished contributions in disease containment efforts by healthcare professionals indicated that our medical education system has achieved its intended outcomes and is socially accountable. On the other hand, we have also identified three major issues that need to be addressed from an educational standpoint: insufficient emphasis on public health emergency preparedness; unsophisticated mechanisms for interdisciplinary cooperation; and inadequate guidance in medical ethics. Whilst these reflections might be seen in its summative form, we would suggest changing it to that of a formative process, where we learn from our assessment through observation and feedback of the gaps, upon which improvement of our present situation can be made. We hope that these lessons may be helpful to our colleagues in the rest of China and around the world, who are engaged in medical educational reform.

Objective: Tumor growth is one of the most lethal attributes of human malignancy. The expression of CCDC7, a novel gene which has multiple functions, has been shown to be associated with tumor growth and poor prognosis in patients with cancer. However, the speci fi c functions of CCDC7 remain unclear. Here, we investigated the molecular mechanisms underlying the effects of CCDC7 on proliferation in cervical cancer. Materials and Methods: The MTT and EdU assays were performed to evaluate the function of CCDC7. The immunohistochemical, quantitative real-time PCR (qRT-PCR), ELISA and Western blot assay were used to detect the gene and protein expression in tissues and cells. A xenograft test was conducted to detect the impact of CCDC7 on tumor development in vivo . Results: In immunohistochemical analysis of 193 cases, normal cervical tissue and cervical cancer tissue show that CCDC7 expression is closely correlated with the development of cervical cancer and was positively correlated with the clinical stage and histological grade. Overexpression or knockdown of CCDC7 affected cell proliferation in cervical cancer cells in vitro. In a nude mouse xenograft model in vivo, knockdown of CCDC7 inhibited cell proliferation and tumor growth. Furthermore, CCDC7 overexpression upregulated interleukin (IL)-6 and vascular endothelial growth factor (VEGF) at mRNA and protein levels, and treatment with recombinant IL-6 or VEGF proteins also increased CCDC7 expression. In a case set of 80 patients with cervical cancer, we found that CCDC7, IL-6, and VEGF affected patient prognosis. Finally, inhibition of various signaling pathways using speci fi c inhibitors indicated that CCDC7 blocked the decrease in cell proliferation observed following suppression of the JAK-STAT3 pathway, suggesting that CCDC7 functioned via this critical signaling network. Conclusion: Those fi ndings indicated that CCDC7 may be a novel target for the treatment of cervical cancer and may have applications as a predictive marker for tumor growth in cervical carcinoma.

The "Four-step Teaching of Encouraging and Sharing" is a learner-centered teaching method that advocates teamwork and gives full play to the role of the teacher in guiding learning. It is an innovative teaching approach to realize students' self-transcendence by stimulating students' internal motivation for independent learning, applying group task-driven learning, and giving teachers' feedback to students' sharing. It consists of four steps: teachers' guiding, students' self-regulated learning, team learning and practice, experience sharing. We have applied this method to the teaching practice of physiology and experimental physiological science with a significant impact on teaching effects. This teaching method has also been implemented to other courses in other majors. To solve the problems of reduced communication and interaction, low learning enthusiasm and motivation in online teaching course during COVID-19 pandemic, we recruited 21 undergraduates from different schools and majors. Using the "Tencent Meeting" platform, the authors tried to apply the whole process of the "Four-step Teaching of Encouraging and Sharing" to the online teaching of physiology. Group tests and questionnaires were used to evaluate teaching effects. The results showed that the implementation of the "Online Four-step Teaching of Encouraging and Sharing (OFST)" was feasible and effective, and to a certain extent alleviated the problems of loneliness and low learning motivation of students during online learning caused by home quarantine, which was particularly helpful for long-distance inter-school and inter-discipline team learning.