The role of toll-like receptors (TLRs) in pan-cancer

BackgroundToll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study''s goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis.MethodsThe expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data.ResultsOur multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research.ConclusionTLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators.

Key Messages

• Toll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.
• In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.
• TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

     

胎儿端脑突触素表达和突触发育的研究

为了探讨突触素(SYN)在不同周龄阶段胎儿端脑额叶中的表达与胎儿额叶皮质突触发育的关系,本研究采用免疫组织化学方法观察突触素在不同周龄阶段胎儿额叶的表达水平,利用计算机图像分析技术测量不同周龄阶段胎儿额叶突触素表达的平均光密度;同时取材、常规电镜技术处理、透射电镜观察额叶突触发育的超微结构变化。结果显示:(1)光镜下各组均可见SYN免疫阳性产物主要表达于胎儿的额叶皮层,其表达量随周龄的增加而增强,各组间呈现显著性差异(P<0.05),其中16～24周胎儿额叶的阳性产物位于神经元的胞浆内,呈均匀的浅黄色,神经元突起内未见阳性产物;25～29周额叶的阳性产物呈黄色,在胞浆和突起内均可见,但阳性产物的量却下降;而30～39周额叶的SYN阳性产物呈棕黄色的点状或颗粒状,主要位于神经元的突起内,神经元胞浆内未见阳性产物,阳性产物的量显著增加;(2)透射电镜下19～36周胎儿大脑额叶均可见到突触样结构,随着周龄的增加,突触的数量逐渐增多,结构逐渐清晰和完整。上述结果提示SYN的表达可以反映胎儿神经系统发育的程度,SYN的表达与突触的发育是一致的;SYN在胎儿大脑额叶的表达部位经历由神经元胞浆内表达为主到神经元终末表达为主的这一过程,可能是由于SYN先是在神经元胞浆内合成,再随着神经元的发育而逐步转移到神经元突起的末梢部位。     

PdPbAg alloy NPs immobilized on reduced graphene oxide/In2O3 composites as highly active electrocatalysts for direct ethylene glycol fuel cells

rGO-modified indium oxide (In₂O₃) anchored PdPbAg nanoalloy composites (PdPbAg@rGO/In₂O₃) were prepared by a facile hydrothermal, annealing and reduction method. Electrochemical tests showed that the as-prepared trimetallic catalyst exhibited excellent electrocatalytic activity and high resistance to CO poisoning compared with commercial Pd/C, mono-Pd and different bimetallic catalysts. Specifically, PdPbAg@rGO/In₂O₃ has the highest forward peak current density of 213.89 mA cm⁻², which is 7.89 times that of Pd/C (27.07 mA cm⁻²). After 3600 s chronoamperometry (CA) test, the retained current density of PdPbAg@rGO/In₂O₃ reaches 78.15% of the initial value. Its excellent electrocatalytic oxidation performance is attributed to the support with large specific surface area and the strong synergistic effect of PdPbAg nanoalloys, which provide a large number of interfaces and achievable reactive sites. In addition, the introduction of rGO into the In₂O₃ matrix contributes to its excellent electron transfer and large specific surface area, which is beneficial to improving the catalytic ability of the catalyst. The study of this novel composite material provides a conceptual and applicable route for the development of advanced high electrochemical performance Pd-based electrocatalysts for direct ethylene glycol fuel cells.

rGO-modified indium oxide (In₂O₃) anchored PdPbAg nanoalloy composites (PdPbAg@rGO/In₂O₃) were prepared by a facile hydrothermal, annealing and reduction method.     

The diagnostic efficacy of diffusion tensor imaging generated by gadolinium-based magnetic resonance imaging for patients with chronic kidney disease

Background:Chronic kidney disease (CKD) can lead to systemic inflammatory responses and other cardiovascular disease. Diffusion tensor imaging findings generated by gadolinium-based MRI (DTI-GBMRI) is regarded as a standard method for assessing the pathology of CKD. To evaluate the diagnostic value of DTI-GBMRI for renal histopathology and renal efficiency, renal fibrosis and damage, noninvasive quantification of renal blood flow (RBF) were investigated in patients with CKD.Methods:CKD patients (n = 186) were recruited and underwent diagnosis of renal diffusion tensor imaging findings generated by MRI (DTI-MRI) or DTI-GBMRI to identify the pathological characteristics and depict renal efficiency. The cortical RBFs and estimated glomerular filtration rate were compared in CKD patients undergone DTI-GBMRI (n = 92) or DTI-MRI (n = 94).Results:Gadolinium enhanced the diagnosis generated by DTI-MRI in renal fibrosis, renal damage, and estimated glomerular filtration rate. The superiority in sensitivity and accuracy of the DTI-GBMRI method in assessing renal function and evaluating renal impairment was observed in CKD patients compared with DTI-MRI. Outcomes demonstrated that DTI-GBMRI had higher accuracy, sensitivity, and specificity than DTI-MRI in diagnosing patients with CKD.Conclusion:In conclusion, DTI-GBMRI is a potential noninvasive method for measuring renal function, which can provide valuable information for clinical CKD diagnosis.     

糖尿病神经病变的评估和预防

糖尿病神经病变是糖尿病最常见和最复杂的并发症之一,可累及全身神经系统的任何部分,大约发生在近50%的糖尿病患者中.通常在1型糖尿病患者中,它出现较晚,而在2型糖尿病的早期就能发现.     

大学生不安全依恋与拖延的关系：正念与自我控制的作用路径

背景 预防和干预大学生的拖延行为具有重要现实意义。已有研究表明,正念、自我控制、不安全依恋和拖延两两相关,但目前关于不安全依恋对拖延的作用机制仍不清楚,且缺乏二者间作用路径的研究。目的 探讨大学生不安全依恋对拖延的影响以及正念与自我控制的作用路径,以期为大学生拖延问题的干预提供参考。方法 于2023年2月—4月,采用整群随机抽样的方法,选取广东省4所高校的514名在校大学生为研究对象。采用非理性拖延量表（IPS）、成人依恋量表（AAS）、正念注意觉知量表（MAAS）和简式自我控制量表（BSCS）进行调查。使用Pearson相关分析考查各量表评分的相关性,使用Bootstrap法进行中介效应检验。结果 大学生AAS评分与IPS评分呈正相关（r=0.382,P<0.01）,与MAAS和BSCS评分均呈负相关（r=-0.242、-0.353,P均<0.01）;IPS评分与MAAS和BSCS评分均呈负相关（r=-0.314、-0.682,P均<0.01）;MAAS评分与BSCS评分呈正相关（r=0.439,P<0.01）。不安全依恋正向预测拖延（β=0.377,P<0.01）,自我控制是不安全依恋与拖延之间的作用路径,间接效应值为0.163（95% CI：0.105~0.223）,占总效应的43.24%,且正念与自我控制可能是不安全依恋与拖延之间的链式作用路径,间接效应值为0.056（95% CI：0.028~0.089）,占总效应的14.85%。结论 不安全依恋可以直接影响大学生拖延,也可以通过自我控制的独立作用路径及正念与自我控制的链式作用路径影响大学生拖延。     

叙事暴露疗法在儿童和青少年创伤后应激障碍患者中应用效果的Meta分析

背景 叙事暴露疗法（NET）结合叙事疗法和暴露疗法的优点,对缓解创伤后应激障碍（PTSD）症状有效,有助于患者对创伤进行深入的认识,也具有较好的安全性。儿童和青少年是PTSD的高发人群,但NET对该人群干预效果的研究结果存在差异。目的 系统评价NET对儿童和青少年PTSD患者的干预效果,为NET的临床应用提供参考。方法 于2022年8月1日,计算机检索Cochrane Library、PubMed、Web of Science、CINAHL、中国知网（CNKI）、中国生物医学文献数据库（SinoMed）、维普数据库和万方数据库,检索时限为建库至2022年6月。采用主题词与自由词相结合的方式进行检索,收集NET治疗儿童和青少年PTSD的文献。根据Cochrane协作网更新的偏倚风险评估手册中对随机对照试验的真实性评价标准（2011）,评价文献质量。采用RevMan 5.4对纳入的随机对照试验进行Meta分析。结果 纳入9篇文献,共包括394例儿童和青少年PTSD患者。Meta分析结果显示,在PTSD症状缓解程度方面,干预后1~3个月（SMD=0.22,95% CI：-0.84~1.28）以及干预后6个月（SMD=0.21,95% CI：-0.75~1.17）,NET与放松疗法的效果比较,差异无统计学意义;干预后1~3个月（SMD=-0.66,95% CI：-1.04~-0.27）以及干预后6个月（SMD=-0.77,95% CI：-1.36~-0.19）,NET的效果均优于常规治疗,差异均有统计学意义。在抑郁症状缓解程度方面,治疗后1~3个月,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.39,95% CI：-0.98~0.21）;干预后6个月,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.74,95% CI：-2.23~0.75）。在心理困扰缓解程度方面,干预后1~3个月,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.54,95% CI：-2.14~1.07）。在食欲亢进缓解程度方面,NET与常规治疗的效果比较,差异无统计学意义（SMD=-0.17,95% CI：-0.54~0.19）。结论 与常规治疗相比,NET对缓解儿童和青少年PTSD症状的效果更佳,且具有中长期效果,但在改善抑郁症状、心理困扰以及食欲亢进方面无明显优势。     

社区严重精神障碍患者危险行为发生风险预测模型

背景 严重精神障碍患者危险行为发生率较一般人群更高,我国对社区严重精神障碍患者危险行为发生风险的预测研究尚不多见,尤其缺乏除传统预测方法之外的数据挖掘技术预测模型的研究和比较。目的 采用Logistic回归分析及分类决策树构建社区严重精神障碍患者危险行为发生风险的预测模型,检验分类决策树模型是否优于Logistic回归模型。方法 于2023年12月,选取2013年—2022年随访记录完整的11 484名社区严重精神障碍在管患者,按8∶2随机分为训练集（n=9 186）与测试集（n=2 298）。在训练集中,分别使用Logistic回归分析和分类决策树建立预测模型,在测试集评价模型的区分度和校准度。结果 1 115例（9.71%）严重精神障碍患者在随访期间出现危险行为。Logistic回归分析结果显示,城市户籍、贫困、有监护人、精神残疾、危险行为史阳性、自知力不全、自知力缺失、有阳性症状是患者发生危险行为的危险因素（OR=1.778、1.459、2.719、1.483、3.890、1.423、2.528、2.124,P均<0.01）;年龄≥60岁、受过教育、医嘱无需用药以及社会功...     

Berberine inhibits IFN-γ signaling pathway in DSS-induced ulcerative colitis

AimsThe potential signaling pathways and core genes in ulcerative colitis (UC) were investigated in this study. Furthermore, potential mechanisms of BBR in treating UC were also explored.MethodsExpression profiling by array of UC patients were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined with the differential analysis. The biological functions of DEGs were analyzed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Gene Set Enrichment Analysis (GSEA) was applied to analyze the expression differences between two different phenotype sample sets. Dextran sulfate sodium (DSS) was applied to establish UC model of mice and lipopolysaccharide (LPS) was utilized to induce inflammatory damage of NCM460 cells. Therapeutic effects of berberine (BBR) on disease performance, pathologic changes and serum supernatant indices were analyzed in vivo. To further investigate the potential mechanisms of BBR in treating UC, the expression of genes and proteins in vivo and in vitro were examined by RT-qPCR, immunohistochemical staining and western blotting.ResultsImmune-inflammatory genes were identified and up-regulated significantly in UC patients. In addition, IFN-γ signaling pathway and its core genes were significantly up-regulated in the phenotype of UC. All disease performance and the pathologic changes of UC in mice were evidently ameliorated by BBR treatment. The pro-inflammatory cytokines of serum, including CXCL9, CXCL1, IL-17 and TNF-α, in UC mice were significantly reduced by treatment of BBR. In terms of mechanisms of BBR in treating UC, the pro-inflammatory and immune-related genes, encoding IFN-γ, IRF8, NF-κB and TNF-α decreased significantly in UC mice followed by BBR treatment. Meanwhile, the expression of IFN-γ and its initiated targets, including IRF8, Ifit1, Ifit3, IRF1, were suppressed significantly by BBR treatment in vivo. The blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR. Furthermore, the blocking of IFN-γ in vitro led to the silence of IFN-γ signaling pathway after exposure to BBR.ConclusionBBR holds anti-inflammatory activity and can treat UC effectively. The anti-inflammatory property of BBR is tightly related to the suppression of IFN-γ signaling pathway, which is crucial in immune-inflammatory responses of the colon mucosa.