OBJECTIVES:Aberrant glucose metabolism serves as a hallmark of glioblastoma (GBM). This study aimed to identify biomarkers linked with glycolysis in GBM, thereby providing a theoretical framework for its treatment. METHODS:We retrieved the gene expression profiles from the GSE 50161 dataset, screened differentially expressed genes (DEGs) and key modules through Weighted Gene Co-expression Network Analysis (WGCNA), and ultimately identified the critical gene via protein-protein interaction (PPI) networks, receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis. In addition, we employed multifaceted immunological, metabolic, and functional assays to experimentally elucidate the regulatory mechanisms of the critical gene within the context of aberrant glucose metabolism in GBM. RESULTS:The brown module was the key module for GBM, and 8 critical genes were obtained for ROC analysis. Peroxidasin (PXDN) was identified as the critical gene associated with glycolysis in GBM. In in vitro experiments, elevated PXDN expression in GBM cell lines was quantified through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. PXDN knockdown significantly reduced glycolytic flux and impeded the malignant phenotypes of GBM cells by downregulating lactate dehydrogenase A (LDHA) expression. In vivo experiments demonstrated that PXDN knockdown effectively suppressed GBM growth. Conversely, LDHA overexpression not only promoted these malignant phenotypes and glycolytic capacity but also substantially reversed the tumor-suppressive effects induced by PXDN knockdown. DISCUSSION:PXDN is identified as a potential diagnostic indicator for GBM, and PXDN promotes malignant progression in GBM by modulating LDHA. Anti-PXDN therapy may represent a viable new approach to combat GBM.

OBJECTIVE: To investigate the risk factors and their diagnostic efficacy for postoperative intestinal mucosal barrier dysfunction (IBD) following severe traumatic brain injury (sTBI). METHODS: There were 140 patients with sTBI enrolled in this study. Univariate and multivariate logistic regression analyses were conducted to assess the relationship between the clinical data and postoperative IBD in sTBI patients and determine the independent risk factors. The diagnostic efficacy of each risk factor was evaluated using the receiver operating characteristic curve and the area under the curve. RESULTS: According to the diagnostic criteria for IBD, the 140 enrolled patients were classified into the IBD group (n = 60) and the non-IBD group (n = 80). The levels of intraoperative initial intracranial pressure (iICP) of patients with IBD were significantly higher compared with those of patients without IBD (P < 0.001). Furthermore, intraoperative iICP presented high diagnostic efficacy for postoperative IBD (area under the curve = 0.91, 95% confidence interval 0.85-0.96, P < 0.001). Patients with higher intraoperative iICP were more prone to suffering unfavorable neurological outcomes. CONCLUSIONS: Intraoperative iICP could act as an independent and quantifiable predictor with high diagnostic efficacy for IBD in patients with sTBI after emergency surgery.

Glioblastoma (GBM) is a highly malignant and aggressive brain tumor with a remarkably poor prognosis and is one of the greatest challenges in the field of neurosurgery. Keratin 80 (KRT80) is primarily expressed in epithelial cells and is involved in the stability and integrity of cellular structures. Although it plays a role in skin and hair follicle development, its function in bridging cancer cells with metabolic pathways is gradually being revealed, such as its activation of glycolysis pathways to promote tumor proliferation. Ring finger protein 8 (RNF8) is an E3 ubiquitin ligase, whose expression has been documented to be significantly reduced in gliomas. Predictions from multiple databases suggest that KRT80 may bind specifically with RNF8. This study aimed to explore the function of KRT80 in GBM procession and the regulatory mechanism between RNF8 and KRT80. We confirmed that KRT80 promoted cell proliferation by constructing overexpression and knockout cell lines. This was also demonstrated by in vivo tumor formation experiments. Besides, higher caspase3/9 activity induced by KRT80 knockout prompted active apoptosis, which was confirmed by flow cytometry showing increased rate of apoptosis. Results also found KRT80 overexpression caused the activation of glycolytic pathways (glucose transporter 1, hexokinase2, and lactate dehydrogenase A) by real-time PCR and the increase of metabolites levels by non-targeted metabolomics. Immunofluorescence co-localization and co-immunoprecipitation assays showed RNF8 attenuated KRT80-induced adverse effects via influencing its ubiquitination degradation. In conclusion, KRT80 is regulated by RNF8-mediated ubiquitination, promoting glycolysis and the progression of GBM. KRT80, regulated by RNF8-mediated ubiquitination, plays a key role in glucose metabolic reprogramming, enhancing energy production and promoting the aggressive progression of GBM.

The CRISPR/Cas9 system has emerged as a revolutionary tool for gene editing, widely used in the biomedical field due to its simplicity, efficiency, and cost-effectiveness. However, evidence suggests that CRISPR/Cas9 can induce off-target effects, leading to unintended mutations that may compromise the precision of gene modifications. Consequently, predicting，detecting and evaluating these off-target effects is crucial for optimizing the accuracy and reliability of CRISPR/Cas9 system. This paper provides an overview of the various methodologies and strategies, used or to be used for identifying off-target effects in CRISPR/Cas9-based genome editing, offering insights to improve the precision and safety of CRISPR applications in research and therapeutics.

The recent discovery of meningeal lymphatic vessels (MLVs) has revolutionized our understanding of immune regulation within the central nervous system (CNS), overturning the long-standing view of the brain as an immune-privileged organ. Glioblastoma (GBM), the most aggressive primary brain tumor, remains therapeutically intractable due to its highly immunosuppressive microenvironment and poor response to conventional and immune-based therapies. Emerging evidence suggests that MLVs play a crucial role in CNS immune surveillance, cerebrospinal fluid drainage, and solute clearance, all of which are directly linked to GBM pathophysiology. This review is motivated by the urgent need to explore novel therapeutic strategies that address GBM's immune escape and therapeutic resistance. We comprehensively analyze the bidirectional interactions between MLVs and GBM, including their role in antigen transport, T cell activation, and tumor dissemination. Furthermore, we evaluate the therapeutic potential of targeting MLVs through lymphangiogenic stimulation or as alternative routes for immune modulation and drug delivery. These approaches offer promising avenues to enhance anti-tumor immunity and may pave the way for next-generation treatment paradigms in GBM.

Sensitive and effective detection of epidermal growth factor receptor ( EGFR ) mutations is crucial for the early screening and diagnosis of non-small cell lung cancer (NSCLC). In this study, we assessed the sensitivity and specificity of the molecular switch technology combined with blocker primers for detecting EGFR exon 19 mutations. We demonstrated that this novel method allows real-time detection of mutated templates on a qPCR platform. Moreover, applying this method to cell-free DNA samples enhances the mutation detection rate.

BACKGROUND:The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape.RESULTS:In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments.CONCLUSIONS:We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

AIM:To optimize the Spontaneous intracerebral hemorrhage (sICH) early hematoma expansion prediction scoring table to adopt appropriate clinical treatment plans and improve the prognosis of sICH patients. MATERIAL AND METHODS:A total of 150 patients with sICH were enrolled, and 44 had early hematoma expansion. According to the selection and exclusion criteria, the study subjects were screened, their NCCT characteristic signs and clinical data were analyzed statistically. The established prediction score was applied to the follow-up study cohort to conduct a pilot study, and the t-test and ROC curve were used to evaluate its predictive ability. RESULTS:Statistical analysis found that initial hematoma volume, GCS score, and NCCT special signs were independent risk factors for early hematoma expansion after sICH (p < 0.05). Thus, a score table was established. Subjects with ≥10 were divided into high-risk group, 6-8 comprised the medium-risk group, and ≤4 were divided into low-risk group. Among 17 patients with acute sICH, 7 developed early hematoma enlargement. The prediction accuracy was 92.41% in the low-risk group, 98.06% in the medium-risk group, and 84.61% in the high-risk group. CONCLUSION:This optimized prediction score table based on the special signs of NCCT shows the high prediction accuracy of sICH early hematoma.

Plaque rupture is a critical concern due to its potential for severe outcomes such as cerebral infarction and myocardial infarction, underscoring the urgency of noninvasive early diagnosis. Magnetic resonance imaging (MRI) has gained prominence in plaque imaging, leveraging its noninvasiveness, high spatial resolution, and lack of ionizing radiation. Ultrasmall iron oxides, when modified with polyethylene glycol, exhibit prolonged blood circulation and passive targeting toward plaque sites, rendering them conducive for MRI. In this study, we synthesized ultrasmall iron oxide nanoparticles of approximately 3 nm via high-temperature thermal decomposition. Subsequent surface modification facilitated the creation of a dual-modality magnetic resonance/fluorescence probe. Upon intravenous administration of the probes, MRI assessment of atherosclerotic plaques and diagnostic evaluation were conducted. The application of Flash-3D sequence imaging revealed vascular constriction at lesion sites, accompanied by a gradual signal amplification postprobe injection. T1-weighted imaging of the carotid artery unveiled a progressive signal ratio increase between plaques and controls within 72 h post-administration. Fluorescence imaging of isolated carotid arteries exhibited incremental lesion-to-control signal ratios. Additionally, T1 imaging of the aorta demonstrated an evolving signal enhancement over 48 h. Therefore, the ultrasmall iron oxide nanoparticles hold immense promise for early and noninvasive diagnosis of plaques, providing an avenue for dynamic evaluation over an extended time frame.

Leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) was reported to be an inhibitory molecule with suppressive functions. sEVs mediate communication between cancer cells and other cells. However, the existence of LILRB2 on sEVs in circulation and the function of sEVs-LILRB2 are still unknown. This study aims to investigate the role of LILRB2 in GBM and determine how LILRB2 in sEVs regulates tumor immunity. LILRB2 expression in normal brain and GBM tissues was detected by immunohistochemistry, and the effect of LILRB2 on prognosis was evaluated in an orthotopic brain tumor model. Next, a subcutaneous tumor model was constructed to evaluate the function of pirb in vivo. The immune cells in the tumor sites and spleen were detected by immunofluorescence staining and flow cytometry. Then, the presence of pirb in sEVs was confirmed by WB. The percentage of immune cells after incubation with sEVs from GL261 (GL261-sEVs) or sEVs from GL261-pirb+ (GL261-sEVs-pirb) was detected by flow cytometry. Then, the effect of pirb on sEVs was evaluated by a tumor-killing assay and proliferation assay. Finally, subcutaneous tumor models were constructed to evaluate the function of pirb on sEVs. LILRB2 was overexpressed in human GBM tissue and was closely related to an immunosuppressive TME in GBM. Then, a protumor ability of LILRB2 was observed in subcutaneous tumor models, which was related to lower CD8 + T cells and higher MDSCs (myeloid-derived suppressor cells) in the tumor and spleen compared to those of the control group. Next, we found that pirb on sEVs (sEVs-pirb) inhibits the function of CD8 + T cells by promoting the formation and expansion of MDSCs. Furthermore, the protumor function of sEVs-pirb was demonstrated in subcutaneous tumor models. We discovered that LILRB2/pirb can be transmitted between GBM cells via sEVs and that pirb on sEVs induces the formation and expansion of MDSCs. The induced MDSCs facilitate the formation of an immunosuppressive TME.

目的:分析定量粪便免疫化学试验(fecal immunochemistry test,FIT)筛查阈值对体检人群结直肠肿瘤早筛价值的影响.方法:以2017年07月至2021年06月在我院接受定量FIT检测并行肠镜检查的1267例人群为研究对象,比较不同性质肿瘤的定量FIT数值和阳性率.通过Logistic回归和受试者工作特征(receiv-er operating characteristic,ROC)曲线分析比较不同性别、年龄和不同阳性阈值下定量FIT对进展期肿瘤的筛检效能.结果:定量FIT筛查阳性率为4.7％,阳性人群肠镜依从性为22.2％.结直肠癌患者的定量FIT数值高于进展期腺瘤和其他肠镜结果.当定量FIT水平为100～199μg/L、200～299μg/L、300～499μg/L和500μg/L以上时,患进展期肿瘤的风险分别是<100μg/L时的4.296倍、4.121倍、6.506倍和10.474倍.不同阳性阈值下,FIT阳性组进展期肿瘤检出率均高于阴性组,且在男性和50～75岁人群中均有统计学差异.在100μg/L时的比值比(odds ratio,OR)最大(总体OR=6.817,95％CI:2.727～17.040;男性OR=5.570,95％CI:2.198～14.115;50～75岁OR=10.178,95％CI:3.158～32.803).此时,定量FIT对进展期肿瘤的灵敏度分别为94.7％、93.0％、96.2％,特异度分别为27.6％、29.6％、28.7％.当阳性阈值由100μg/L升高至500μg/L时,FIT诊断进展期肿瘤的灵敏度下降,特异度升高,但阳性预测值和阴性预测值变化不大.结论:定量FIT阳性阈值在100μg/L时筛查进展期结直肠肿瘤的灵敏度较好,但特异度较低,是应用在体检人群伺机性筛查中较好的结直肠肿瘤早筛参考指标.

We investigated the effect of mRNA-VEGF@ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles on the repair of human brain microvascular endothelial cell (HBMECs) injury and its related mechanisms. mRNA-VEGF@USPIO nanoparticles were designed, prepared, and characterized using NTA and UV spectrophotometry. Cell viability was determined using the CCK-8. Cells in the control, TNF-α, and mRNA-VEGF@USPIO groups were sequenced and the differentially expressed genes (DEGs) were identified. Finally, a functional analysis of the DEGs was performed. Both NTA and spectrophotometry results indicated that mRNA-VEGF@USPIO was successfully constructed. TNF-α significantly reduced cell viability and promoted apoptosis compared with the control group (p < 0.05), whereas mRNA-VEGF@USPIO nanoparticles reversed the changes caused by TNF-α. Via sequencing, 9063 DEGs were identified between the control and TNF-α groups, 9125 DEGs were identified between the control and mRNA-VEGF@USPIO groups, and 211 DEGs were identified between the TNF-α and mRNA-VEGF@USPIO groups. Additionally, 71 overlapping DEGs were identified in the three groups using Venn diagrams. These overlapping DEGs were mainly enriched in cytokine-cytokine receptor interactions and the TNF signaling pathway, NF-κB signaling pathway, and NOD-like receptor signaling pathway. This study shows that mRNA-VEGF@USPIO nanoparticles can repair HBMECs injury.

Objective: To establish a clinical practical prediction model for hematoma expansion（HE） in spontaneous intracerebral hemorrhage. Methods: The clinical and imaging data of 283 patients with spontaneous intracerebral hemorrhage from May 1, 2018 to May 31, 2021 in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. Significant variables in univariate analysis（P＜0.05） were included in multivariate logistic analysis, and stepwise regression was used to screen independent risk factors for prediction model of HE. R language was applied to draw Nomogram. Bootstrap method was used to repeat the sampling of the data in this study 1 000 times for internal verification. Receiver operating characteristic curve, clinical decision curve, and calibration curve were used to evaluate the discriminating ability, clinical practicability and reliability of the model. Results: HE model incorporated standard deviation of red blood distribution width（RDW-SD）, initial hematoma volume, vortex sign, island sign, and mixed sign. The area under receiver operating characteristic curve（AUC） value of the HE model was 0.867. The sensitivity and specificity were 0.728 and 0.876, respectively, with Youden index of 0.605. The internal verification showed that the C-index of the model was 0.859, and the standard error was 0.014. The preliminary external verification indicate that HE model had a good predictive ability. Conclusion: The HE model constructed based on clinical-imaging data, including RDW-SD, initial hematoma volume, vortex sign, island sign, and mixed sign, had a good predictive efficacy.

Many patients with acute ischemic stroke (AIS) are found to accompany with leukoaraiosis (LA) in brain imaging. The risk factors of LA in patients with AIS were examined in this study. Patients with AIS were recruited and underwent head magnetic resonance imaging. According to Fazekas scores, patients were divided into LA group and non-LA group. We compared demographic and laboratory characteristics in two groups. Multivariate logistic regression analysis demonstrated that high-density lipoprotein (HDL), age, stroke history, admission SBP, and homocysteine were independent risk factors for LA in patients with AIS (P < 0.05). Multinomial logistic regression analysis demonstrated that HDL was an independent risk factor for moderate LA (OR 4.151, 95% CI 1.898–9.078, P < 0.001) and severe LA (OR 3.151, 95% CI 1.350–7.358, P = 0.008). In order to further explore the correlation between HDL level and the severity of LA, HDL was categorized in quartiles and multinomial logistic regression analysis was presented. Regression analysis showed that HDL ≥ 1.34 mmol/L was correlated with moderate and severe LA after adjusting for corresponding confounding factors in different models. After 1-year follow-up, patients were divided into regular statin therapy group and irregular statin therapy group. There was no significant difference in HDL level between two groups; however, the proportion of patients with increased Fazekas scores in regular statin therapy group was significantly less than that in the irregular statin therapy group (P < 0.05). In conclusion, HDL was an independent risk factor for LA and associated with the severity of LA in patients with AIS; regular statin therapy may be negatively related with the progress of LA. These results provide more evidences for controlling risk factors and severity of LA in patient with AIS.

教育强国是中华民族伟大复兴的基础工程,医学教育的发展与改革承担着培养合格的医疗卫生人才和提升全民健康的重任.时代使命要求越来越多的医学院校和专家学者需要及时更新先进的临床教育教学理念,了解国内外医学发展的现状和趋势,不断更新现有医学技术、开拓创新.笔者重点探讨"四证合一"医学专业硕士研究生通过云录播平台在临床技能录播视频学习中的课程设计及学习效果,通过"云端"整合院内外前沿技术资源来拓展临床医学研究生的学习视野,从而缓和现有医学专业硕士研究生时空受限、工学矛盾、同质化教学等问题.

2021年1月,国务院在关于推进乡村振兴,加快农业农村现代化的意见中指出,要坚持把解决好"三农"问题作为全党工作重中之重,举全党全社会之力加快农业农村现代化.农村的发展离不开农村金融的要素配置,而农商行作为我国农村金融的重要组成部分,则直接关系到农村经济的高质量发展.本文以江苏省农商行信用风险管理为研究对象,在析现阶段农商行信用风险管理现状的基础上,指出其发展中存在的部分问题并针对性地提出几点建议.

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro , SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan–Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro , PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.

Abstract IntroductionAt the end of 2019, a new coronavirus suddenly swept the world. In order to prevent the epidemic from spreading to the campus, China's Ministry of Education asked all universities to postpone the opening of school. With the rapid development of Internet technology, the Internet has inevitably become an important teaching way during the epidemic. Online face-to-face communication technology and a wide range of medical network open courses provide convenient teaching conditions for medical students and teachers, but also put forward a great challenge to the traditional medical teaching.MethodsBy summarizing the teaching situation of our hospital during the epidemic, SWOT analysis was used to analyze the advantages, disadvantages, opportunities and threats of network medical education, and put forward corresponding countermeasures and suggestions.ResultsCompared with traditional medical teaching, internet teaching has its advanced and desirable aspects, which is manifested in obvious teaching convenience and rich resources. However, there are also some defects that are difficult to make up in a short time due to the imperfect network development and the distance between teachers and students.Conclusion"Internet + education" is the inevitable direction of modern medical teaching reform and development, especially in the special period of epidemic prevention and control. In order to ensure the teaching progress and quality, online teaching is bound to become one of the most effective measures at this stage. This requires medical colleges to actively do a good job in epidemic prevention and control, make full use of Internet resources, strengthen the teacher team-building, improve the assessment and evaluation system and the comprehensive quality of medical students.

摘 要：中国经济在改革开放以后发展得非常迅速，商业银行也在这一阶段迅速发展，但行业内部竞争压力和外部风险与日俱增，因此，合理分析商业银行竞争水平，对于我国商业银行及整个金融业发展都尤为重要。