Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It's vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

New innovations and educational process in undergraduate neurology education in blended learning.

Many undergraduate students suffer from 'neurophobia,' which refers to a lack of knowledge or confidence in neurology, and this can influence their career choices. Various measures have been taken to address this issue, including the implementation of new technologies and methodologies. Significant advancements have been made in the development of blended learning, and the integration of student-centered learning modules, multimedia, and web-based devices has become a common teaching approach. Nonetheless, the optimal delivery form, as well as assessment for the selected learning format and teaching quality in both theory and clinical practice, are being investigated. The purpose of this review is to provide a summary of the current understanding of blended learning as well as innovative methods, technologies, and assessments of undergraduate neurology education. It aims to highlight opportunities for implementing a novel, comprehensive learning model with a suitable blended learning method within a framework of customized technology-assessment processes for future neurology classes, encompassing both theoretical and clinical training.

C1orf109 promotes malignant phenotype of liver cancer via wnt signaling pathway in a CK2-dependent manner.

Chromosome 1 open reading frame 109 (C1orf09) is a protein whose expression pattern and biological function in humans, particularly in malignant tumors, have not been explored. In this study, both bioinformatics and immunohistochemical staining revealed that C1orf109 was overexpressed in the cytoplasm of liver cancer cells, and the positive ratio of C1orf109 in liver cancer samples (42.5%, 37/87) was significantly higher than that in normal liver tissues (10%, 3/30, P = 0.0012). C1orf109 expression was correlated with an advanced TNM stage (P = 0.017) and vascular invasion (P = 0.023) and predicted the poor overall survival of patients with liver cancer (P = 0.001). C1orf109 facilitated tumor growth, colony formation, migration, and invasion by activating Wnt signaling by upregulating non-phosphorylated ß-catenin and its downstream target genes such as CyclinD1, c-myc, and MMP7. Our results also suggest that C1orf109 interacts and co-localizes with casein kinase II (CK2) to activate Wnt signaling. Treatment with a CK2-specific inhibitor markedly counteracted the increased expression of CyclinD1, c-Myc, and MMP7, as well as the upregulation of tumor proliferation and invasion caused by C1orf109 overexpression. Taken together, our results indicate that C1orf109 accelerates liver cancer cell proliferation and invasion by strengthening the Wnt signaling pathway in a CK2-dependent manner.

Efficacy and Safety of Enhanced Recovery After Surgery Pathway in Minimally Invasive Colorectal Cancer Surgery: A Systemic Review and Meta-Analysis.

Background: Enhanced recovery after surgery (ERAS) has been proven valuable for colorectal cancer (CRC) patients who received traditional surgery. While for those receiving minimally invasive surgery (MIS), its efficacy and safety remain debatable. Materials and Methods: Databases, including PubMed, EMBASE, Cochrane libraries, and Web of science, were searched for relevant articles from their inception to February 23, 2022. Eligible articles were subjected to quality assessment and data extraction. The comparison between ERAS and traditional care (TC) was performed. Primary outcomes of this study were postoperative length of stay (LOS), postoperative complications, and mortality. Secondary outcomes were 30-day readmission, 30-day reoperation, time to the first anal exhaust, and defecation. Results: Thirteen cohort studies covering 4308 patients were included. Patients in the ERAS group had significantly shorter LOS (weight mean differences [WMD]: -1.89; 95% confidence interval [CI]: -2.33 to -1.45; P < .001), lower incidence of postoperative complications (risk ratios [RR]: 0.73; 95% CI: 0.5-0.88; P < .001), lower 30-day readmission rate (RR: 0.75; 95% CI: 0.61-0.92; P < .05), and shorter time to the first defecation (WMD: -1.93; 95% CI: -3.26 to -0.59; P < .001), but unimproved mortality, reoperation rate, and time to the first anal exhaust (P > .05) compared with those in the TC group. Conclusions: ERAS was effective and safe for CRC patients receiving MIS from a real-world perspective. Hence, the implementation of ERAS should be recommended for minimally invasive CRC surgery. Clinical Trial Registration Number: CRD42022321333.

Applicability of five nutritional screening tools in Chinese patients undergoing colorectal cancer surgery: a cross-sectional study.

OBJECTIVES: To identify the most appropriate nutritional risk screening tool for patients undergoing colorectal cancer surgery, five nutritional screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), Short Form of Mini Nutritional Assessment (MNA-SF), Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST) and Nutritional Risk Index (NRI), were employed to evaluate the nutritional risk at admission and short-term clinical outcome prediction. DESIGN: A cross-sectional study. SETTING: A comprehensive affiliated hospital of a university in Shenyang, Liaoning Province, China. PARTICIPANTS: 301 patients diagnosed with colorectal cancer were continuously recruited to complete the study from October 2020 to May 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Within 48 hours of hospital admission, five nutritional screening tools were used to measure the nutritional risk and to determine their relationship with postoperative short-term clinical outcomes. RESULTS: The nutritional risk assesed by the five tools ranged from 25.2% to 46.2%. Taking the Subject Global Assessment as the diagnostic standard, MNA-SF had the best consistency (κ=0.570, p<0.001) and MST had the highest sensitivity (82.61%). Multivariate Logistic regression analysis after adjusting confounding factors showed that the NRS 2002 score ≥3 (OR 2.400, 95% CI 1.043 to 5.522) was an independent risk factor for postoperative complications and was the strongest predictor of postoperative complications (area under the curve 0.621, 95% CI 0.549 to 0.692). The scores of NRS 2002 (r=0.131, p<0.001), MNA-SF (r=0.115, p<0.05) and NRI (r=0.187, p<0.05) were poorly correlated with the length of stay. There was no correlation between the five nutritional screening tools and hospitalisation costs (p>0.05). CONCLUSIONS: Compared with the other four nutritional screening tools, we found that NRS 2002 is the most appropriate nutritional screening tool for Chinese patients with colorectal cancer.

miR­1 inhibits the progression of colon cancer by regulating the expression of vascular endothelial growth factor.

MicroRNA (miR)­1 is associated with various human malignancies through repressing tumor growth, migration and angiogenesis. Recently, high­throughput transcriptional profiling confirmed that miR­1 is markedly downregulated in metastatic colorectal cancer; however, its biological functions and the specific underlying mechanisms in colorectal cancer (CRC) require further investigation. In this study, the expression of miR­1 in 111 CRC and paired normal tissue samples was measured using quantitative polymerase chain reaction analysis, and the association between miR­1 expression and clinical characteristics was evaluated. miR­1 was found to be significantly downregulated in CRC tissues compared with paired normal tissues, and in CRC cell lines compared with non­cancer cells (P<0.001), and was negatively associated with tumor size (P=0.001), differentiation (P=0.011), lymph node metastasis (P=0.001) and TNM stage (P=0.001). Further experiments revealed that miR­1 inhibited the migration and invasion of HCT116 and ClonA1 cells, and inhibited cell proliferation by affecting the cell cycle. Vascular endothelial growth factor (VEGF) was found to be a potential target of miR­1 by biological prediction, and further investigation confirmed that miR­1 significantly inhibited the expression and paracrine function of VEGF. In CRC tissues, the expression of VEGF was negatively correlated with miR­1. The low expression of miR­1 in CRC may be one of the reasons for the abnormally high expression of VEGF; the upregulation of miR­1 expression may inhibit cancer progression by downregulating VEGF. These findings indicate that treatment with miR­1 may be a novel method of tumor suppression, and provide a theoretical and experimental basis for the further targeted treatment of CRC through the regulation of miR­1 and VEGF expression.

Neuroplasticity and behavioral effects of fluoxetine after experimental stroke.

The brain can undergo self-repair and has the ability to compensate for functions lost after a stroke. The plasticity of the ischemic brain is influenced by several factors including aging and pharmacotherapy. Fluoxetine is an antidepressant which enhances serotonergic neurotransmission through selective inhibition of neuronal reuptake of serotonin. In clinical practice, fluoxetine alleviates the symptoms of post-stroke depression (PSD), helps motor recovery in stroke patients. In animal experiments, chronic administration of fluoxetine induces increased excitability of mature granule cells (GCs), enhancing axonal and dendritic reorganization, as well as promoting neurogenesis or angiogenesis in the dentate gurus (DG), but the effect of fluoxetine in the subventricular zone (SVZ) remains controversial. Meanwhile, chronic treatment with fluoxetine did not reverse age-dependent suppression of proliferation cells in the DG. Interestingly, although fluoxetine has been found to enhance neurogenesis in the DG in stroke rats, this property is not consistent with the behavioral recovery. More studies into this issue will be required to reveal how to translate enhanced neuronal plasticity into behavioral benefits. This review provides an update of the current knowledge about the neurogenesis and the fate of the newly generated cells after the use of fluoxetine, as well as its ability to promote a behavioral recovery after stroke in clinical and experimental results and attempts to define the therapeutic properties of fluoxetine in regenerative neuroscience.

Comparative efficacy and acceptability of antidepressant treatment in poststroke depression: a multiple-treatments meta-analysis.

OBJECTIVE: The aim of this study is to create a rank order of the comparative efficacy and acceptability (risk of all-cause discontinuation) of antidepressant treatment in poststroke depression (PSD) by integrating direct and indirect evidence. DESIGN: Multiple-treatments meta-analysis of randomised controlled trials. PARTICIPANTS: Patients with depression following stroke. INTERVENTIONS: 10 antidepressants and placebo in the acute treatment of PSD. OUTCOME MEASURES: The primary outcomes were the overall efficacy, defined as the mean change of the total depression score. The secondary outcome was the acceptability, defined as risk of all-cause discontinuation. These estimates as standardised mean differences or ORs with 95% CIs. RESULTS: We identified 12 suitable trials, with data from 707 participants. All drugs were significantly more effective than placebo apart from sertraline, nefiracetam and fluoxetine. Most of the comparisons for acceptability revealed no significant differences except that paroxetine had significantly lower all-cause discontinuation than doxepin, citalopram and fluoxetine. Standardised mean differences compared with placebo for efficacy varied from -6.54 for the best drug (reboxetine) to 0.51 for the worst drug (nefiracetam). ORs compared with placebo for acceptability ranged from 0.09 for the best drug (paroxetine) to 3.42 for the worst drug (citalopram). For the efficacy rank, reboxetine, paroxetine, doxepin and duloxetine were among the most efficacious treatments, the cumulative probabilities of which were 100%, 85.7%, 83.2%, 62.4%, respectively. With respect to the acceptability rank, paroxetine, placebo, sertraline and nortriptyline were among the most acceptable treatments, the cumulative probabilities of which were 92.4%, 63.5%, 57.3%, 56.3%. CONCLUSION: After weighing the efficacy and acceptability, we conclude that paroxetine might be the best choice when starting acute treatment for PSD, and fluoxetine might be the worst choice. TRIAL REGISTRATION NUMBER: This systematic review has been registered in the Prospective Register of Systematic Review Protocols (PROSPERO) public database (CRD42017054741; http://www.crd.york.ac.uk/PROSPERO).

dl-3-n-butylphthalide promotes neuroplasticity and motor recovery in stroke rats.

BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks. Biotinylated dextran amine (BDA) was injected into the contralateral sensorimotor cortex on day 14 after ischemia to trace the sprouting of corticospinal tract (CST) fibers into the denervated cervical spinal cord. The expressions of Nogo-A, Nogo-R, Rho-A, and ROCK in the perilesional cortex, the expressions of BDA, PSD-95, and vGlut1 in the denervated spinal cord, 5-bromo-20-deoxyuridine (BrdU)/DCX-positive cells in the subventricular zone (SVZ) of the injured hemisphere were detected by immunofluorescence. The rats' behavioral abilities were measured on postoperative days 30-32 in the beam-walking, cylinder and sticky label tests. RESULTS: dl-NBP treatment significantly increased the number and length of crossing CST fibers, enhanced significantly the expression levels of synapse-associated proteins including PSD95 and VGlut-1 in the denervated cervical spinal cord, elevated the number of BrdU+/DCX+ cells in SVZ, and reduced markedly those of Rho-A+, ROCK+, Nogo-A+ and Nogo-R+ cells in perilesional cortex. In addition, dl-NBP improved the behavioral performance of the ischemic rats. CONCLUSION: dl-NBP enhanced the behavioral recovery after cerebral ischemia in rats, possibly by increasing axonal growth and neurogenesis.

Safety and Efficacy of Thrombolysis in Cervical Artery Dissection-Related Ischemic Stroke: A Meta-Analysis of Observational Studies.

BACKGROUND: Although thrombolysis is considered to be the first-line treatment for ischemic stroke, there remains an ongoing controversy on the safety and efficacy of thrombolysis in cervical artery dissection (CAD). The aim of this meta-analysis was to assess observational data related to the safety and efficacy of thrombolysis in CAD-related ischemic stroke. METHODS: We performed a systematic search of the efficacy of thrombolysis treatment in CAD-related ischemic stroke with appropriate observational studies identified for the study. The meta-analysis models in Comprehensive Meta-Analysis V2 software were applied to calculate the merged rates of favorable outcome (modified Rankin Scale, mRS 0-2), excellent outcome (mRS 0-1), intracranial hemorrhage (ICH), symptomatic ICH (SICH), mortality and recurrent stroke between thrombolysis and non-thrombolysis in CAD-related stroke. The difference of outcomes and adverse events between the 2 groups was compared by analyzing the pooled OR value and chi-square test using the software SPSS. RESULTS: A total of 846 patients were identified from 10 studies (174 with thrombolysis; 672 with non-thrombolysis). The meta-analysis detected no significant statistical difference in the proportion of CAD-related stroke patients enjoying a favorable outcome at the 3 months' follow-up between the thrombolysis and non-thrombolysis groups (53.7 vs. 58.2%, OR 0.782, x03C7;2 = 0.594, p > 0.05); non-thrombolysis was slightly superior than thrombolysis in terms of excellent outcome (52.4 vs. 34.4%, OR 0.489, x03C7;2 = 9.143, p = 0.002). There was no significant difference in SICH, mortality and recurrent stroke rates between the 2 groups (all p > 0.05). ICH rate was higher in the thrombolysis group of CAD-related stroke patients compared to that in the non-thrombolysis group (12.3 vs. 7.4%, OR 2.647, x03C7;2 = 4.127, p = 0.042). CONCLUSION: Thrombolysis seems to be equally safe and will achieve an efficacy similar to the efficacy of non-thrombolysis in patients with acute ischemic stroke due to CAD. It is also as effective as thrombolysis in stroke from miscellaneous causes. Therefore, CAD patients experiencing a stroke should not be denied thrombolysis therapy. However, this will need to be confirmed in large-scale randomized studies, especially involving intravenous thrombolysis treatment.