CT-Based Intratumoral and Peritumoral Radiomics Nomograms for the Preoperative Prediction of Spread Through Air Spaces in Clinical Stage IA Non-small Cell Lung Cancer.

The study aims to investigate the value of intratumoral and peritumoral radiomics and clinical-radiological features for predicting spread through air spaces (STAS) in patients with clinical stage IA non-small cell lung cancer (NSCLC). A total of 336 NSCLC patients from our hospital were randomly divided into the training cohort (n = 236) and the internal validation cohort (n = 100) at a ratio of 7:3, and 69 patients from the other two external hospitals were collected as the external validation cohort. Univariate and multivariate analyses were used to select clinical-radiological features and construct a clinical model. The GTV, PTV5, PTV10, PTV15, PTV20, GPTV5, GPTV10, GPTV15, and GPTV20 models were constructed based on intratumoral and peritumoral (5 mm, 10 mm, 15 mm, 20 mm) radiomics features. Additionally, the radscore of the optimal radiomics model and clinical-radiological predictors were used to construct a combined model and plot a nomogram. Lastly, the ROC curve and AUC value were used to evaluate the diagnostic performance of the model. Tumor density type (OR = 6.738) and distal ribbon sign (OR = 5.141) were independent risk factors for the occurrence of STAS. The GPTV10 model outperformed the other radiomics models, and its AUC values were 0.887, 0.876, and 0.868 in the three cohorts. The AUC values of the combined model constructed based on GPTV10 radscore and clinical-radiological predictors were 0.901, 0.875, and 0.878. DeLong test results revealed that the combined model was superior to the clinical model in the three cohorts. The nomogram based on GPTV10 radscore and clinical-radiological features exhibited high predictive efficiency for STAS status in NSCLC.

Understanding unmet medical needs through medical crowdfunding in China.

OBJECTIVES: Online medical crowdfunding has gained popularity in recent years in China. The objective of this study was to identify unmet medical needs in the public healthcare system through analysis of Chinese medical crowdfunding data. STUDY DESIGN: Text information extraction and statistical analysis based on large-scale data. METHODS: From 19 June 2011 to 15 March 2020, data from 30,704 medical crowdfunding projects were collected from Tencent GongYi, which is one of the largest Chinese medical crowdfunding platforms. Text mining methods were used to extract data on the medical conditions and locations of the applicants of medical crowdfunding. In addition, 125 medical crowdfunding projects initiated by leukaemia patients in Chongqing and Nanyang were further investigated through manual data extraction, and the factors impacting the fundraising goals were explored using a generalised linear model. RESULTS: The most common conditions using medical crowdfunding to raise funds were as follows: cancer (31.87%), chronic conditions (18.14%), accidental injury (7.80%) and blood system-related conditions (7.75%). Treatments for cancer and blood system-related conditions are expensive and have serious long-term impacts on the lives of patients. Results showed that the cities of Nanyang and Chongqing had the largest number of crowdfunding projects. CONCLUSIONS: This study found that the medical conditions that prompted individuals to apply for crowdfunding were those with long treatment cycles, complexities and expensive medical or non-medical costs. Furthermore, discrepancies in health insurance policies between different regions and residents seeking treatments outside their insurance locations were also important factors that triggered medical crowdfunding applications. Adjusting health insurance policies accordingly may improve the efficiency of utilising health insurance resources and reduce the financial burden on patients.

Nomogram based on clinical characteristics and radiological features for the preoperative prediction of spread through air spaces in patients with clinical stage IA non-small cell lung cancer: a multicenter study.

PURPOSE: To investigate the value of clinical characteristics and radiological features for predicting spread through air spaces (STAS) in patients with clinical stage IA non-small cell lung cancer (NSCLC). METHODS: A total of 336 patients with NSCLC from our hospital were randomly divided into two groups, i.e., the training cohort (n = 236) and the internal validation cohort (n = 100) (7:3 ratio). Furthermore, 69 patients from two other hospitals were collected as the external validation cohort. Eight clinical patient characteristics were recorded, and 20 tumor radiological features were quantitatively measured and qualitatively analyzed. In the training cohort, the differences in clinical characteristics and radiological features were compared using univariate and multivariate analysis. A nomogram was created, and the predictive efficacy of the model was evaluated in the validation cohorts. The receiver operating characteristic curve and area under the curve (AUC) value were used to evaluate the discriminative ability of the model. In addition, the Hosmer-Lemeshow test and calibration curve were used to evaluate the goodness-of-fit of the model, and the decision curve was used to analyze the model's clinical application value. RESULTS: The best predictors included gender, the carcinoembryonic antigen (CEA), consolidation-to-tumor ratio (CTR), density type, and distal ribbon sign. Among these, the tumor density type [odds ratio (OR): 6.738] and distal ribbon sign (OR: 5.141) were independent risk factors for predicting the STAS status. Moreover, three different STAS prediction models were constructed, i.e., a clinical, radiological, and combined model. The clinical model comprised gender and the CEA, the radiological model included the CTR, density type, and distal ribbon sign, and the combined model comprised the above two models. A DeLong test results revealed that the combined model was superior to the clinical model in all three cohorts and superior to the radiological model in the external validation cohort; the cohort AUC values were 0.874, 0.822, and 0.810, respectively. The results also showed that the combined model had the highest diagnostic efficacy among the models. The Hosmer-Lemeshow test showed that the combined model showed a good fit in all three cohorts, and the calibration curve showed that the predicted probability value of the combined model was in good agreement with the actual STAS status. Finally, the decision curve showed that the combined model had a better clinical application value than the clinical and radiological models. CONCLUSION: The nomogram created in this study, based on clinical characteristics and radiological features, has a high diagnostic efficiency for predicting the STAS status in patients with clinical stage IA NSCLC and may support the creation of personalized treatment strategies before surgery.

Identification of hub genes and pathways in lung metastatic colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent types of malignant tumours. Metastasis is the leading cause of cancer-related mortality, with lung metastases accounting for 32.9% of all metastatic CRCs. However, since the biological mechanism of lung metastatic CRC is poorly understood, limited therapeutic targets are available. In the present study, we aimed to identify the key genes and molecular processes involved in CRC lung metastasis. METHODS: The differentially expressed genes (DEGs) between primary and lung metastatic CRC patients were obtained from the Gene Expression Omnibus (GEO) database via the GEO2R tool. The enriched biological processes and pathways modulated by the DEGs were determined with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome Gene Sets analyses. The search tool Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct a protein-protein interaction (PPI) network among DEGs. RESULTS: The DEGs were enriched in surfactant metabolism, cell-cell communication and chemokine signaling pathways. The defined hub genes were included CLU, SFTPD, CCL18, SPP1, APOE, BGN and MMP3. Among them, CLU, SFTPD and CCL18 might be associated with the specific lung tropism metastasis in CRC. In addition, the expression and prognostic values of the hub genes in CRC patients were verified in database of The Cancer Genome Atlas (TCGA) and GEO. Moreover, the protein levels of the hub genes were detected in primary and lung metastatic CRC cells, serum or tissues. Furthermore, SFTPD was confirmed to facilitate cellular proliferation and lung metastasis in CRC. CONCLUSION: This bioinformatics study may provide a better understanding of the candidate therapeutic targets and molecular mechanisms for CRC lung metastasis.

Targeting CDK12 obviates the malignant phenotypes of colorectal cancer through the Wnt/ß-catenin signaling pathway.

Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and lies third in terms of morbidity due to the limited number of effective druggable targets. Since cancer stem cells (CSCs) are considered to be one of the roots of tumorigenesis, outgrowth and metastasis, targeting CSCs may be a promising strategy to reverse the malignant phenotypes of CRC. Cyclin-dependent kinase 12 (CDK12) has been reported to be involved in the self-renewal of CSCs in various cancers, rendering it an attractive potential target against CSCs to consequently limit the malignant phenotypes in CRC. In the present study, we aimed to investigate whether CDK12 can be a potential therapeutic target for patients with CRC and clarify its underlying mechanism. We found that CDK12, but not CDK13 is required for CRC survival. CDK12 was found to drive tumor initiation according to the colitis-associated colorectal cancer mouse model. In addition, CDK12 promoted CRC outgrowth and hepatic metastasis in the subcutaneous allograft and liver metastasis mouse models, respectively. In particular, CDK12 was able to induce the self-renewal of CRC CSCs. Mechanistically, the activation of Wnt/ß-catenin signaling mediated by CDK12 was implicated in stemness regulation and malignant phenotype maintenance. These findings indicate that CDK12 is a candidate druggable target in CRC. Therefore, the CDK12 inhibitor SR-4835 warrants clinical trial testing in patients with CRC.

CDK12 orchestrates super-enhancer-associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer.

BACKGROUND: Hepatic metastasis is the primary and direct cause of death in individuals with colorectal cancer (CRC) attribute to lack of effective therapeutic targets. The present study aimed to identify potential druggable candidate targets for patients with liver metastatic CRC. METHODS: The transcriptional profiles of super-enhancers (SEs) in primary and liver metastatic CRC were evaluated in publicly accessible CRC datasets. Immunohistochemistry of human CRC tissues was conducted to determine the expression level of CDK12. Cellular proliferation, survival and stemness were examined upon CDK12 inhibition by shCDK12 or a selective CDK12 inhibitor named SR-4835 with multiple in vitro and in vivo assays. RNA sequencing and bioinformatics analyses were carried out to investigate the mechanisms of CDK12 inhibition in CRC cells. RESULTS: We identified CDK12 as a driver gene for direct hepatic metastasis in CRC. Suppression of CDK12 led to robust inhibition of proliferation, survival and stemness. Mechanistically, CDK12 intervention preferentially repressed the transcription of SE-associated genes. Integration of the SE landscape and RNA sequencing, BCL2L1 and CCDC137 were identified as SE-associated oncogenic genes to strengthen the abilities of cellular survival, proliferation and stemness, eventually increasing liver metastasis of CRC. CONCLUSIONS: Our data highlight the potential of CDK12 and SE-associated oncogenic transcripts as therapeutic targets for patients with liver metastatic CRC.

The Application Effect of Evidence-Based Care in Gastrointestinal Surgical Pipeline Nursing.

With the improvement of the higher nursing education system, the overall quality and work ability of clinical nurses have also been significantly improved. Most nursing staff have a positive attitude towards evidence-based nursing medicine but lacking of the knowledge and skills about evidence-based nursing. Clinical nurses are still short of the ability to evaluate relevant research data, which is one of the cause of interference for the clinical nurses to use the latest research results reasonably and effectively at present. The purpose of this paper is to explore the application effect of evidence-based nursing in gastrointestinal surgical pipeline nursing and to clarify the impact of evaluation ability on nurses in clinical practice, investigate, and discuss the application effect of evidence-based nursing in gastrointestinal surgical pipeline nursing. This paper selects the clinical nurses of the three top three hospitals in a province as the research object, using the ways of general data questionnaire, the general individual performance sensitivity scale, the evidence-based nursing application behavior questionnaire, the evidence-based nursing application behavior willingness questionnaire, and the evaluation ability training needs questionnaire to collect data for 100 cases of gastrointestinal surgery clinical nurses. Analyze nurses' awareness level of evidence-based nursing, the willingness of evidence-based nursing behavior, and the relevance of evidence-based nursing behaviors. Use multiple regression analysis methods to explore its influencing factors, and use data statistics to analyze the role and effect of evidence-based nursing in the gastrointestinal surgery pipeline. The research results show that the evaluation ability has a significant promotion effect on clinical nursing application, and it is one of the important factors for clinical nurses to use evidence-based nursing. Clinical nurses have a higher demand for evaluation ability training, and basically here, the application effect of evidence-based nursing in the gastrointestinal surgical pipeline nursing is relatively good.

Effects of antiseizure medications on alternative psychosis and strategies for their application.

Forced normalization (FN) is a unique phenomenon that is often seen in the treatment of epilepsy. FN is characterized by abnormal mental behavior and disordered emotions in epilepsy patients despite a significantly improved electroencephalogram and successful seizure control; the occurrence of FN seriously affects patients' quality of life. The causes of FN include antiseizure medications (ASMs), epilepsy surgery and vagus nerve stimulation, with ASMs being the most common cause. However, with the timely reduction or discontinuation of ASMs and the use of antipsychotic drugs, the overall prognosis is good. Here, we perform an extensive review of the literature pertaining to FN, including its epidemiology, possible mechanisms, clinical features, treatment and prognosis.

DHX9 contributes to the malignant phenotypes of colorectal cancer via activating NF-κB signaling pathway.

Colorectal cancer (CRC) is the leading cause of cancer-related mortality worldwide, which makes it urgent to identify novel therapeutic targets for CRC treatment. In this study, DHX9 was filtered out as the prominent proliferation promoters of CRC by siRNA screening. Moreover, DHX9 was overexpressed in CRC cell lines, clinical CRC tissues and colitis-associated colorectal cancer (CAC) mouse model. The upregulation of DHX9 was positively correlated with poor prognosis in patients with CRC. Through gain- and loss-of function experiments, we found that DHX9 promoted CRC cell proliferation, colony formation, apoptosis resistance, migration and invasion in vitro. Furthermore, a xenograft mouse model and a hepatic metastasis mouse model were utilized to confirm that forced overexpression of DHX9 enhanced CRC outgrowth and metastasis in vivo, while DHX9 ablation produced the opposite effect. Mechanistically, from one aspect, DHX9 enhances p65 phosphorylation, promotes p65 nuclear translocation to facilitate NF-κB-mediated transcriptional activity. From another aspect, DHX9 interacts with p65 and RNA polymerase II (RNA Pol II) to enhance the downstream targets of NF-κB (e.g., Survivin, Snail) expression to potentiate the malignant phenotypes of CRC. Together, our results suggest that DHX9 may be a potential therapeutic target for prevention and treatment of CRC patients.

Response to antiepileptic drugs after unsuccessful epilepsy surgery: A multivariate analysis of 103 patients.

OBJECT: Epilepsy patients may still have seizures after surgery, and there have been few studies on the response to antiepileptic drugs (AEDs) after surgery failure. The purpose of this study was to analyze the response to AEDs after unsuccessful epilepsy surgery. METHODS: Patients who underwent unsuccessful epilepsy surgery between January 1999 and January 2019 were evaluated. Patient demographics, etiology, factors related to surgery and AED use patterns were assessed. RESULTS: After excluding the 5 patients who were lost to follow-up and the 2 patients who died, the records of 103 consecutive patients were analyzed. Ninety patients (87.4 %) had seizure recurrence within one year after surgery, 2 (1.9 %) patients had recurrence from one year to two years after surgery, and 11 (10.7 %) patients had recurrence two or more years after surgery (2-10 years). After surgery failure, the patients tried at least 2 kinds of AEDs with different mechanisms for more than 2 years. The average total number of AEDs used was 5.97, the average number of AEDs used before surgery was 3.21, and the average number of AEDs used after surgery was 4.02. After retreatment with AEDs, 10 patients (9.7 %) were seizure-free, 18 patients' (17.5 %) seizures were alleviated, and 75 patients (72.8 %) had seizures as they did prior to the adjustments. The number of AEDs used before and after surgery and the total number of AEDs were not significantly different among the seizure free group, alleviated seizure group and no change group. There were no significant differences in seizure onset age, surgery age, etiology, time between seizure onset and surgery, magnetic resonance imaging, seizure type, localization and lateralization of the surgery site among the three groups. CONCLUSIONS: The results showed that a small percentage of patients (27.2 %) who undergo unsuccessful epilepsy surgery benefit from AED adjustments; however, the vast majority of patients (72.8 %) do not benefit from AED adjustments.

An FMRFamide Neuropeptide in Cuttlefish Sepia pharaonis: Identification, Characterization, and Potential Function.

Neuropeptides are released by neurons that are involved in a wide range of brain functions, such as food intake, metabolism, reproduction, and learning and memory. A full-length cDNA sequence of an FMRFamide gene isolated from the cuttlefish Sepia pharaonis (designated as SpFMRFamide) was cloned. The predicted precursor protein contains one putative signal peptide and four FMRFamide-related peptides. Multiple amino acid and nucleotide sequence alignments showed that it shares 97% similarity with the precursor FMRFamides of Sepiella japonica and Sepia officinalis and shares 93% and 92% similarity with the SpFMRFamide gene of the two cuttlefish species, respectively. Moreover, the phylogenetic analysis also suggested that SpFMRFamide and FMRFamides from S. japonica and S. officinalis belong to the same sub-branch. Tissue expression analysis confirmed that SpFMRFamide was widely distributed among tissues and predominantly expressed in the brain at the three development stages. The combined effects of SpFMRFamide+SpGnRH and SpFLRFamide+SpGnRH showed a marked decrease in the level of the total proteins released in the CHO-K1 cells. This is the first report of SpFMRFamide in S. pharaonis and the results may contribute to future studies of neuropeptide evolution or may prove useful for the development of aquaculture methods for this cuttlefish species.

Computational study of the effects of arterial bifurcation on the temperature distribution during cryosurgery.

BACKGROUND: Thermally significant blood flows into locally cooled diseased tissues and warm them during cryosurgery so that the iceball is often hard to cover the whole diseased volume. This paper is aimed at investigating the effects of large arterial bifurcation on the temperature distribution during cryosurgery through simulation method. METHODS: A parametric geometry model is introduced to construct a close-to-real arterial bifurcation. The three-dimensional transient conjugate heat transfer between bifurcated artery and solid tissues with phase change during cryosurgery is performed by finite volume method. RESULTS: The discussion was then made on the effects of the relative position between cryoprobe and artery bifurcation, the inlet velocity of root artery and the layout of multiple cryoprobes on the temperature distribution and iceball evolution. The results show that the thermal interaction between blood flow and iceball growth near bifurcation is considerable complex. The thermal effects of bifurcation could modulate the iceball morphology, severely weaken its freezing volume and prevent the blood vessel from being frozen. CONCLUSION: The present work is expected to be valuable in optimizing cryosurgery scheme of the situation that the bifurcated artery is embedded into the disease tissue.