Immunomodulatory functions of the circ_001678/miRNA-326/ZEB1 axis in non-small cell lung cancer via the regulation of PD-1/PD-L1 pathway.

High-throughput circular RNA (circRNA) sequencing identified circRNA_001678 (circ_001678) as an upregulated circRNA in non-small cell lung cancer (NSCLC) tissues. Hence, the current study sought to investigate the function and the underlying mechanism of circRNA_001678 in immune escape of NSCLC. Briefly, commercially purchased NSCLC cell lines were adopted for in vitro experiment to evaluate the effects of circ_001678 over-expression or knockdown on cell biological functions, including proliferation, migration and invasive abilities. In addition, the effects of circ_001678 on the in vivo tumorigenicity ability were evaluated for verification. Accordingly, we uncovered that circ_001678 over-expression augmented NSCLC progression in vitro and enhanced tumorigenicity ability in vivo. The interaction between circ_001678 and miR-326 predicted online was verified by means of luciferase and RNA pull-down assays. Furthermore, circ_001678 could sponge miR-326 to up-regulate ZEB1. On the other hand, the tumor-promoting effects of circ_001678 could be inhibited by anti-PD-L1/PD-1 treatment. Mechanistically, circ_001678 led to the activation of the PD-1/PD-L1 pathway to promote CD8+ T cell apoptosis, thereby inducing NSCLC cell immune escape via regulation of the miR-326/ZEB1 axis. To conclude, our findings revealed that circ_001678 sponges miR-326 to up-regulate ZEB1 expression and induce the PD-1/PD-L1 pathway-dependent immune escape, thereby promoting the malignant progression of NSCLC.

Preparation and evaluation of fenbendazole methyl-ß-cyclodextrin inclusion complexes.

As an orally effective benzimidazole anthelmintic agent, fenbendazole was not only widely used in agriculture and animal husbandry to prevent and treat parasites, but also shows anti-cancer effects against several types of cancer, exhibits anti-cancer effects in paclitaxel and doxorubicin-resistant cancer cells. However, fenbendazole's poor in water solubility (0.3 µg/mL), limits its clinical applications. Even great efforts were made toward increasing its water solubility, the results were not significant to reach anti-cancer drug delivery requirement (5-10 mg/mL). Through single factor and orthogonal strategy, many complex conditions were designed and used to prepare the complexes, the inclusion complex with methyl-ß-cyclodextrin with 29.2 % of inclusion rate and 89.5% of inclusion yield can increase drug's water solubility to 20.21 mg/mL, which is the best result so far. Its structure was confirmed by differential scanning calorimetry, scanning electron microscopic image, 1D and 2D NMR spectra in D2O. In its in vitro pharmacokinetic study, fenbendazole was 75% released in 15 min., in its in vivo pharmacokinetic study, the bio-availabilities of fenbendazole, its major metabolic anthelmintic agent oxfendazole and its minor metabolic anthelmintic agent oxfendazole were increased to 138%, 149% and 169% respectively, which would allow for fewer drug doses to achieve the same therapeutic effect and suggest that the complex can be used as a potential anticancer agent.

Microfluidics-enabled fluorinated assembly of EGCG-ligands-siTOX nanoparticles for synergetic tumor cells and exhausted t cells regulation in cancer immunotherapy.

Immune checkpoint inhibitor (ICI)-derived evolution offers a versatile means of developing novel immunotherapies that targets programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) axis. However, one major challenge is T cell exhaustion, which contributes to low response rates in "cold" tumors. Herein, we introduce a fluorinated assembly system of LFNPs/siTOX complexes consisting of fluorinated EGCG (FEGCG), fluorinated aminolauric acid (LA), and fluorinated polyethylene glycol (PEG) to efficiently deliver small interfering RNA anti-TOX (thymus high mobility group box protein, TOX) for synergistic tumor cells and exhausted T cells regulation. Using a microfluidic approach, a library of LFNPs/siTOX complexes were prepared by altering the placement of the hydrophobe (LA), the surface PEGylation density, and the siTOX ratio. Among the different formulations tested, the lead formulation, LFNPs3-3/siTOX complexes, demonstrated enhanced siRNA complexation, sensitive drug release, improved stability and delivery efficacy, and acceptable biosafety. Upon administration by the intravenous injection, this formulation was able to evoke a robust immune response by inhibiting PD-L1 expression and mitigating T cell exhaustion. Overall, this study provides valuable insights into the fluorinated assembly and concomitant optimization of the EGCG-based delivery system. Furthermore, it offers a promising strategy for cancer immunotherapy, highlighting its potential in improving response rates in ''cold'' tumors.

Randomly Methylated ß-Cyclodextrin Inclusion Complex with Ketoconazole: Preparation, Characterization, and Improvement of Pharmacological Profiles.

As a powerful imidazole antifungal drug, ketoconazole's low solubility (0.017 mg/mL), together with its odor and irritation, limited its clinical applications. The inclusion complex of ketoconazole with randomly methylated ß-cyclodextrin was prepared by using an aqueous solution method after cyclodextrin selection through phase solubility studies, complexation methods, and condition selection through single factor and orthogonal strategies. The complex was confirmed by FTIR (Fourier-transform infrared spectroscopy), DSC (differential scanning calorimetry), TGA (thermogravimetric analysis), SEM (scanning electron microscope images), and NMR (Nuclear magnetic resonance) studies. Through complexation, the water solubility of ketoconazole in the complex was increased 17,000 times compared with that of ketoconazole alone, which is the best result so far for the ketoconazole water solubility study. In in vitro pharmacokinetic studies, ketoconazole in the complex can be 100% released in 75 min, and in in vivo pharmacokinetic studies in dogs, through the complexation, the Cmax was increased from 7.56 µg/mL to 13.58 µg/mL, and the AUC0~72 was increased from 22.69 µgh/mL to 50.19 µgh/mL, indicating that this ketoconazole complex can be used as a more efficient potential new anti-fungal drug.

Inhibitory role of bone marrow mesenchymal stem cells-derived exosome in non-small-cell lung cancer: microRNA-30b-5p, EZH2 and PI3K/AKT pathway.

Exosomal microRNA (miRNA) exerts potential roles in non-small-cell lung cancer (NSCLC). The current study elucidated the role of miR-30b-5p shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC-related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR-30b-5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs-derived exosomes overexpressing miR-30b-5p were used to establish subcutaneous tumorigenesis models to study the effects of miR-30b-5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC-exo-miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC-exo-miR-30b-5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR-30b-5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC-exo-miR-30b-5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC-derived exosomes-loaded miR-30b-5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis.

The Use of Cyclodextrin Inclusion Complexes to Increase the Solubility and Pharmacokinetic Profile of Albendazole.

Albendazole is the preferred deworming drug and has strong insecticidal effects on human and animal helminth parasites, showing remarkable activity against hepatocellular carcinoma and colorectal cancer cells. However, it is classified as being in class II in the Biopharmaceutics Classification System due to its poor water solubility (0.2 mg/L) and high permeability, which make the clinical application of albendazole impractical. Through complexation with methyl-ß-cyclodextrin, as the best result so far, albendazole's water solubility was increased by 150,000 times, and albendazole could be 90% released during the first 10 min. In an in vivo pharmacokinetic study, the Cmax and Tmax of the active metabolized sulfoxide were changed from 2.81 µg/mL at 3 h to 10.2 µg/mL at 6 h and the AUC0-48 was increased from 50.72 h⁎µg/mL to 119.95 h⁎µg/mL, indicating that the inclusion complex obtained can be used as a new oral therapeutic anti-anthelmintic and anti-tumor agent formulation.

Challenge of evolving Klebsiella pneumoniae infection in patients on hemodialysis: from the classic strain to the carbapenem-resistant hypervirulent one.

Loss of renal function may render hemodialysis patients more susceptible to infectious diseases, which is the second of all-causes mortality in this population. In addition to infection caused by the classic Klebsiella pneumoniae (cKp), however, hemodialysis staffs are now facing new challenge with growing prevalence of the carbapenem-resistant Kp (CR-Kp) and hypervirulent Kp (hvKp) as they are respectively associated with increased drug-resistance and virulence. We therefore chose to share our recent experience in treating severe infections either caused (cKp, CR-Kp, hvKp) or complicated (CR-hvKp) by these strains in hemodialysis patients. Based upon yet beyond published works, we further came up with the detection of intracranial lesion, novel diagnostic approach using unique biomarkers followed by selection of appropriate antibiotics, management of metastasic abscesses and bracing for the most lethal scenario in the order of cKp, CR-Kp, hvKp and CR-hvKp, respectively. Since reports of complicated hvKp infection in hemodialysis patients were rare, we also discussed in details this clinical entity focusing on its epidemiology, mechanism of increased virulence and involvement of the arteriovenous fistula as insidious source of persistent septicemia. By covering the full spectrum of clinically relevant Kp stains specifically from the viewpoint of nephrology, our work had highlighted the importance of infection control in uremic state and vice versa. As such, it may greatly raise the awareness of dialysis staffs against the challenge of evolving Klebsiella pneumoniae infection in hemodialysis patients and expeditiously reach a higher degree of readiness which was proved to be the key determinant of ultimate survival.

Reduction of miR-744 delivered by NSCLC cell-derived extracellular vesicles upregulates SUV39H1 to promote NSCLC progression via activation of the Smad9/BMP9 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Extracellular vehicles (EVs) are nano-sized particles containing proteins, lipids, and miRNAs secreted by various cells, which play important roles in the development of lung cancer by regulating a wide range of signaling pathways. This study focused on elucidating a potential mechanism by which EVs promote the development of NSCLC. METHODS: Expression levels of miR-744, SUV39H1, Smad9, and BMP4 in clinical tissue samples of NSCLC patients and cell lines were quantified by RT-qPCR and/or western blot analysis. The interaction between SUV39H1 and miR-744 was identified by dual-luciferase reporter assay. miR-744, SUV39H1, and BMP4 expression levels were modulated in A549 and H460 cells, in order to evaluate their effects on cell proliferation, colony formation and cell cycle. A NSCLC xenograft mouse model was used to verify the in vitro findings. NSCLC cell-derived EVs and normal bronchial epithelial cell-derived EVs were isolated and their roles in NSCLC development were evaluated in vivo and in vitro. RESULTS: miR-744 expression was lower in cancer cell-derived derived EVs than in normal lung epithelial cell-derived EVs. Reduced miR-744 expression in EVs upregulated SUV39H1 in NSCLC cells and further increased BMP4 levels to promote NSCLC development. BMP4 was upregulated in NSCLC cells upon suppression of Smad9 mediated by SUV39H1. Reduced miR-744 expression transferred from cancer cell-derived EVs into NSCLC cells enhanced cancer development. CONCLUSION: Overall, our findings unveiled a mechanism whereby miR-744 delivered by NSCLC-derived EVs upregulated SUV39H1, activating the Smad9/BMP9 axis and thus promoted cancer development.

Acute necrotising pancreatitis: measurements of necrosis volume and mean CT attenuation help early prediction of organ failure and need for intervention.

OBJECTIVES: This study explored the early predictive value of volume and mean CT density of necrosis for adverse outcomes in patients with acute necrotising pancreatitis (ANP). METHODS: A total of 155 patients with ANP who underwent CECT within 7 days of symptom onset were included. The necrosis volume, mean CT density, and modified CT severity index (mCTSI) were calculated. C-reactive protein (CRP) and blood urea nitrogen (BUN) levels both 48 h after symptom onset were reviewed. Adverse outcomes were recorded. The predictive value of each indicator was assessed using ROC curve analysis. RESULTS: There were significant associations between necrosis volume and mean CT density and organ failure (OF), persistent OF (POF), and need for intervention (p < 0.001 for all). For predicting OF, the area under the curve (AUC) was significantly higher for necrosis volume than for mCTSI and BUN (AUC: 0.84 vs 0.67, p = 0.0011; 0.84 vs 0.71, p = 0.0193, respectively). For predicting POF and need for intervention, the AUCs for necrosis volume were significantly higher than those for mCTSI (AUC: 0.79 vs 0.66, p = 0.0045; 0.77 vs 0.61, p = 0.0019, respectively), but did not significantly differ from those for CRP and BUN. For predicting OF, a significantly better predictive value was achieved with mean CT density than with mCTSI (AUC: 0.79 vs 0.67, p = 0.0163). There were no significant differences in predictive value between mean CT density, CRP, and BUN. CONCLUSIONS: The volume and mean CT density of necrosis based on CECT can provide early prediction of OF, POF, and need for intervention. KEY POINTS: • Compared to mCTSI, necrosis volume might be used to more accurately diagnose organ failure and persistent organ failure and might be better associated with the need for intervention. • Necrosis volume and mean CT density based on CECT are reliable quantitative predictors for organ failure, persistent organ failure, and intervention in acute pancreatitis.

Long non-coding RNA H19 is responsible for the progression of lung adenocarcinoma by mediating methylation-dependent repression of CDH1 promoter.

Lung adenocarcinoma is a common histologic type of lung cancer with a high death rate globally. Increasing evidence shows that long non-coding RNA H19 (lncRNA H19) and CDH1 methylation are involved in multiple tumours. Here, we tried to investigate whether lncRNA H19 or CDH1 methylation could affect the development of lung adenocarcinoma. First, lung adenocarcinoma tissues were collected to detect CDH1 methylation. Then, the regulatory mechanisms of lncRNA H19 were detected mainly in concert with the treatment of overexpression of lncRNA H19, siRNA against lncRNA H19, overexpression of CDH1 and demethylating agent A-5az in lung adenocarcinoma A549 cell. The expression of lncRNA H19 and epithelial-mesenchymal transition (EMT)-related factors as well as cell proliferation, sphere-forming ability, apoptosis, migration and invasion were detected. Finally, we observed xenograft tumour in nude mice so as to ascertain tumorigenicity of lung adenocarcinoma cells. LncRNA H19 and methylation of CDH1 were highly expressed in lung adenocarcinoma tissues. A549 cells with silencing of lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation by demethylating agent 5-Az had suppressed cell proliferation, sphere-forming ability, apoptosis, migration and invasion, in addition to inhibited EMT process. Silencing lncRNA H19 could reduce methylation level of CDH1. In vivo, A549 cells with silencing lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation exhibited low tumorigenicity, reflected by the smaller tumour size and lighter tumour weight. Taken together, this study demonstrates that silencing of lncRNA H19 inhibits EMT and proliferation while promoting apoptosis of lung adenocarcinoma cells by inhibiting methylation of CDH1 promoter.

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro.

The involvement of several microRNAs (miRs) in the initiation and development of tumors through the suppression of the target gene expression has been highlighted. The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis. In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their roles in NSCLC and the underlying mechanism. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. Quantitative RT-PCR, Western blot analysis, and dual-luciferase reporter gene assay further identified that CDKN3 could be negatively regulated by miR-181d-5p. Moreover, the upregulation of miR-181d-5p or silencing of CDKN3 could inactivate the Akt signaling pathway. A549 with the lowest miR-181d-5p and H1975 with the highest CDKN3 among the five NSCLC cell lines (H1299, A549, H1975, NCI-H157, and GLC-82) were adopted for in vitro experiments, in which expression of miR-181d-5p and CDKN3 was altered by transfection of miR-181d-5p mimic/inhibitor or siRNA-targeting CDKN3. Afterwards, cell proliferation, apoptosis, invasion, migration, and angiogenesis, as well as epithelial-mesenchymal transition (EMT), were evaluated, and tumorigenicity was assessed. In addition, an elevation in miR-181d-5p or depletion in CDKN3 led to significant reductions in proliferation, invasion, migration, angiogenesis, EMT, and tumorigenicity of NSCLC cells, coupling with increased cell apoptosis. In conclusion, this study highlights the tumor-suppressive effects of miR-181d-5p on NSCLC via Akt signaling pathway inactivation by suppressing CDKN3, thus providing a promising therapeutic strategy for the treatment of NSCLC.

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression.

Colorectal cancer (CRC) is the third most common malignancy in the world, and long noncoding RNA (lncRNA) plays a critical role in carcinogenesis. Here, we report a novel lncRNA, MAPKAPK5-AS1, that acts as a critical oncogene in CRC. In addition, we attempted to explore the functions of MAPKAPK5-AS1 on tumor progression in vitro and in vivo. Quantitative RT-PCR was used to examine the expression of MAPKAPK5-AS1 in CRC tissues and cells. Expression of MAPKAPK5-AS1 was significantly upregulated in 50 CRC tissues, and increased expression of MAPKAPK5-AS1 was found to be associated with greater tumor size and advanced pathological stage in CRC patients. Knockdown of MAPKAPK5-AS1 significantly inhibited proliferation and caused apoptosis in CRC cells. We also found that p21 is a target of MAPKAPK5-AS1. In addition, we are the first to report that MAPKAPK5-AS1 plays a carcinogenic role in CRC. MAPKAPK5-AS1 is a novel prognostic biomarker and a potential therapeutic candidate for CRC cancer.

Screening of specific nucleic acid aptamers binding tumor markers in the serum of the lung cancer patients and identification of their activities.

Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.

Current role of magnetic resonance imaging on assessing and monitoring the efficacy of phototherapy.

Phototherapy, also known as photobiological therapy, is a non-invasive and highly effective physical treatment method. Its broad use in clinics has led to significant therapeutic results. Phototherapy parameters, such as intensity, wavelength, and duration, can be adjusted to create specific therapeutic effects for various medical conditions. Meanwhile, Magnetic Resonance Imaging (MRI), with its diverse imaging sequences and excellent soft-tissue contrast, provides a valuable tool to understand the therapeutic effects and mechanisms of phototherapy. This review explores the clinical applications of commonly used phototherapy techniques, gives a brief overview of how phototherapy impacts different diseases, and examines MRI's role in various phototherapeutic scenarios. We argue that MRI is crucial for precise targeting, treatment monitoring, and prognosis assessment in phototherapy. Future research and applications will focus on personalized diagnosis and monitoring of phototherapy, expanding its applications in treatment and exploring multimodal imaging technology to enhance diagnostic and therapeutic precision and effectiveness.

Upregulation of lncRNA PINK1-AS Predicts the Distant Metastasis of Patients with Small Cell Lung Cancer.

PINK1-AS has been shown to participate in gastric cancer, while its role in other tumors is unclear. This study was carried out to explore the participation of PINK1-AS in small cell lung cancer (SCLC). In this study, the expression of PINK1-AS in SCLC and paired non-cancer tissues from 60 SCLC patients and in plasma samples from 60 SCLC patients and 60 healthy controls was analyzed with RT-qPCR. Chi-squared t test was applied to analyze the associations between plasma expression levels of PINK1-AS and the clinical factors of the patients. Patients were followed up for 5 years to explore the role of PINK1-AS in the prognosis of SCLC. ROC curve analysis was applied to explore the role of PINK1-AS in the prediction of distant metastasis. Transwell assays were performed to evaluate the role of silencing and overexpression of PINK1-AS in the invasion and migration of SCLC cells. We found that PINK1-AS was upregulated in SCLC tissues compared to that in non-cancer tissues. Plasma expression levels of PINK1-AS were increased in SCLC patients compared to that in the controls. High plasma expression levels of PINK1-AS were closely associated with worse survival. Plasma expression of PINK1-AS was only closely correlated with distant tumor metastasis, but not other factors. High plasma expression levels of PINK1-AS effectively separated patients with distant metastasis from non-metastatic patients. Moreover, PINK1-AS positively regulated the migration and invasion of SCLC cells. Therefore, the upregulation of PINK1-AS predicts the distant metastasis of patients with SCLC.

Screening and application of inhibitory aptamers for DNA repair protein apurinic/apyrimidinic endonuclease 1.

The base excision repair (BER) pathway is crucial for DNA repair, and apurinic/apyrimidinic endonuclease 1 (APE1) is a critical enzyme in this pathway. Overexpression of APE1 has been linked to multidrug resistance in various cancers, including lung cancer, colorectal cancer, and other malignant tumors. Therefore, reducing APE1 activity is desirable to improve cancer treatment. Inhibitory aptamers, which are versatile oligonucleotides for protein recognition and function restriction, are a promising tool for this purpose. In this study, we developed an inhibitory aptamer for APE1 using systematic evolution of ligands by exponential (SELEX) technology. We used carboxyl magnetic beads as the carrier and APE1 with a His-Tag as the positive screening target, while the His-Tag itself served as the negative screening target. The aptamer APT-D1 was selected based on its high binding affinity for APE1, with a dissociation constant (Kd) of 1.306 ± 0.1418 nM. Gel electrophoresis analysis showed that APT-D1 at a concentration of 1.6 µM could entirely inhibit APE1 with 21 nM. Our results suggest that these aptamers can be utilized for early cancer diagnosis and the treatment, and as an essential tool for studying the function of APE1.

Improvement of solubility and pharmacokinetic profile of hepatoprotector icariin through complexation with HP-γ-cyclodextrin.

Icariin as a hepatoprotector from Herba epimedii can expand the cardiovascular and cerebral blood vessels, promote hematopoietic functions, enhance the immune system and show anti-liver tumor activities. However, its low solubility (0.02 mg/mL) limits its clinical applications as food and medical supplements. Through complexation with HP-γ-cyclodextrin by using a trace amount of water-soluble polymer, the water solubility of icariin was increased by 654 times, which is the best result to date for the water solubility study of icariin. In an in vitro pharmacokinetic study, the complexation increased the dissolution rate of icariin by 80 times, and the icariin complex can be 100% released in the first few minutes. Through complexation, in an in vivo dog pharmacokinetic study, the C max of icariin was increased about 5 times, the AUC0-120 was increased about 20 times and the clearance of icariin was changed from 11.17 L/h/kg to 0.65 L/h/kg. The half-life time was changed from 0.68 h to 6.38 h and the relative bioavailability was increased by nearly 20 times, indicating that less drug is needed for the same therapeutic effect by using the icariin complex, and the complex can be used as a potential potent hepatoprotector or anti-liver cancer drug.

A Clinic-Radiomics Model for Predicting the Incidence of Persistent Organ Failure in Patients with Acute Necrotizing Pancreatitis.

Background: Persistent organ failure (POF) is the leading cause of death in patients with acute necrotizing pancreatitis (ANP). Although several risk factors have been identified, there remains a lack of efficient instruments to accurately predict the incidence of POF in ANP. Methods: Retrospectively, the clinical and imaging data of 178 patients with ANP were collected from our database, and the patients were divided into training (n = 125) and validation (n = 53) cohorts. Through computed tomography image acquisition, the volume of interest segmentation, and feature extraction and selection, a pure radiomics model in terms of POF prediction was established. Then, a clinic-radiomics model integrating the pure radiomics model and clinical risk factors was constructed. Both primary and secondary endpoints were compared between the high- and low-risk groups stratified by the clinic-radiomics model. Results: According to the 547 selected radiomics features, four models were derived from features. A clinic-radiomics model in the training and validation sets showed better predictive performance than pure radiomics and clinical models. The clinic-radiomics model was evaluated by the ratios of intervention and mechanical ventilation, intensive care unit (ICU) stays, and hospital stays. The results showed that the high-risk group had significantly higher intervention rates, ICU stays, and hospital stays than the low-risk group, with the confidence interval of 90% (p < 0.1 for all). Conclusions: This clinic-radiomics model is a useful instrument for clinicians to evaluate the incidence of POF, facilitating patients' and their families' understanding of the ANP prognosis.

Development and validation of a clinical-radiomics model to predict recurrence for patients with hepatocellular carcinoma after curative resection.

PURPOSE: Recurrence is the leading cause of death in hepatocellular carcinoma (HCC) patients with curative resection. In this study, we aimed to develop a preoperative predictive model based on high-throughput radiomics features and clinical factors for prediction of long- and short-term recurrence for these patients. METHODS: A total of 270 patients with HCC who were followed up for at least 5 years after curative hepatectomy between June 2014 and December 2017 were enrolled in this retrospective study. Regions of interest were manually delineated in preoperative T2-weighted images using ITK-SNAP software on each HCC tumor slice. A total of 1197 radiomics features were extracted, and the recursive feature elimination method based on logistic regression was used for radiomics signature building. Tenfold cross-validation was applied for model development. Nomograms were constructed and assessed by calibration plot, which compares nomogram-predicated probability with observed outcome. Receiver-operating characteristic was then generated to evaluate the predictive performance of the model in the development and test cohorts. RESULTS: The 10 most recurrence-free survival-related radiomics features were selected for the radiomics signatures. A multiparametric clinical-radiomics model combining albumin and radiomics score for recurrence prediction was further established. The integrated model demonstrated good calibration and satisfactory discrimination, with the area under the curve (AUC) of 0.864, 95% CI 0.842-0.903, sensitivity of 0.889, and specificity of 0.644 in the test set. Calibration curve showed good agreement concerning 5-year recurrence risk predicted by the nomogram. In addition, the AUC of 1-, 2-, 3-, and 4-year recurrence was 0.935 (95% CI 0.836-1.000), 0.861 (95% CI 0.723-0.999), 0.878 (95% CI 0.762-0.994), and 0.878 (95% CI 0.762-0.994) in the test set, respectively. CONCLUSIONS: The clinical-radiomics model integrating radiomics features and clinical factors can improve recurrence predictions beyond predictions made using clinical factors or radiomics features alone. Our clinical-radiomics model is a valid method to predict recurrence that should improve preoperative prognostic performance and allow more individualized treatment decisions.

Serum-derived extracellular vesicles promote the growth and metastasis of non-small cell lung cancer by delivering the m6A methylation regulator HNRNPC through the regulation of DLGAP5.

PURPOSE: Serum-derived extracellular vesicles (EVs) have been reported to play an important role in non-small cell lung cancer (NSCLC). The current study sought to explore the effect of serum-EVs delivering m6A methylation regulator heterogeneous nuclear ribonucleoprotein C (HNRNPC) on the development of NSCLC through the regulation of discs large-associated protein 5 (DLGAP5). METHODS: NSCLC-related RNA-Seq and clinical data were first obtained from the TCGA database to screen differentially expressed m6A-related regulators, which were intersected with the differential genes in NSCLC-related microarray GSE43458 obtained from the GEO database for survival analysis and clinical correlation analysis. Correlation between HNRNPC and DLGAP5 expression was evaluated. Serum-EVs were isolated and identified, and the uptake of EVs by A549 cells was visualized using fluorescence microscopy. In vivo xenograft tumor models and tumor metastasis models were constructed in nude mice to observe growth and metastasis of NSCLC cells. RESULTS: HNRNPC was associated with poor prognosis and metastasis of NSCLC, and further implicated in the regulation of DNA replication and cell cycle-related pathways. HNRNPC might promote the growth and metastasis of NSCLC by identifying m6A modification of DLGAP5 mRNA. Serum-EVs delivered HNRNPC to NSCLC cells in vitro. In vivo experimentation further confirmed that serum-EVs could deliver HNRNPC to promote the growth and metastasis of NSCLC cells in nude mice. CONCLUSIONS: Our findings highlight that serum-EVs can deliver HNRNPC to NSCLC cells, wherein HNRNPC recognizes the m6A modification of DLGAP5 mRNA, thus ultimately promoting NSCLC growth and metastasis.