Apatinib inhibits tumour progression and promotes antitumour efficacy of cytotoxic drugs in oesophageal squamous cell carcinoma.

Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumours. The function and mechanism of apatinib in oesophageal squamous cell carcinoma (ESCC) remain unknown. In present study, we found that the development of ESCC in patients was controlled by treatment of combination of apatinib and a chemotherapeutic drug. Moreover, apatinib efficiently promotes cell apoptosis, inhibits cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and activity of the Akt/mTOR pathway in ESCC cells. Western blot analysis showed that apatinib significantly increased vimentin protein levels, decreased Bcl2, matrix metalloproteinase 9 (MMP9), E-cadherin, p-Akt and p-mTOR protein levels in ESCC cells. Furthermore, apatinib enhanced chemosensitivity of cytotoxic drugs paclitaxel (TAX), 5-fluorouracil (5-FU) and cisplatin (DDP) by upregulating expression of vimentin protein, and downregulating expression of Bcl2, MMP9 and E-cadherin protein in vitro. Compared with single-agent groups, the combination of apatinib with each chemotherapeutic drug significantly repressed tumour growth and angiogenesis through blocking the expression of Ki67 and VEGFR-2 in vivo. Taken together, apatinib efficiently inhibits cell growth through blocking Bcl2 and Akt/mTOR pathway, and suppresses metastasis via inhibiting MMP9 and EMT in ESCC cells. Apatinib promoted antitumour effect of chemotherapeutic agents through promoting cell apoptosis and inhibiting EMT and angiogenesis in ESCC.

NUR77 exerts a protective effect against inflammatory bowel disease by negatively regulating the TRAF6/TLR-IL-1R signalling axis.

Nur77, an immediate-early response gene, participates in a wide range of biological functions. Its human homologue, NUR77, is known by several names and has the HGNC-approved gene symbol NR4A1. However, the role of Nur77 in inflammatory bowel disease (IBD) and its underlying mechanisms remain elusive. Here, using public data from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) on the most recent genome-wide association studies (GWAS) for ulcerative colitis (UC) and Crohn's disease (CD), we found that genetic variants of the NUR77 gene are associated with increased risk for both UC and CD. Accordingly, Nur77 expression was significantly reduced in colon tissues from patients with UC or CD and mice treated with DSS. Nur77 deficiency increased the susceptibility of mice to DSS-induced experimental colitis and prevented intestinal recovery, whereas treatment with cytosporone B (Csn-B), an agonist for Nur77, significantly attenuated excessive inflammatory response in the DSS-induced colitis mouse model. Mechanistically, NUR77 acts as a negative regulator of TLR-IL-1R signalling by interacting with TRAF6. This interaction prevented auto-ubiquitination and oligomerization of TRAF6 and subsequently inhibited NF-κB activation and pro-inflammatory cytokine production. Taken together, our GWAS-based analysis and in vitro and in vivo studies have demonstrated that Nur77 is an important regulator of TRAF6/TLR-IL-1R-initiated inflammatory signalling, and loss of Nur77 may contribute to the development of IBD, suggesting Nur77 as a potential target for the prevention and treatment of IBD.

Low-Voltage, High-Pitch Computerized Tomography Angiography of the Infrarenal Aorta and Lower Extremity Vessels: Assessment of Radiation Dose, Image Quality With Hybrid Iterative Reconstruction, and Efficacy of Test Injection Using a Monitoring Scan at Knee Level.

OBJECTIVES: Our aim was to assess image quality and radiation dose of low-voltage high-pitch computed tomography angiography of the infrarenal aorta and lower extremities and evaluate the efficacy of test injection technique using a monitoring scan at knee level. METHODS: A total of 60 patients with suspected peripheral arterial disease were divided into 2 groups: group 1 (30 patients, 80 kVp, high pitch [3.2], and hybrid iterative reconstruction [sinogram-affirmed iterative reconstruction]) and group 2 (30 patients, 120 kVp, low pitch [1.0], and filtered back projection reconstruction). The test injection technique at knee level was used to determine the scan delay time in group 1. The image quality and radiation exposure were compared. RESULTS: There were significant differences between the 2 groups in mean (SD) arterial attenuation (80 vs 120 kVp: 507.78 [103.01] vs 317.54 [62.03] Hounsfield units, P < 0.001), mean (SD) signal-to-noise ratio (51.04 [20.29] vs 34.66 [9.94], P < 0.001), and contrast-to-noise ratio (44.83 [17.93] vs 28.26 [9.60], P < 0.001). No difference in subjective image quality was found between the 2 groups (all P > 0.05). The imaging time was significantly shorter in group 1 (2.70 [0.11] vs 14.65 [0.90s], P < 0.001). The mean (SD) effective dose was significantly lower in the 80 kVp group (0.76 [0.06] vs 4.29 [0.63] mSv, P < 0.001). CONCLUSIONS: The 80-kVp high-pitch computed tomography angiography of the lower limbs using sinogram-affirmed iterative reconstruction yields reduction of radiation exposure as well as obtains acceptable image quality if acquisition protocols are used in conjunction with the test injection technique using monitoring scan at knee level to determine the delay time.

Identification and validation of a novel six-gene signature based on mucinous adenocarcinoma-related gene molecular typing in colorectal cancer.

BACKGROUND AND OBJECTIVES: Colorectal mucinous adenocarcinoma (MAC) is a particular pathological type that has yet to be thoroughly studied. This study aims to investigate the characteristics of colorectal MAC-related genes in colorectal cancer (CRC), explore the role of MAC-related genes in accurately classifying CRC, and further construct a prognostic signature. METHODS: CRC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). MAC-related differentially expressed genes (DEGs) were analyzed in TCGA samples. Based on colorectal MAC-related genes, TCGA CRC samples were molecularly typed by the non-negative matrix factorization (NMF). According to the molecular subtype characteristics, the RiskScore signature was constructed through univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Clinical significance in CRC of the RiskScore signature was analyzed. A nomogram was further built based on the RiskScore signature. RESULTS: From the colorectal MAC-related genes, three distinct molecular subtypes were identified. A RiskScore signature composed of six CRC subtype-related genes (CALB1, MMP1, HOXC6, ZIC2, SFTA2, and HYAL1) was constructed. Patients with high-RiskScores had the worse prognoses. RiskScores led to differences in gene mutation characteristics, antitumor drug sensitivity, and tumor microenvironment of CRC. A nomogram based on the signature was developed to predict the one-, three-, and five-year survival of CRC patients. CONCLUSION: MAC-related genes were able to classify CRC. A RiskScore signature based on the colorectal MAC-related molecular subtype was constructed, which had important clinical significance for guiding the accurate stratification of CRC patients.

Dual immunotherapy in advanced or metastatic non-small cell lung cancer: A network meta-analysis.

Objectives: Recently, there has been extensive research on dual immunotherapy for advanced or metastatic non-small cell lung cancer (NSCLC), yet a comprehensive evaluation is lacking. This study aimed to rank the available treatment options and assess the efficacy and safety of dual immunotherapy regimens through the implementation of a Bayesian network meta-analysis (NMA). Materials and methods: A thorough search was conducted to recognize eligible randomized controlled trials (RCTs) on March 20, 2023. Overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were evaluated to identify the efficacy and safety of dual immunotherapy regimens. The surface under the cumulative ranking curve (SUCRA) and P score were employed to rank the treatments. Results: Eleven clinical trials involving six different regimens were included in this study. The combination of anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) antibodies with anti-T-cell immunoglobulin and ITIM domain (TIGIT) antibodies emerged as the most promising regimen for improving OS and PFS, followed by anti-PD-1/PD-L1 + anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) + chemotherapy treatment and anti-PD-1/PD-L1 + anti-CTLA-4 treatment. The forest plots demonstrated that these three regimens were all superior to chemotherapy. The above results were observed in both unselected treatment line and first-line settings. The least likely to be associated with TRAEs and grade ≥3 TRAEs were respectively anti-CTLA-4 treatment and anti-PD-1/PD-L1 + anti-TIGIT treatment, with anti-PD-1/PD-L1 + anti-CTLA-4 + chemotherapy treatment to be the worst. Conclusions: This NMA validated the promising efficacy and safety of dual immunotherapy in advanced or metastatic NSCLC. Among them, anti-PD-1/PD-L1 + anti-TIGIT regimen emerges as a highly potential therapeutic approach. Ongoing research efforts should focus on improving treatment regimens, identifying biomarkers, and managing TRAEs to optimize the patient benefits of dual immunotherapy.

A Novel Predictor of Pathologic Complete Response for Neoadjuvant Immunochemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma.

Purpose: Neoadjuvant immunochemotherapy (nICT) for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) has attracted widespread attention recently, whose safety and clinical benefit was observed in clinical researches. This study aimed to develop and validate a novel predictor systemic inflammation-tumor markers index (SITI) to predict the pathological complete response (pCR) for resectable LA-ESCC patients receiving nICT. Patients and Methods: A total of 147 LA-ESCC patients who underwent nICT followed by surgery from February 2020 to April 2022 were included in the study. The dynamic change of inflammatory indexes was compared at baseline, after two cycles of nICT and postoperative one month. Least absolute shrinkage and selection operator (LASSO) regression was performed to avoid collinearity and identify key indexes, with SITI constructed. After univariate and multivariate stepwise forward logistic analyses, a nomogram for pCR prediction was developed. Results: 41(27.9%) patients achieved pCR among 147 resectable LA-ESCC patients received nICT. Compared with baseline, most inflammatory indexes were significantly decreased at postoperative one month. 5 key indexes were identified and then a predictive index named SITI was constructed. The result showed that lower SITI and earlier clinical tumor node metastasis (cTNM) stage were more likely to achieve pCR. The nomogram for pCR prediction had excellent discrimination performance (C-index = 0.791). Conclusion: The SITI is an independent predictor for pCR in resectable LA-ESCC patients received nICT. To our knowledge, our nomogram is the first model using systemic inflammation-tumor markers for pCR prediction and may be a promising predictor to effectively differentiate pCR for nICT in LA-ESCC patients.

Perioperative treatment and biomarker analysis of LP002, an anti-PD-L1 antibody, plus chemotherapy in resectable gastric and gastroesophageal junction cancer.

BACKGROUND: The addition of immune checkpoint inhibitors to perioperative chemotherapy in operable gastric or gastroesophageal junction (GEJ) cancer has become one of the research hotspots, while reliable biomarkers for efficacy are lacking. We conducted a phase 1 trial to assess the safety and efficacy of LP002, an anti-PD-L1 antibody, plus chemotherapy as perioperative treatment in patients with gastric or GEJ cancer. METHODS: We enrolled patients with resectable and PD-L1 positive gastric or GEJ cancers. Eligible patients received three preoperative and six postoperative cycles of intravenous LP002 with cisplatin and 5-fluorouracil, repeated every 2 weeks. The primary endpoint was safety. Secondary endpoints included rate of margin-free (R0) resection and pathological complete response (pCR). We also characterized changes in the tumor immune microenvironment using multiplex immunofluorescence (MIF) staining and next-generation sequencing (NGS) with pre- and post-treatment tumor samples. RESULTS: Thirty patients were enrolled, of whom 28 had GEJ cancer. With a median follow-up of 7.9 months, all patients completed preoperative treatment, and 27 patients underwent surgery. Twenty-four patients underwent R0 resection. Six patients (20.0%) had Mandard tumor regression grade (TRG) 1-3, including one achieving pCR. Twenty-seven patients had treatment-related adverse events (TRAEs), while grade 3-4 TRAEs were observed in 11 patients. No treatment-related deaths occurred. MIF staining revealed that TRG 1-3 group was associated with a higher density of PD-L1+/CD68+ cells in the pre-treatment tumor parenchyma than TRG 4-5 group (p = 0.048). NGS studies with paired pre- and post-treatment tumor samples revealed the disappearance of pre-existing mutations, the emergence of new mutations, and variations in the abundance of mutations after preoperative LP002 and chemotherapy. Meanwhile, tumor mutational burden decreased in patients with TRG 1-3 (p = 0.0313). CONCLUSIONS: LP002 plus cisplatin and 5-fluorouracil are safe in patients with gastric or GEJ cancer, and patient selection via appropriate biomarkers is needed in the future.

Reactivation of mutant p53 in esophageal squamous cell carcinoma by isothiocyanate inhibits tumor growth.

p53 mutations are prevalent in human cancers; approximately half of patients with esophageal cancer present these mutations. Mutant p53 (mutp53) exerts oncogenic functions that promote malignant tumor progression, invasion, metastasis, and drug resistance, resulting in poor prognosis. Some small molecules have been shown to mitigate the oncogenic function of mutp53 by restoring its wild-type activity. Although these molecules have been evaluated in clinical trials, none have been successfully used in the clinic. Here, we investigated the antitumor effects of phenethyl isothiocyanate (PEITC) in p53-mutant esophageal squamous cell carcinoma (ESCC) and elucidated its mechanism to identify new therapeutic strategies. We observed that p53R248Q is a DNA contact mutation and a structural mutation and that PEITC can restore the activity of p53R248Q in vitro and in vivo, further clarifying the antitumor activity of PEITC in cancers with different types of p53 mutations. PEITC can inhibit ESCC growth, induce apoptosis, and arrest cell cycle progression and has a preferential selectivity for ESCC with p53 mutations. Mechanistic studies showed that PEITC induced apoptosis and arrested cells at G2/M transition in cells expressing the p53R248Q mutant by restoring the wild-type conformation and transactivation function of p53; these effects were concentration dependent. Furthermore, PEITC inhibited the growth of subcutaneous xenografts in vivo and restored p53 mutant activity in xenografts. According to these findings, PEITC has antitumor effects, with its ability to restore p53R248Q activity being a key molecular event responsible for these effects.

The efficacy and safety of nanoparticle albumin bound-paclitaxel-based regimen as second- or third-line treatment in patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: There are limited reports on nanoparticle albumin bound-paclitaxel (nab-paclitaxel) regimens as second- or third-line treatments for advanced esophageal squamous cell carcinoma (ESCC). Additionally, its safety and efficacy in ESCC patients after failure of first-line programmed cell death protein-1 (PD-1) blockade plus chemotherapy have not been reported. In this study, we aimed to assess the efficacy and tolerability of nab-paclitaxel regimens as second- or later-line treatment in advanced ESCC. METHODS: We retrospectively reviewed clinical data of advanced ESCC patients who participated in a randomized phase III clinical study and received serplulimab or placebo plus chemotherapy at our institution, and consecutive patients who received subsequent nab-paclitaxel-based regimens as second- or later-line treatment were included for data collection and analysis. RESULTS: A total of 39 patients were included, 25 (64.1%) received serplulimab plus chemotherapy and 14 (35.9%) received chemotherapy alone as first-line treatment. Treatment strategies included nab-paclitaxel monotherapy (7/39, 17.9%), or in combination with other chemotherapy (19/39, 48.7%), with anti-PD-1 antibodies (12/39, 30.8%) or with nimotuzumab (1/39, 2.6%). Overall, the objective response rate (ORR) and disease control rate (DCR) were 33.3% (13/39) and 61.5% (24/39), respectively. With a median follow-up of 9.7 months, the median progression-free survival and median overall survival were 5.0 and 7.9 months, respectively. The most common adverse events were neuropathy peripheral (30.8%), anemia (30.8%), neutrophil count decreased (23.1%), and nausea (20.5%). CONCLUSIONS: Nab-paclitaxel-based regimen could be a safe and effective option as second- or later-line treatment in patients with advanced ESCC, regardless of their previous exposure to PD-1 inhibitors.

First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial.

First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m2) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48-0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov ( NCT03958890 ).

A novel prognostic and therapeutic target biomarker based on necroptosis-related gene signature and immune microenvironment infiltration in gastric cancer.

Background: Gastric cancer is a major global public health burden worldwide. Although treatment strategies are continuously improving, the overall prognosis remains poor. Necroptosis is a newly discovered form of cell death associated with anti-tumor immunity. Methods: Gastric cancer (GC) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were downloaded. Bioinformatics analysis was performed to construct a necroptosis-related risk model and to establish cancer subtypes. Potential associations of the tumor immune microenvironment and immunotherapy response with necroptosis-related prognostic risk score (NRG risk score) were comprehensively explored. 16 GC and paired normal tissues were collected and RT-PCR was performed to examine expression of NRG related genes. Results: GC samples were stratified into three subtypes according to prognostic necroptosis gene expression. A necroptosis risk model based on 12 genes (NPC1L1, GAL, RNASE1, PCDH7, NOX4, GJA4, SLC39A4, BASP1, BLVRA, NCF1, PNOC, and CCR5) was constructed and validated. The model was significantly associated with the OS and PFS of GC patients and the tumor immune microenvironment including immune cell infiltration, microsatellite instability (MSI) status, tumor mutational burden (TMB) score, immune checkpoint, and human leukocyte antigen (HLA) gene expression. A prognostic nomogram based on the NRG_score was additionally constructed. A low NRG risk score was correlated with high tumor immunogenicity and might benefit from immunotherapy. Conclusion: We have identified a useful prognostic model based on necroptosis-related genes in GC and comprehensively the relationship between necroptosis and tumor immunity. Predicting value to immunotherapy response is promising, and further research to validate the model in clinical practice is needed.

Assessment of kidney function in chronic kidney disease by combining diffusion tensor imaging and total kidney volume.

OBJECTIVE: This study aimed to investigate the value and feasibility of combining fractional anisotropy (FA) values from diffusion tensor imaging (DTI) and total kidney volume (TKV) for the assessment of kidney function in chronic kidney disease (CKD). MATERIALS AND METHODS: Fifty-one patients were included in this study. All MRI examinations were performed with a 3.0 T scanner. DTI was used to measure FA values, and TKV was obtained from DTI and T2-weighted imaging (T2WI). Patients were divided into three groups (mild, moderate, severe) according to eGFR, which was calculated with serum creatinine. Differences in the FA values of the cortex and medulla were analysed among the three groups, and the relationships of FA values, TKV, and the product of the FA values and TKV with eGFR were analysed. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficiency of the FA values, TKV, and the product of the FA values and TKV for kidney function in different CKD stages. RESULTS: Medullary FA values (m-FA), TKV, and the product of the m-FA values and TKV (m-FA-TKV) were significantly correlated with eGFR (r = 0.653, 0.685, and 0.797, respectively; all P < 0.001). ROC curve analysis showed that m-FA-TKV exhibited better diagnostic performance than m-FA values (P = 0.022). CONCLUSION: m-FA-TKV obtained by DTI significantly improves the accuracy of kidney function assessment in CKD patients.

MiR-204 suppresses the progression of acute myeloid leukemia through HGF/c-Met pathway.

Acute myeloid leukemia (AML) was confirmed to be associated with hematopoietic insufficiency, as well as abnormal proliferation, differentiation or survival of myeloid progenitors. Multiple studies reported that microRNA-204 (miR-204) and Hepatocyte growth factor (HGF) played important roles in types of cancers. However, the potential molecular regulatory mechanism between miR-204 and HGF in AML remains to be further defined. Real-time PCR (RT-PCR) was adopted to detect the expression of miR-204 and HG. Relative protein levels were detected by western blot assay. The viability, cell cycle, apoptosis, migration, and invasion were analyzed by MTT, flow cytometry, and transwell assays. Moreover, the target relationship between miR-204 and HGF was predicted by MiRcode website and confirmed by luciferase reporter, RNA pull-down, and western blot assays. Our data suggested that miR-204 was downregulated in AML serum samples and cells. MiR-204 overexpression repressed cell proliferation, migration, invasion, and induced cell apoptosis in AML cells. HGF was upregulated in AML samples and cells, and HGF knockdown inhibited the malignancy of AML cells. In addition, HGF was directly targeted by miR-204. HGF overexpression reversed the effects of miR-204 mimic on AML cell proliferation, apoptosis, migration, and invasion. Besides, miR-204 regulated the c-Met signaling by targeting HGF, thereby regulating the downstream protein levels related to cell proliferation, apoptosis, migration, and invasion in AML cells. In conclusion, miR-204 could regulate AML progression through regulating the HGF/c-Met pathway.

Metformin Downregulates PD-L1 Expression in Esophageal Squamous Cell Catrcinoma by Inhibiting IL-6 Signaling Pathway.

PURPOSE: To characterize the mechanism by which metformin inhibits PD-L1 expression in esophageal squamous cell carcinoma (ESCC) and to evaluate the effect of metformin on the antitumor immune response. METHODS: The Cancer Genome Atlas (TCGA) database was used to analyze the correlations between IL-6 and prognosis and between IL-6 and PD-L1 gene expression in esophageal cancer. Reverse transcription-quantitative polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence were used to study the mechanism by which metformin affects PD-L1 expression. Additionally, T cell function was assessed in a coculture system containing ESCC cells and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6. In an in vivo assay, we used a model established with NPIdKO™ mice, which have a reconstituted immune system generated by transplanting PBMCs through intravenous injection, to evaluate the effect of metformin on tumors. RESULTS: The TCGA esophageal cancer data showed that IL-6 expression was positively correlated with PD-L1 expression and that patients with high IL-6 expression had a significantly lower overall survival rate than patients with low IL-6 expression. PD-L1 expression in ESCC cell lines was significantly inhibited by metformin via the IL-6/JAK2/STAT3 signaling pathway but was not correlated with the canonical AMPK pathway. In the coculture system, the metformin pretreatment group showed higher T cell activation and better T cell killing function than the control group. Animal experiments confirmed that metformin downregulated PD-L1 expression and that combination treatment with metformin and PD-1 inhibitors synergistically enhanced the antitumor response. CONCLUSIONS: Metformin downregulated PD-L1 expression by blocking the IL-6/JAK2/STAT3 signaling pathway in ESCC, which enhanced the antitumor immune response.

Peri-thrombus vascular hyperintensity sign: detection of intracranial thrombus location and length in acute ischemic stroke.

PURPOSE: The aim of the study was to investigate the diagnostic accuracy of peri-thrombus vascular hyperintensity sign (PVHS) on three-dimensional (3D) black-blood (BB) contrast-enhanced MRI for the detection of intracranial thrombus location and length in acute ischemic stroke (AIS) patients. MATERIALS AND METHODS: Consecutive AIS patients who underwent MRI including 3D BB contrast-enhanced MRI sequence within 8 h of clinical onset were prospectively evaluated. Two readers independently reviewed the 3D BB contrast-enhanced MRI data to assess the presence and location of PVHS. Findings were compared with those of contrast-enhanced MR angiography (CE-MRA) as the reference standard. RESULTS: The PVHS was identified in 49% (63/129) of AIS patients with good agreement. The PVHS had 100% specificity, 88% negative predictive value, 89% sensitivity, and 100% positive predictive value for detection of acute arterial occlusions. Eight patients showed discordant thrombus locations between 3D BB contrast-enhanced MRI and CE-MRA. Median thrombus length in patients with complete occlusion was 9.61 mm. CONCLUSION: The PVHS on 3D BB contrast-enhanced MRI is a highly specific tool for evaluating the location and length of a thrombus in AIS patients.

Penumbra-based radiomics signature as prognostic biomarkers for thrombolysis of acute ischemic stroke patients: a multicenter cohort study.

BACKGROUND AND PURPOSE: This study aimed at developing a radiomics signature (R score) as prognostic biomarkers based on penumbra quantification and to validate the radiomics nomogram to predict the clinical outcomes for thrombolysis for acute ischemic stroke (AIS) patients. METHODS: In total, 168 patients collected from seven centers were retrospectively included. A score of mismatch was defined as MIS. Based on a short-term clinical label, 456 radiomics features were evaluated with feature selection methods. R score was constructed with the selected features. To compare the predictive capabilities of the clinical factors, MIS, and R score, three nomograms were developed and evaluated, according to the short-term clinical assessment on day 7. Finally, the radiomics nomogram was validated by predicting the 3-month clinical outcomes of AIS patients, in an external cohort. RESULTS: R scores were found to be significantly higher in patients with favorable clinical outcomes in both training and validation datasets. The predictive value of the radiomics nomogram estimating favorable clinical outcomes was modest, with a concordance index (C-index) of 0.695 [95% confidence interval (CI) 0.667-0.723) in an external validation dataset. In addition, the area under curve (AUC) of the radiomics nomogram predicting favorable clinical outcome reached 0.886 (95% CI 0.809-0.963) on day 7 and 0.777 (95% CI 0.666-0.888) at 3 months. CONCLUSIONS: The radiomics signature is an independent biomarker for estimating the clinical outcomes in AIS patients. By improving the individualized prediction of the clinical outcome for AIS patients 3 months after onset, the radiomics nomogram adds more value to the current clinical decision-making process.

Predictive Significance Of Preoperative Systemic Immune-Inflammation Index Determination In Postoperative Liver Metastasis Of Colorectal Cancer.

PURPOSE: Systemic inflammation and immune dysfunction have been proved to be significantly associated with cancer progression and metastasis in colorectal cancer (CRC). The aim of this retrospective study was to investigate the association between preoperative systemic immune-inflammation index (SII) and postoperative liver metastasis in CRC. PATIENTS AND METHODS: This retrospective study evaluated 182 patients with CRC who underwent surgical resection. The inflammation-based prognostic factors, including SII, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI), were calculated based on preoperative laboratory data. The univariate and multivariate logistic regression analysis was performed to identify the risk factors correlated with postoperative liver metastasis in CRC. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were respectively used to assess the predictive ability and clinical usefulness of SII for postoperative liver metastasis in CRC. RESULTS: The univariate and multivariable analysis confirmed SII was independently correlated with postoperative liver metastasis in CRC (p<0.001), and the ROC and DCA analysis demonstrated SII was superior to other inflammation-based factors in terms of predictive ability. CONCLUSION: SII is an independent predictive indicator of postoperative liver metastasis for patients with colorectal cancer.

A Deep Learning-Based Radiomics Model for Differentiating Benign and Malignant Renal Tumors.

OBJECTIVES: To investigate the effect of transfer learning on computed tomography (CT) images for the benign and malignant classification on renal tumors and to attempt to improve the classification accuracy by building patient-level models. METHODS: One hundred ninety-two cases of renal tumors were collected and identified by pathologic diagnosis within 15 days after enhanced CT examination (66% male, 70% malignant renal tumors, average age of 62.27 ±â€¯12.26 years). The InceptionV3 model pretrained by the ImageNet dataset was cross-trained to perform this classification. Five image-level models were established for each of the Slice, region of interest (ROI), and rectangular box region (RBR) datasets. Then, two patient-level models were built based on the optimal image-level models. The network's performance was evaluated through analysis of the receiver operating characteristic (ROC) and five-fold cross-validation. RESULTS: In the image-level models, the test results of model trained on the Slice dataset [accuracy (ACC) = 0.69 and Matthews correlation coefficient (MCC) = 0.45] were the worst. The corresponding results on the ROI dataset (ACC = 0.97 and MCC = 0.93) were slightly better than those on the RBR dataset (ACC = 0.93 and MCC = 0.85) when freezing the weights before the mixed6 layer. Compared with the image-level models, both patient-level models could discriminate better (ACC increased by 2%-5%) on the RBR and Slice datasets. CONCLUSIONS: Deep learning can be used to classify benign and malignant renal tumors from CT images. Our patient-level models could benefit from 3D data to improve the accuracy.

[SIRT1 participates in epithelial-mesenchymal transition of EC-9706 and Eca-109 cells in vitro by regulating Snail expression].

OBJECTIVE: To explore the role of SIRT1 in the occurrence of epithelial-mesenchymal transition (EMT) in EC-9706 and Eca-109 cells and the possible mechanism. METHODS: Three chemically synthesized siRNA targeting SIRT1 were transfected into EC-9706 and Eca-109 cells with the non-transfected cells and cells transfected with the negative siRNAs as controls. Real-time PCR and Western blotting were used to detect the expressions of SIRT1, E-cadherin, vimentin, Snail, Twist1 and ZEB in the cells. Transwell invasion assay and wounding healing assay were used to examine the changes in the invasion and metastasis abilities of the cells after transfection. RESULTS: EC-9706 and Eca-109 cells transfected with SIRT1 siRNA1 and SIRT1 siRNA3 showed significantly decreased mRNA and protein expressions of SIRT1 (P < 0.05). Transwell invasion assay and wounding healing assay showed that transfection with SIRT1 siRNA1 and SIRT1 siRNA3 caused significantly lowered invasion and metastasis abilities in EC-9706 and Eca-109 cells (P < 0.05). In EC-9706 and Eca-109 cells transfected with SIRT1 siRNA1 and SIRT1 siRNA3, the expression level of E-cadherin was significantly increased while the expressions of vimentin, Snail and Twist were significantly lowered (P < 0.05). CONCLUSIONS: SIRT1 participates in the invasion and metastasis of EC-9706 and Eca- 109 cells probably by inducing EMT via regulating the expression of Snail.

Development and validation of a penumbra-based predictive model for thrombolysis outcome in acute ischemic stroke patients.

The use of thrombolysis in acute ischemic stroke is restricted to a small proportion of patients because of the rigid 4·5-h window. With advanced imaging-based patient selection strategy, rescuing penumbra is critical to improving clinical outcomes. In this study, we included 155 acute ischemic stroke patients (84 patients in training dataset, age from 43 to 80, 59 males; 71 patients in validation dataset, age from 36 to 80, 45 males) who underwent MR scan within the first 9-h after onset, from 7 independent centers. Based on the mismatch concept, penumbra and core area were identified and quantitatively analyzed. Moreover, predictive models were developed and validated to provide an approach for identifying patients who may benefit from thrombolytic therapy. Predictive models were constructed, and corresponding areas under the curve (AUC) were calculated to explore their performances in predicting clinical outcomes. Additionally, the models were validated using an independent dataset both on Day-7 and Day-90. Significant correlations were detected between the mismatch ratio and clinical assessments in both the training and validation datasets. Treatment option, baseline systolic blood pressure, National Institutes of Health Stroke Scale score, mismatch ratio, and three regional radiological parameters were selected as biomarkers in the combined model to predict clinical outcomes of acute ischemic stroke patients. With the external validation, this predictive model reached AUCs of 0·863 as short-term validation and 0·778 as long-term validation. This model has the potential to provide quantitative biomarkers that aid patient selection for thrombolysis either within or beyond the current time window.