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Propose The early diagnosis of hepatocellular carcinoma (HCC) with ferritin heavy chain (Fth) modified by alpha-fetoprotein (AFP) promoter has been studied. However, no study has focused on the considerable upregulation and specific targeting effects of transferrin receptors (TfR) caused by the transfection of plasmids encoded with the AFP promoter. Thus, the objective of our study was to investigate whether the transfection of Fth gene modified with AFP promoter (AFP@Fth) could be used for early diagnosis and enhanced treatment of HCC. Methods The AFP@Fth plasmid was transfected into AFP positive cells. The expression of intracellular Ferritin was verified by Western blot, and the upregulation of TfR was confirmed by immunofluorescence and flow cytometry analysis. Cellular iron accumulation resulting in decreased imaging signals was examined by magnetic resonance imagining. Doxorubicin liposome modified with transferrin (Tf-LPD) was prepared to investigate the efficiency of the subsequent treatment after transfection. The enhanced drug distribution and effects were investigated both in vitro and in vivo. Results Both Ferritin and TfR were overexpressed after transfection. The transfected cells showed higher intracellular iron accumulation and resulted in a lower MR T2-weighted imaging (T2WI) intensity, suggesting that the transfection of AFP@Fth could be a potential strategy for early diagnosis of liver cancer. The following treatment efficacy was revealed by Tf-LPD. As compared with un-transfected cells, transfected cells exhibited higher uptake of transferrin-modified liposomes (Tf-LP), which was due to the specific interaction between Tf and TfR overexpressed on the transfected cells. This is also the reason why Tf-LPD showed better in vitro and in vivo anticancer ability than doxorubicin loaded liposome (LPD). These results suggested that transfection of AFP@Fth could result in enhanced therapy of liver cancer. Conclusion Transfection of AFP@Fth could be used for early diagnosis and for enhanced treatment of live cancers.

Aims To explore the relationship between the circulating neutrophil‐to‐lymphocyte ratio (NLR) and the remote diffusion‐weighted imaging lesions (R‐DWILs) after spontaneous intracerebral hemorrhage (ICH). Methods Consecutive patients with spontaneous ICH were prospectively collected from November 2016 to May 2018 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections on admission or in hospital. Blood samples were obtained at 24‐48 hours after ICH ictus, while all complete MRI scans were performed at 5‐8 days. R‐DWILs were defined as focal hyperintensities remote from the site of the ICH or the peri‐hematoma regions. NLR was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. Multivariate binary logistic regression models were generated to evaluate the relationship between NLR and R‐DWILs. Results One hundred sixty‐three subjects met eligibility criteria (age 62.3 ± 13.6 years, 60.7% males), of whom 31(19.0%) experienced R‐DWILs. Higher circulating NLR was documented in patients with R‐DWILs. With the best cutoff value of 6.01, elevated NLR was independently associated with the presence of R‐DWILs (OR = 3.170, 95% CI 1.306‐7.697, P = .011) in the bivariate logistic regression analysis with adjustment for age, sex, atrial fibrillation, previous ischemic stroke/TIA, SBP on admission, hematoma volume, and IVH. Conclusions This study provides significant evidence of the association between circulating NLR and R‐DWILs in spontaneous ICH patients. Patients with NLR > 6.01 at 24‐48 hours after ICH ictus should be paid more attention to when evaluating R‐DWILs.

To evaluate the qualitative image quality and quantitative apparent diffusion coefficient (ADC) value of reduced field-of view (rFOV) and full field-of-view (fFOV) diffusion-weighted imaging (DWI) sequences at 3.0 T in patients with gastric cancer. Fifty-three patients (37 males, 16 females; mean age, 63.3 ± 10.3 years) with 60 lesions with gastric cancer who underwent magnetic resonance (MR) scans, including both rFOV-DWI and fFOV-DWI, were retrospectively analyzed. Two observers subjectively evaluated image quality for both the fFOV-DWI and rFOV-DWI sequences regarding the anatomic details, distortion, lesion conspicuity, artifacts, and overall image quality. The mean ADC values of gastric cancer were calculated. The Wilcoxon test and paired samples t test were used. Interobserver agreement was assessed using kappa statistics. The mean scores based on the 2 observers demonstrated significant differences in image quality in terms of anatomic details, distortion, lesion conspicuity, artifacts and overall image quality at both b values between rFOV-DWI and fFOV-DWI (P

Aim: Prognostic factors in patients with distant metastatic pancreatic neuroendocrine tumors (PNETs) remain uncertain. The purpose of our study is to establish a nomogram to predict survival outcomes in patients with metastatic PNETs. Methods: A total of 878 patients diagnosed with PNETs in the Surveillance, Epidemiology and End Results database between 2004 and 2016 were retrospectively identified. The Kaplan–Meier survival analysis with log-rank test was used to analyze survival outcomes. The nomogram was established after a univariate and multivariate Cox analysis. Results: The independent prognostic variables, including age, tumor grade and primary site surgery were applied to develop a nomogram. The original concordance index was 0.773 (95% CI: 0.751–0.795), and the bias-corrected concordance index was 0.769 (95% CI: 0.748–0.791). The internal calibration curves showed well consistency and veracity in predicting cancer-specific survival probabilities. Conclusion: A nomogram was constructed and verified to predict survival outcomes in patients with distant-stage PNETs.

Stress-induced hyperglycemia (SIH) is the relative transient increase in glucose during a critical illness such as intracerebral hemorrhage (ICH) and is likely to play an important role in the pathogenesis of remote diffusion-weighted imaging (DWI) lesion (R-DWIL) in primary ICH. We sought to determine the association between SIH and the occurrence of R-DWILs. We prospectively enrolled primary ICH patients within 14 days after onset from November 2016 to May 2018. In these patients, cerebral magnetic resonance imaging was performed within 14 days after ICH onset. R-DWIL was defined as a hyperintensity signal in DWI with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. SIH was measured by stress-induced hyperglycemia ratio (SHR). SHR was calculated by fasting blood glucose (FBG) divided by estimated average glucose derived from glycosylated hemoglobin. The included patients were dichotomized into two groups by the 50th percentile of SHR, and named as SHR (−P50) group and SHR (P50+) group, respectively. We evaluated the association between SHR and R-DWIL occurrence using multivariable logistic regression modeling adjusted for potential confounders. Among the 288 patients enrolled, forty-six (16.0%) of them had one or more R-DWILs. Compared with the patients in the lower 50% of SHR (SHR [−P50]), the odds ratio (OR) [95% confidence interval (CI)] for the higher 50% of SHR (SHR [P50+]) group for R-DWIL occurrence was 3.13 (1.39–7.07) in the total population and 6.33 (2.19–18.30) in population absent of background hyperglycemia after adjusting for potential covariates. Similar results were observed after further adjusted for FBG. Our study demonstrated that SIH was associated with the occurrence of R-DWILs in patients with primary ICH within 14 days of symptom onset.

Background and purpose The aim of this study was to examine the association amongst remote diffusion-weighted imaging lesions (R-DWILs), imaging markers of cerebral small vessel disease (cSVD) and total cSVD burden in patients with primary intracerebral haemorrhage (ICH). Methods In total, 344 consecutive primary ICH patients were enrolled prospectively. R-DWILs on magnetic resonance imaging as well as four imaging markers of cSVD, including cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), lacunes and enlarged perivascular spaces, were rated with validated scales. The total cSVD score was calculated by adding up these four markers. Univariate and multivariate analyses were performed. Results Remote DWI lesions were detected in 57 (16.6%) primary ICH patients. On multivariate logistic regression analysis, the presence of CMBs [odds ratio (OR) 5.26, 95% confidence interval (CI) 1.72-16.12], of high-grade WMHs (OR 4.68, 95% CI 2.01-10.90), the presence of lacunes (OR 2.69, 95% CI 1.20-6.06), mixed CMBs (OR 2.93, 95% CI 1.35-6.36), mixed lacunes (OR 3.60, 95% CI 1.25-10.37), periventricular WMHs (OR 2.19, 95% CI 1.40-3.44), deep WMHs (OR 1.92, 95% CI 1.24-2.97) and total WMHs (OR 1.52, 95% CI 1.20-1.94) were associated with the presence of R-DWILs. A significant association was also found between high-grade total cSVD score and R-DWILs (OR 1.97, 95% CI 1.36-2.84). This association remained significant in patients stratified by an age of 60 years or more than 60 years. Conclusions Remote DWI lesions are correlated with the severity of each imaging marker of cSVD and with the total burden of cSVD.

Background and purpose Remote diffusion-weighted imaging lesions (R-DWILs) have been detected in patients with spontaneous intracerebral hemorrhage (ICH) and may be correlated with clinical outcome. However, the mechanisms and characteristics of R-DWILs have not been fully elucidated. In this study, we sought to demonstrate the clinical characteristics of R-DWILs in spontaneous ICH. Methods We prospectively collected data with spontaneous ICH patients from November 2016 to December 2017. In these patients, cerebral magnetic resonance imaging was performed within 28 days after ICH onset. R-DWIL was defined as a hyperintensity signal in diffusion-weighted imaging with corresponding hypointensity in apparent diffusion coefficient, and at least 20 mm apart from the hematoma. We compared two groups of patients with or without R-DWIL with the demographic and clinical characteristics, laboratory parameters, and imaging characteristics, by using univariate and multivariate analysis. Results Of the 222 patients enrolled, a total of 75 R-DWILs were observed in 41 patients (18.5%). Among these lesions, the cortical and subcortical areas were the predominant locations with a proportion of 77.3%. The median diameter of R-DWILs was 7 mm (range 2–20 mm). Twelve patients were found having more than one lesion, with five among which showed R-DWILs in multiple cerebral arterial territories. In multivariate modeling, higher fasting glucose (OR 1.231; 95% CI 1.035–1.465; p = 0.019) and more severe white matter hyperintensity (WMH) (OR 6.589; 95% CI 2.975–14.592; p

Objective: Remote diffusion-weighted imaging (DWI) lesions (R-DWIL) found in intracerebral hemorrhage (ICH) patients are considered as an additional marker of cerebral small vessel disease (cSVD). This study aimed to investigate the association of renal dysfunction and R-DWIL, as well as the total burden of cSVD on magnetic resonance imaging among patients with primary ICH. Methods: One hundred and twenty-six consecutive patients were prospectively enrolled. R-DWIL on DWI, as well as other imaging markers of cSVD, including lacunes, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. Renal dysfunction was evaluated either by reduced estimated glomerular filtration rate (eGFR) or the presence of proteinuria or increased cystatin C. Results: After adjustments for potential confounders by logistic regression, impaired eGFR [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.73-20.78], proteinuria (OR 3.07, 95% CI 1.25-7.54) and increased cystatin C (OR 2.73, 95% CI 1.11-6.72) were correlated with presence of R-DWIL. A similar association was also found between cystatin C levels (OR 3.16, 95% CI 1.39-7.19), proteinuria (OR 2.79, 95% CI 1.34-5.83) and the comprehensive cSVD burden. Conclusions: Renal dysfunction are associated with the presence of R-DWIL, and total burden of cSVD in patients with primary ICH.

Several mechanisms are involved in the neuroprotection of propofol against ischemia, but influences of propofol on the binding properties of glutamate receptors and the uptake of glutamate in brain ischemia are not known. The present study was undertaken to investigate these issues in rat global brain ischemic model using methods of neuropathological evaluation, radioligand binding assay with and uptake test for L-(3)H-glutamate. It was shown that propofol used in anesthetic doses protected pyramidal neurons in the hippocampal CA1 subfield against delayed neuronal death normally induced by global brain ischemia. Simultaneously, the propofol decreased the value of maximal number of binding sites (Bmax), increased the value of equilibrium dissociation constant (Kd), and increased the glutamate uptake in the CA1 subfield. These findings indicate that it is, at least partly, via modulating the binding properties of glutamate receptors and the uptake of glutamate that propofol protects neurons against ischemic injury.