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Aim This study investigated the effects of insulin glargine and exenatide on the muscle mass of patients with newly diagnosed type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods We performed a post-hoc analysis of our previously study, a 24-week randomized controlled multicenter clinical trial (ClinicalTrials.gov, NCT02303730). Seventy-six patients were randomly assigned 1:1 to receive insulin glargine or exenatide treatment. The changes in psoas muscle area (PMA) (mm2) were obtained with the cross-sectional Dixonfat magnetic resonance images at the fourth lumber vertebra. Results There were no significant differences in age, BMI, gender, and PMA in insulin glargine and exenatide groups at baseline. After treatment, PMA tended to increase by 13.13 (–215.52, 280.80) mm2 in the insulin glargine group and decrease by 149.09 (322.90–56.39) mm2 in the exenatide group (both p> 0.05). Subgroup analysis showed a 560.64 (77.88, 1043.40) (mm2) increase of PMA in the insulin group relative to the Exenatide group in patients with BMI<28 kg/m2 (p 0.031) after adjusting for gender, age, and research center. Interaction analysis showed an interaction between BMI and treatment (p 0.009). However, no interaction was observed among subgroups with a BMI≥28 kg/m2 or with different genders and ages. Conclusion Compared to exenatide, insulin glargine can relativity increase PMA in patients with T2DM having BMI<28 kg/m2 and NAFLD. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to develop a novel noninvasive model to detect advanced fibrosis based on routinely available clinical and laboratory tests. Materials and Methods: A total of 309 patients who underwent liver biopsy were randomly divided into the estimation group (n = 201) and validation group (n = 108). The model was developed using multiple regression analysis in the estimation group and further verified in the validation group. Diagnostic accuracy was evaluated using the receiver operating characteristic (ROC) curve. Results: The model was named NAFLD Fibrosis Index (NFI): −10.844 + 0.046 × age − 0.01 × platelet count + 0.19 × 2h postprandial plasma glucose (PG) + 0.294 × conjugated bilirubin − 0.015 × ALT + 0.039 × AST + 0.109 × total iron binding capacity −0.033 × parathyroid hormone (PTH). The area under the ROC curve (AUC) of NFI was 0.86 (95% CI: 0.79–0.93, p < 0.001) in the estimation group and 0.80 (95% CI: 0.69–0.91, p < 0.001) in the validation group, higher than NFS, FIB4, APRI, and BARD, and similar to FibroScan (NFI AUC = 0.77, 95% CI: 0.66–0.89, p = 0.001 vs. FibroScan AUC = 0.76, 95% CI: 0.62–0.90, p = 0.002). By applying the low cut‐off value (−2.756), advanced fibrosis could be excluded among 49.3% and 48% of patients in the estimation group (sensitivity: 93.1%, NPV: 97.9%, specificity: 55.2%, and PPV: 26.0%) and validation group (sensitivity: 81.3%, NPV: 94.2%, specificity: 53.3%, and PPV: 23.2%), respectively, allowing them to avoid liver biopsy. Conclusions: The study has established a novel model for advanced fibrosis, the diagnostic accuracy of which is superior to the current clinical scoring systems and is similar to FibroScan. [ABSTRACT FROM AUTHOR]

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80–120 mg S-1, days 1–14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80–120 mg S-1, days 1–14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31–13.24]. The median PFS was 7.16 months (95% CI, 5.19–12.32) for patients treated with AS and 6.41 months (95% CI, 3.72–8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51–1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019. [ABSTRACT FROM AUTHOR]

Hexyl aminolevulinate (HAL) is a lipophilic derivative of 5‐aminolevulinic acid (5‐ALA) and can induce more protoporphyrin IX (PpIX) formation and stronger fluorescence intensity (FI) than 5‐ALA, which will greatly facilitate photodynamic diagnosis and therapy. The main drawback of HAL is its low solubility in neutral aqueous media. In this study, surfactants were used to increase HAL solubility in the cell culture medium and serum, followed by in vitro fluorescence formation measurement in human pancreatic cancer cells (SW1990) and in vivo fluorescence detection in tumor‐bearing mice. The results showed that Tween 80 (TW80) and Kolliphor® HS 15 (HS15) increased the solubility of HAL in the selected media. Although TW80 and HS15 exhibited in vitro cytotoxicity at high concentrations (5 mg mL−1), they facilitated fluorescent signal formation at the early stage of cell incubation. When surfactants were used, the FI should be determined without the routine washing process because surfactant‐containing culture medium caused the loss of synthesized PpIX during the washing process. When HAL dissolved in TW80 solution was injected intraperitoneally into pancreatic cancer‐bearing mice at a dose of 50 mg kg−1, the tumors exhibited red fluorescence, which indicated that systemic administration of surfactant‐solubilized HAL might be applicable for tumor fluorescence detection in vivo. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the efficacy of exenatide and insulin glargine in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).Methods: We performed a 24-week randomized controlled multicentre clinical trial. Seventy-six patients were randomly assigned 1:1 to receive exenatide or insulin glargine treatment. The endpoints included changes in liver fat content (LFC), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) measured by magnetic resonance spectroscopy, blood glucose, liver enzymes, lipid profile, body weight, and Fibrosis-4 index (FIB-4).Results: LFC, VAT, SAT, and FIB-4 were significantly reduced after exenatide treatment (ΔLFC, -17.55 ± 12.93%; ΔVAT, -43.57 ± 68.20 cm2 ; ΔSAT, -28.44 ± 51.48 cm2 ; ΔFIB-4, -0.10 ± 0.26; all P < .05). In comparison, only LFC (ΔLFC, -10.49 ± 11.38%; P < .05), and not VAT, SAT, or FIB-4 index (all P > .05), was reduced after insulin glargine treatment. Moreover, exenatide treatment resulted in greater reductions in alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transpeptidase (GGT) than insulin glargine (P < 0.05). The body weight, waist circumference, postprandial plasma glucose, and low-density lipoprotein cholesterol (LDL-C) in the exenatide group also presented greater reductions than the insulin glargine group (P < .05). The proportion of adverse events were comparable between the two groups.Conclusion: Both exenatide and insulin glargine reduced LFC in patients with drug-naive T2DM and NAFLD; however, exenatide showed greater reductions in body weight, visceral fat area, liver enzymes, FIB-4, postprandial plasma glucose, and LDL-C. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To explore the potential value of radiomic features-derived approach in assessing PD-L1 expression status in nonsmall cell lung cancer (NSCLC) patients.Materials and Methods: A cohort of 399 stage I-IV NSCLC patients were enrolled. Tumor segmentation was performed to select essential primary lesions of NSCLC cases after PET/CT images acquisition. Features were extracted, then filtered with automatic relevance determination and minimized with LASSO model based on its relevance of PD-L1 expression status. Finally, we built predictive models with features from the CT, the PET, and the PET/CT images, respectively, for differentiating different status of specific PD-L1 types. Five-fold cross validation was practiced to evaluate the signatures' accuracy, and the receiver operating characteristic as well as the corresponding area under the curve (AUC) was reckoned for each model.Results: With the total of 24 selected features which were significantly associated with PD-L1 expression levels, models based on CT-, PET-, PET/CT-derived features were built and compared. For PD-L1 (SP142) expression level over 1% prediction, models that comprised radiomic features from the CT, the PET, and the PET/CT images resulted in an AUC of 0.97, 0.61, and 0.97, respectively; models for over 50% prediction resulted with AUC of 0.80, 0.65, and 0.77. For PD-L1 (28-8) expression level prediction, predictive models of over 1% expression scored at 0.86, 0.62, and 0.85; and signatures of over 50% expression reached the score of AUCs at 0.91, 0.75, and 0.88, respectively.Conclusion: The radiomic-based predictive approach, especially CT-derived predictive model, may anticipate PD-L1 expression status in NSCLC patients relatively accurate. It may be helpful in guiding immunotherapy in clinical practice and deserves further analysis. [ABSTRACT FROM AUTHOR]

The facile fabrication of Gd-labeled superparamagnetic Fe3O4 nanoparticles (NPs) and fluorescent CuInS2 (CIS) quantum dots conjugated with arginine-glycine-aspartic acid (RGD) peptides has been demonstrated, for tri-mode targeted T1-, T2-weighted magnetic resonance (MR) and fluorescence imaging of pancreatic cancer. The core–shell nanocomposites formed are water-dispersible, stable and biocompatible, as confirmed by MTT assay on BXPC-3 cells. Relaxivity measurements show a T1 relaxivity (r1) of 1.56 mM−1 s−1 and a T2 relaxivity (r2) of 23.22 mM−1 s−1, which enable T1- and T2-weighted MR imaging of cancer cells in vitro and in vivo. The MR imaging data clearly indicate that the multifunctional NPs can specifically target cancer cells with αvβ3 integrin over-expression on the cell surface, through a receptor-mediated delivery pathway. The T1-weighted positive and T2-weighted negative enhancement in the MR imaging significantly improves the diagnosis accuracy, and fluorescence imaging of tumor tissue can assist in clinical surgery. These findings suggest that these multifunctional NPs could be used as a platform for bimodal imaging (both MR and fluorescence) in various biological systems. [ABSTRACT FROM AUTHOR]

We synthesized cadmium-free CuInS2–Zn1−xMnxS core–shell quantum dots (QDs) for use in dual-mode optical and magnetic resonance (MR) imaging techniques. Manganese content was in the rang of 0.2–2.3% and varies with the amount of Mn2+ content in the reaction. These materials presented a high quantum yield (QY) of 52% in organic solvent. The CuInS2–Zn1−xMnxS nanoparticles were subsequently transferred to the aqueous phase by the aid of cetyltrimethylammonium bromide (CTAB), and the QY values in water reached 18%. Relaxivity measurements showed that these materials had a T1 relaxivity (r1) of 7.2 mM−1 s−1 on the 3.0 T scanner, suggesting the possibility of using the nanoparticles as a T1 contrast agent. The nanomaterials for both optical and MR imaging in aqueous solution were applied to cells in culture. These results showed that the QY and manganese concentration in the nanoparticles was sufficient to produce contrast for both modalities at relatively low concentrations of nanoparticles. [ABSTRACT FROM AUTHOR]

Purpose: Theranostic nanoplatforms are promising approaches for diagnosis and treatment. Here, we report a drug-loaded nanomicelle system with biocleavable gadolinium (Gd) chelates as a multifunctional biodegradable agent for simultaneous magnetic resonance imaging (MRI) and drug delivery.Methods: Self-assembled nanomicelles based on stearic acid-grafted chitooligosaccharide were utilized as vehicles. Gd chelates, DTPA-Gds, were linked to the nanomicelles via redox-responsive disulfide bonds, and hydrophobic drugs were encapsulated in the micelle cores. MRI and cargo delivery were investigated in orthotopic pancreatic tumor-bearing mice.Results: In vivo MRI demonstrated that the biodegradable agent was cleaved by endogenous thiols after intravenous injection, and the released DTPA-Gds were eliminated rapidly. At the same time, the agent resulted in a greater contrast enhancement of T1-weighted MR signal intensity at the tumor region than Magnevist®, and the tumor boundaries were clearly defined for at least 2 h. In addition, the agent possessed high drug-loading and tumor-targeting capacities. Loading content and encapsulation efficiency of docetaxel were 3.2% and 99.4%, respectively. Compared with Taxotere®, the commercially available docetaxel injection, the docetaxel-loaded agent significantly increased the drug concentration in tumor tissue in vivo.Conclusion: The fabricated multifunctional agent may serve as a biodegradable nanoscale MRI contrast agent and as a drug delivery system for tumor diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate Cytokeratin 19 expression in hepatocellular carcinoma (HCC) with diffusion parameters derived from mono-exponential model (MEM), stretched exponential model (SEM), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) imaging, and fractional order calculus (FROC) model and compare their predictive performance.Method: 61 patients with pathologically confirmed primary HCC were included in this prospective study. All the DWIs were acquired using a 3.0 T MR scanner with 10b-values (0-2000 s/mm2). The apparent diffusion coefficient (ADC), distributed diffusion coefficient (DDC), heterogeneity index (α), apparent kurtosis coefficient (AK), apparent diffusion coefficient (AD), pseudo-diffusion coefficient (Dp), true diffusion coefficient (Dt), perfusion fraction (f), diffusion coefficient (D), fractional order parameter (β), and a microstructural quantity (μ) were calculated. The diagnostic efficacy of various diffusion parameters for predicting CK19 expression of HCC was compared.Results: ADC, DDC, Dt, Dp, AD, and D were significantly lower in CK19-positive HCCs than in CK19-negative HCCs (P ≤ 0.05). β was significantly higher in CK19-positive group (P = 0.001). AD (AUC = 0.845) had the greatest AUC values in differentiating CK19-positive and CK19-negative HCC with individual parameters. The combination of β, AD, and Dp generated the highest area under the ROC curve (AUC = 0.881) compared with individual parameters.Conclusions: ADC, DDC, Dt, Dp, D, and β may serve as noninvasive and quantitative imaging markers and holds great potential in accurately accessing CK19 status of HCC. More importantly, the combination of different diffusion parameters yielded better diagnostic performance. [ABSTRACT FROM AUTHOR]