A multifunctional pH-sensitive polymeric nanoparticle system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. The nanoparticles were self-assembled using the multi-block polymer poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and the pH-sensitive material poly(l-histidine)-poly(ethylene glycol)-biotin (PLH-PEG-biotin). The anti-hepatocellular carcinoma (HCC) drug sorafenib was encapsulated inside the nanoparticles. Gd ions were chelated to the DTPA groups which were distributed on the nanoparticle surface. Biotinylated vascular endothelial growth factor receptor (VEGFR) antibodies were linked to the surface biotin groups of nanoparticles through the avidin linker to form the target pH-sensitive theranostic nanoparticles (TPTN). TPTN exhibited spherical or ellipsoidal shapes, uniform particle size distribution (181.4 ± 3.4 nm), positive zeta potential (14.95 ± 0.60 mV), high encapsulation efficiency (95.02 ± 1.47%) and drug loading (2.38 ± 0.04%). The pH-sensitive sorafenib release from TPTN was observed under different pH values (47.81% at pH = 7.4 and 99.32% at pH = 5.0, respectively). In cell cytotoxicity studies, TPTN showed similar antitumor effect against HepG2 cells compared to solubilized sorafenib solution after pre-incubation in acid PBS (pH = 5.0) for 1 h in vitro (P > 0.05). In in vivo anti-tumor studies, TPTN showed significantly higher antitumor effect in H22 tumor (VEGFR overexpressed cell line) bearing mice compared to the solubilized sorafenib solution (oral or i.v. administration) group (P < 0.05). In the MRI test, the T1 relaxivity value of TPTN was 17.300 mM(-1) s(-1) which was 3.6 times higher than Magnevist® (r1 = 4.8 mM(-1) s(-1)). As a positive contrast agent, TPTN exhibited higher resolution and longer imaging time (more than 90 min) in the MRI diagnosis of tumor-bearing mice compared to Magnevist® (more than 60 min). Furthermore, histological examination of TBN (blank TPTN, without sorafenib loaded) showed no visible tissue toxicity compared to normal saline. Thus, TPTN possessed dual-loading drugs and imaging agents, active targeting and pH-triggered drug release properties in one platform with good biocompatibility. All of these results indicated that TPTN was a promising theranostic carrier which could be a platform for the development of novel multifunctional theranostic agents.

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Multifunctional nanotheranostic agents have been highly commended due to the application to image-guided cancer therapy. Herein, based on the chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) and graphene oxide (GO), we develop a pH-responsive FePt-based multifunctional theranostic agent for potential in vivo and in vitro dual modal MRI/CT imaging and in situ cancer inhibition. The fcc-FePt will release highly active Fe ions due to the low pH in tumor cells, which would catalyze HO decomposition into reactive oxygen species (ROS) within the cells and further induce cancer cell apoptosis. Conjugated with folic acid (FA), the iron platinum-dimercaptosuccinnic acid/PEGylated graphene oxide-folic acid (FePt-DMSA/GO-PEG-FA) composite nanoassemblies (FePt/GO CNs) could effectively target and show significant toxicity to FA receptor-positive tumor cells, but no obvious toxicity to FA receptor-negative normal cells, which was evaluated by WST-1 assay. The FePt-based multifunctional nanoparticles allow real-time monitoring of Fe release by T-weighted MRI, and the selective contrast enhancement in CT could be estimated in vivo after injection. The results showed that FePt-based NPs displayed excellent biocompatibility and favorable MRI/CT imaging ability in vivo and in vitro. Meanwhile, the decomposition of FePt will dramatically decrease the T-weighted MRI signal and increase the ROS signal, which enables real-time and in situ visualized monitoring of Fe release in tumor cells. In addition, the self-sacrificial decomposition of fcc-FePt will be propitious to the self-clearance of the as-prepared FePt-based nanocomposite in vivo. Therefore, the FePt/GO CNs could serve as a potential multifunctional theranostic nanoplatform of MRI/CT imaging guided cancer diagnosis and therapy in the clinic.

Coronavirus disease 2019 (COVID-19) is a newly emerged infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been pandemic all over the world. This study described acute kidney injury (AKI) at early stage of COVID-19 and its clinical significance. Three-hundred and fifty-five COVID-19 patients with were recruited and clinical data were collected from electronic medical records. Patient's prognosis was tracked and risk factors of AKI was analyzed. Of 355 COVID-19 patients, common, severe and critical ill cases accounted for 63.1%, 16.9% and 20.0%, respectively. On admission, 56 (15.8%) patients were with AKI. Although AKI was more common in critical ill patients with COVID-19, there was no significant association between oxygenation index and renal functional indices among COVID-19 patients with AKI. By multivariate logistic regression, male, older age and comorbidity with diabetes were three important independent risk factors predicting AKI among COVID-19 patients. Among 56 COVID-19 patients with AKI, 33.9% were died on mean 10.9 day after hospitalization. Fatality rate was obviously higher among COVID-+19 patients with AKI than those without AKI (RR=7.08, P<0.001). In conclusion, male elderly COVID-19 patients with diabetes are more susceptible to AKI. AKI at early stage may be a negative prognostic indicator for COVID-19.

Purpose:To determine how dynamic contrast-enhanced (DCE) MRI at 3T correlates with rectal carcinoma angiogenesis. Materials and Methods:Three-dimensional (3D) DCE MRI was performed in 38 patients (23 males, 15 females, mean age 60 years) with histologically-confirmed rectal carcinoma at 3T. Time-intensity curves (TICs) were used to measure peak enhancement ratio (ER peak ), time to peak enhancement (T peak ), first enhancement time (T first-enhance ), and uptake rate for rectal tumor, normal rectal wall, and gluteal muscle. After tumor resection, microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression were determined using immunohistochemistry (IHC) stains on available specimens (N ϭ 24) to correlate with DCE MRI.Results: Rectal carcinoma showed higher ER peak (3.0 Ϯ 0.9 vs. 1.9 Ϯ 0.9, P Ͻ 0.001), higher uptake rate (2.8 Ϯ 1.5/ minute vs. 1.2 Ϯ 0.9/minute, P Ͻ 0.001), earlier T peak (88 Ϯ 56 seconds vs. 124 Ϯ 72 seconds, P ϭ 0.027), and earlier T first-enhance (34 Ϯ 6 seconds vs. 40 Ϯ 7 seconds, P ϭ 0.008) than normal rectal wall. Adenocarcinoma had shorter T peak compared to signet cell carcinoma (77 Ϯ 48 seconds vs. 160 Ϯ 62 seconds, P ϭ 0.004). T peak was negatively correlated with MVD (r ϭ -0.516, P ϭ 0.01) and the mean T peak was significantly earlier for the VEGF-positive group compared to the VEGF-negative group (57 Ϯ 17 seconds vs. 107 Ϯ 64 seconds, P ϭ 0.021).Conclusion: DCE MRI parameters help predict rectal tumor angiogenesis measured by MVD and VEGF expression and discriminate malignant from normal tissue.