Background: As one typical cardiovascular disease, atherosclerosis severely endanger people’ life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. However, current drugs failed to meet clinical demands.Methods: Nanomedicine and nanotechnology hold great potential in addressing the issue. In this report, we engineered a simvastatin (Sim)-loaded theranostic agent based on porous manganese-substituted prussian blue (PMPB) analogues. The biomimetic PMPB carrier could scavenge ROS and mitigate inflammation in vitro and in vivo. Especially after combining with Sim, the composite Sim@PMPB NC was expected to regulate the processes of atherosclerosis. As well, Mn²⁺release from PMPB was expected to enhance MRI.Results: The composite Sim@PMPB NC performed the best in regulating the hallmarks of atherosclerosis with above twofold decreases, typically such as oxidative stress, macrophage infiltration, plaque density, LDL internalization, fibrous cap thickness and foam cell birth, etc.Moreover, H₂O₂-induced Mn²⁺release from PMPB NC in atherosclerotic inflammation could enhance MRI for visualizing plaques. Moreover, Sim@PMPB exhibited high biocompatibility according to references and experimental results.Conclusions: The biomimetic Sim@PMPB theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and also localized and magnified atherosclerosis, which enabled the monitoring of H₂O₂-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis.Graphic

EVA1A (also known as transmembrane protein 166) is a transmembrane protein involved in the regulation of autophagy that acts as an adaptor protein to recruit or bind proteins in the lysosome or endoplasmic reticulum. In the present study, we identified EVA1A as a target of microRNA-125b (miR-125b), a member of a highly conserved family of miRNAs that has been proposed as a biomarker for hepatocellular carcinoma (HCC). Analysis of oxaliplatin-sensitive and oxaliplatin-resistant HCC cell lines showed that miR-125b is downregulated in resistant cells and its overexpression in sensitive cells decreased resistance to oxaliplatin by inhibiting cell proliferation, migration and epithelial–mesenchymal transition (EMT). EVA1A expression was shown to be upregulated in tissue samples from oxaliplatin-resistant HCC patients, and its ectopic expression partially induced autophagy and reversed the effect of miR-125b on inhibiting the growth of oxaliplatin-resistant cell lines and xenograft tumors. Taken together, our results suggest that miR-125b plays a role in the resistance of HCC cells to chemotherapy via a mechanism involving the downregulation of EVA1A-mediated autophagy.

To evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation (BRFA) of benign thyroid nodules by comparison with a matched untreated control group. The therapeutic efficacy and safety in 35 patients who were subjected to a single session of ultrasound-guided percutaneous BRFA (Group A) for benign thyroid nodules were compared with those in 35 untreated patients (Group B) with benign nodules. The benign nature of all the nodules was confirmed by ultrasound-guided fine-needle aspiration biopsy (FNAB), and all the patients had normal thyroid functions. BRFA was performed with a bipolar electrode (CelonProSurge 150–T20) with an output power of 20 W. Nodule volume, thyroid function and clinical symptoms of all the patients were compared before treatment and during follow-up. In Group A, the BRFA procedures were completed with a mean time of 10.02 ± 3.30 min (range, 5.47–16.03 min) and with a mean total energy deposition of 10.747 ± 3704 J (range, 5510–17.770 J). The procedures were tolerated well in all the patients without causing any major complications. At the 6-month follow-up, all of the nodule volume decreased significantly (from 8.81 ± 8.66 to 1.59 ± 1.55 ml, p < 0.001) in Group A, whereas the nodule volume increased from 6.90 ± 3.77 to 7.87 ± 3.95 ml in Group B (p < 0.001). All (100%) the 35 nodules in Group A had volume reduction ratios (VRRs) of >50%, among which 3 (8.57%) had VRRs >90%. In Group A, the clinical symptoms of the patients who had symptoms before BRFA disappeared, whereas in Group B, the patients had no resolution of clinical symptoms at the 6-month follow-up. Ultrasound-guided percutaneous BRFA seems to be an effective and safe method for the treatment of benign thyroid nodules. It may gain a wide use in clinical practice. Based on the comparable efficacy and clinical symptoms between the BRFA and untreated groups, the technique of BRFA can be used as an effective and safe method for the treatment of benign thyroid nodules.

Obesity, a surging global health challenge, necessitates effective, accessible and innovative therapeutic models. Here we develop a spatiotemporally controllable microneedle (MN) drug delivery platform for sono-gene therapy to fight obesity. The platform delivers the methoxy polyethylene glycol-polyethyleneimine (mPEG-PEI) modified metal-organic frameworks (MOFs) sonosensitizer and the clustered regularly interspaced short palindromic repeats-activating (CRISPRa)/CRISPRa-uncoupling protein 1 (UCP1) system intradermally to adipocytes. Overall, this therapy platform is capable of achieving two major strategies of “annihilation” and “countermeasure”: one is to kill redundant white adipocytes by sonodynamic therapy, and the other is to promote the browning of white adipocytes through the controllable release of CRISPRa-UCP1 system and sonodynamic effect. Obese male mice treated with this sono-gene therapy shows significant ameliorate in glucose tolerance and insulin sensitivity, successfully achieves weight loss and restrains weight rebound. This study may enable a standard treatment paradigm for sono-gene therapy of obesity and other metabolic diseases.

Due to the increasing rates of physical examination and application of advanced ultrasound machines, incidences of benign thyroid nodules (BTNs) and papillary thyroid microcarcinoma (PTMC) were dramatically up-regulated in recent years. Thermal ablation (TA) has been widely used and regarded as a safe and effective method to eliminate or reduce BTNs and recurrent low-risk PTMC. However, conclusions using TA to treat primary PTMC are controversial. Recently, several long-term and prospective studies on TA treatment of BTNs and primary PTMC have been reported. Here, we review current literatures and progress on TA treatment of BTNs and PTMC and underline the way to get the best treatment outcomes, providing a comprehensive insight into the research progresses in this field.

Objective:To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers.Methods:45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded.Results:On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous...