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To develop a preoperative prediction model to identify macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) and evaluate the model's diagnostic performance in differentiating MTM-HCC from HCC.We conducted a mono-center retrospective study in a grade A tertiary hospital in China. Consecutive patients with suspected HCC from February 2019 to December 2020 were eligible for inclusion. All consenting patients underwent CEUS examination and were histologically diagnosed. Based on the clinical and US features between the two groups, we developed a binary logistic regression model and a nomogram for predicting MTM-HCC.A total of 161 patients (median age, 57 years; interquartile range, 48-64 years; 129 men) were included in the analysis. Twenty-seven of the HCCs (16.8%) were of the MTM subtype. Binary logistic regression analysis indicated that PVP hypoenhancement (OR = 15.497; 95% CI: 1.369, 175.451; p = 0.027), AFP454.6 ng/mL (OR = 8.658; 95% CI: 3.030, 24.741; p0.001), ALB ≤ 29.9 g/L (OR = 3.937; 95% CI: 1.017, 15.234; p = 0.047), halo sign (OR = 3.868; 95% CI: 1.314, 11.391; p = 0.016), and intratumoral artery (OR = 2.928; 95% CI: 1.039, 8.255; p = 0.042) were predictors for MTM subtype. Combining any two criteria showed a high sensitivity (100.0%); combining all five criteria showed a high specificity (99.2%); and the AUC value of the logistic regression model was 0.88 (95% CI: 0.81, 0.92).BMUS and CEUS could be used for identifying patients suspected of having MTM-HCC. Combining clinical information, BMUS, and CEUS features could achieve a noninvasive diagnosis of MTM-HCC.• Contrast-enhanced ultrasound examination helps clinicians to identify MTM-HCCs preoperatively. • PVP hypoenhancement, high AFP levels, low ALB levels, halo signs, and intratumoral arteries could be used to predict MTM-HCCs. • A logistic regression model and nomogram were built to noninvasively diagnose MTM-HCCs with an AUC value of 0.88 (95% CI: 0.81, 0.92).

Oxidative stress induced by reactive oxygen species (ROS) is one of the major pathological mechanisms of acute kidney injury (AKI). Inorganic nanomaterial-mediated antioxidant therapy is considered a promising method for the prevention of AKI; however, currently available antioxidants for AKI exhibit limited clinical efficacy due to the glomerular filtration threshold (∼6 nm). To address this issue, we developed ultrasmall RuO2 nanoparticles (RuO2NPs) (average size ≈ 2 nm). The NPs show excellent antioxidant activity and low biological toxicity. In addition, they can pass through the glomerulus to be excreted. These properties in combination make the ultrasmall RuO2NPs promising as a nanozyme for the prevention of AKI. The NP catalytic properties mimic the activity of catalase, peroxidase, superoxide dismutase, and glutathione peroxidase. The nanozyme can be efficiently and rapidly absorbed by human embryonic kidney cells while significantly reducing ROS-induced apoptosis by eliminating excess ROS. After intravenous injection, the ultrasmall RuO2NPs significantly inhibit the development of AKI in mice. In vivo toxicity experiments demonstrate the biosafety of the NPs after long-term preventing. The multienzyme-like activity and biocompatibility of the ultrasmall RuO2NPs makes them of great interest for applications in the fields of biomedicine and biocatalysis.

An RGD-peptide conjugated ruthenium(ii) complex has been developed, which functions as a two-photon absorption (TPA) photodynamic therapy (PDT) agent for ablating tumours by selectively targeting the mitochondria of integrin αvβ3-rich tumour cells. This approach offers a new and effective design and application for tumour-targeting metallo-anticancer drugs via two-photon PDT.

Objectives To investigate factors that may lead to false-positive or false-negative results in a computer-aided diagnostic system (S-Detect; Samsung Medison Co, Ltd, Seoul, Korea) for ultrasound (US) examinations of solid breast lesions. Methods This prospective study was approved by the Institutional Review Board of Sun Yat-sen Memorial Hospital. All patients signed and provided written informed consent before biopsy or surgery. From September 2017 to May 2018, 269 consecutive women with 338 solid breast lesions were included. All lesions were examined with US and S-Detect before biopsy or surgical excision. The final US assessments made by radiologists and S-Detect were matched to the pathologic results. Patient and lesion factors in the "true" and "false" S-Detect groups were compared, and multivariate logistic regression analyses were used to identify the factors associated with false S-Detect results. Results The mean age of the patients ± SD was 42.6 ± 12.9 years (range, 18-77 years). Of the 338 lesions, 209 (61.8%) were benign, and 129 (38.2%) were malignant. Larger lesions, the presence of lesion calcifications detected by B-mode US, and grades of 2 and 3 according to Adler et al (Ultrasound Med Biol 1990; 16:553-559) were significantly associated with false-positive S-Detect results (odds ratio [OR], 1.071; P = .006; OR, 5.851; P = .001; OR, 1.726; P = .009, respectively). Smaller lesions and the absence of calcifications detected by B-mode US in malignant solid breast lesions were significantly associated with false-negative S-Detect results (OR, 1.141; P = .015; OR, 7.434; P = .016). Conclusions Larger benign lesions, the presence of lesion calcifications, and high degrees of vascularity are likely to show false-positive S-Detect results. Smaller malignant lesions and the absence of calcifications are likely to show false-negative S-Detect results.

Amphiphilic polymers containing brush-shaped poly(polyethylene glycol methyl ether acrylate) (PEGA) as a hydrophilic segment may form a stable hydrophilic shell for a polymeric micelle due to a strong interaction among the brush shaped molecules. In this paper, polymeric micelles with brush-shaped poly(PEGA) as hydrophilic shell were designed and formulated as nanocarriers for a new ruthenium (II) complex anticancer drug to address its poor water solubility. Well defined brush-shaped poly(PEGA)-containing amphiphilic block polymers were synthesised by reversible addition-fragmentation chain transfer (RAFT) polymerisation. The as-prepared amphiphilic polymers formed stable polymeric micelle nanocarriers for the hydrophobic ruthenium (II) complex, resulting in greatly increased solubility of the drug by inhibiting its aggregation in aqueous environment. Cytotoxicity studies demonstrated that the use of polymeric micelle nanocarriers increased the drug’s toxicity to human liver cancer cells (SK-HEP-1) by 3 fold under dark and 12 fold under light conditions. However, both bare drug and encapsulated drug showed no toxicity to the normal cells, demonstrating the drug’s potential targeting capacity to cancer cells.

Oxidative stress induced by reactive oxygen species (ROS) is one of the major pathological mechanisms of acute kidney injury (AKI). Inorganic nanomaterial-mediated antioxidant therapy is considered a promising method for the prevention of AKI; however, currently available antioxidants for AKI exhibit limited clinical efficacy due to the glomerular filtration threshold (∼6 nm). To address this issue, we developed ultrasmall RuO

Ir(iii) complex modified gold nanorods, Ir@AuNRs, were developed as mitochondria-targeted theranostic nanoagents. Their hypoxia imaging and photothermal therapeutic properties were demonstrated in vitro and in vivo.

Taxol is the first-line drug for cancer treatment. However, tumor resistance to Taxol is still a significant challenge in clinical practice. Here, we studied the synergistic effect of a ruthenium (II) polypyridyl complex, Δ-[Ru(bpy)

In the present study, a cyclometalated iridium(III) complex, [Ir(ppy)2(HPIP)]Cl (IrT, ppy = 2-phenylpyridine, HPIP = 2-(2-hydroxyphenyl)imidazo[4,5-f]1,10-phenanthroline), was synthesized and characterized. IrT exhibited more cytotoxicity than cisplatin did against several screened cancer cell lines. In particular, the cytotoxicity of IrT against the cisplatin-resistant cell line A549-CP/R is approximately 10 times higher than that of cisplatin. In addition, this complex could perform theranostic functions by simultaneously imaging and tracking mitochondrial morphological changes. Further study suggested that IrT induced changes in the mitochondrial membrane potential and triggered apoptosis via an intrinsic mitochondria-mediated pathway. Thus, IrT exhibited both antitumor and imaging properties, indicating that IrT may be a viable drug candidate as a mitochondria-targeted theranostic anticancer agent.

The toxicity and antitumor activity of a ruthenium(II) complex [Ru(dmp)2(ipad)](ClO4)2 (Ru1) was evaluated. In vivo experiments demonstrated that Ru1 dose-dependently inhibited growth of a human liver carcinoma cell line (BEL-7402) that was xenotransplanted into nude mice. TUNEL assays showed that Ru1 induced apoptosis in tumor tissue cells. However, a toxicological examination indicated that high doses of Ru1 can cause kidney damage and lead to elevated levels of serum creatinine. In addition, Ru1 appeared to be genotoxic and hematologically toxic in a dose-dependent manner. The obtained results provided basic information regarding the further design of ruthenium(II) antitumor drugs.

Nucleus-targeting NPs based on RuO2 (RuO2NPs) were developed by controlling the size and the surface charge of nanoparticles (NPs). This study not only demonstrates a facile approach for the fabrication of ultrasmall CS-RuO2NPs with good biocompatibility and excellent photothermal properties but also their unique potential for the nucleus-targeted low-temperature PTT.

Metastasis is a major health threat for most cancer patients, thus anti-metastasis treatments that reduce cell migration and invasion are critical for cancer treatment. In this study, four anthraquinone-bridged diruthenium(II) complexes, [(bpy)2Ru(L)Ru(bpy)2]4+ (Ru1, L = 1,4-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione; Ru2, L = 1,5-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione; Ru3, L = 2,6-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione; and Ru4, L = 2,7-bis(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)anthracene-9,10-dione) were synthesized and characterized. These Ru(II) complexes exhibited multi-targeted anti-metastatic properties against human hepatocarcinoma MHCC97-H cells that included the inhibition of migration and invasion. Further investigation of the intracellular mechanisms revealed that Ru(II) complexes suppressed the phosphorylation of ERK and AKT. Moreover, significant reduction of the extracellular and intracellular expression of the metastatic regulatory proteins MMP-2 and MMP-9 was also observed after Ru1–Ru4 treatment. In addition, these Ru(II) complexes negatively modulate the actin cytoskeleton by inhibiting Cdc42 protein expression, arresting the cells in the G2/M phase. The results indicate that these ruthenium(II) complexes have potential as drug candidates for anti-metastatic therapies.

Hypoxia is a common feature of most solid tumors and its precise imaging is of great importance to therapy planning. Here we demonstrated that a ruthenium(II) anthraquinone complex [Ru(bpy)2(ipad)](ClO4)2 (Ru-ipad, where bpy = 2,2′-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline), is a powerful optical probe that can detect repeated cycles of hypoxia–normoxia in living cells in real time. This hypoxia probe also showed cytotoxicity against hypoxic 2D cancer monolayer cultures and 3D multicellular tumor spheroids (MCTSs). The cytotoxicity of Ru-ipad was in accordance with its suppression of the hypoxia-inducible factor-1α (HIF-1α) protein in tumor cells. Therefore, Ru-ipad not only has the potential to detect hypoxia with high sensitivity but also displays hypoxia-targeted antitumor effects through the inhibition of HIF-1α expression. The discovery of this dual-function ruthenium(II) anthraquinone complex may represent an important advance in hypoxic solid tumor treatment.

A cyclometalated iridium(III) complex, [Ir(ppy)2(PCN)]Cl (Ir1, ppy = 2-phenylpyridine, PCN = 2-(4-cyanophenyl)imidazo[4,5-f] [1,10] phenanthroline), was synthesized and characterized in the present study. Ir1 inhibited the proliferation, migration and invasion of MDA-MB-231 human breast cancer cells in a dose-dependent manner. Moreover, Ir1 down-regulated the phosphorylation of AKT/ERK signal pathways. According to confocal fluorescence microscopy analysis, Ir1 was primarily localized within the mitochondria and induced apoptosis through an intrinsic mitochondria-mediated apoptotic pathway. Thus, Ir1 exhibited both antimetastatic and antineoplastic properties, indicating that Ir1 may be a viable drug candidate in antimetastasis and anticancer therapies.

Ruthenium complexes are a new generation of metal antitumor drugs that are currently of great interest in multidisciplinary research. In this review article, we introduce the applications of ruthenium complexes in the diagnosis and therapy of tumors. We focus on the actions of ruthenium complexes on DNA, mitochondria, and endoplasmic reticulum of cells, as well as signaling pathways that induce tumor cell apoptosis, autophagy, and inhibition of angiogenesis. Furthermore, we highlight the use of ruthenium complexes as specific tumor cell probes to dynamically monitor the active biological component of the microenvironment and as excellent photosensitizer, catalyst, and bioimaging agents for phototherapies that significantly enhance the diagnosis and therapeutic effect on tumors. Finally, the combinational use of ruthenium complexes with existing clinical antitumor drugs to synergistically treat tumors is discussed.

Radiofrequency ablation (RFA) is considered to be a potentially curative therapy for hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can promote rapid progression of the residual tumor. The mechanisms underlying IRFA-induced tumor promotion remain poorly understood. In the present study, we have established a subcutaneous xenograft mouse model and monitored the location and extent of IRFA by dual monitoring with ultrasonography and a thermal imager. For the first time, we provide evidence of the activation of autophagic pathways in mice exposed to IRFA. We show that autophagy plays an important role in relapse and proliferation after IRFA and that hydroxychloroquine (HCQ) can suppress these effects. Our findings indicate that autophagy is involved in experimental IRFA and that inhibition of autophagy may be a novel approach in the treatment of local recurrences of HCC after IRFA in the clinic.

Correction for ‘Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy’ by Libing Ke et al., Chem. Commun., 2019, 55, 10273–10276.

Objective To investigate the effects of percutaneous cryoablation on uterine fibroids using computed tomographic (CT) guidance after uterine artery embolization.

The purpose of this study was to analyze the ultrasonic elastography features of phyllodes tumors of the breast comparing with fibroadenomas. A retrospective database was queried for the patients diagnosed as phyllodes tumors and fibroadenomas at Sun Yat-sen Memorial Hospital from January 2008 to August 2012. Three hundred and fifty lesions from 323 consecutive patients were included in the study. All the cases were examined by conventional ultrasonography and ultrasound elastography. Ultrasound elastography was used to calculate strain ratio of the lesions with bilateral breast tissue at the same depth as reference. There were 36 phyllodes tumors (27 benign, 8 borderline, 1 malignant) and 314 fibroadenomas (158 the pericanalicular type, 103 the intracanalicular type, 53 other special types). The strain ratio for phyllodes tumors (3.19 ± 2.33) was significantly higher than for fibroadenomas (1.69 ± 0.88) (p

Objective To provide an overview of recent studies on transarterial chemoembolization-related hepatic and biliary damage (TRHBD) in patients with malignant hepatic tumors (MHT) and to explore the reasons for TRHBD. Methods Literature on the treatments for MHT by TACE was sought in PubMed and the related information was summarized. Results TRHBD is found to occur in the hepatic parenchymal cells, biliary tree and blood-vascular system. The damage is mainly due to ischemia resulting from embolic materials such as gelatin sponge and lipiodol. In addition, clinicians’ skill levels in non-superselective catheterization, the health condition of the patients, and the chemical agents used may also be related to the damage. Most of the deterioration can be reversed if the patients are diagnosed and treated properly and promptly. Conclusions Understanding the mechanisms of TRHBD more comprehensively is helpful in developing effective methods for prevention and treatment.

Background There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors. Methods Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model. Results The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells (p