The Role of Contrast-Enhanced Ultrasound Plus Color Parametric Imaging in the Differential Diagnosis of Subpleural Pulmonary Lesions.

OBJECTIVES: To distinguish benign and malignant subpleural pulmonary lesions (SPLs) with contrast-enhanced ultrasound (CEUS) and color parametric imaging (CPI), and evaluate the role of CEUS plus CPI in the differential diagnosis of pathological types of SPLs. METHODS: One hundred and thirty-six patients underwent CEUS with a Logiq E9 XD Clear ultrasonic machine equipped with a 3.5- to 5.0-MHz C5-1 transducer in our center were enrolled in our study, including 27 cases of benign lesions and 109 cases of malignant lesions. The ultrasound contrast agent used in this study was SonoVue. CEUS images and CPI of all cases were reviewed and analyzed by the resident and staff radiologist groups separately. RESULTS: With CEUS alone, by both the two groups, the main enhancement pattern of benign SPLs was arborization (P < .001), while centripetal enhancement pattern occurred more frequently in malignant SPLs (P < .001). With CEUS plus CPI, by both the two groups, the main enhancement pattern of benign SPLs was arborization (P < .001), while those of malignant SPLs were centripetal (P < .001) and eccentric (P < .05). The diagnosis performance of CEUS plus CPI was significantly higher than that of CEUS alone in both the resident (area under the curve [AUC] = 0.857 vs 0.677, P < .001) and staff (AUC = 0.866 vs 0.681, P < .001) groups. Moreover, CPI offered remarkable inter-consistency improvements in the enhancement pattern determination between the two groups. CONCLUSION: The CEUS enhancement patterns would provide information of blood perfusion patterns in the differential diagnosis of benign and malignant SPLs. The diagnosis performance could be significantly improved by CEUS plus CPI compared with CEUS alone.

Heterologous expression of pediocin/papA in Bacillus subtilis.

Listeria monocytogenes is a food-borne pathogen. Pediocin is a group IIα bacteriocin with anti-listeria activity that is naturally produced by Pediococcus acidilactic and Lactobacillus plantarum. The pedA/papA gene encodes pediocin/plantaricin. In native hosts, the expression and secretion of active PedA/PapA protein rely on the accessory protein PedC/PapC and ABC transporter PedD/PapD on the same operon. The excretion machines were also necessary for pediocin protein expression in heterologous hosts of E. coli, Lactobacillus lactis, and Corynebacterium glutamicum. In this study, two vectors carrying the codon sequence of the mature PapA peptide were constructed, one with and one without a His tag. Both fragments were inserted into the plasmid pHT43 and transformed into Bacillus subtilis WB800N. The strains were induced with IPTG to secrete the fused proteins PA1 and PA2. Supernatants from both recombinant strains can inhibit Listeria monocytogenes ATCC54003 directly. The fused protein possesses inhibition activity as a whole dispense with removal of the leading peptide. This is the first report of active pediocin/PapA expression without the assistance of PedCD/PapCD in heterogeneous hosts. In addition, the PA1 protein can be purified by nickel-nitrilotriacetic acid (Ni-NTA) metal affinity chromatography.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastasis from pancreatic adenocarcinoma.

OBJECTIVE: To analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for pancreatic adenocarcinoma liver metastasis (PALM). METHODS: Between January 2010 and July 2021, 20 patients (13 males) with an average age of 58.9 ± 11.7 years who underwent RFA for PALM were included. The mean maximum diameter of PALMs was 2.6 ± 1.1 cm (1.0-6.0 cm). Survival curves were built using the Kaplan-Meier method and compared by the log-rank test. Multivariable analyses were performed by using the Cox proportional hazards model. RESULTS: Twenty patients with 29 PALMs underwent 23 RFA sessions. Technical efficacy was achieved in 28 PALMs (28/29, 96.6%). The mean overall survival (OS) after RFA was 14.6 months and the 1-, 2-year survival rates were 39.5%, 18.1%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.023) and extrahepatic metastasis before RFA (p = 0.038) were identified as independent prognostic factors for OS in patients with PALM. Additionally, the mean progression-free survival (PFS) after RFA was 11.5 months and 1-, 2- year survival rates were 26.0%, 17.3%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.016) and extrahepatic metastasis before RFA (p = 0.043) were also identified as independent prognostic factors for PFS in patients with PALM. CONCLUSION: RFA is a safe and effective treatment for patients with PALM, especially in patients with normal serum level of CA199 or the patients without extrahepatic metastases before RFA.

The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for limited hepatocellular carcinoma (HCC), the efficacy of this treatment for recurrent HCC has not been thoroughly investigated. Purpose To compare the long-term outcomes and analyze the prognostic factors for outcomes after RFA for initial HCC versus as a second-line treatment for recurrent HCC. Materials and Methods This retrospective study included 560 patients with solitary tumors 5 cm or smaller (263 initial HCCs, 297 -recurrent HCCs) who underwent percutaneous US-guided RFA from January 2005 to December 2016. Of 297 patients with -recurrent HCC, 134 had previously undergone hepatectomy, 128 had undergone transarterial chemoembolization (TACE), and 35 had undergone local ablation therapy. Overall survival (OS) between initial HCC and recurrent HCC was compared before and after propensity score matching. Prognostic factors for all patients were analyzed with the log-rank test and Cox proportional hazards model. Results A total of 560 patients (mean age, 60 years ± 12 [standard deviation]; 441 men) were evaluated. Before matching, the OS rates at 1, 3, 5, and 10 years were 92.6%, 73.9%, 59.3%, and 39.6%, respectively, in patients with recurrent HCC and 92.8%, 75.4%, 63.3%, and 44.7% in patients with initial HCC (P = .27). After matching, the OS rates at 1, 3, 5, and 10 years were 94.8%, 75.7%, 61.6%, and 47.3% in the initial HCC group and 91.9%, 71.2%, 58.7%, and 45.2% in the recurrent HCC group (P = .32). Among patients with recurrent HCC, no significant difference in mean OS was noted for local recurrence versus distant recurrence (81.6 months ± 5.1 vs 83.8 months ± 6.6, P = .82) or previous treatment modality (82.0 months ± 7.3 in the resection group, 82.7 months ± 5.3 in the TACE group, and 79.3 months ± 10.8 in the local ablation group; P = .83). Local tumor progression after previous local ablation (10 of 35 [28.6%]) was higher than that after previous hepatectomy (15 of 134 [11.2%], P = .04). Multivariable analysis demonstrated that tumor size (hazard ratio, 1.58; 95% CI: 1.06, 2.36; P = .02), portal hypertension (hazard ratio, 1.52; 95% CI: 1.03, 2.26; P = .04), Child-Pugh class (hazard ratio, 2.01; 95% CI: 1.02, 3.96; P = .045), and serum α-fetoprotein level (hazard ratio, 1.62; 95% CI: 1.10, 2.39; P = .01) were independent predictive factors for recurrent HCC outcomes. Conclusion Radiofrequency ablation provides similar long-term survival for solitary hepatocellular carcinoma of 5 cm or less, regardless of whether treatment is initial or salvage therapy. © RSNA, 2021 Online supplemental material is available for this article.

Long-term outcomes and prognostic analysis of percutaneous radiofrequency ablation in liver metastasis from breast cancer.

OBJECTIVE: To evaluate the long-term efficacy and prognostic factors of ultrasound-guided percutaneous radiofrequency ablation (RFA) for breast cancer liver metastasis (BCLM). METHODS: Between 2000 and 2015, 69 patients who underwent ultrasound-guided percutaneous RFA for BCLM and had regular follow-up examinations were included. All patients had undergone resection of the primary breast cancer and had received chemotherapy, endocrine therapy or both after surgery. The sample included two males and 67 females with an average age of 50.3 ± 10.0 years (31-76 y). The mean maximum diameter of metastatic lesions in the liver was 2.9 ± 1.4 cm (1.0-6 cm). Thirty-five patients had a single metastasis, while 34 patients had multiple liver metastases (2-5 lesions). Survival results were generated using Kaplan-Meier estimates and a multivariate analysis was performed using the Cox regression model. RESULTS: In total, 92 RFA sessions were performed and 135 BCLM lesions were treated. Major complications occurred in one of the 92 sessions (1.1%). Technical efficacy was achieved in 92.6% of lesions (125/135 lesions). Local tumor progression occurred in 11.6% (8/69) of patients and new intrahepatic metastasis occurred in 55.1% (38/69) of patients. From the time of initial RFA, the median overall survival was 26 months, and the one-, two-, three- and five -year survival rates were 81.8, 50.1, 25.3 and 11.0%, respectively. Based on the multivariate analysis, the following three factors were identified as independent prognostic factors for overall survival: tumor size (p = .017), positive estrogen receptor status (p = .009) and extrahepatic metastatic disease (p = .001). The median progression-free survival was 24 months, and the one-, two-, three- and five -year survival rates after RFA were 77.4, 47.0, 23.7 and 8.5%, respectively. Additionally, the independent prognostic factors for progression-free survival included tumor size (p = .011), ER positivity (p = .001), margin size (p = .017) and extrahepatic metastatic disease (p < .001). CONCLUSION: The results of this study showed that RFA is a safe and locally effective method for the treatment of BCLM, especially in patients with lesions measuring less than 3 cm in diameter, a single liver metastasis, positive estrogen receptor status and no extrahepatic metastases. Also, patients with margin size >10 mm had no local tumor progression.

Activation of PPARα by Oral Clofibrate Increases Renal Fatty Acid Oxidation in Developing Pigs.

The objective of this study was to evaluate the effects of peroxisome proliferator-activated receptor α (PPARα) activation by clofibrate on both mitochondrial and peroxisomal fatty acid oxidation in the developing kidney. Ten newborn pigs from 5 litters were randomly assigned to two groups and fed either 5 mL of a control vehicle (2% Tween 80) or a vehicle containing clofibrate (75 mg/kg body weight, treatment). The pigs received oral gavage daily for three days. In vitro fatty acid oxidation was then measured in kidneys with and without mitochondria inhibitors (antimycin A and rotenone) using [1-14C]-labeled oleic acid (C18:1) and erucic acid (C22:1) as substrates. Clofibrate significantly stimulated C18:1 and C22:1 oxidation in mitochondria (p < 0.001) but not in peroxisomes. In addition, the oxidation rate of C18:1 was greater in mitochondria than peroxisomes, while the oxidation of C22:1 was higher in peroxisomes than mitochondria (p < 0.001). Consistent with the increase in fatty acid oxidation, the mRNA abundance and enzyme activity of carnitine palmitoyltransferase I (CPT I) in mitochondria were increased. Although mRNA of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (mHMGCS) was increased, the ß-hydroxybutyrate concentration measured in kidneys did not increase in pigs treated with clofibrate. These findings indicate that PPARα activation stimulates renal fatty acid oxidation but not ketogenesis.

Clofibrate increases long-chain fatty acid oxidation by neonatal pigs.

BACKGROUND: Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonates. OBJECTIVE: To increase efficiency of milk fat utilization by newborn pigs, the effect of clofibrate on in vivo and in vitro long-chain fatty acid (LCFA) oxidation was evaluated. METHODS: Newborn male pigs were administered 5 mL of vehicle (2% Tween 80) with or without clofibrate (75 mg/kg body weight) once daily via i.g. gavage for 4 d. Total LCFA oxidative capacity was measured in respiration chambers after gastric infusion (n = 5 per treatment) with isoenergetic amounts of [1-(14)C]triglycerides (TGs), either oleic acid (18:1n-9) TG [3.02 mmol/kg body weight (BW)(0.75)] or erucic acid (22:1n-9) TG (2.46 mmol/kg BW(0.75)). Total expired (14)CO2 was collected and quantified at 20-min intervals over 24 h. Hepatic in vitro LCFA oxidation was determined simultaneously using [1-(14)C]oleic acid and erucic acid substrates. RESULTS: The in vivo 24-h accumulative [1-(14)C]TG oxidation (percentage of energy intake/kg BW(0.75)) tended to increase with clofibrate supplementation (P = 0.10), although there was no difference in the peak or mean utilization rate. The maximal extent of oleic acid TG oxidation was 1.6-fold that of erucic acid TG (P < 0.006). Hepatic in vitro LCFA oxidation increased 61% with clofibrate (P < 0.0008). The increase in mitochondria was 4-fold greater than in peroxisomes. The relative abundance of mRNA increased 2- to 3-fold for hepatic peroxisome proliferator-activated receptor α and its target genes (fatty acyl-coenzyme A oxidase and carnitine palmitoyltransferase) in the pigs that were administered clofibrate (P < 0.04). CONCLUSION: Clofibrate may improve in vivo LCFA oxidative utilization in neonatal pigs.

IFN-α/ß/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype.

Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8+ T-cell responses. Interferon (IFN)-α/ß/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8+ T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/ß/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/ß/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 (GBP1) could represent the IFN-α/ß/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.

Overexpression of PLK1 Molecule Following Incomplete Thermal Ablation Promotes the Proliferation and Invasion of Residual Hepatocellular Carcinoma.

TAT, a widely used treatment for HCC, can exacerbate the progression of residual HCC. The present study investigated the mechanism of action of PLK1 following ITA of HCC. The PLK1 levels in HCC were determined using qRT-PCR from clinical patient samples, IHC from tissue microarray, and data from globally high-throughput data and microarrays. The PLK1 levels and their effect on the biological phenotype of heat-stress HCC cells were evaluated through in vitro experiments. We detected PLK1 abnormal expression in HCC models of nude mice subjected to ITA. We detected the effects of different PLK1 expression levels on EMT pathway proteins. PLK1 exhibited an overexpression in HCC tissues with an SMD of 1.19 (3414 HCC and 3036 non-HCC tissues were included), distinguishing HCC from non-HCC effectively (AUC = 0.9). The qRT-PCR data from clinical HCC patient samples and IHC from HCC tissue microarray results also indicated an overexpressed level. In the incomplete ablation models, an increased PLK1 expression was found in both heat-stress cells and subcutaneous tumors. The upregulation of PLK1 following ITA was found to enhance the malignancy of HCC and exacerbate the proliferation, migration, and invasion of residual HCC cells, whereas PLK1 knockdown suppressed the biological malignancy of HCC cells. Meanwhile, PLK1 has different regulatory effects on various EMT pathway proteins. PLK1 promotes the progression of residual HCC by activating EMT pathway after ITA, which might provide a novel idea for the treatment and prognosis of residual HCC.

Intra-individual comparison of Sonazoid contrast-enhanced ultrasound and SonoVue contrast-enhanced ultrasound in diagnosing hepatocellular carcinoma.

PURPOSE: To assess whether the diagnostic performance of Sonazoid contrast-enhanced ultrasound (SZUS) is non-inferior to that of SonoVue contrast-enhanced ultrasound (SVUS) in diagnosing hepatocellular carcinoma (HCC) in individuals with high risk. MATERIALS AND METHODS: This prospective study was conducted from October 2020 to May 2022 and included participants with a high risk of HCC who underwent SZUS and SVUS. All lesions were confirmed by clinical or pathological diagnosis. Each nodule was classified according to the Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System version 2017 (CEUS LI-RADS v2017) for SVUS and SZUS and the modified CEUS LI-RADS (using Kupffer phase defect instead of late and mild washout) for SZUS. The diagnostic performance of both two modalities for all observations was compared. Analysis of the vascular phase and Kupffer phase imaging characteristics of CEUS was performed. RESULTS: One hundred and fifteen focal liver lesions from 113 patients (94 HCCs, 12 non-HCC malignancies, and 9 benign lesions) were analysed. According to CEUS LI-RADS (v2017), SVUS and SZUS showed similar sensitivity (71.3% vs. 72.3%) and specificity (85.7% vs. 81.0%) in HCC diagnosis. However, the modified CEUS LI-RADS did not significantly improve the diagnostic efficacy of Sonazoid compared to CEUS LI-RADS v2017, having equivalent sensitivity (73.4% vs. 72.3%) and specificity (81.0% vs. 81.0%). The agreement between SVUS and SZUS for all observations was 0.610 (95% CI 0.475, 0.745), while for HCCs it was 0.452 (95% CI 0.257, 0.647). CONCLUSION: Using LI-RADS v2017, SZUS and SVUS showed non-inferior efficacy in evaluating HCC lesions. In addition, adding Kupffer phase defects to SZUS does not notably improve its diagnostic efficacy.

RAD21: A Key Transcriptional Regulator in the Development of Residual Liver Cancer.

Objective: Thermal ablation is a commonly used therapy for hepatocellular carcinoma (HCC). Nevertheless, inadequate ablation can lead to the survival of residual HCC, potentially causing rapid progression. The underlying mechanisms for this remain unclear. This study explores the molecular mechanism responsible for the rapid progression of residual HCC. Methods: We established an animal model of inadequate ablation in BALB/c nude mice and identified a key transcriptional regulator through high-throughput sequencing. Subsequently, we conducted further investigations on RAD21. We evaluated the expression and clinical significance of RAD21 in HCC and studied its impact on HCC cell function through various assays, including CCK-8, wound healing, Transwell migration and invasion. In vitro experiments established an incomplete ablation model verifying RAD21 expression and function. Using ChIP-seq, we determined potential molecules regulated by RAD21 and investigated how RAD21 influences residual tumor development. Results: High RAD21 expression in HCC was confirmed and correlated with low tumor cell differentiation, tumor growth, and portal vein thrombosis. Silencing RAD21 inhibited the migration, invasion, and proliferation significantly in liver cancer cells. Patients with high RAD21 levels showed elevated multiple inhibitory immune checkpoint levels and a lower response rate to immune drugs. Heat treatment intensified the malignant behavior of liver cancer cells, resulting in increased migration, invasion, and proliferation. After subjecting it to heat treatment, the results indicated elevated RAD21 levels in HCC. Differentially expressed molecules regulated by RAD21 following incomplete ablation were primarily associated with the VEGF signaling pathway, focal adhesion, angiogenesis, and hepatocyte growth factor receptor signaling pathway etc. Conclusion: The upregulation of RAD21 expression after incomplete ablation may play a crucial role in the rapid development of residual tumors and could serve as a novel therapeutic target.

Enhancing the affinity of novel GLS1 allosteric inhibitors by targeting key residue Lys320.

Aim: A series of novel GLS1 irreversible allosteric inhibitors targeting Lys320 might have robust enzyme inhibitory activity and potent antitumor activity. Materials & methods: Novel GLS1 allosteric inhibitors targeting Lys320 were synthesized and their anticancer activity was assessed. Moreover, GLS1 protein was used as a model system to analyze the reactivity of these electrophilic groups in GLS1 irreversible allosteric inhibitors with other amino acids, including tyrosine, histidine, serine and threonine, using biochemical and biophysical assays. Results: AC16 exhibited robust GLS1 inhibitory activity, antiproliferative effect in vitro, good plasma stability and potential covalent addition with GLS1 K320. Conclusion: This study opens a novel avenue for the design of robust irreversible GLS1 inhibitors targeting the allosteric site K320.

The added value of color parameter imaging for the evaluation of focal liver lesions with "homogenous hyperenhancement and no wash out" on contrast enhanced ultrasound.

Objective: The purpose of this study was to investigate the added value of color parameter imaging (CPI) in the differential diagnosis of focal liver lesions (FLLs) with "homogeneous hyperenhancement but not wash out" on contrast-enhanced ultrasound (CEUS). Methods: A total of 101 patients with 108 FLLs were enrolled in this study. All the FLLs received US and CEUS examinations. The stored CEUS clips of target lesions were postprocessed with CPI analysis by radiologists. The receiver operator characteristic (ROC) curve was used to evaluate the added value of CPI. The McNamara test was used to compare the diagnostic sensitivity, specificity, and accuracy between CEUS and CPI patterns. Univariate and multivariate logistic regression analyses were used to develop a CPI nomogram. The C index and calibration curve were used to evaluate the predictive ability of the nomogram. The intraclass correlation coefficient was used to test the reproducibility and reliability of CPI. Decision curve analysis (DCA) was used to evaluate the added value of applying CPI. Results: The following CPI features were more frequently observed in malignant FLLs: eccentric perfusion (malignant: 70.0% vs. benign: 29.2%, p < 0.001), feeding artery (51.7% vs. 4.2%, p < 0.001), mosaic (63.3% vs. 6.3%, p < 0.001), red ingredients >1/3 (90.0% vs. 14.6%, p < 0.001). In addition, centripetal (43.8% vs. 18.3%, p = 0.004), peripheral nodular (54.2% vs. 1.7%, p < 0.001), subcapsular vessel (12.5% vs. 0.0%, p = 0.004), spoke-wheel vessels (25.0% vs. 5.0%, p = 0.003), branched vessels (22.9% vs. 5.0%, p = 0.006), blue and pink ingredients >2/3 (85.4% vs. 10.0%, p < 0.001) were more observed in benign FLLs. A nomogram incorporating peripheral nodular, spoke-wheel vessels, and red ingredients >1/3 was constructed. The model had satisfactory discrimination (AUC = 0.937), and the optimal diagnostic threshold value was 0.740 (0.983, 0.850). By the DCA, the model offered a net benefit over the treat-all-patients scheme or the treat-none scheme at a threshold probability 5%-93%. Conclusion: Using CPI can detect and render subtle information of the main features of FLLs on CEUS; it is conducive to the radiologist for imaging interpretation, and a combining read of the CEUS and CPI of the FLLs with features of "homogenous hyperenhancement and no washout" can improve significantly the diagnostic performance of CEUS for FLLs.

An evaluation of 20-year survival of radiofrequency ablation for hepatocellular carcinoma as first-line treatment.

OBJECTIVES: To evaluate the changes in clinical characteristics, overall survival (OS), and progression-free survival (PFS) by investigating a 20-year cohort of patients with HCC who underwent RFA treatment. METHODS: From 2000 to 2020, 505 consecutive patients with HCC underwent ultrasound-guided percutaneous RFA as first-line therapy at a tertiary cancer hospital. We divided the cohort according to the time when hepatitis-B antiviral therapy was covered by national medical insurance coverage (early 2011), including the first decade (2000-2010) and second decade (2011-2020). The prognostic factors for OS were analyzed by the Cox proportional hazard model. OS and PFS in different groups were compared using the Kaplan-Meier method. To reduce selection bias, matched groups of patients were selected using the propensity score matching (PSM) method. RESULTS: In total, 726 RFA sessions were performed to treat 867 HCC lesions. Patients treated in the second decade were younger (p =.047), had smaller tumors (p <.001), had lower Child-Pugh scores (p <.001), and had a higher proportion of antiviral treatment (p <.001). A total of 96.0% of patients achieved technical efficacy from the initial RFA. After PSM analysis, improved PFS was found for the second decade (median, 68 vs. 49 months, p =.003), but no significant difference in OS was observed between the two groups (median, 71 vs. 65 months, p =.20). CONCLUSIONS: This study demonstrated that improved PFS was achieved in patients with HCC receiving RFA as first-line treatment in the second decade. However, long-term OS was not significantly increased compared to the first decade suggesting that while RFA treatment has improved, it still might not substantially affect OS results.

CircFUNDC1 knockdown alleviates oxygen-glucose deprivation-induced human brain microvascular endothelial cell injuries by inhibiting PTEN via miR-375.

BACKGROUND: The maintenance of human brain microvascular endothelial cell (HBMEC) function is crucial to improve the outcomes of ischemic stroke (IS). Emerging evidence shows that circular RNAs (circRNAs) are involved in IS progression. This study aimed to investigate the role of circRNA FUN14 domain containing 1 (circFUNDC1) in oxygen-glucose deprivation (OGD)-treated HBMECs. METHODS: The expression of circFUNDC1, miR-375 and phosphatase and tensin homolog (PTEN) mRNA was detected by quantitative real-time PCR (qPCR). Cell viability, apoptosis, migration and angiogenesis were determined by CCK-8 assay, flow cytometry assay, transwell assay and tube formation assay. The protein level of PTEN was detected by western blot. The relationship between miR-375 and circFUNDC1 or PTEN was confirmed by pull-down assay, dual-luciferase reporter assay and RIP assay. Exosomes were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RESULTS: CircFUNDC1 expression was increased in peripheral blood of IS patients and OGD-treated HBMECs. CircFUNDC1 knockdown alleviated OGD-induced cell apoptosis and promoted OGD-blocked cell viability, migration and angiogenesis of HBMECs. MiR-375 was a target of circFUNDC1, and miR-375 restoration played similar effects with circFUNDC1 knockdown. The inhibition of miR-375 reversed the effects of circFUNDC1 knockdown. In addition, PTEN was a downstream target of miR-375, and PTEN overexpression abolished the effects of miR-375 restoration. The expression of circFUNDC1 was elevated in serum-derived exosomes of IS patients, and circFUNDC1 harbored diagnostic values. CONCLUSION: CircFUNDC1 knockdown alleviates OGD-induced HBMECs injuries by inhibiting PTEN via enriching miR-375.

Enhancement of Copper Uptake of Yeast Through Systematic Optimization of Medium and the Cultivation Process of Saccharomyces cerevisiae.

Copper is an essential trace element for living organisms. Copper enriched by yeast of Saccharomyces cerevisiae is regarded as the biologically available organic copper supplement with great potentiality for application. However, the lower uptake ratio of copper ions makes the production of copper enriched by yeast uneconomically and environmentally unfriendly. In this study, S. cerevisiae Cu-5 with higher copper tolerance and intracellular copper accumulation was obtained by screening of our yeast strains collection. To increase the uptake ratio of copper ions, the medium composition and cultivation conditions for strain Cu-5 were optimized systematically. A medium comprised of glucose, yeast extract, (NH4)2SO4, and inorganic salts was determined, then a novel cultivation strategy including pH control at 5.5 and increasing amounts of yeast extract for a higher concentration of copper ion in the medium was developed. The uptake ratios of copper ions were more than 90% after combining 50 to 100 mg/L copper ions with 3.5 to 5.0 g/L yeast extract, which is the highest until now and is conducive to the cost-effective and environmentally friendly production of bioactive copper in yeast-enriched form.

Computer-Aided Color Parameter Imaging of Contrast-Enhanced Ultrasound Evaluates Hepatocellular Carcinoma Hemodynamic Features and Predicts Radiofrequency Ablation Outcome.

Computer-aided color parameter imaging (CPI) is a novel technique for contrast-enhanced ultrasound (CEUS) that can highlight hemodynamic features of focal lesions. The purpose of the study was to investigate the role of CPI in evaluation of hepatocellular carcinoma (HCC) hemodynamic features and prognosis after radiofrequency ablation (RFA). One hundred twenty-one patients with HCC underwent CEUS with CPI analysis before RFA. Eighty-nine patients had pathologically proven well- to moderately differentiated HCC (WM-HCC), and 32 patients had poorly differentiated or undifferentiated HCC (PU-HCC). Perfusion features of CEUS and contrast-enhanced computed tomography/magnetic resonance imaging were compared with CPI parameters for WM-HCC and PU-HCC. The results indicated that 67.4% of WM-HCC had a centrifugal perfusion CPI pattern, whereas 84.4% of PU-HCC tumors had a centripetal pattern (p < 0.001, odds ratio = 11.2). The specificity, sensitivity and accuracy of the CPI perfusion pattern regarding HCC pathological grade were higher than those with routine CEUS (84.4% vs. 9.4%, p < 0.001; 67.4% vs. 3.4%, p < 0.001; 71.9% vs. 5.0%, p < 0.001). Moreover, multivariable analysis revealed that the CPI perfusion pattern was an independent risk factor for progression-free survival post-RFA (centripetal group: 28.3 ± 4.1 mo vs. centrifugal group: 45.8 ± 4.4 mo, p = 0.002). A novel CPI technique for CEUS could non-invasively provide valuable hemodynamic information and predict prognosis for HCC patients treated by RFA.

The physical and mental health of the medical staff in Wuhan Huoshenshan Hospital during COVID-19 epidemic: A Structural Equation Modeling approach.

INTRODUCTION: Early in the epidemic of coronavirus disease 2019, the Chinese government recruited a proportion of healthcare workers to support the designated hospital (Huoshenshan Hospital) in Wuhan, China. The majority of front-line medical staff suffered from adverse effects, but their real health status during COVID-19 epidemic was still unknown. The aim of the study was to explore the latent relationship of the physical and mental health of front-line medical staff during this special period. METHODS: A total of 115 military medical staff were recruited between February 17th and February 29th, 2020 and asked to complete questionnaires assessing socio-demographic and clinical characteristics, self-reported sleep status, fatigue, resilience and anxiety. RESULTS: 55 medical staff worked within Intensive Care and 60 worked in Non-intensive Care, the two groups were significantly different in reported general fatigue, physical fatigue and tenacity (P<0.05). Gender, duration working in Wuhan, current perceived stress level and health status were associated with significant differences in fatigue scores (P<0.05), the current perceived health status (P<0.05) and impacted on the resilience and anxiety of participants. The structural equation modeling analysis revealed resilience was negatively associated with fatigue (ß=-0.52, P<0.01) and anxiety (ß=-0.24, P<0.01), and fatigue had a direct association with the physical burden (ß=0.65, P<0.01); Fatigue mediated the relationship between resilience and anxiety (ß=-0.305, P=0.039) as well as resilience and physical burden (ß=-0.276, P=0.02). CONCLUSION: During an explosive pandemic situation, motivating the effect of protective resilience and taking tailored interventions against fatigue are promising ways to protect the physical and mental health of the front-line medical staff.

The Incidence, Risk Factors, and Patterns of Peripherally Inserted Central Catheter-Related Venous Thrombosis in Cancer Patients Followed Up by Ultrasound.

PURPOSE: A peripherally inserted central catheter (PICC) is associated with venous thromboembolism (VTE) especially in patients suffering from cancer. We analyzed the incidence, risk factors, and patterns of PICC-related VTE in cancer patients. PATIENTS AND METHODS: Patients with cancer who underwent PICC placement were evaluated retrospectively. Routine, prospective ultrasound post-PICC placement was used for asymptomatic and symptomatic patients to identify VTE. Multivariable logistic regression models with odds ratios (ORs) were used to examine VTE risk factors. RESULTS: Of 2353 PICCs placed, 165 patients (7.01%) developed PICC-related VTE with a median thrombosis time of 12 days. After adjustment of multivariable analysis, patients with PICC-related VTE were more likely to have a ratio of PICC diameter:vein diameter >0.35 (adjusted OR, 1.689; 95% CI, 1.023-2.789) and high level of triglycerides (1.561; 1.096-2.223). The prevalence of A (adjusted OR, 1.680; 95% CI, 1.009-2.798), B (1.835; 1.137-2.961), and AB (3.275; 1.840-5.829) blood group was significantly higher than that of the O blood group in VTE patients. Venous recanalization was observed in 44.8% (74/165) patients after anticoagulation therapy, and more often in patients with combined deep VTE than in patients with isolated superficial VTE (OR, 17.942; 95% CI, 5.427-59.316). The recanalization time was 20±5 (range, 10-31) days. CONCLUSION: The non-O blood group, larger ratio of PICC diameter:vein diameter, and high level of triglycerides were significantly associated with PICC-related VTE. Almost half of cases of PICC-related deep VTE could be reversed by anticoagulation treatment.