Glutathione ameliorates the meiotic defects of copper exposed ovine oocytes via inhibiting the mitochondrial dysfunctions.

Regardless of the essential role of copper (Cu) in the physiological regulation process of mammalian reproduction, excessive exposure to Cu triggers the meiotic defects of porcine oocytes via compromising the mitochondrial functions. However, the connections between the excessive Cu exposure and meiotic defects of ovine oocytes have not been reported. In this study, the effect of copper sulfate (CuSO4) exposure on the meiotic potentials of ovine oocytes was analyzed. Subsequently, the ameliorative effect of glutathione (GSH) supplementation on the meiotic defects of CuSO4 exposed ovine oocytes was investigated. For these purposes, the in vitro maturation (IVM) of ovine cumulus oocyte complexes (COCs) was conducted in the presence of 5, 10, 20 and 40 µg/mL of CuSO4 supplementation. Subsequently, different concentrations of GSH (2, 4 and 8 mM) were added to the IVM medium containing CuSO4 solution. After IVM, the assay, including nuclear maturation, spindle organization, chromosome alignment, cytoskeleton assembly, cortical granule (CGs) dynamics, mitochondrial function, reactive oxygen species (ROS) generation, apoptosis, epigenetic modification and fertilization capacity of ovine oocytes were performed. The results showed that excessive Cu exposure triggered the meiotic defects of ovine oocytes via promoting the mitochondrial dysfunction related oxidative stress damage. Moreover, the GSH supplementation, not only ameliorated the decreased maturation potential and fertilization defect of CuSO4 exposed oocytes, but inhibited the mitochondrial dysfunction related oxidative stress damage, ROS generation, apoptosis and altered H3K27me3 expression in the CuSO4 exposed oocytes. Combined with the gene expression pattern, the finding in the present study provided fundamental bases for the ameliorative effect of GSH supplementation on the meiotic defects of CuSO4 exposed oocytes via inhibiting the mitochondrial dysfunctions, further benefiting these potential applications of GSH supplementation in the mammalian IVM system and livestock breeding suffering from the excessive Cu exposure.

Liver Stiffness Measured by Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVES: To evaluate the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D SWE) to predict symptomatic post-hepatectomy liver failure (SPHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 119 patients who underwent hepatectomy for HCC between August 2018 and July 2019 were enrolled. Preoperative assessments for LS and other clinicopathological tests were performed in all patients. Univariate and multivariate analyses were conducted for the risk factors of SPHLF. Further subgroup analysis was performed according to multivariate analysis results. RESULTS: SPHLF occurred in 38 patients (31.9%). The best cutoff value of LS for predicting SPHLF was 9.5 kPa. Multivariate analysis identified LS ≥ 9.5 kPa, greater Child-Turcotte-Pugh (CTP) grade, and major hepatectomy as independent predictors of SPHLF. Based on the extent of hepatectomy, CTP grade could stratify the risk of SPHLF in the minor hepatectomy group (12.2% vs. 100.0%, p = 0.001), whereas LS was superior in predicting SPHLF in the major hepatectomy group (18.9% vs. 72.4%, p < 0.001). In patients with CTP grade A, LS could further stratify the risks of SPHLF in both the minor and major hepatectomy groups (3.7% vs. 22.7%, p = 0.043; 17.6% vs. 70.4%, p < 0.001, respectively). CONCLUSIONS: LS measured using 2D SWE could predict SPHLF using the best cutoff value of 9.5 kPa. CTP grade was a stronger indicator of SPHLF in minor hepatectomy, whereas LS was more effective in selecting candidates for major hepatectomy. LS could further stratify the risk of SPHLF in CTP grade A patients, regardless of the extent of hepatectomy.

Accurate prediction of responses to transarterial chemoembolization for patients with hepatocellular carcinoma by using artificial intelligence in contrast-enhanced ultrasound.

OBJECTIVES: We aimed to establish and validate an artificial intelligence-based radiomics strategy for predicting personalized responses of hepatocellular carcinoma (HCC) to first transarterial chemoembolization (TACE) session by quantitatively analyzing contrast-enhanced ultrasound (CEUS) cines. METHODS: One hundred and thirty HCC patients (89 for training, 41 for validation), who received ultrasound examination (CEUS and B-mode) within 1 week before the first TACE session, were retrospectively enrolled. Ultrasonographic data was used for building and validating deep learning radiomics-based CEUS model (R-DLCEUS), machine learning radiomics-based time-intensity curve of CEUS model (R-TIC), and machine learning radiomics-based B-Mode images model (R-BMode), respectively, to predict responses (objective-response and non-response) to TACE with reference to modified response evaluation criteria in solid tumor. The performance of models was compared by areas under the receiver operating characteristic curve (AUC) and the DeLong test was used to compare different AUCs. The prediction robustness was assessed for each model. RESULTS: AUCs of R-DLCEUS, R-TIC, and R-BMode were 0.93 (95% CI, 0.80-0.98), 0.80 (95% CI, 0.64-0.90), and 0.81 (95% CI, 0.67-0.95) in the validation cohort, respectively. AUC of R-DLCEUS shows significant difference compared with that of R-TIC (p = 0.034) and R-BMode (p = 0.039), whereas R-TIC was not significantly different from R-BMode. The performance was highly reproducible with different training and validation cohorts. CONCLUSIONS: DL-based radiomics method can effectively utilize CEUS cines to achieve accurate and personalized prediction. It is easy to operate and holds good potential for benefiting TACE candidates in clinical practice. KEY POINTS: • Deep learning (DL) radiomics-based CEUS model can accurately predict responses of HCC patients to their first TACE session by quantitatively analyzing their pre-operative CEUS cines. • The visualization of the 3D CNN analysis adopted in CEUS model provided direct insight into what computers "see" on CEUS cines, which can help people understand the interpretation of CEUS data. • The proposed prediction method is easy to operate and labor-saving for clinical practice, facilitating the clinical treatment decision of HCCs with very few time costs.

Feasibility and outcomes of percutaneous radiofrequency ablation for intrahepatic recurrent hepatocellular carcinoma after liver transplantation: a single-center experience.

PURPOSE: To evaluate the feasibility, effectiveness, and treatment outcomes of percutaneous radiofrequency ablation (RFA) in the application of intrahepatic recurrent hepatocellular carcinoma (r-HCC) after liver transplantation (LT). METHODS: From April 2008 to December 2019, a total of 37 patients (34 male and 3 female, mean age: 48.7 ± 10.5 years) with 61 r-HCCs after LT treated by RFA as a first-line option were enrolled. The technical success, recurrence-free survival (RFS), overall survival (OS) and complications were evaluated. RESULTS: After the first session of RFA, three patients were detected with residual foci. All of them received additional session of RFA and two tumors were successfully ablated. Therefore, the technical success was 97.3% (36/37). During the follow-up period, a total of 7 tumors developed local tumor progression (LTP) after 2.2-10.8 months. The LTP rate was 11.7% for r-HCC in the transplanted liver. The median RFS was 4.8 months (95% confidence interval [CI]: 2.2-7.3 months). The 1-, 3-, and 5-year cumulative OS rates were 68.5%, 40.3%, and 40.3%, respectively. Multivariate analyses revealed that tumor size was the only independent predictor for RFS (hazard ratio [HR] = 2.557, 95% CI, 1.015-6.444; p = .046) and limited extrahepatic metastasis was the only independent prognostic factors of OS after RFA for post-LT r-HCC (HR = 4.031, 95%CI, 1.218-13.339; p = .022). Major complications after RFA occurred in two patients (2/37, 5.4%). CONCLUSION: Percutaneous RFA is safe and effective for intrahepatic r-HCC after LT, especially for those without limited extrahepatic metastasis.

Transarterial Chemoembolization Followed by Radiofrequency Ablation for Hepatocellular Carcinoma: Impact of the Time Interval between the Two Treatments on Outcome.

PURPOSE: To compare the efficacy of radiofrequency (RF) ablation after transarterial chemoembolization within or beyond 30 days for medium-large or multiple recurrent hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: In this single-center retrospective study conducted from 2007 through 2015, 135 patients with a single recurrent HCC (>3 cm) or multiple (2-5 tumors) recurrent HCCs underwent transarterial chemoembolization plus RF ablation. A total of 62 patients underwent RF ablation after transarterial chemoembolization within 30 days (sequential group) and 73 patients underwent RF ablation after transarterial chemoembolization beyond 30 days (delayed group). Outcomes of interests included overall survival (OS), progression-free survival (PFS), and complete response (CR) rate. RESULTS: The median OS and PFS were 49.8 and 38.0 months for sequential group, and 31.0 and 11.6 months for the delayed group. The sequential group experienced significantly better OS (hazard ratio [HR]: 0.517; P = .002) and PFS (HR, 0.621; P = .021). Among patients with multiple tumors or a single tumor >5 cm, the sequential group still had significantly longer OS (P = .022; P = .018, respectively) and PFS (P = 0.042; P = .036, respectively) than the delayed group, although no significant differences were observed among patients with solitary 3- to 5-cm tumors (P = .138; P = .803, respectively). The sequential group had a significantly better CR rate than the delayed group (85.4% vs. 68.5%, respectively; P = .035). Significant predictors of OS and PFS included maximum tumor size, number of tumors, and time interval between transarterial chemoembolization and RF ablation. CONCLUSIONS: Transarterial chemoembolization plus sequential RF ablation within 30 days was more effective for recurrent HCCs than transarterial chemoembolization plus delayed RF ablation. The time interval within 30 days is required for treating large or multiple HCCs but may not be necessary for solitary medium-sized HCC.

Anticancer bioactive peptides suppress human colorectal tumor cell growth and induce apoptosis via modulating the PARP-p53-Mcl-1 signaling pathway.

AIM: We have reported novel anticancer bioactive peptides (ACBPs) that show tumor-suppressive activities in human gastric cancer, leukemia, nasopharyngeal cancer, and gallbladder cancer. In this study, we investigated the effects of ACBPs on human colorectal cancer and the underlying mechanisms. METHODS: Cell growth and apoptosis of human colorectal tumor cell line HCT116 were measured using cell proliferation assay and flow cytometry, respectively. The expression levels of PARP, p53 and Mcl1A were assessed with Western blotting and immunohistochemistry. For evaluation of the in vivo antitumor activity of ACBPs, HCT116 xenograft nude mice were treated with ACBPs (35 µg/mL, ip) for 10 days. RESULTS: Treatment of HCT116 cells with ACBPs (35 µg/mL) for 4-6 days significantly inhibited the cell growth. Furthermore, treatment of HCT116 cells with ACBPs (35 µg/mL) for 6-12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1. Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues. CONCLUSION: Administration of ACBPs inhibits human colorectal tumor cell growth and induces apoptosis in vitro and in vivo through modulating the PARP-p53-Mcl-1 signaling pathway.

Anticancer bioactive peptide (ACBP) inhibits gastric cancer cells by upregulating growth arrest and DNA damage-inducible gene 45A (GADD45A).

Recently, we reported that anticancer bioactive peptide (ACBP), purified from goat spleens immunized with human gastric cancer extracts, significantly inhibited gastric cancer cells in vitro and gastric tumors in vivo via repressing cell growth and promoting apoptosis, making it a promising potential biological anticancer drug. However, it is not known what genes are functionally required for the ACBP effects. Here, we first found that two tumor suppressor genes, cyclin-dependent kinase inhibitor 2B (CDKN2B) and growth arrest and DNA damage-inducible alpha (GADD45A), were upregulated significantly in the cells with ACBP treatment by microarray screening and the findings were validated by real-time RT-PCR. Next, GADD45A mRNA and protein expressions were downregulated in the gastric cancer cells by lentivirus-mediated RNAi; then, cell viability, cell cycle, and apoptosis were assayed by MTT and flow cytometry. Interestingly, our results indicated that cell viability was not dependent on GADD45A without ACBP treatment; however, cell sensitivity to ACBP was significantly decreased in ACBP-treated gastric cancer cells with GADD45A downregulation. Therefore, we demonstrate that GADD45A was functionally required for ACBP to inhibit gastric cancer cells, suggesting that GADD45A may become a biomarker for ACBP sensitivity. Our findings have significant implications on the molecular mechanism understanding, biomarker development, and anticancer drug development of ACBP.

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms.

Colorectal cancer (CRC) is a significant global health burden, with high morbidity and mortality rates. It is often diagnosed at middle to advanced stage, affecting approximately 35% of patients at the time of diagnosis. Currently, chemotherapy has been used to improve patient prognosis and increase overall survival. However, chemotherapy can also have cytotoxic effects and lead to adverse reactions, such as inhibiting bone marrow hematopoiesis, causing digestive dysfunction, hand-foot syndrome, and even life-threatening conditions. In response to these adverse effects, researchers have proposed using Traditional Chinese Medicine (TCM) as an option to treat cancer. TCM research focuses on prescriptions, herbs, and components, which form essential components of the current research in Chinese medicine. The study and implementation of TCM prescriptions and herbs demonstrate its distinctive holistic approach to therapy, characterized by applying multi-component and multi-target treatment. TMC components have advantages in developing new drugs as they consist of single ingredients, require smaller medication dosages, have a precise measure of pharmacodynamic effects, and have a clear mechanism of action compared to TCM prescriptions and herbs. However, further research is still needed to determine whether TMC components can fully substitute the therapeutic efficacy of TCM prescriptions. This paper presents a comprehensive analysis of the research advancements made in TCM prescriptions, herbs, and components. The findings of this study can serve as a theoretical basis for researchers who are interested in exploring the potential of TCM for the treatment of colorectal cancer.

Alleviative Effect of Lactoferrin Interventions Against the Hepatotoxicity Induced by Titanium Dioxide Nanoparticles.

The current study was designed to investigate the alleviative effect of lactoferrin interventions against the hepatotoxicity induced by titanium dioxide nanoparticles (TiO2-NPs). Thirty male Wistar rats were divided into six groups with 5 rats in each group. The first and second groups were intragastrically administered normal saline and TiO2-NPs (100 mg/kg body weight) as the negative control (NC) and TiO2-NP groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to TiO2-NPs (100 mg/kg body weight). The sixth group was intragastrically administered Fuzheng Huayu (FZHY) capsules at a concentration of 4.6 g/kg body weight in addition to TiO2-NPs (100 mg/kg body weight) as the positive control group. After treatment for 4 weeks, the concentrations of lactoferrin were optimized based on the liver index and function results. Subsequently, the alleviative effects of lactoferrin interventions against TiO2-NP-induced hepatotoxicity in rat liver tissues, including the effects on histological damage, oxidative stress-related damage, inflammation, fibrosis, DNA damage, apoptosis, and gene expression, were investigated using histopathological, biochemical, and transcriptomic assays. The results showed that 200 mg/kg lactoferrin interventions for 4 weeks not only ameliorated the liver dysfunction and histopathological damage caused by TiO2-NP exposure but also inhibited the oxidative stress-related damage, inflammation, fibrosis, DNA damage, and apoptosis in the liver tissues of TiO2-NP-exposed rats. The transcriptomic results confirmed that the alleviative effect of lactoferrin interventions against the TiO2-NP exposure-induced hepatotoxicity was related to the activation of the PI3K/AKT signaling pathway.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

PWP1 is overexpressed in hepatocellular carcinoma and facilitates liver cancer cell proliferation.

Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients. Although dysregulated Periodic tryptophan protein 1 homolog (PWP1/endonuclein) expression has been detected in several tumors, the potential regulatory effect of PWP1 on LIHC remains uncertain. Here we evaluated the expression of PWP1 using multiple online platforms, and demonstrated that PWP1 upregulation was consistently observed in LIHC relative to non-tumor liver tissues and correlated with unfavorable prognosis. Moreover, HCC prognosis was significantly influenced by the methylation status of various CpG sites in the PWP1 gene. Lastly, we provide direct evidence that PWP1 acts as a driver of HCC progression by showing that siRNA-mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro. These data strongly suggest that PWP1 silencing may be an effective therapeutic strategy to treat LIHC.

Anti-Cancer Potency of Copper-Doped Carbon Quantum Dots Against Breast Cancer Progression.

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.

[Anaplastic large cell lymphoma: an array-based comparative genomic hybridization study].

OBJECTIVE: To use array-based comparative genomic hybridization (aCGH) technology to study the molecular cytogenetic abnormalities of anaplastic large cell lymphoma (ALCL) at genome level. METHODS: ALK protein expression and molecular genetic abnormalities were detected by immunohistochemistry and fluorescence in situ hybridization, respectively, in 25 cases of ALCL. Any chromosomal gains/losses were detected by aCGH and correlated with ALK status. RESULTS: aCGH showed that chromosomal alterations in all 25 ALCL cases, and the frequency of chromosomal gains was higher than that of the losses. Chromosomal gains at 5p13.2, 3q21.1, 2q21.3, 3p25.1, 14q32.33, and 17q21.2 regions were detected in more than 50% of the ALCL cases; gains at 4q27, 6p22.1, 20p11.21, 2q22.3, 4q35.1, 1p36.22, 8p23.1, 8p12, 11q14.1, 12q13.13, and 19p13.3 regions were detected in 30%-50% of the ALCL cases; chromosomal losses at 3q26.1 and 3q26.31 regions were detected in 36.0% (9/25) and 24.0% (6/25) of the ALCL cases, respectively. Chromosomal gains at 2q21.3, 6p22.1 and 3p25.1 regions showed significant differences between ALK (+) and ALK (-) ALCL groups (P < 0.05). CONCLUSIONS: aCGH demonstrates complex molecular genetic variations in all ALCL cases. Gains at 2q21.3, 6p22.1 and 3p25.1 regions are significantly different between ALK (+) and ALK (-) ALCL groups, suggesting that the pathogenesis of ALK (+) and ALK (-) ALCL may involve different signaling pathway.

Glutathione and selenium nanoparticles have a synergistic protective effect during cryopreservation of bull semen.

Introduction: In the present study, the synergistic protective effect of co-supplementation of glutathione (GSH) with selenium nanoparticles (SeNPs) on the cryopreservation efficiency of bull semen was analyzed. Methods: After collection, the ejaculates of Holstein bulls were subsequently diluted with a Tris extender buffer supplemented with different concentrations of SeNPs (0, 1, 2, and 4 µg/ml), followed by semen equilibration at 4°C and assessment of sperm viability and motility. Subsequently, the ejaculates of Holstein bulls were pooled, split into four equal groups, and diluted with a Tris extender buffer supplemented with basic extender (negative control group, NC group), 2 µg/ml SeNPs (SeNPs group), 4 mM GSH (GSH group), and 4 mM GSH plus 2 µg/ml SeNPs (GSH + SeNPs group). After cryopreservation, motility, viability, mitochondrial activity, plasma membrane integrity, acrosome integrity, concentration of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), and ability of frozen-thawed sperm cells to support in vitro embryonic development were evaluated. Results and discussion: No side effect of SeNPs concentrations applied in the current study on the motility and viability of equilibrated bull spermatozoa was found. Meanwhile, supplementation of SeNPs significantly promoted the motility and viability of equilibrated bull spermatozoa. Furthermore, the co-supplementation of GSH with SeNPs effectively protected bull spermatozoa from cryoinjury as expressed by promoting semen motility, viability, mitochondrial activity, plasma membrane integrity, and acrosome integrity. Finally, the enhanced antioxidant capacity and embryonic development potential in the frozen-thawed bull spermatozoa cryopreserved by co-supplementation of GSH with SeNPs further confirmed the synergistic protective effect of co-supplementation of GSH with SeNPs on the cryopreservation of bull semen.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma.

BACKGROUND: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.

[Retrospective analysis of ultrasonography for autoimmune pancreatitis].

OBJECTIVE: To explore the sonographic characteristics of autoimmune pancreatitis (AIP). METHODS: The ultrasonographic features and clinical data of 8 AIP patients were analyzed retrospectively and compared with the findings of computed tomography and magnetic resonance imaging. RESULTS: Ultrasound images showed diffuse pancreatic swelling (n = 6), focal pancreatic head thickening (n = 1) and tail enlargement (n = 1). In 7 patients, pancreatic echogenicities were of Grade 1 or less while the other 1 patient Grade 2. Among them, 6 showed hyperechoic "pseudocapsule". And enlarged gallbladder, dilated biliary and pancreatic ducts were seen in 2 patients with jaundice. CONCLUSION: Ultrasonic features play an important role in an early diagnosis of AIP.

MicroRNA-20a-5p regulates the epithelial-mesenchymal transition of human hepatocellular carcinoma by targeting RUNX3.

BACKGROUND: MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms. METHODS: We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 ( RUNX3 ) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC. RESULTS: MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion. CONCLUSIONS: Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.

The "stiff rim" sign of hepatocellular carcinoma on shear wave elastography: correlation with pathological features and potential prognostic value.

PURPOSE: To explore the pathologic basis, the influencing factors and potential prognostic value of the stiff rim sign in two-dimensional shear wave elastography (2D-SWE) of hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent tumor 2D-SWE examination before resection were prospectively enrolled. The stiff rim sign was defined as increased stiffness in the peritumoral region. Interobserver and intraobserver variability of the stiff rim sign was assessed. The correlation between the stiff rim sign and pathological characteristics was analyzed. Multivariate analysis was performed to examine clinical and radiological factors influencing the appearance of stiff rim sign. The Kaplan-Meier method was used to analyze the relationship between recurrence-free survival (RFS) and the stiff rim sign. RESULTS: The stiff rim sign on 2D-SWE was present in 44.7% of HCC lesions. Interobserver agreement and intraobserver agreement for the stiff rim sign were substantial (κ = 0.772) and almost perfect (κ = 0.895), respectively. Pathologically, the stiff rim sign was associated with capsule status, capsule integrity, capsule thickness, proportion of peritumoral fibrous tissue, and peritumoral fibrous arrangement. Multivariate analysis showed that tumor size was an independent clinical predictor for the appearance of stiff rim sign (OR 1.201, p = 0.008). Kaplan-Meier analysis showed RFS was significantly poorer in the stiff rim sign (+) group than the stiff rim sign (-) group in solitary tumors smaller than 5 cm (p = 0.007) and solitary tumors with intratumoral stiffness less than 33.7 kPa (p = 0.007). CONCLUSION: The stiff rim sign on 2D-SWE was mainly correlated with peritumoral fibrous tissue status and was a poor prognostic indicator for HCC.

Beneficial Effect of Selenium Doped Carbon Quantum Dots Supplementation on the in vitro Development Competence of Ovine Oocytes.

Background: After the synthesis of selenium doped carbon quantum dots (Se/CDs) via a step-by-step hydrothermal synthesis method with diphenyl diselenide (DPDSe) as precursor, the beneficial effects of Se/CDs' supplementation on the in vitro development competence of ovine oocytes were firstly investigated in this study by the assay of maturation rate, cortical granules' (CGs) dynamics, mitochondrial activity, reactive oxygen species (ROS) production, epigenetic modification, transcript profile, and embryonic development competence. Results: The results showed that the Se/CDs' supplementation during the in vitro maturation (IVM) process not only enhanced the maturation rate, CGs' dynamics, mitochondrial activity and embryonic developmental competence of ovine oocytes, but remarkably decreased the ROS production level of ovine oocytes. In addition, the expression levels of H3K9me3 and H3K27me3 in the ovine oocytes were significantly up-regulated after the Se/CDs' supplementation, in consistent with the expression levels of 5mC and 5hmC. Moreover, 2994 up-regulated differentially expressed genes (DEGs) and 846 repressed DEGs were found in the oocytes after the Se/CDs' supplementation. According to the analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), these DEGs induced by the Se/CDs' supplementation were positively related to the progesterone mediated oocyte maturation and mitochondrial functions. And these remarkably up-regulated expression levels of DEGs related to oocyte maturation, mitochondrial function, and epigenetic modification induced by the Se/CDs' supplementation further confirmed the beneficial effect of Se/CDs' supplementation on the in vitro development competence of ovine oocytes. Conclusion: The Se/CDs prepared in our study significantly promoted the in vitro development competence of ovine oocytes, benefiting the extended research about the potential applications of Se/CDs in mammalian breeding technologies.

Feasibility of liver stiffness measured using two-dimensional shear wave elastography in assessing preoperative liver function for patients with hepatocellular carcinoma.

OBJECTIVES: To evaluate the feasibility of liver stiffness (LS) measured using two-dimensional shear wave elastography (2D SWE) in assessing preoperative liver function for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 143 patients who underwent surgical resection for HCC between August 2018 and December 2019 were enrolled prospectively. LS measurement, liver function tests including serum biochemical indicators, and indocyanine green (ICG) clearance test were performed preoperatively. Child-Pugh (CP) score, Albumin-bilirubin (ALBI) score and Model for End-Stage Liver Disease score were calculated. ICG retention rate at 15 min (ICG R15) and ICG elimination rate constant (ICG K) were determined automatically. Fibrosis stage was determined based on pathological findings. The association between LS and serum biochemical indicators, liver function scores, and the ICG results were analyzed. RESULTS: Weak to moderate correlations were identified between LS and biochemical indicators of liver function (all p < 0.01). Weak correlation was identified between LS and CP score, and between LS and ALBI score (all p < 0.001). Moderate correlation was identified between LS and ICG R15 (Pearson r = 0.62, p < 0.001), and between LS and ICG K value (Pearson r = - 0.49, p < 0.001). The best cutoff of LS to discriminate a normal ICG R15 was 10.6 kPa, with area under the curve (AUC), sensitivity, specificity of 0.874, 0.900 and 0.724, respectively. CONCLUSIONS: LS determined using 2D SWE could be a potential tool for the preoperative evaluation of liver function in patients with HCC.