Value of Multimodal Data From Clinical and Sonographic Parameters in Predicting Recurrence of Hepatocellular Carcinoma After Curative Treatment.

OBJECTIVE: The objective of the work described here was to assess the value of the combination of pre-operative multimodal data-including clinical data, contrast-enhanced ultrasound (CEUS) information and liver stiffness measurement (LSM) based on 2-D shear wave elastography (SWE)-in predicting early (within 1 y) and late (after 1 y) recurrence of hepatocellular carcinoma (HCC) after curative treatment. METHODS: We retrospectively included 101 patients with HCC who met the Milan criteria and received curative treatment. The multimodel data from clinical parameters, LSM by 2-D SWE and CEUS enhancement patterns were collected. The association between different variables in HCC recurrence was accessed using a Cox proportional hazard model. On the basis of the independent factors of early recurrence, models with different source variables were established (Clinical Model, CEUS-Clinical Model, SWE-Clinical Model, CEUS-SWE-Clinical Model). The goodness-of-fit of models was evaluated and the performance trends of different models were calculated by time-dependent area under the curve (AUC). RESULTS: Two-dimensional SWE, CEUS enhancement patterns and clinical parameters (spleen length, multiple tumors, α-fetoprotein, albumin and prothrombin time) were independently associated with early recurrence (all p values <0.05). Multiple tumors and a decrease in albumin independently contributed to the late recurrence. The model fit of CEUS-SWE-Clinical Model was superior to other models in predicting early recurrence (all p values <0.05). The AUCs of the CEUS-Clinical Model were higher from 2 mo to 7 mo, while the SWE-Clinical Model had higher AUCs from 9 mo to 12 mo. CONCLUSION: CEUS enhancement patterns and 2-D SWE were independent predictors of HCC early recurrence as the two factors contributed to the predictive performance at different times. The multimodal model, which included diverse data in predicting early HCC recurrence, had the best goodness-of-fit.

Study on the correlation between B vitamins and breast cancer.

BACKGROUND: Relevant studies suggest that serum vitamin level is related to the risk of breast cancer, and dietary pattern and drug supplementation can significantly affect the level of vitamin in the body. Therefore, intervention of vitamin level in the body is expected to be a potential strategy to reduce the risk of breast cancer. However, the current epidemiological findings of serum vitamin levels and breast cancer risk are inconsistent, and the relationship between serum vitamin and breast cancer is still controversial. In this study, we compared the serum vitamin expression levels of healthy people, benign breast patients, and breast cancer patients, and evaluated the relationship between B vitamin levels and breast cancer risk. METHODS: The study used liquid chromatography-tandem mass spectrometry to determine the serum vitamin levels of 520 people who attended Yunnan Cancer Hospital from September 2020 to December 2020. After screening by exclusion criteria, 38 patients with benign breast diseases, 87 patients with breast cancer and 91 healthy controls were finally included. The kruskal-wallis H test was used to compare the differences in serum vitamin levels of subjects. Χ2 test was used to evaluate the relationship between B vitamin level and age,BMI,TNM staging,Ki-67,Her-2,surgery and chemotherapy, and other baseline characteristics and through binary logistic regression analysis, calculating odds ratio and 95% confidence interval (CI) to evaluate the relationship between B vitamins and breast cancer risk. CONCLUSION: The levels of VitB1 and VitB5 in the serum of breast cancer patients and patients with benign breast diseases were higher than those in the healthy control group, while the expression levels of VitB3 in breast cancer patients were lower than those in the healthy control group and the breast benign disease groups. The level of VitB1 was positively correlated with breast cancer risk. The VitB3 level was negatively correlated with breast cancer risk. The VitB5 level is not significantly related to the risk of breast cancer.

Inter-reader agreement of CEUS LI-RADS among radiologists with different levels of experience.

OBJECTIVES: To investigate the inter-reader agreement of contrast-enhanced ultrasound (CEUS) of Liver Imaging Reporting and Data System version 2017 (LI-RADS v2017) categories among radiologists with different levels of experience. MATERIALS AND METHODS: From January 2014 to December 2014, a total of 326 patients at high risk of hepatocellular carcinoma (HCC) who underwent CEUS were included in this retrospective study. All lesions were classified according to LI-RADS v2017 by six radiologists with different levels of experiences: two residents, two fellows, and two specialists. Kappa coefficient was used to assess consistency of LI-RADS categories and major features among radiologists with different levels of experience. The diagnostic performance of HCC was described by accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). RESULTS: Inter-reader agreement among radiologists of different experience levels was substantial agreement for arterial phase hyperenhancement, washout appearance, and early or late washout. Inter-reader agreement for LI-RADS categories was moderate to substantial. When LR-5 was used as criteria to determinate HCC, the AUC of LI-RADS for HCC was 0.67 for residents, 0.72 for fellows, and 0.78 for specialist radiologists. When compared between residents and specialists, accuracy, sensitivity, and AUC were significantly different (all p < 0.05). However, there were no significant differences in specificity, PPV, and NPV between the two groups. CONCLUSION: CEUS LI-RADS showed good diagnostic consistency among radiologists with different levels of experience, and consistency increased with experience levels. KEY POINTS: • The inter-reader agreement for LI-RADS categories was moderate to substantial agreement (κ, 0.60-0.80). • When compared between residents and specialists, accuracy, sensitivity, and AUC showed significantly different (all p < 0.05). However, there were no significant differences for specificity, PPV, and NPV between these two groups. • Among the radiologists with more than 1 year of experience, there was no significant difference in the diagnostic performance of HCC, suggesting that CEUS LI-RADS is a good standardized categorization system for high-risk patients.

Hydrophilic Flexible Ether Containing, Cross-Linked Anion-Exchange Membrane Quaternized with DABCO.

Anion-exchange membranes (AEM) with high ion content usually suffer from excessive water absorption and dilution effects that impair conductivity and mechanical properties. We herein report a novel ether containing a cross-linking strategy without adopting high ion-exchange capacity (IEC). The ether-containing cross-links and the quaternized structure are created simultaneously by introducing an ether-containing flexible hydrophilic spacer between two 1,4-diazabicyclo[2,2,2,2]octane or DABCO molecules; the resultant bi-DABCO structure was further employed to react with chloromethylated polysulfone. The long spacer with the ether moiety may benefit the hydroxide ion transport, and the cross-links will control the swelling and water absorption of the AEM. The two ether groups in the long spacer of the cross-links will also shield the DABCO cation from OH- attack due to an electron-donating effect. The prepared membranes exhibited an improved conductivity of 31 mS/cm (at 25 °C) at a comparatively low IEC (1.08 mmol/g) with a rational water absorption and low swelling ratio (95.0 and 27.1%, respectively); they also displayed an enhanced alkaline stability in 1 M NaOH aqueous solution at 80 °C for 150 h. The density functional theory study and physical characterization after the alkaline treatment further confirm the better chemical stability of the cross-linked membrane over its counterpart. Our work presents an effective strategy to balance AEM conductivity and robustness.

Granulocyte colony-stimulating factor and stromal cell-derived factor-1 combination therapy: A more effective treatment for cerebral ischemic stroke.

BACKGROUND: Drugs that promote angiogenesis include statins, recombinant human granulocyte colony-stimulating factor, and stromal cell-derived factor-1. Low doses of atorvastatin could significantly increase the vascular expressions of endothelial growth factor, and the number of peripheral blood endothelial progenitor cells (EPCs), thus improving angiogenesis and local blood flow. G-CSF is an EPC-mobilization agent used in ischemia studies for targeting angiogenesis after cerebral ischemia via EPCs. In previous clinical trials, consistent conclusions have not been reached about the effectiveness of G-CSF on ischemic stroke. Therefore, the therapeutic effect of G-CSF and its combination with other medicines need further experimental verification. It is known that atorvastatin, rhG-CSF, and SDF-1 are considered the most promising neuroprotective candidates, but a comprehensive comparison of their effects is lacking. AIMS: To compare the effects of atorvastatin, stromal cell-derived factor-1, and recombinant human granulocyte colony-stimulating factor on ischemic stroke. METHODS: Adult male Sprague-Dawley rats were randomly allocated to three groups: normal, sham-operated, and middle cerebral artery occlusion operated. Middle cerebral artery occlusion operated rats were further allocated into saline, atorvastatin, recombinant human granulocyte colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 groups. Neurological function evaluation, cerebral infarction and the blood-brain barrier integrity analysis, identification of angiogenic factors, assessment of angiogenesis, expression of growth-associated protein-43, neuroglobin, glial cell-derived neurotrophic factor, and cleaved caspase 3, were performed. RESULTS: Compared with atorvastatin or recombinant human granulocyte colony-stimulating factor alone, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 treatment improved neurological performance, reduced cerebral infarction and blood-brain barrier disruption after stroke, and increased the content of stromal cell-derived factor-1, vascular endothelial growth factor, monocyte chemotactic protein 1, and basic fibroblast growth factor in peripheral blood. In addition, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 promoted greater angiogenesis than atorvastatin or recombinant human granulocyte colony-stimulating factor alone and increased the expression of growth-associated protein-43, neuroglobin, and glial cell-derived neurotrophic factor, while decreasing the levels of cleaved caspase 3 in the brain after ischemic stroke. CONCLUSIONS: Combination therapy with recombinant human granulocyte colony-stimulating factor and stromal cell-derived factor-1 is more effective than atorvastatin or recombinant human granulocyte colony-stimulating factor alone in protecting against stroke-induced damage and could be an optimal therapeutic strategy for stroke.

Amphoteric-Side-Chain-Functionalized "Ether-Free" Poly(arylene piperidinium) Membrane for Advanced Redox Flow Battery.

To solve the stability issue of cost-effective nonfluorinated membranes, an ether-free poly(arylene piperidinium) (PBPip)-based membrane is first applied in redox flow batteries (RFBs). For improved efficiencies of RFB, amphoteric side chains are introduced onto the PBPip. Without an ether bond in the polymer backbone, the membrane shows a good stability in a strong oxidation environment. The Fourier transform infrared (FTIR) spectra exhibit no obvious changes over 30 days of oxidation test. Different from traditional blended amphoteric membranes, the amphoteric side chain allows both cation- and anion-exchange capacities to increase with grafting degree, which leads to a very high total ion-exchange capacity (IEC) (4.19 mmol g-1). Outstanding ion-conduction ability (area resistance: 0.22 Ω cm2) comparable to Nafion 212 (0.24 Ω cm2) is consequently achieved. Ionic cross-linking structure between cationic and anionic groups results in a low swelling rate (13.9%). Combined with the repelling effect of positively charged piperidinium, a low VO2+ permeability (1.31 × 10-8 cm2 s-1) is accomplished. On the basis of these good properties, the membrane exhibits excellent vanadium battery performances, especially at high current densities. The VE and EE both exceed 80% even at 200 mA cm-2. The battery performances have no obvious reductions after 500 cycles. These results indicate that this work provides a new orientation to design the membrane for RFB.

[Study on antimicrobial effect of the mixture of Chinese medicine-chitosan to Candida albicans and the possibility as denture adhesive].

PURPOSE: To observe the antimicrobial effect and the tensile bond strength of water-soluble chitosan after adding different Chinese medicines to Candida albicans. METHODS: The extract of 6 kinds of Chinese medicine by decoction in different concentrations were mixed with chitosan, and the most effective mixture inhibiting Candida albicans and the minimal inhibitory concentration (MIC) were explored; Then the tensile bond strength of the mixture was tested and compared with Protefix denture adhesive. The data was analyzed with SPSS17.0 software package. RESULTS: The antibacterial effect of polyphylla-chitosan mixture was the best among the 6 kinds of Chinese medicine- chitosan mixture, and its MIC was 1.563 mg/mL. The tensile bond strength of polyphylla-chitosan mixture at 0 h and 12 h when immersed in artificial saliva were significantly larger than Protefix denture adhesive. The average value and the maximum value was significantly greater than the Protefix denture adhesive (P<0.05). CONCLUSIONS: Polyphylla-chitosan mixture has good antibacterial effect on Candida albicans and large tensile bond strength.

Down-regulated Na(+)/K(+)-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats.

This study was aimed to examine whether the Na(+)/K(+) adenosine triphosphatase (Na(+)/K(+)-ATPase) activity in ischemic penumbra is associated with the pathogenesis of ischemia/reperfusion-induced brain injury. An experimental model of cerebral ischemia/reperfusion was made by transient middle cerebral artery occlusion (tMCAO) in rats and the changes of Na(+)/K(+)-ATPase activity in the ischemic penumbra was examined by Enzyme Assay Kit. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 6 h, 24 h, 48 h, 3 d and 7 d after tMCAO. Enzyme Assay analyses revealed the activity of Na(+)/K(+)-ATPase was decreased in the ischemic penumbra of model rats after focal cerebral ischemia/reperfusion compared with sham-operated rats, and reduced to its minimum at 48 h, while the infarct volume was enlarged gradually. In addition, accompanied by increased brain water content, apoptosis-related bcl-2 and Bax proteins, apoptotic index and neurologic deficits Longa scores, but fluctuated the ratio of bcl-2/Bax. Correlation analysis showed that the infarct volume, apoptotic index, neurologic deficits Longa scores and brain water content were negatively related with Na(+)/K(+)-ATPase activity, while the ratio of bcl-2/Bax was positively related with Na(+)/K(+)-ATPase activity. Our results suggest that down-regulated Na(+)/K(+)-ATPase activity in ischemic penumbra might be involved in the pathogenesis of cerebral ischemia/reperfusion injury presumably through the imbalance ratio of bcl-2/Bax and neuronal apoptosis, and identify novel target for neuroprotective therapeutic intervention in cerebral ischemic disease.

Expression and localization of estrogen receptor in human breast cancer and its clinical significance.

The aim of this study was to analyze the clinicopathologic significance of ERα protein that localized in the cell cytoplasm and/or cell membrane of human breast cancer and explore what kind of protein that the cytoplasm/membrane ERα belongs to. ERα expressions in 61 cases of breast cancer are detected by immunohistochemistry, grouping is performed according to the positive staining of different subcellular localizations, the expression levels of ERα66 and ERα36 in cancer tissues of groups with different subcellular localizations are detected by Western blot, and correlation between the indicators and its clinicopathologic significance are analyzed by combining with the clinical pathological parameters. Localization by immunohistochemical staining in breast cancer cells shows that there are two types of ERα­in the cell nucleus and/or the cell membrane; there are four groups as ER nuclear staining positive + membrane staining positive (N+/C+), 23 cases; ER nuclear staining positive + membrane staining negative (N+/C-), 16 cases; ER nuclear staining negative + membrane staining positive (N-/C+), 8 cases; and ER nuclear staining negative + membrane staining negative (N+/C+), 14 cases. ER expression in the cytoplasm and/or membrane of cancer cells is correlated with the high expression of HER-2, the lymphatic metastasis, and the late clinical stage. Western blot results show that ER protein in breast cancer tissues mainly consists of ERα66 and ERα36 bands, and among all the groups, all the cases from the N+/C+ group (n = 23) have both ERα66 and ERα36 expressions; in the N+/C- group, 14 cases of which only have the ERα66 expression without ERα36 expression and 2 cases of which have both ERα66 and ERα36 expression; all the cases from the N-/C+ group have only the ERα36 expression without ERα66 expression; and in the N-/C- group, there is no either ERα66 or ERα36 expression. The expression level of ERα36 relates to the age of patients, the menopause, the lymphatic metastasis, and the tumor size (p < 0.05), and no statistical significance was shown between it and the family history of patients as well as the clinical staging parameters (p > 0.05). The expression level of ERα66 relates to the tumor size of breast cancer and the clinical stages (p < 0.05), and no statistical significance was shown between it and the age of patients, the history of menopause, and the family history as well as the parameters of lymphatic metastasis (p > 0.05). ER protein expression of human breast cancer is localized in the cell nucleus and/or the cell membrane, with poor prognosis of cytoplasm/membrane-positive patients; ER protein that localized in the nucleus is mainly ERα66 and that localized in the cytoplasm and/or membrane is mainly ERα36.

The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma.

Histological grade has already been recognized as a very important prognostic factor for ovarian papillary serous carcinoma (OPSC). On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC consisting of types I (low-grade) and II (high-grade) cancers. High-grade OPSC is responsible for most ovarian cancer deaths. The goal of our investigation was to identify the differences in key miRNAs and possible regulators through miRNA microarray chip analysis, as well as functional target prediction and clinical outcome between the low and high-grade OPSC patients. The pathogenic basis in differentiation of ovarian cancer subtypes was studied to provide insight into diagnosis and therapy for high-grade cases. Through microarray analysis, we found that miR-30a* and miR-30e* were the top 2 significantly different miRNAs between type I and type II OPSC patients, and both were remarkably downregulated in the latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a* and miR-30e*, and showed a significant upregulation in type II patients. As ATF3 and MYC are often associated with aggressive behavior and poor differentiation, especially in human cancers, these results are in good agreement with our findings and point toward a regulating differentiation function of the miR-30a* and miR-30e* genes. Further analysis using leave­one-out cross predictions and Kaplan-Meier survival analysis strongly suggested that miR-30a* and miR-30e* can be used as biomarkers to tailor histological grade before starting the regimen, and they showed important roles in ovarian cancer differentiation resulting in poorer prognosis. In general, miR-30a* and miR-30e* coupled with expression data that reveal pathogenic regulation to predict histological differentiation, may operate to direct the formation of early detection and therapeutic approaches to individual OPSC patients, especially differentiation therapy to high-grade cases.

Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition.

BACKGROUND: Lycorine, a natural alkaloid extracted from Amaryllidaceae, has shown various pharmacological effects. Recent studies have focused on the potential antitumor activity of lycorine. In our previous study, we found that lycorine decrease the cell viability of leukemia HL-60 cells and multiple myeloma KM3 cells and induces cell apoptosis. However, the effect and molecular mechanism of lycorine on human chronic myelocytic leukemia cells has yet to be determined. METHODS: Human chronic myelocytic leukemia cells K562 were treated with lycorine. Cell viability was monitored using the method of CCK-8. The histone deacetylase (HDAC) enzymatic activity was detected by HDAC colorimetric assay, and the cell cycle was analyzed by flow cytometry. The expression of cell-cycle related proteins were identified using Western blot. RESULTS: In the present study, we further revealed that lycorine can inhibit the proliferation of K562 cells. Analysis of HDAC activity showed that lycroine decreases HDAC enzymatic activities in K562 cells in a dose-dependent manner. Inhibition of HDAC activity has been associated with cell-cycle arrest and growth inhibition. We evaluated the cell cycle distribution after lycorine treatment and found that lycorine causes cell-cycle arrest in the G0/G1 phase. To investigate the mechanism behind this cell cycle arrest, G1-related proteins were assayed by Western blot. After lycorine treatment, cyclin D1 and cyclin-dependent kinase 4 expressions were inhibited and retinoblastoma protein phosphorylation was reduced. Lycorine treatment also significantly upregulated the expression of p53 and its target gene product, p21. CONCLUSIONS: These results suggest that inhibition of HDAC activity is responsible for at least part of the induction of cell-cycle arrest in the G0/G1 phase by lycorine and provide a mechanistic framework for further exploring the use of lycorine as a novel antitumor agent.

Inducing-apoptotic activity of the ethanol extract of Duchesnea indica Focke on treatment of herpes simplex encephalitis.

This study explores the inducing-apoptotic activity of the ethanol extract of Duchesnea indica Focke on treatment of herpes simplex encephalitis. Cell models were employed and divided into 4 groups: normal group, virus group, Duchesnea indica group and dexamethasone group. Cytopathic effect examination was employed to detect apoptosis of PC-12 and BV-2 cells. ELISA was used to measure TNF-α, IL-1ß, and Greiss method to measure NO secretion. Flow cytometry assay for caspase-3 expressions was performed. As a result, the ethanol extract of Duchesnea indica could protect the neuron cell model from impairment by virus. In the cell model of microglia stimulated by herpes simplex virus (HSV), with the ethanol extract intervention, TNF-α, IL-1ß and NO levels were significantly decreased and cell death of BV-2 cells were markedly increased. The expression level of caspase-3 was notably elevated after the extract intervention. In conclusion, the ethanol extract of Duchesnea indica can reduce HSV-induced inflammatory injury on neuron due to the induction of microglia apoptosis.

Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer.

BACKGROUND: Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC). Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα) expression level in postoperative NSCLC patients who received adjuvant chemotherapy. METHODS: Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC). The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS) were analyzed. RESULTS: TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036), non-adenocarcinoma (P = 0.004), earlier pathological TNM stage (P = 0.001) or pathological N stage (P < 0.001), and high expression of TopIIα (P = 0.012) were correlated with better DFS, whereas age, smoking history, different chemotherapy regimens, T stage and expression level of Ki67 were of no prognostic significance. Further stratified analysis showed that vinorelbine (NVB)-containing adjuvant regimens were generally associated with better DFS than regimens without NVB in patients with low TopIIα expression, though the difference was not statistically significant (P = 0.065). Pairwise comparisons for patients with low TopIIα expression indicated that the NVB-containing regimen was associated with better DFS than the docetaxel (TXT)-containing regimen (P = 0.047). COX multivariate analysis showed that pathological TNM stage, histological subtype and expression level of TopIIα to be independent of risk factors affecting DFS in postoperative NSCLC patients who received chemotherapy. CONCLUSIONS: High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.

The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro.

Opposing functions of activated microglia, namely neuroprotection or neurotrophy versus neurodestruction or neurotoxicity, have been observed in a number of experimental models of neurotrauma and neurodegenerative diseases. However, the mechanism(s) involved in the determination of which function activated microglia execute under a given set of conditions still remains to be elucidated. Our current in vitro study has revealed that a neuroprotective/neurotrophic or a neurodestructive/neurotoxic microglial function may be configured by the equilibrium among various microglial factors released into the microenvironment. When NSC-34 neurons were treated with lower concentrations of lipopolysaccharide-stimulated BV-2 microglial conditioned medium (LPS-BVCM), viability of the NSC-34 neurons increased, outgrowth of neuronal processes was promoted, and the formation of 2,5-hexanedione-induced aggregates was prevented. However, when NSC-34 neurons were treated with higher concentrations of the same LPS-BVCM, neuronal viability was reduced, apoptosis was induced and outgrowth of neuronal processes was prevented. Measurement of the cytokines tumor necrotic factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the LPS-BVCM has shown that the upregulation in expression for each cytokine varied both temporally and quantitatively. It is postulated that an alteration in the concentration of the LPS-BVCM might significantly affect the functional balance of microglial factors in the microenvironment with a resultant different microglial function.