Evaluating blood supply changes in the osteonecrosis of the femoral head using gadobutrol-based steady-state MR angiography.

OBJECTIVES: Assess the feasibility of using gadobutrol-based steady-state (SS) MR angiography (MRA) to evaluate the blood supply changes of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Participants were recruited in this prospective study from December 2021 to May 2022 in a single center. The number of superior retinacular arteries (SRAs), inferior retinacular arteries (IRAs), anterior retinacular arteries (ARAs), and overall retinacular arteries (ORAs), as well as the affected rates of SRA and IRA, were determined and compared between healthy and ONFH hips and between hips across the Association Research Circulation Osseous (ARCO) staging I-IV. RESULTS: Twenty healthy and 64 ONFH hips were evaluated in 54 participants. There were significant differences between ARCO I-IV for the number of ORAs (mean of 3.5, 2.3, 1.7, and 0.8 for ARCO I-IV, respectively; p < .001), SRAs (median of 2.5, 1, 0.5, and 0 for ARCO I-IV, respectively; p < .001), and the affected rate of SRAs (20.00%, 65.22%, 77.78%, 92.31% for ARCO I-IV, respectively, p = 0.002). There were significant differences between ONFH and healthy hips for the number of ORAs (median of 5 vs. 2; p < .001), SRAs (median of 3 vs. 1; p < .001), IRAs (median of 1 vs. 1; p < .001), ARAs (median of 0 vs. 0; p = 0.04), and also the affected rate of SRAs (5.00% vs. 67.20%, p < .001) and IRAs (30% vs. 84.4%, p < .001). CONCLUSION: Gadobutrol-enhanced SS MRA is a feasible method for evaluation of hemodynamics in ONFH. CLINICAL RELEVANCE STATEMENT: Gadobutrol-enhanced magnetic resonance angiography can evaluate blood supply changes of ONFH and therefore helps to aid in the diagnosis and guide treatment of ONFH. KEY POINTS: • Gadobutrol-enhanced magnetic resonance angiography showed changes in the retinacular artery related to the severity of femoral osteonecrosis. • Gadobutrol-enhanced magnetic resonance angiography revealed a reduced blood supply to the ischemic necrotic femoral head compared to the healthy counterparts.

Comparison and Optimization of Cardiovascular Risk Scores in Predicting the 4-Year Outcome of Patients with Obstructive Coronary Arteries Disease.

Objective: How well cardiovascular risk models perform in selected atherosclerosis patients for predicting outcomes is unknown. We sought to compare the performance of cardiovascular risk models (Framingham, Globorisk, SCORE2 & SCORE2-OP, and an updated new model) in predicting the 4-year outcome of patients with obstructive coronary artery disease (CAD). Methods: Patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) were recruited. Obstructive CAD was defined from CCTA as ≥ 50% stenosis. Computed tomography images, the scores of the cardiovascular risk models, and 4-year composite endpoints were assessed. Whether the patients underwent revascularization within 60 days after CCTA was also recorded. Multivariate regression analysis and receiver operating characteristics (ROC) curve analysis were performed. Results: A total of 95 patients (mean age: 69.5 ± 10.33 years; 69 males) with obstructive CAD were included in this study. After the ROC analysis, the Framingham, Globorisk, SCORE2 & SCORE2-OP risk score showed prediction values with AUC 0.628 (95% CI: 0.532-0.725), 0.647 (95% CI: 0.542-0.742), 0.684 (95% CI: 0.581-0.776), respectively. Multivariate regression analysis showed that, among the three risk models, only SCORE2 & SCORE2-OP risk score was associated with composite endpoints (hazard ratio: 1.050; 95% CI: 1.021-1.079; p = 0.001) after adjusting for confounding factors. The AUC of the new risk model by combing SCORE2 & SCORE2-OP risk score with revascularization and the number of obstructive vessels in predicting composite endpoints reached 0.898 (95% CI: 0.819-0.951). Conclusion: The SCORE2 & SCORE2-OP risk score combined with the number of obstructive vessels and revascularization is predictive for adverse outcomes in patients with obstructive CAD.

Evaluating prostate cancer bone metastasis using accelerated whole-body isotropic 3D T1-weighted Dixon MRI with compressed SENSE: a feasibility study.

OBJECTIVES: The study aimed to assess the efficiency of whole-body high-resolution compressed sensing-sensitivity encoding isotropic T1-Weighted Dixon (CSI-T1W-Dixon) scans in evaluating bone metastasis. METHODS: Forty-five high-risk prostate cancer patients with bone metastases were enrolled prospectively and underwent whole-body MRI sequences, which included the following: pre- and post-contrast CSI-T1W-Dixon and conventional multi-planar T1-Weighted Dixon (CMP-T1W-Dixon) (coronal, sagittal, and axial scans), short tau inversion recovery (STIR), and DWI. Comparison between the CMP-T1W-Dixon and CSI-T1W-Dixon images was done for the subjective image quality, the quantitative contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). Furthermore, the diagnostic performance based on per-lesion and per-patient basis utilizing non-contrast T1-weighted (T1)/T1+ contrasted T1-weighted (T1C)/T1 + T1C + STIR + DWI sequences was compared between the CSI-T1W-Dixon and CMP-T1W-Dixon methods using reference standards (combining biopsy data and 6-month imaging follow-up). RESULT: The CSI-T1W-Dixon images produced fewer image artifacts in the axial and coronal planes compared to the CMP-T1W-Dixon images. Also, the CSI-T1W-Dixon images provided better a CNR in fat-only images of all three planes and water-only images of the axial plane (p < 0.05). The CSI-T1W-Dixon showed a higher sensitivity than the CMP-T1W-Dixon techniques in analyzing T1-only images on a per-lesion basis (82.7% vs. 53.8% for sensitivity, p = 0.03). On a per-patient basis, no difference was found in the diagnostic capacity between the CSI-T1W-Dixon and CMP-T1W-Dixon sequences either alone or in combinations (p = 0.57-1). CONCLUSION: High-resolution CSI-T1W-Dixon with higher image quality and diagnostic capacity can replace the CMP-T1W-Dixon method in evaluating bone metastasis in clinical practice. KEY POINTS: • Compressed sensing isotropic acquisition for 3D T1-weighted Dixon images can improve the image quality with fewer artifacts compared to the anisotropic multiplanar acquisition. • Compressed sensing isotropic acquisition can save 67% of scanning time compared to anisotropic multiplanar acquisition. • Compressed sensing isotropic 3D T1-weighted Dixon images can offer better diagnostic performance with higher sensitivity compared to anisotropic multiplanar images.

Construction and validation of a m6A RNA methylation and ferroptosis-related prognostic model for pancreatic cancer by integrated bioinformatics analysis.

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.

20-hydroxyeiscosatetraenoic acid may be as a predictor of malignant middle cerebral artery infarction in patients with massive middle cerebral artery infarction.

BACKGROUND: Early identification of massive middle cerebral artery infarction (MCAI) at risk for malignant MCAI (m-MCAI) may be useful in selecting patients for aggressive therapies. The aim of this study was to determine whether CYP metabolites may help to predict impending m-MCAI. METHODS: This is a prospective, two-center observational study in 256 patients with acute massive MCAI. Plasma levels of 20-hydroxyeicosatetraenoic acid (20-HETE), epoxyeicosatrienoic acids, and dihydroxyeicosatrienoic acids were measured at admission. Brain computed tomography (CT) was performed at admission and repeated between day 3 and 7, or earlier if there was neurological deterioration. The primary outcome was m-MCAI. The m-MCAI was diagnosed when follow-up brain CT detected a more than two-thirds space-occupying MCAI with midline shift, compression of the basal cisterns, and neurological worsening. RESULTS: In total of 256 enrolled patients, 77 (30.1%) patients developed m-MCAI. Among the 77 patients with m-MCAI, 60 (77.9%) patients died during 3 months of stroke onset. 20-HETE level on admission was significantly higher in patients with m-MCAI than those without m-MCAI. There was an increase in the risk of m-MCAI with increase of 20-HETE levels. The third and fourth quartiles of 20-HETE levels were independent predictors of m-MCAI (OR: 2.86; 95% CI: 1.16 - 6.68; P = 0.025, and OR: 4.23; 95% CI: 1.35 - 8.26; P = 0.002, respectively). CONCLUSIONS: Incidence of m-MCAI was high in patients with massive MCAI and the prognosis of m-MCAI is very poor. Elevated plasma 20-HETE may be as a predictor for m-MCAI in acute massive MCAI, and it might useful in clinical practice in therapeutic decision making.

Radiomics Model Based on MR Images to Discriminate Pancreatic Ductal Adenocarcinoma and Mass-Forming Chronic Pancreatitis Lesions.

BACKGROUND: It is difficult to identify pancreatic ductal adenocarcinoma (PDAC) and mass-forming chronic pancreatitis (MFCP) lesions through conventional CT or MR examination. As an innovative image analysis method, radiomics may possess potential clinical value in identifying PDAC and MFCP. To develop and validate radiomics models derived from multiparametric MRI to distinguish pancreatic ductal adenocarcinoma (PDAC) and mass-forming chronic pancreatitis (MFCP) lesions. METHODS: This retrospective study included 119 patients from two independent institutions. Patients from one institution were used as the training cohort (51 patients with PDAC and 13 patients with MFCP), and patients from the other institution were used as the testing cohort (45 patients with PDAC and 10 patients with MFCP). All the patients had pathologically confirmed results, and preoperative MRI was performed. Four feature sets were extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and the artery (A) and portal (P) phases of dynamic contrast-enhanced MRI, and the corresponding radiomics models were established. Several clinical characteristics were used to discriminate PDAC and MFCP lesions, and clinical model was established. The results of radiologists' evaluation were compared with pathology and radiomics models. Univariate analysis and the least absolute shrinkage and selection operator algorithm were performed for feature selection, and a support vector machine was used for classification. The receiver operating characteristic (ROC) curve was applied to assess the model discrimination. RESULTS: The areas under the ROC curves (AUCs) for the T1WI, T2WI, A and, P and clinical models were 0.893, 0.911, 0.958, 0.997 and 0.516 in the primary cohort, and 0.882, 0.902, 0.920, 0.962 and 0.649 in the validation cohort, respectively. All radiomics models performed better than clinical model and radiologists' evaluation both in the training and testing cohorts by comparing the AUC of various models, all P<0.050. Good calibration was achieved. CONCLUSIONS: The radiomics models based on multiparametric MRI have the potential ability to classify PDAC and MFCP lesions.

Bamboo Transposon Research: Current Status and Perspectives.

Bamboo, a fast-growing non-timber forest plant with many uses, is a valuable species for green development. However, bamboo flowering is very infrequent, extending, in general, for up to 120 years. Ecologically, bamboo species are generally better adapted to various environments than other grasses. Therefore, the species deserves a special status in what could be called Ecological Bioeconomy. An understanding of the genetic processes of bamboo can help us sustainably develop and manage bamboo forests. Transposable elements (TEs), jumping genes or transposons, are major genetic elements in plant genomes. The rapid development of the bamboo reference genome, at the chromosome level, reveals that TEs occupy over 63.24% of the genome. This is higher than found in rice, Brachypodium, and sorghum. The bamboo genome contains diverse families of TEs, which play a significant role in bamboo's biological processes including growth and development. TEs provide important clues for understanding the evolution of the bamboo genome. In this chapter, we briefly describe the current status of research on TEs in the bamboo genome, their regulation, and transposition mechanisms. Perspectives for future research are also provided.

Improving the accuracy of pre-operative evaluation of neurovascular conflict in trigeminal neuralgia using magnetic resonance subtraction.

PURPOSE: To investigate the ability of magnetic resonance (MR) subtraction to evaluate neurovascular conflict (NVC) and to compare it with conventional MR protocols. METHODS: This prospective study included 82 patients with trigeminal neuralgia who underwent microvascular decompression for NVC. All patients had a pre-operative examination using 3T MRI. The MRI protocols used comprised 3D balanced (B)-fast field echo (FFE), 3D steady-state magnetic resonance angiography (MRA), and 3D T1-FFE sequences. MR subtraction images were obtained by subtracting native images from B-FFE and steady-state MRA. NVC evaluation was performed using subtraction images (MR subtraction) and combination images (conventional MR protocols using B-FFE and T1-FFE in combination). Clinical assessment of the degree of compression, the type of compressing vessel, and the location of conflict were undertaken by two independent observers. The two methods were then compared using surgical criteria. RESULTS: MR subtraction exhibited greater accuracy than the conventional method in terms of the estimated severity of conflict (87.80% vs. 57.32%, p < 0.05), and demonstrated better consistency with surgical findings (k = 0.794 vs. k = 0.365, p < 0.05). For the type of compressing vessel and the location of conflict, both methods were highly accurate and agreed to a similar extent with surgical findings (p = 0.987, compressing vessel; p = 0.665, location of conflict). CONCLUSION: MR subtraction proved reliable in NVC pre-operative evaluation, with increased accuracy when estimating severity. This result strongly supports the wider use of MR subtraction as the preferred choice in clinical application.

Dynamic evaluation of lung involvement during coronavirus disease-2019 (COVID-19) with quantitative lung CT.

PURPOSE: To identify and quantify lung changes associated with coronavirus disease-2019 (COVID-19) with quantitative lung CT during the disease. METHODS: This retrospective study reviewed COVID-19 patients who underwent multiple chest CT scans during their disease course. Quantitative lung CT was used to determine the nature and volume of lung involvement. A semi-quantitative scoring system was also used to evaluate lung lesions. RESULTS: This study included eighteen cases (4 cases in mild type, 10 cases in moderate type, 4 cases in severe type, and without critical type cases) with confirmed COVID-19. Patients had a mean hospitalized period of 24.1 ± 7.1 days (range: 14-38 days) and underwent an average CT scans of 3.9 ± 1.6 (range: 2-8). The total volumes of lung abnormalities reached a peak of 8.8 ± 4.1 days (range: 2-14 days). The ground-glass opacity (GGO) volume percentage was higher than the consolidative opacity (CO) volume percentage on the first CT examination (Z = 2.229, P = 0.026), and there was no significant difference between the GGO volume percentage and that of CO at the peak stage (Z = - 0.628, P = 0.53). The volume percentage of lung involvement identified by AI demonstrated a strong correlation with the total CT scores at each stage (r = 0.873, P = 0.0001). CONCLUSIONS: Quantitative lung CT can automatically identify the nature of lung involvement and quantify the dynamic changes of lung lesions on CT during COVID-19. For patients who recovered from COVID-19, GGO was the predominant imaging feature on the initial CT scan, while GGO and CO were the main appearances at peak stage.

The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer.

Cervical cancer is the leading cause of cancer-related death among women worldwide. Identifying an effective treatment with fewer side effects is imperative, because all of the current treatments have unique disadvantages. Aldo-keto reductase family 1 member B1 (AKR1B1) is highly expressed in various cancers and is associated with tumor development, but has not been studied in cervical cancer. In the current study, we used CRISPR/Cas9 technology to establish a stable HeLa cell line with AKR1B1 knockout. In vitro, AKR1B1 knockout inhibited the proliferation, migration and invasion of HeLa cells, providing evidence that AKR1B1 is an innovative therapeutic target. Notably, the clinically used epalrestat, an inhibitor of aldose reductases, including AKR1B1, had the same effect as AKR1B1 knockout on HeLa cells. This result suggests that epalrestat could be used in the clinical treatment of cervical cancer, a prospect that undoubtedly requires further research. Moreover, aiming to determine the underlying regulatory mechanism of AKR1B1, we screened a series of differentially regulated genes (DEGs) by RNA sequencing and verified selected DEGs by quantitative RT-PCR. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs revealed a correlation between AKR1B1 and cancer. In summary, epalrestat inhibits the progression of cervical cancer by inhibiting AKR1B1, and thus may be a new drug for the clinical treatment of cervical cancer.

Magnetic resonance imaging for preoperative staging of pancreatic cancer based on the 8th edition of AJCC guidelines.

BACKGROUND: Preoperative staging of pancreatic cancer determines the choice of treatment. Magnetic resonance imaging (MRI) plays an important role in preoperative staging of pancreatic cancer. The American Joint Committee on Cancer (AJCC) TNM staging system was revised to its 8th version in 2016, there has been no report correlating the 8th edition of the AJCC TNM staging with preoperative MRI examinations and pathological findings. The purpose of our study is to determine the staging accuracy and evaluate the resectability by using MRI about pancreatic cancer compared with intraoperative or pathological findings according to the 8th edition of the AJCC TNM staging system. METHODS: One hundred thirty-two patients with a pathological diagnosis of pancreatic cancer who underwent preoperative MRI were identified. The clinical data, MRI findings and pathological findings were analyzed. Preoperative MRI staging and resectability evaluation were compared with pathological findings. The accuracy of MRI for preoperative T and N staging was evaluated, and the sensitivity, specificity and accuracy of MRI in evaluating the resectability were assessed. All the staging and resectability assessments were according to the 8th edition of the AJCC TNM staging system. RESULTS: Analysis showed that the accuracy of MRI for evaluation of the T and N stages was 82.6% (109/132) and 74.2% (98/132), respectively. The sensitivity and specificity of MRI in assessing the resectability were 94.2% and 71.4%, respectively. Integrating the 8th edition of the AJCC TNM stage, no significant differences were identified between the preoperative MRI and pathological results for the staging of pancreatic cancer (P=0.805). CONCLUSIONS: MRI is highly accurate for T staging and moderately accurate for N staging. MRI provides important preoperative evaluation of the stage and resectability of pancreatic cancer based on the 8th edition of the AJCC TNM staging system.

Detection of vascularity of femoral head using sub-millimeter resolution steady-state magnetic resonance angiography-initial experience.

OBJECTIVE: The purpose of this study was to use the steady-state (SS) magnetic resonance angiography (MRA) with a sub-millimeter resolution to detect the arteries supplying to the femoral head (FH). MATERIALS AND METHOD: SS MRA scanning of hips was performed bilaterally in 15 healthy volunteers. A blood pool contrast agent was used. The scanning protocol included a 0.8-mm3 isotropic T1-fast field echo sequence with spectral fat suppression technique. Two highly qualified radiologists independently evaluated the medial circumflex femoral artery (MCFA), the lateral circumflex femoral artery (LCFA), and the three retinacular arteries including superior retinacular artery (SRA), inferior retinacular artery (IRA), and anterior retinacular artery (ARA). The intraosseous branches of the three retinacular arteries were also evaluated. An orthopaedic surgeon was consulted in case of disagreement. Observation by the two radiologists and support from the orthopaedic surgeon served as the end result. Agreement between the two observer radiologists was evaluated. RESULTS: Interobserver agreement between the two radiologists was found to be substantial to perfect. Of the 30 hips, the LCFA and MCFA were detected in all hips; the SRA and IRA were detected in most hips (100%, 90%), and the ARA was detected in 13 hips (43%). The intraosseous branches of SRA and IRA were detected in 30 and 22 hips (100%, 73%), respectively, while the intraosseous branches of ARA were detected in 11 hips (37%). CONCLUSION: The main arteries supplying the FH can be detected by the SS MRA, making it a novel method to detect the vascularity of FH.

Nuclear export signal (NES) of transposases affects the transposition activity of mariner-like elements Ppmar1 and Ppmar2 of moso bamboo.

Ppmar1 and Ppmar2 are two active mariner-like elements (MLEs) cloned from moso bamboo (Phyllostachys edulis (Carrière) J. Houz) genome possessing transposases that harbour nuclear export signal (NES) domain, but not any nuclear localization signal (NLS) domain. To understand the functions of NES in transposon activity, we have conducted two experiments, fluorescence and excision frequency assays in the yeast system. For this, by site-directed mutagenesis, three NES mutants were developed from each of the MLE. In the fluorescence assay, the mutants, NES-1, 2 and 3 along with the wild types (NES-0) were fused with fluorescent proteins, enhanced yellow fluorescent protein (EYFP) and enhanced cyan fluorescent protein (ECFP) were co-transformed into yeast system. To differentiate protein localisation under the NES influence, ECFP alone was fused to wild and mutant NES domains either on N- or C-terminal and not to EYFP. Fluorescence assay revealed that blue fluorescence of ECFP was more intense than the red fluorescence of the EYFP in the yeast cell matrix. Further, ECFP had a wider localisation in the cellular matrix, but EYFP was largely located in the nucleus. The NES-1 domain was related to the comparatively high spread of ECFP, while NES-2 and NES-3 indicated a low spread, implying that NES activity on nuclear export increased when the NES is made leucine-rich, while the signalling activity was reduced when the leucine content was lowered in the NES domain. In the transposon excision assay, the mutant and wild type NES of both the Ppmar elements were integrated into an Ade2 vector, and within the Ade2 gene. Co-transformation of the vector together with non-autonomous Ppmar transposons and NES-lacking transposases was used to assess the differential excision frequencies of the mutants NES domains. In both the MLEs, NES-1 had the highest excision suppression, which was less than half of the excision frequency of the wild type. NES-2 and NES-3 elements showed, up to three times increase in transposon excision than the wild types. The results suggested that NES is an important regulator of nuclear export of transposase in Ppmar elements and the mutation of the NES domains can either increase or decrease the export signalling. We speculate that in moso bamboo, NESs regulates the transposition activity of MLEs to maintain the genome integrity.

Effects of TACE and preventive antiviral therapy on HBV reactivation and subsequent hepatitis in hepatocellular carcinoma: a meta-analysis.

BACKGROUND AND AIM: The impact of transarterial chemoembolization (TACE) and preventive antiviral therapy on the occurrence of hepatitis B virus (HBV) reactivation and subsequent hepatitis remains controversial. This meta-analysis aimed to evaluate the effect of TACE and preventive antiviral therapy on the risk of HBV reactivation and subsequent hepatitis. Meanwhile, we explored the role of HBeAg status in HBV reactivation after TACE. METHODS: We performed this meta-analysis with 11 included studies to assess the effect of TACE and preventive antiviral therapy on predicting clinical outcomes in HBV-related hepatocellular carcinoma (HCC). The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Central Register of Controlled were searched for the included articles (from 2000 to December 2017). RESULTS: Our results showed that TACE significantly increased the risk of HBV reactivation (OR: 3.70; 95% CI 1.45-9.42; P < 0.01) and subsequent hepatitis (OR: 4.30; 95% CI 2.28-8.13; P < 0.01) in HCC patients. There was no significant difference in HBV reactivation after TACE between HBeAg positive and negative patients (OR: 1.28; 95% CI 0.31-5.34; P = 0.73). Preventive antiviral therapy could statistically reduce the rate of HBV reactivation (OR: 0.08; 95% CI 0.02-0.32; P < 0.01) and hepatitis (OR: 0.22; 95% CI 0.06-0.80; P = 0.02) in those with TACE treatment. CONCLUSIONS: The present study suggested that TACE was associated with a higher possibility of HBV reactivation and subsequent hepatitis. Preventive antiviral therapy is significantly in favor of a protective effect.

High expression of Anxa2 and Stat3 promote progression of hepatocellular carcinoma and predict poor prognosis.

AIM: To elucidate whether the interaction between Anxa2 and Stat3 could promote the progression of hepatocellular carcinoma (HCC) and that high co-expression of Anxa2 and Stat3 could predict poor prognosis in HCC patients. METHODS: We investigated Anxa2 and Stat3 expression using Western blot analysis in 4 HCC and adjacent nontumor tissues and using immunohistochemistry in 100 patients' paraffin sections. Then we assessed the expression of Stat3, Anxa2 and co-expression of Stat3 and Anxa2 with relevant clinical pathological parameters and their prognostic value in HCC patients. The recurrence and overall survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models. RESULTS: The incidence of high Stat3 expression in HCC tissues (35%) was significantly higher than that in non-HCC tissues (8%) (P < 0.001). The same result was observed in Anxa2 (P < 0.001). Also, the overexpression of Stat3 or Anxa2 showed a significant relationship with the recurrence of the 100 HCC patients (P = 0.012; P = 0.003). Additionally, tumor size >3 cm in diameter, multiple tumor number, and the presence of microvascular tumor thrombus were also significantly associated with recurrence in 100 patients. Then, all enrolled patients were divided into four groups according to IHC score of Stat3 and Anxa2, and the results indicated a significant difference in recurrence time between the subgroups (P < 0.001). What's more, co-highexpression of Stat3 and Anxa2 was related to the presence of microvascular tumor thrombus (P = 0.003) and poor tumor differentiation (P < 0.001), but not relevant with other clinical features (All P > 0.05). CONCLUSION: The expression of Stat3, Anxa2, or co-high-expression of the two proteins was associated with HCC recurrence and survival.

Correlation between S100A11 and the TGF-ß1/SMAD4 pathway and its effects on the proliferation and apoptosis of pancreatic cancer cell line PANC-1.

S100A11 as a S100 protein family member has been documented to play dual-direction regulation over cancer cell proliferation. We explored the role of S100A11 in the proliferation and apoptosis of pancreatic cancer cell line PANC-1 and the potential mechanisms involving the TGF-ß1/SMAD4/p21 pathway. S100A11 and TGF-ß1 protein expressions in 30 paraffin-embedded specimens were evaluated by immunohistochemistry. S100A11 and TGF-ß1 expression in PANC-1 cell line was suppressed using small interfering RNA (siRNA), respectively. Subsequently, pancreatic cancer cell apoptosis was measured by Cell Counting Kit-8 and flow cytometry, and S100A11 and TGF-ß1/SMAD4/p21 pathway proteins and genes were detected with Western blotting and quantitative polymerase chain reaction (qPCR). S100A11 cytoplasmic/nuclear protein translocation was examined using NE-PER® cytoplasm/nuclear protein extraction in cells interfered with TGF-ß1 siRNA. Our results showed that S100A11 expression was positively correlated with TGF-ß1 expression in pancreatic cancerous tissue. Silencing TGF-ß1 down-regulated intracellular P21WAF1 expression by 90%, blocked S100A11 from cytoplasm entering nucleus, and enhanced cell proliferation. Silencing S100A11 down-regulated intracellular P21 expression and promoted cell apoptosis without significantly changing TGF-ß1 and SMAD4 expression. Our findings revealed that S100A11 and TGF-ß1/SMAD4 signaling pathway were related but mutually independent in regulating PANC-1 cells proliferation and apoptosis. Other independent mechanisms might be involved in S100A11's regulation of pancreatic cell growth. S100A11 could be a potential gene therapy target for pancreatic cancer.

Actin related protein 3 (ARP3) promotes apoptosis of intestinal epithelial cells in ulcerative colitis.

Apoptosis in intestinal epithelial cells (IECs) promotes the development of ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Actin related protein 3 (ARP3) promotes endothelial dysfunction. The expression and function of ARP3 in UC remains unclear. In this study, the expression of apoptotic markers as p53, Bax, Cleaved-Caspease9 and Cleaved-Caspease3 were proved to be increased in the intestinal epithelial cells (IECs) of UC patients and in a mouse disuccinimidyl suberate(DSS)-induced colitis model; meanwhile, ARP3 expression was elevated. ARP3 expression levels and the severity of symptoms in patients with UC were positively correlated. By knocking down ARP3 in a TNF-α-treated NCM-460 cell colitis model, the apoptotic markers described above were all decreased. In conclusion, our data indicates that ARP3 might promote the apoptosis of IECs in UC, revealing a potential molecular target for treating UC.

ß2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway.

Psychological stress has been recognized as a well-documented risk factor associated with ß2-adrenergic receptor (ß2-AR) in the development of pancreatic cancer. Aldo-keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of ß2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and ß2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing ß2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of ß2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased ß2-AR levels and increased that of p-ERK1/2. Taken together, ß2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the ß2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.

A Comparison of Traditional and Novel Methods for the Separation of Exosomes from Human Samples.

Exosomes are discrete populations of small (40-200 nm in diameter) membranous vesicles that are released into the extracellular space by most cell types, eventually accumulating in the circulation. As molecular messengers, exosomes exert a broad array of vital physiologic functions by transporting information between different cell types. Because of these functional properties, they may have potential as biomarker sources for prognostic and diagnostic disease. Recent research has found that exosomes have potential to be utilized as drug delivery agents for therapeutic targets. However, basic researches on exosomes and researches on their therapeutic potential both require the existence of effective and rapid methods for their separation from human samples. In the current absence of a standardized method, there are several methods available for the separation of exosomes, but very few studies have previously compared the efficiency and suitability of these different methods. This review summarized and compared the available traditional and novel methods for the extraction of exosomes from human samples and considered their advantages and disadvantages for use in clinical laboratories and point-of-care settings.

Sex comb on midleg like-2 is a novel specific marker for the diagnosis of gastroenteropancreatic neuroendocrine tumors.

Sex comb on midleg like-2 (SCML2) is a polycomb-group protein that encodes transcriptional repressors essential for appropriate development in the fly and in mammals. On the basis of previous findings, the present study aimed to explore the possibility of developing SCML2 into a new diagnostic marker for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 64 paired GEP-NET tissues and adjacent non-tumorous tissues were obtained from patients who had undergone surgical resection between January 2009 and January 2014, and the expression of SCML2 and two neuroendocrine markers, namely synaptophysin (Syn) and chromogranin A (CgA), in the tissues was assessed by immunohistochemistry. Strong SCML2 staining was observed predominantly in the cell nuclei of GEP-NET tissues, and the overall expression rate and staining intensity of SCML2 were higher than those of Syn or CgA, respectively. Spearman rank correlation analysis demonstrated that SCML2 was not correlated with either Syn or CgA, while the combined detection of SCML2 with Syn or with CgA increased the diagnostic sensitivity to 100%. SCML2 expression in GEP-NETs was associated with several clinicopathological parameters, such as histological type, tumor grade, depth of invasion and clinical stage. Kaplan-Meier survival curves revealed that patients with higher SCML2 expression had lower survival rates than those with lower expression levels, while Cox proportional hazards regression analysis revealed that SCML2 was not an independent prognostic factor for GEP-NET patients. Therefore, SCML2 may have potential as a specific marker for joint use with other markers to improve the diagnostic efficiency of GEP-NETs.