Differential diagnosis of breast mucinous carcinoma with an oval shape from fibroadenoma based on ultrasonographic features.

BACKGROUND: Approximately 50% of breast mucinous carcinomas (MCs) are oval and have the possibility of being misdiagnosed as fibroadenomas (FAs). We aimed to identify the key features that can help differentiate breast MC with an oval shape from FA on ultrasonography (US). METHODS: Seventy-six MCs from 71 consecutive patients and 50 FAs with an oval shape from 50 consecutive patients were included in our study. All lesions pathologically diagnosed. According to the Breast Imaging Reporting and Data System (BI-RADS), first, the ultrasonographic features of the MCs and FAs were recorded and a final category was assessed. Then, the differences in ultrasonographic characteristics between category 4 A (low-risk group) and category 4B-5 (medium-high- risk group) MCs were identified. Finally, other ultrasonographic features of MC and FA both with an oval shape were compared to determine the key factors for differential diagnosis. The Mann-Whitney test, χ2 test or Fisher's exact test was used to compare data between groups. RESULTS: MCs with an oval shape (81.2%) and a circumscribed margin (25%) on US were more commonly assessed in the low-risk group (BI-RADS 4 A) than in the medium-high-risk group (BI-RADS 4B-5) (20%, p < 0.001 and 0%, p = 0.001, respectively). Compared with those with FA, patients with MC were older, and tended to have masses with non-hypoechoic patterns, not circumscribed margins, and a posterior echo enhancement on US (p < 0.001, p < 0.001, and p = 0.003, respectively). CONCLUSION: The oval shape was the main reason for the underestimation of MCs. On US, an oval mass found in the breast of women of older age with non-hypoechoic patterns, not circumscribed margins, and a posterior echo enhancement was associated with an increased risk of being an MC, and should be subjected to active biopsy.

Gut microbiota enhance energy accumulation of black-necked crane to cope with impending migration.

Less is known about the role of gut microbiota in overwintering environmental adaptation in migratory birds. Here, we performed metagenomic sequencing on fresh fecal samples (n = 24) collected during 4 periods of overwintering (Dec: early; Jan: middle I; Feb: middle II; Mar: late) to characterize gut microbial taxonomic and functional characteristics of black-necked crane (Grus nigricollis). The results demonstrated no significant change in microbial diversity among overwintering periods. Analysis of compositions of microbiomes with bias correction (ANCOM-BC) determined 15 Proteobacteria species enriched in late overwintering period. Based on previous reports, these species are associated with degradation of chitin, cellulose, and lipids. Meanwhile, fatty acid degradation and betalain biosynthesis pathways are enriched in late overwintering period. Furthermore, metagenomic binning obtained 91 high-quality bins (completeness >70% and contamination <10%), 5 of which enriched in late overwintering period. Carnobacterium maltaromaticum, unknown Enterobacteriaceae, and Yersinia frederiksenii have genes for chitin and cellulose degradation, acetate, and glutamate production. Unknown Enterobacteriaceae and Y. frederiksenii hold genes for synthesis of 10 essential amino acids required by birds, and the latter has genes for γ-aminobutyrate production. C. maltaromaticum has genes for pyridoxal synthesis. These results implied the gut microbiota is adapted to the host diet and may help black-necked cranes in pre-migratory energy accumulation by degrading the complex polysaccharide in their diet, supplying essential amino acids and vitamin pyridoxal, and producing acetate, glutamate, and γ-aminobutyrate that could stimulate host feeding. Additionally, enriched Proteobacteria also encoded more carbohydrate-active enzymes (CAZymes) and antibiotic resistance genes (ARGs) in late overwintering period. KEY POINTS: • Differences in gut microbiota function during overwintering period of black-necked cranes depend mainly on changes in core microbiota abundance • Gut microbiota of black-necked crane adapted to the diet during overwintering period • Gut microbiota could help black-necked cranes to accumulate more energy in the late overwintering period.

Predicting the risk of axillary lymph node metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features and the use of nomograms: a prospective single-center observational study.

OBJECTIVES: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. METHODS: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. RESULTS: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. CONCLUSION: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. KEY POINTS: • We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. • Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes ( ≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. • Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately.

Ultrasound-Guided Vacuum-assisted Biopsy Versus Surgical Resection in Patients With Breast Desmoid Tumor.

BACKGROUND: Recent studies suggest that desmoid tumors can be managed more conservatively rather than undergoing wide surgical resection (SR). Ultrasound-guided vacuum-assisted biopsy (UGVAB) is a minimally invasive technique. This retrospective study aimed to compare the outcome in patients with breast desmoid tumor (BDT) who received UGVAB alone versus SR. MATERIALS AND METHODS: The pathology database was searched for patients diagnosed with BDT ≤ 3 cm from 2007 to 2019. All patients underwent breast ultrasound examination and were then performed UGVAB alone or local SR. The Kaplan-Meier method with a log-rank test was used as a univariate analysis to compare the relapse-free survival (RFS) rates between UGVAB and SR groups. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 39 patients were included. The median follow-up was 41 mo (range, 5-110 mo). The incidence of tumor recurrence was 23.1% (9/39). The 3-y cumulative RFS was 83.1% and 95.8% in the UGVAB and SR group, respectively, which was not significantly different between the two groups (P = 0.131, log-rank test). Multivariate analysis also revealed that treatment strategy (UGVAB versus SR) was not associated with an increased risk of relapse events (P = 0.274). CONCLUSIONS: Small desmoid tumors (≤3 cm) after UGVAB alone did not have a significantly compromised RFS compared with those who underwent SR. UGVAB may be an alternative and relatively conservative method for the diagnosis and local control of BDT with a smaller size. A prospective, randomized study with large sample size is needed to confirm this observation.

Prognostic Value of Modified IHC4 Score in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

BACKGROUND: This study aimed to investigate whether an immunohistochemical prognostic model (IHC4 score) can predict the prognosis and the chemotherapy benefit in patients with estrogen receptor-positive (ER+)/human epidermal growth receptor 2-negative (HER2-) metastatic breast cancer (MBC). MATERIALS AND METHODS: We developed a method to calculate the modified IHC4 (mIHC4) scores based on routine pathological reports and compared them with the original IHC4 scores that were much more difficult to calculate. Univariate and multivariate analyses were used to study the prognostic factors of progression-free survival (PFS) and overall survival (OS). The predictive value of mIHC4 score was also investigated. RESULTS: The Sun Yat-sen Memorial Hospital data set included 315 patients with newly diagnosed ER+ MBC with a median follow-up of 25.6 months. Univariate and multivariate analysis showed that higher mIHC4 scores in metastatic lesions, but not the ones in primary tumors, were significantly associated with worse PFS and OS. The prognostic value of mIHC4 scores for PFS was validated using an independent Chinese Society of Clinical Oncology- Breast Cancer (CSCO-BC) data set. More importantly, subpopulation treatment effect pattern plot analysis showed that first-line endocrine therapy achieved better PFS and OS than chemotherapy in low-risk patients with ER+/HER2- MBC, whereas first-line chemotherapy was associated with improved PFS and OS compared with endocrine therapy in high-risk ones. The predictive value of mIHC4 score for PFS in selecting first-line endocrine therapy versus chemotherapy was also confirmed in the CSCO-BC data set. CONCLUSION: mIHC4 scores in metastatic lesions are prognostic for the PFS and OS in patients with ER+ MBC. Low or high mIHC4 score may indicate the survival benefit in choosing first-line endocrine therapy or chemotherapy in patients with ER+/HER2- MBC, respectively. IMPLICATIONS FOR PRACTICE: The modified IHC4 (mIHC4) score is easy to implement and able to predict patients with advanced and/or metastatic breast cancer. In addition, with the help of the mIHC4 score, physicians might be able to recommend chemotherapy or endocrine therapy as the first-line treatment for patients with high and low risk as predicted by the mIHC4 score.

Fermented barley ß-glucan regulates fat deposition in Caenorhabditis elegans.

BACKGROUND: Barley contains a relatively high concentration of the mixed-linkage (1 → 3) (1 → 4) ß-glucan, which has been reported to be a functional food with prebiotic potential. In the current study we compared the properties of two neutral barley ß-glucans, obtained from raw barley: raw barley ß-glucan (RBG) and Lactobacillus plantarum dy-1-fermented barley (FBG). RESULTS: Molecular characteristics revealed that the molecular weight of barley ß-glucan decreased from 1.13 × 105 D to 6.35 × 104 D after fermentation. Fermentation also improved the water / oil holding capacity, solubility, and swelling capacity of barley ß-glucan. Both RBG and FBG significantly improved the locomotive behavior of nematodes, thereby increasing their energy consumption and reducing fat deposition - the effect was more significant with FBG. These effects could potentially depend on nhr-49, TGF-daf-7 mediated pathways and so on, in which nhr-49 factor is particularly required. CONCLUSION: These results suggested that fermentation may enhance in vitro physiological activities of barley ß-glucan, thereby altering the effects on the lipid metabolism in vivo. © 2020 Society of Chemical Industry.

Multiple metastases of bones and sigmoid colon after mastectomy for ductal carcinoma in situ of the breast: a case report.

BACKGROUND: The prognosis of ductal carcinoma in situ (DCIS) is reportedly well. Extremely rare patients with DCIS develop distant breast cancer metastasis without locoregional or contralateral recurrence. This is the first report of multiple bones and sigmoid colon metastases from DCIS after mastectomy. CASE PRESENTATION: A 43-year-old woman was diagnosed with DCIS, and she received mastectomy, followed by endocrine therapy and target therapy. During the following-up, convulsions and pain on the legs were complaint. Therefore, Computed Tomography (CT) on bones and positron emission tomography (PET) for whole body were examined in order. Multiple bones and sigmoid colon were under the suspect of metastases, which were then verified by biopsy in the left ilium and colonoscopy respectively. CONCLUSIONS: This case reveals the heterogeneous behavior and the potential poor outcome of DCIS, regular examination and surveillance are necessary even though the distant metastasis rate in DCIS is low.

Development and validation of nomograms predicting survival in Chinese patients with triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Nomograms predicting outcomes of TNBC are needed for risk management. METHODS: Nomograms were based on an analysis of 296 non-metastatic TNBC patients treated at Sun Yat-sen Memorial Hospital from 2002 to 2014. The end points were disease-free survival (DFS) and overall survival (OS). Predictive accuracy and discriminative ability were evaluated by concordance index (C-index), area under the curve (AUC) and calibration curve, and compared with the American Joint Committee on Cancer (AJCC) staging system, PREDICT and CancerMath. Models were subjected to bootstrap internal validation and external validation using independent cohorts of 191 patients from the second Xiangya Hospital and Peking University Shenzhen Hospital between 2007 and 2012. RESULTS: On multivariable analysis of training cohort, independent prognostic factors were stromal tumor-infiltrating lymphocytes (TILs), tumor size, node status, and Ki67 index, which were then selected into the nomograms. The calibration curves for probability of DFS and OS showed optimal agreement between nomogram prediction and actual observation. The C-index of nomograms was significantly higher than that of the seventh and eighth AJCC staging system for predicting DFS (training: 0.743 vs 0.666 (P = 0.003) and 0.664 (P = 0.024); validation: 0.784 vs 0.632 (P = 0.02) and 0.607 (P = 0.002)) and OS (training: 0.791 vs 0.683 (P = 0.004) and 0.677 (P < 0.001); validation: 0.783 vs 0.656 (P = 0.006) and 0.606 (P = 0.001)). Our nomograms had larger AUCs compared with PREDICT and CancerMath. In addition, the nomograms showed good performance in stratifying different risk groups of patients both in the training and validation cohorts. CONCLUSION: We have developed novel and practical nomograms that can provide individual prediction of DFS and OS for TNBC based on stromal TILs, tumor size, node status, and Ki67 index. Our nomograms may help clinicians in risk consulting and selection of long term survivors.

Ductal Lavage for Patients With Nonlactational Mastitis: A Single-Arm, Proof-of-Concept Trial.

BACKGROUND: Surgery, steroids, and/or observations alone have been proposed for patients with nonlactational mastitis (NLM), but most of these studies were retrospective. The optimal treatment for these patients remains unclear. This prospective, single-arm, proof-of-concept trial aimed to evaluate the feasibility and safety of ductal lavage as a novel treatment for patients with NLM. METHODS: Eligible patients with NLM received an intraductal infusion of corticosteroids and antimicrobial agents and returned the next day for a breast massage. This cycle was repeated for 2 wk, and we followed up these patients for 1 y. Patients did not receive surgery or steroids after ductal lavage. The primary endpoint was the time to complete response (CR). RESULTS: This trial included 32 patients with a median (range) age of 32 (20-53). Skin erythema and tenderness were the major symptoms. The median (range) visual analog score was 5 (0-9). There were 21 (65.6%), 4 (12.5%), and 7 (21.9%) patients diagnosed as idiopathic granulomatous mastitis, periductal mastitis, and unspecific NLM, respectively. During the ductal lavage, the median (range) number of cannulated ducts at first attempt was 5 (3-8). Ductal lavage significantly reduced the visual analog score and mastitis score (M-score) (P < 0.01). Within a median follow-up of 15.6 mo, 93.8% (30/32) of patients achieved CR. The median (range) time to CR was 6 (0.5-21) mo. Three patients (10.0%) relapsed. No adverse events associated with ductal lavage were observed. CONCLUSIONS: Ductal lavage for patients with NLM is feasible and safe, and a definitive randomized controlled trial for further investigation is warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02794688.

The 3p14.2 tumour suppressor ADAMTS9 is inactivated by promoter CpG methylation and inhibits tumour cell growth in breast cancer.

Chromosome region 3p12-14 is an important tumour suppressor gene (TSG) locus for multiple cancers. ADAMTS9, a member of the metalloprotease large family, has been identified as a candidate 3p14.2 TSG inactivated by aberrant promoter CpG methylation in several carcinomas, but little known about its expression and function in breast cancer. In this report, ADAMTS9 expression and methylation was analysed in breast cancer cell lines and tissue samples. ADAMTS9 RNA was significantly down-regulated in breast cancer cell lines (6/8). After treating the cells with demethylation agent Aza and TSA, ADAMTS9 expression was dramatically increased. Bisulphite genomic sequencing and methylation-specific PCR detected promoter methylation, which was associated with decreased ADAMTS9 expression. Hypermethylation was also detected in 130/219 (59.4%) of primary tumours but only in 4.5% (2/44) of paired surgical margin tissues. Ectopic expression of ADAMTS9 in tumor cells induced significant growth suppression, cell cycle arrest at the G0/G1 phase, enhanced apoptosis and reduced cell migration and invasion. Conditioned culture medium from ADAMTS9-transfected BT549 cells markedly disrupted tube formation ability of human umbilical vein endothelial cell (HUVEC) in Matrigel. Furthermore, ADAMTS9 inhibited AKT signaling and its downstream targets (MDM2, p53, p21, p27, E-cadherin, VIM, SNAIL, VEGFA, NFκB-p65 and MMP2). In addition, we demonstrated, for the first time, that ADAMTS9 inhibits AKT signaling, through suppressing its upstream activators EGFR and TGFß1/TßR(I/II) in breast cancer cells. Our results suggest that ADAMTS9 is a TSG epigenetically inactivated in breast cancer, which functions through blocking EGFR- and TGFß1/TßR(I/II)-activated AKT signaling.

Arabinoxylan activates lipid catabolism and alleviates liver damage in rats induced by high-fat diet.

BACKGROUND: Arabinoxylan was thought to have the potential to change lipid metabolism and redox homeostasis in human and animal. However, the effect of arabinoxylan on the liver damage induced by high-fat diet needs further exploiting. RESULTS: Six-weeks-old 30 male Sprague-Dawley Rats were assigned randomly to three groups (n = 10 per group), i.e. a control diet (CON) group, a high-fat diet (HF) group and a high-fat diet supplemented with arabinoxylan (6% AX, HF-AX) group. Results showed that final body weight and liver weight were similar in CON group and HF-AX group, but higher in the HF group. In serum, the HF-AX group showed lower triglyceride concentrations than did the HF group. In liver, higher lipoprotein lipase, hepatic lipase, total lipase, and acyl-CoA oxidase activities and lower triglyceride and cholesterol level were observed in the HF-AX group than in the HF group. For the redox homeostasis, arabinoxylan supplemented in HF increased T-SOD activity and GSH-PX activity and reduced MDA + 4-HNE level in liver and/or compared with those in the HF group. Lipid droplets and liver cell damage were observed in the HF group compared with the CON and HF-AX groups. CONCLUSION: Arabinoxylan could improve lipid metabolic disorder and alleviate liver damage in rats induced by high-fat diet via activating lipid catabolism and suppressing lipid peroxidation. © 2017 Society of Chemical Industry.

Comparison of T2, T1rho, and diffusion metrics in assessment of liver fibrosis in rats.

PURPOSE: To evaluate the value of T2 , T1 rho, and diffusion metrics in assessment of liver fibrosis in rats. MATERIALS AND METHODS: Liver fibrosis in a rat model (n = 72) was induced by injection of carbon tetrachloride (CCl4 ) at 3T. T2 , T1 rho, and diffusion parameters (apparent diffusion coefficient (ADC), Dtrue ) via spin echo (SE) diffusion-weighted imaging (DWI) and stimulated echo acquisition mode (STEAM) DWI with three diffusion times (DT: 80, 106, 186 msec) were obtained in surviving rats with hepatic fibrosis (n = 52) and controls (n = 8). Liver fibrosis stage (F0-F6) was identified based on pathological results using the traditional liver fibrosis staging method for rodents. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analysis were employed to determine the diagnostic accuracy. RESULTS: Mean T2 , T1 rho, ADC, and Dtrue with DT = 186 msec correlated with the severity of fibrosis with r = 0.73, 0.83, -0.83, and -0.85 (all P < 0.001), respectively. The average areas under the ROC curve at different stages for T1 rho and diffusion parameters (DT = 186 msec) were larger than those of T2 and SE DWI (0.92, 0.92, and 0.92 vs. 0.86, 0.82, and 0.83). The corresponding average sensitivity and specificity for T1 rho and diffusion parameters with a long DT were larger (89.35 and 88.90, 88.36 and 89.97, 90.16 and 87.13) than T2 and SE DWI (90.28 and 79.93, 85.30 and 77.64, 78.21 and 82.41). The performances of T1 rho and Dtrue (DT = 186 msec) were comparable (average AUC: 0.92 and 0.92). CONCLUSION: Among the evaluated sequences, T1 rho and STEAM DWI with a long DT may serve as superior imaging biomarkers for assessing liver fibrosis and monitoring disease severity. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:741-750.

[Clinical Characteristics of Patients with Type 2 Diabetes Mellitus and Obstructive Sleep Apnea Syndrome].

OBJECTIVES: To compare the clinical characteristics and prevalence of chronic complications in type 2 diabetes mellitus (T2DM) patients with various degrees of obstructive sleep apnea syndrome (OSAS). METHODS: A total of 170 patients with T2DM and OSAS were enrolled in this study. These participants were divided into three groups with low, medium and high apnea-hypopnea index (AHI), respectively. The demographic characteristics, biochemical indicators and chronic complications of the patients in the three groups were compared. Multivariate Logistic regression analysis was performed to determine the associations between chronic complications and OSAS. RESULTS: The patients with severe OSAS had higher waist circumference (P=0.045), higher BMI (P=0.069), higher prevalence of diabetic peripheral neuropathy (DPN), and higher prevalence of diabetic retinopathy (DR) than the patients with mild-moderate OSAS. Similar levels of macrovascular complications were found in the three groups (P>0.05). The logistic regression analyses showed that DPN (OR=1.024, 95%CI 1.002-1.046) and chronic kidney disease (OR=1.026, 95%CI 1.004-1.049) were independent predictors of AHI, adjusting for the lowest oxygen saturation, gender, age, diabetic duration, family history of diabetes, BMI, and HbA1c. Other microvascular and macrovascular complications were not predictors of AHI. CONCLUSIONS: Patients with T2DM and severe OSAS have a higher risk of DPN and DR. Particular attention should be paid to T2DM patients with severe OSAS to prevent complications.

Benign Phyllodes Tumor of the Breast Diagnosed After Ultrasound-Guided Vacuum-Assisted Biopsy: Surgical Excision or Wait-and-Watch?

BACKGROUND: The role of tumor-free resection in the treatment of benign phyllodes tumors (PTs) is still unknown. Ultrasound-guided vacuum-assisted biopsy (UGVAB) has been used for complete removal of benign breast lesions. This retrospective study aimed to compare the risk of relapse between patients with benign PT who undergo UGVAB and those who receive surgical excision (SE). METHODS: Benign PT patients with a pathology diagnosis who had received treatment between 2005 and 2013 at the authors' hospital were identified. The patients who received UGVAB did not receive any SE. In the SE group, wide local excision or mastectomy was performed when appropriate. The Kaplan-Meier curve and Cox proportional hazards regression were used to analyze and compare the relapse-free survival (RFS) between the patients in the two groups. RESULTS: The study enrolled 225 female patients with benign PT. The patients in the UGVAB group (n = 108) had significantly smaller tumors, more fibroadenoma, a higher body mass index (BMI), and a lower Breast Imaging-Reporting and Data System classification than the patients in the SE group (n = 117). The 5-year cumulative RFS was 81.6 and 88.7 % (p = 0.11) respectively for the patients receiving UGVAB and SE during a median follow-up period of 35.5 months. After adjustment for age, tumor size, BMI, or presence of fibroadenoma, treatment (UGVAB vs. SE) was not associated with increased risk for relapse events (hazard ratio 0.34; 95 % confidence interval 0.08-1.43; p = 0.14). No distant metastasis or death events occurred. CONCLUSIONS: The patients with benign PT who received UGVAB alone did not have a significantly more compromised RFS than those who underwent SE. A prospective, randomized study is needed to confirm this observation.

AdHu5-apoptin induces G2/M arrest and apoptosis in p53-mutated human gastric cancer SGC-7901 cells.

The use of anticancer therapeutic agents is limited largely by their severe toxicity to normal tissues. The development of novel agents with tumor-specific cell-killing and effective gene delivery properties is thus very desirable. We used human adenovirus serotype 5 (AdHu5) as a vehicle to deliver the apoptin gene to specifically target gastric cancer in a recombinant gene delivery approach. AdHu5-apoptin is a safe and efficacious agent for the treatment of gastric cancer (GC). Our results show that apoptin protein encoded by the apoptin gene delivered via AdHu5 significantly inhibited the proliferation of SGC-7901 GC cells. Apoptin reduced the clone number by more than 75% and resulted in cell cycle arrest in the G2/M phase for 48% of the GC cells. It also induced cleavage of caspase-3, caspase-7, and caspase-9 in the GC cells. Intratumoral and peritumoral in vivo injection of AdHu5-apoptin significantly suppressed tumor growth and induced apoptosis in xenogeneic tumors in mice. The apoptosis induced by AdHu5-apoptin was independent of anti-apoptotic Bcl-2 and Bcl-xL proteins and the p53 pathway. Taken together, our results show that AdHu5-apoptin has great potential as a therapeutic agent for effective treatment of gastric tumors.

Integrated transcriptomics and metabolomics unravel the metabolic pathway variations for barley ß-glucan before and after fermentation with L. plantarum DY-1.

The results of our previous study showed that the structure and function of ß-glucan in barley were changed after fermentation by L. plantarum DY-1. In this study, the antioxidant activities of RBG (regular barley ß-glucan, unfermented) and FBG (barley ß-glucan, fermented with L. plantarum DY-1) were evaluated by adopting an in vivo animal model, Caenorhabditis elegans (C. elegans). We also carried out an integrated transcriptomic and metabolomic profiling for RBG and FBG to delineate their signature pathways. RBG treatment has better effects on SOD enzyme activity and ROS levels than FBG, while FBG treatment has better effects on the CAT enzyme activity and MDA content than RBG in C. elegans. Transcription group analysis showed that FBG mainly decreases the expression of the Cyp-D gene to inhibit the calcium signaling pathway, promotes the Wnt signaling pathway by up-regulating the GSK-3ß gene and improving the oxidative damage of C. elegans; RBG mainly inhibits calcium signal pathways by reducing the expression of ANT-solute carrier family 25 genes, promoting life adjustment pathways by reducing the expression of the HSP-12.6 gene to improve the oxidative stress of C. elegans. Joint analysis showed that the difference between FBG and RBG in the regulation of oxidative stress is mainly reflected in the metabolism pathway of arachidonic acid. Under the regulation of FBG, the expression of the C03H5.4 gene was decreased, the expression of leukotriene A4, prostaglandin G2, arachidonic acid and phosphatidylcholine was decreased, and the expression of 14,15-DiHETrE was increased. Under the regulation of RBG, the expression of gene C03H5.4 was up-regulated, the expression of metabolites such as leukotriene B4 was up-regulated, and the expression of arachidonic acid and phosphatidylcholine was down-regulated.

Effects of L.plantarum dy-1 fermentation time on the characteristic structure and antioxidant activity of barley ß-glucan in vitro.

This article explored the effect of Lactobacillus plantarum dy-1 (L. plantarum dy-1) fermentation on the basic physicochemical properties and associated in vitro antioxidant activity of barley ß-glucan, including its molecular weight, monosaccharide composition, characteristic structure and rheology. Its DPPH, ABTS, hydroxyl radical scavenging capacity, and ferric reducing antioxidant potential (FRAP) were measured at different fermentation times. The results showed that the molecular weight of barley ß-glucan was decreased from 1.052 × 105 Da to 4.965 × 104 Da within 0-24 h by L. plantarum dy-1 fermentation, but there was no effect on its characteristic structure. The water- and oil-holding properties of barley ß-glucan were significantly enhanced with increased fermentation time, and the fluid viscous behavior of barley ß-glucan was enhanced at 6% concentration, while elastic characteristics were weakened. The fermentation had no significant effect on the scavenging effect of DPPH and ABTS radicals of barley ß-glucan, but the hydroxyl radical scavenging activity and total antioxidant capacity of FRAP were enhanced with increased fermentation time. Fermentation time may change the physicochemical properties and enhance antioxidant activity of barley ß-glucan by reducing its molecular weight.

Epigenetic identification of mitogen-activated protein kinase 10 as a functional tumor suppressor and clinical significance for hepatocellular carcinoma.

BACKGROUND: Mitogen-activated protein kinase 10 (Mapk10) is a member of the c-jun N-terminal kinases (jnk) subgroup in the MAPK superfamily, and was proposed as a tumor suppressor inactivated epigenetically. Its role in hepatocellular carcinoma (HCC) has not yet been illustrated. We aimed to investigate the expression and epigenetic regulation of mapk10 as well as its clinical significance in HCC. RESULTS: Mapk10 was expressed in almost all the normal tissues including liver, while we found that the protein expression of MAPK10 was significantly downregulated in clinical samples of HCC patients compared with these levels in adjacent normal tissues (29/46, P < 0.0001). Clinical significance of MAPK10 expression was then assessed in a cohort of 59 HCC cases, which indicated its negative expression was significantly correlated with advanced tumor stage (P = 0.001), more microsatellite nodules (P = 0.025), higher serum AFP (P = 0.001) and shorter overall survival time of HCC patients. Methylation was further detected in 58% of the HCC cell lines we tested and in 66% of primary HCC tissues by methylation-specific PCR (MSP), which was proved to be correlated with the silenced or downregulated expression of mapk10. To get the mechanisms more clear, the transcriptional silencing of mapk10 was reversed by pharmacological demethylation, and ectopic expression of mapk10 in silenced HCC cell lines significantly inhibited the colony formation ability, induced apoptosis, or enhanced the chemosensitivity of HCC cells to 5-fluorouracil. CONCLUSION: Mapk10 appears to be a functional tumor suppressor gene frequently methylated in HCC, which could be a valuable biomarker or a new diagnosis and therapy target in a clinical setting.

Establishment and Validation of a Preoperative MRI-based Nomogram for Predicting the Risk of Malignancy in Patients with Breast Tumor.

Purpose: To establish a preoperative nomogram incorporating morphological and dynamic contrast-enhanced (DCE) features to individually predict the risk of malignancy in patients with breast tumor. Methods A total of 447 consecutive female patients who were divided into the primary cohort (n=326) and the validation cohort (n=121) were enrolled between March 2015 to January 2018. Univariate and multivariate logistic regression analyses were used to identify the potential independent indicators of malignancy. An MRI-based nomogram integrating morphological features and kinetic curves was developed to achieve individualized risk prediction of malignancy in patients with breast masses. The discrimination, calibration ability and clinical utility of the MRI-based model were assessed using C-index, calibration curve and decision curve analysis. Results: Age, tumor size, margin, internal enhancement characteristics, and kinetic curve were confirmed as the independent predictors of malignancy. The AUC of MRI-based nomogram was 0.940 (95% CI: 0.911-0.970) and 0.894 (95% CI: 0.816-0.974) in the primary cohort and validation cohort, respectively. 447 patients were subdivided into the low-risk group (n=107) and high-risk group (n=340) based on the optimal cut-off value of 21.704. The high-risk patients had a higher likelihood of harboring malignancy. Conclusion: The MRI-based nomogram can be used to achieve an accurate individualized risk prediction of malignancy and reduce unnecessary breast biopsy.

Barley ß-glucan resist oxidative stress of Caenorhabditis elegans via daf-2/daf-16 pathway.

ß-glucan is an important functional active component with relatively high content in barley. It is reported to possess various biological activities, including anti-oxidative stress, but its mechanism of action remains obscure. In the current study, C. elegans was used as an in vivo animal model to explore its anti-oxidative stress mechanism. We found that both RBG (raw barley ß-glucan) and FBG (fermented barley ß-glucan) could significantly reduce the ROS level in C. elegans under oxidative emergency conditions. In addition, both FBG and RBG had positive effects on SOD and CAT enzyme activity, and FBG treatment obviously reduced the MDA content in nematodes under oxidative stress. Moreover, FBG and RBG pretreatment could extend the median lifespan of C. elegans under oxidative stress. The CB1370 and CF1038 mutants further confirmed that daf-2 and daf-16 were necessary for FBG or RBG to participate in anti-oxidative stress, and the RT-PCR results also evidenced that ß-glucans resist oxidative stress in C. elegans partially through the daf-2/daf-16 pathway. In summary, barley ß-glucan has high potential to defense oxidative stress as a natural polysaccharide.