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.

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.

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.

Effects of cofD gene knock-out on the methanogenesis of Methanobrevibacter ruminantium.

This study aimed to investigate the effects of cofD gene knock-out on the synthesis of coenzyme F420 and production of methane in Methanobrevibacter ruminantium (M. ruminantium). The experiment successfully constructed a cofD gene knock-out M. ruminantium via homologous recombination technology. The results showed that the logarithmic phase of mutant M. ruminantium (12 h) was lower than the wild-type (24 h). The maximum biomass and specific growth rate of mutant M. ruminantium were significantly lower (P < 0.05) than those of wild-type, and the maximum biomass of mutant M. ruminantium was approximately half of the wild-type; meanwhile, the proliferation was reduced. The synthesis amount of coenzyme F420 of M. ruminantium was significantly decreased (P < 0.05) after the cofD gene knock-out. Moreover, the maximum amount of H2 consumed and CH4 produced by mutant were 14 and 2% of wild-type M. ruminantium respectively. In conclusion, cofD gene knock-out induced the decreased growth rate and reproductive ability of M. ruminantium. Subsequently, the synthesis of coenzyme F420 was decreased. Ultimately, the production capacity of CH4 in M. ruminantium was reduced. Our research provides evidence that cofD gene plays an indispensable role in the regulation of coenzyme F420 synthesis and CH4 production in M. ruminantium.

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.

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.

The community structure and microbial linkage of rumen protozoa and methanogens in response to the addition of tea seed saponins in the diet of beef cattle.

BACKGROUND: This study investigated changes in rumen protozoal and methanogenic communities, along with the correlations among microbial taxa and methane (CH4) production of six Belmont Red Composite beef steers fed tea seed saponins (TSS). Animals were fed in three consecutive feeding periods, a high-grain basal diet for 14 d (BD period) then a period of progressive addition of TSS to the basal diet up to 30 g/d for 20 d (TSS period), followed by the basal diet for 13 d without TSS (BDP post-control period). RESULTS: The study found that TSS supplementation decreased the amount of the protozoal genus Entodinium and increased Polyplastron and Eudiplodinium genera. During BDP period, the protozoa community of steers did not return to the protozoal profiles observed in BD period, with higher proportions of Metadinium and Eudiplodinium and lower Isotricha. The addition of TSS was found to change the structure of methanogen community at the sub-genus level by decreasing the abundance of methanogens in the SGMT clade and increasing the abundance of methanogens in the RO clade. The correlation analysis indicated that the abundance of SGMT clade methanogens were positively correlated with Isotricha, and Isotricha genus and SGMT clade methanogens were positively correlated with CH4 production. While RO clade were positively correlated with the proportion of Metadinium genus, which was negatively correlated with CH4 emission. CONCLUSIONS: These results suggest that different genera of rumen protozoa ciliates appear to be selectively inhibited by TSS, and the change in methanogen community at the subgenus level may be due to the mutualistic relationships between methanogens and rumen ciliates.

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.

Re-excision or "wait and watch"-a prediction model in breast phyllodes tumors after surgery.

BACKGROUND: The prognosis of breast phyllodes tumors (PTs) largely depending on the pathological grading, which lacks objectivity. This study aimed to develop a nomogram based on clinicopathological features to evaluate the recurrence probability of PTs following surgery. METHODS: Data from 334 patients with breast PTs, who underwent surgical treatment at Sun Yat-sen Memorial Hospital from January 2005 to December 2014, were used to develop a prediction model. Additionally, data of 36 patients from Peking University Shenzhen Hospital (cohort 1) and data of 140 patients from Sun Yat-sen University Cancer Center (cohort 2) during the same period were used to validate the model. The medical records and tumor slides were retrospectively reviewed. The log-rank and Cox regression tests were used to develop a clinical prediction model of breast PTs. All statistical analyses were performed using R and STATA. RESULTS: Of all 334 patients included in the primary cohort, 224 had benign, 91 had borderline, and 19 had malignant tumors. The 1-, 3-, and 5-year recurrence-free survival was 98.5%, 97.9%, and 96.8%, respectively. Ultrasound-guided vacuum-assisted biopsy (UGVAB) is a non-inferior treatment application in benign PTs compared with open surgery [hazard ratio (HR), 2.38; 95% confidence interval (CI), 0.59-9.58]. Width of surgical margin, mitoses, and tumor border were identified as independent risk factors for breast PTs. A nomogram was developed based on these three variables. The C-index of internal and external validation was 0.71, 0.67 (cohort 1) and 0.73 (cohort 2), respectively. CONCLUSIONS: The study model presented more concise and objective variables to evaluate the recurrence-free survival of patients after surgery, which can help deciding whether to do a re-excision or "wait and watch".

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.

Effects of fermentation on structural characteristics and in vitro physiological activities of barley ß-glucan.

The effects of fermentation by Lactobacillus plantarum dy-1 on the main structural changes of barley ß-glucan and their in vitro activities were studied. Molecular characteristics, infrared spectroscopy, monosaccharide composition, methylation, 1D and 2D-NMR analyses and scanning electron microscopy revealed that both (raw barley ß-glucan) RBG and fermented barley ß-glucan (FBG) are polysaccharides predominanted by ß-(1→3) and ß-(1→4) linked glucose. However, different molecular weight (decreasing from 1.13×105 D to 6.35×104 D), the ratio of the ß-(1→3) residues to the ß-(1→4) residues (ranging from 1:1.98-1:2.50 to 1:1.8-1:2.24) and microstructure features (transforming from a rod-like to sheet-like structure) were observed. Bioassay results showed that FBG exhibited improved inhibitory activities of α-amylase, α-glucosidase and lipase, as well as the adsorption of cholesterol under acidic conditions compared to RBG. These results suggested that fermentation may enhance in vitro physiological activities of barley ß-glucan, especially related to glucose and lipid metabolism.

Identification of DHX36 as a tumour suppressor through modulating the activities of the stress-associated proteins and cyclin-dependent kinases in breast cancer.

The nucleic acid guanine-quadruplex structures (G4s) are involved in many aspects of cancer progression. The DEAH-box polypeptide 36 (DHX36) has been identified as a dominant nucleic acid helicase which targets and disrupts DNA and RNA G4s in an ATP-dependent manner. However, the actual role of DHX36 in breast cancer remains unknown. In this study, we observed that the gene expression of DHX36 was positively associated with patient survival in breast cancer. The abundance of DHX36 is also linked with pathologic conditions and the stage of breast cancer. By using the xenograft mouse model, we demonstrated that the stable knockdown of DHX36 via lentivirus in breast cancer cells significantly promoted tumour growth. We also found that, after the DHX36 knockdown (KD), the invasion of triple-negative breast cancer cells was enhanced. In addition, we found a significant increase in the number of cells in the S-phase and a reduction of apoptosis with the response to cisplatin. DHX36 KD also desensitized the cytotoxic cellular response to paclitaxel and cisplatin. Transcriptomic profiling analysis by RNA sequencing indicated that DHX36 altered gene expression profile through the upstream activation of TNF, IFNγ, NFκb and TGFß1. High throughput signalling analysis showed that one cluster of stress-associated kinase proteins including p53, ROCK1 and JNK were suppressed, while the mitotic checkpoint protein-serine kinases CDK1 and CDK2 were activated, as a consequence of the DHX36 knockdown. Our study reveals that DHX36 functions as a tumour suppressor and may be considered as a potential therapeutic target in breast cancer.

Functional Components, Antioxidant Activity and Hypoglycemic Ability Following Simulated Gastro-Intestinal Digestion of Pigments from Walnut Brown Shell and Green Husk.

To assess the effects of digestion on the functional components of walnut pigment and their bioactivities, we developed an in vitro model simulating gastro-intestinal digestion. Results showed an increase in the contents of flavonoids and conjugated phenols (with retention rates higher than 100%) in husk pigment after digestion. The lowest of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging abilities was reached in the group with the minimum flavonoid content after digestion. Close correlation was observed between free phenol content and total reducing power, as the reducing power among different groups of husk pigment was in consistent with free phenols changes. The inhibitory effect of walnut pigment on α-amylase with/without digestion enzyme was similar. However, shell pigment showed improved inhibitory effect on α-glucosidase activity, with an increased inhibitory rate of 5.42%. In general, the antioxidant activity and hypoglycemic ability of walnut pigment were prone to chemical and enzymatic changes during simulated digestion, which were also related to the alteration of flavonoids and phenols.

Differential expression of HER2 and downstream proteins in prediction of advanced tumor phenotypes and overall survival of patients with Epstein-Barr virus-positive vs. negative gastric cancers.

This study evaluated the associations of HER2 protein, HER2 gene amplification, and positivity for p-AKT, p-ERK, and p-PLCγ proteins with clinicopathological status and overall survival (OS) of patients who had Epstein-Barr virus-associated gastric cancer (EBVaGC; n = 58) or EBV-negative GC (EBVnGC; n = 329). Tissue samples were subjected to immunohistochemistry and fluorescence in situ hybridization (FISH). Results showed that EBVaGC less expressed HER2 and amplified HER2 gene. p-AKT (p =  0.035) and p-ERK (p =  0.001) were inhibited in EBVaGC than in EBVnGC, while p-PLCγ (p =  0.034) was upregulated. Among EBVaGC patients, p-ERK positivity was associated with Lauren classification (p = 0.023), and p-PLCγ positivity was inversely associated with TNM stage (p = 0.041) and lymph node metastasis (p = 0.041). In contrast, among EBVnGC patients, HER2 expression was associated with distant metastasis (p = 0.043) and p-AKT positivity was associated with intestinal subtype (p < 0.004), lymph node metastasis (p = 0.031), distant metastasis (p < 0.001), and elder age (>60y, p < 0.004). Overall analysis showed that EBVaGC patients presented better OS than EBVnGC patients (p = 0.044). Among EBVaGC patients, p-AKT positivity (p = 0.008) was associated with worse OS; as well as, HER2 high expression (p < 0.001), p-AKT positivity (p = 0.010), and p-PLCγ (p <  0.001) were associated with worse OS in EBVnGC patients. Multivariate analysis showed that distant metastasis (95% CI: 1.559 to 4.028, p <  0.001), HER2 high expression (95% CI: 1.058 to 2.454, p =  0.026), and p-PLCγ positivity (95% CI: 1.056 to 2.435, p = 0.027) were independent prognostic predictors of OS in EBVnGC patients. Our results indicated that p-AKT positive patients presented worse OS than p-AKT negative ones in EBVaGC, as well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC patients.

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.