Zinc transporter ZnT5 is associated with epithelial mesenchymal transition via SMAD1 in breast cancer.

Zinc levels in breast cancer tissues have been reported to be higher than those in normal tissues. In addition, the expression levels of zinc transporters, including ZnT5 and ZnT6, are reportedly higher in breast cancer than in normal breast tissues. ZnT5 and ZnT6 also contribute to heterodimer formation and are involved in several biological functions. However, the functions of ZnT5 and ZnT6 heterodimers in breast cancer remain unknown. Therefore, we first investigated the immunolocalization of ZnT5 and ZnT6 in pathological breast cancer specimens and in MCF-7 and T-47D breast cancer cells. Next, we used small interfering RNA to assess cell viability and migration in ZnT5 knockdown MCF-7 and T-47D cells. Immunohistochemical analysis showed that the number of ZnT5-positive breast cancer cells was inversely correlated with the pathologic N factor status. ZnT5 knockdown had no effect on cell viability in the presence of 100 µM ZnCl2 in MCF-7 and T-47D cells. In a wound healing assay, 100 µM ZnCl2 treatment inhibited cell migration of MCF-7 and T-47D cells, whereas ZnT5 knockdown promoted cell migration, decreased E-cadherin expression and increased vimentin, slug and matrix metalloproteinase 9 expression. Antibody arrays showed that ZnT5 knockdown increased the expression of SMAD1, and that dorsomorphin treatment inhibited the promotion of migratory ability induced by ZnT5 knockdown. The results of this study revealed that both ZnT5 may be involved in less aggressive breast cancer subtypes, possibly through inhibition of cell migration.

Pathogenomics for accurate diagnosis, treatment, prognosis of oncology: a cutting edge overview.

The capability to gather heterogeneous data, alongside the increasing power of artificial intelligence to examine it, leading a revolution in harnessing multimodal data in the life sciences. However, most approaches are limited to unimodal data, leaving integrated approaches across modalities relatively underdeveloped in computational pathology. Pathogenomics, as an invasive method to integrate advanced molecular diagnostics from genomic data, morphological information from histopathological imaging, and codified clinical data enable the discovery of new multimodal cancer biomarkers to propel the field of precision oncology in the coming decade. In this perspective, we offer our opinions on synthesizing complementary modalities of data with emerging multimodal artificial intelligence methods in pathogenomics. It includes correlation between the pathological and genomic profile of cancer, fusion of histology, and genomics profile of cancer. We also present challenges, opportunities, and avenues for future work.

Ginsenosides: changing the basic hallmarks of cancer cells to achieve the purpose of treating breast cancer.

In 2021, breast cancer accounted for a substantial proportion of cancer cases and represented the second leading cause of cancer deaths among women worldwide. Although tumor cells originate from normal cells in the human body, they possess distinct biological characteristics resulting from changes in gene structure and function of cancer cells in contrast with normal cells. These distinguishing features, known as hallmarks of cancer cells, differ from those of normal cells. The hallmarks primarily include high metabolic activity, mitochondrial dysfunction, and resistance to cell death. Current evidence suggests that the fundamental hallmarks of tumor cells affect the tissue structure, function, and metabolism of tumor cells and their internal and external environment. Therefore, these fundamental hallmarks of tumor cells enable tumor cells to proliferate, invade and avoid apoptosis. Modifying these hallmarks of tumor cells represents a new and potentially promising approach to tumor treatment. The key to breast cancer treatment lies in identifying the optimal therapeutic agent with minimal toxicity to normal cells, considering the specific types of tumor cells in patients. Some herbal medicines contain active ingredients which can precisely achieve this purpose. In this review, we introduce Ginsenoside's mechanism and research significance in achieving the therapeutic effect of breast cancer by changing the functional hallmarks of tumor cells, providing a new perspective for the potential application of Ginsenoside as a therapeutic drug for breast cancer.

Induction of SGK1 via glucocorticoid-influenced clinical outcome of triple-negative breast cancer patients.

PURPOSE: Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive breast malignancy. Glucocorticoid (GC)-glucocorticoid receptor (GR) pathway plays a pivotal role in the cellular responses to various stresses including chemotherapy. Serum- and glucocorticoid-induced kinase-1 (SGK1) is known as an important downstream effector molecule in the GR signaling pathway, we attempted to explore its clinicopathological and functional significance in TNBC in which GR is expressed. METHODS: We first immunolocalized GR and SGK1 and correlated the results with clinicopathological variables and clinical outcome in 131 TNBC patients. We also evaluated the effects of SGK1 on the cell proliferation and migration in TNBC cell lines with administration of dexamethasone (DEX) to further clarify the significance of SGK1. RESULTS: The status of SGK1 in carcinoma cells was significantly associated with adverse clinical outcome in TNBC patients examined and was significantly associated with lymph node metastasis, pathological stage, and lymphatic invasion of the patients. In particular, SGK1 immunoreactivity was significantly associated with an increased risk of recurrence in GR-positive TNBC patients. Subsequent in vitro studies also demonstrated that DEX promoted TNBC cell migration and the silencing of gene expression did inhibit the cell proliferation and migration of TNBC cells under DEX treatment. CONCLUSIONS: To the best of our knowledge, this is the first study to explore an association between SGK1 and clinicopathological variables and clinical outcome of TNBC patients. SGK1 status was significantly positively correlated with adverse clinical outcome of TNBC patients and promoted carcinoma cell proliferation and migration of carcinoma cells.

A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Shen-Kui-Tong-Mai granules on a rat model with chronic heart failure.

OBJECTIVES: This study aimed to comprehensively investigate the potential active components and therapeutic mechanisms of Shen-Kui-Tong-Mai granule (SKTMG) in the treatment of heart failure. METHODS: Network pharmacology combined with ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), molecular docking, and in vivo validation was performed to identify the active components and the potential targets for SKTMG to improve chronic heart failure (CHF). KEY FINDINGS: The network pharmacology identified 192 active compounds and 307 potential consensus targets for SKTMG. On the other hand, network analysis discovered 10 core target genes related to the MAPK signal pathway. These genes include AKT1, STAT3, MAPK1, P53, SRC, JUN, TNF, APP, MAPK8 and IL6. The molecular docking results revealed that the SKTMG components were luteolin, quercetin, astragaloside IV and kaempferol, which could bind AKT1, MAPK1, P53, JUN, TNF and MAPK8. Additionally, SKTMG inhibited phosphorylation of AKT, P38, P53 and c-JUN, and reduced TNF-α expression in CHF rats. CONCLUSIONS: The present results demonstrated that network pharmacology combined with UHPLC-MS/MS, molecular docking and in vivo validation can facilitate the identification of active components and the potential targets for SKTMG to improve CHF.

Prognostic nomogram for predicting cancer-specific survival in patients with resected hilar cholangiocarcinoma: a large cohort study.

Background: The aim of the study was to establish and validate a novel prognostic nomogram of cancer-specific survival (CSS) in resected hilar cholangiocarcinoma (HCCA) patients. Methods: A training cohort of 536 patients and an internal validation cohort of 270 patients were included in this study. The demographic and clinicopathological variables were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate Cox regression analysis were performed in the training cohort, followed by the construction of nomogram for CSS. The performance of the nomogram was assessed by concordance index (C-index) and calibration plots and compared with the American Joint Committee on Cancer (AJCC) staging systems. Decision curve analysis (DCA) was applied to measure the predictive power and clinical value of the nomogram. Results: The nomogram incorporating age, tumor size, tumor grade, lymph node ratio (LNR) and T stage parameters was with a C-index of 0.655 in the training cohort, 0.626 in the validation cohort, compared with corresponding 0.631, 0.626 for the AJCC 8th staging system. The calibration curves exhibited excellent agreement between CSS probabilities predicted by nomogram and actual observation in the training cohort and validation cohort. DCA indicated that this nomogram generated substantial clinical value. Conclusions: The proposed nomogram provided a more accurate prognostic prediction of CSS for individual patients with resected HCCA than the AJCC 8th staging system, which might be served as an effective tool to stratify resected HCCA patients with high risk and facilitate optimizing therapeutic benefit.

FE65 defines the efficacy of tamoxifen treatment via osteopontin expression in estrogen receptor-positive breast cancer.

BACKGROUND: Metastasis and endocrine therapy resistance are clinical challenges in the treatment of estrogen receptor (ER) -positive breast tumors. Therefore, mechanistic exploration of tamoxifen (TAM) resistance is considered pivotal to improve the prognosis of ER positive breast cancer patients. We previously demonstrated the correlation between FE65 and ER, and subsequently explored the effects of FE65 on TAM and potential interaction between FE65 and Osteopontin (OPN) in ER-positive breast cancer. METHODS: We immunolocalized FE65 and OPN in ER-positive breast cancers and correlated the results with their clinicopathological variables. We then performed proximity ligation and proliferation assays to correlate TAM resistance with FE65 expression. The RT2 Profiler Human PCR Array Human Estrogen Receptor Signaling was also used to profile 96 ER related genes. Hoechst 33342 Staining was used to evaluate apoptosis. RESULTS: FE65 immunoreactivity was significantly associated with higher pathological N factor of the cases examined, and a potential correlation with tamoxifen resistance of the ER-positive patients. FE65 knockdown significantly increased the proportion of apoptotic carcinoma cells. The statistically significant positive correlation between FE65 and OPN was detected in this study. Subsequent immunohistochemical analyses revealed that OPN status was significantly associated with cancer metastasis and overall survival of 142 patients and FE65 status. CONCLUSIONS: We firstly demonstrated the clinicopathological significance of FE65 in ER-positive breast cancer patients and results indicated that the effects of FE65 on ER-positive breast cancer patients were mediated through OPN expression. In addition, results suggested the clinical value of FE65 as potential prognostic factor and surrogate marker of TAM therapy in ER-positive breast cancer patients.

FE65 in breast cancer and its clinicopathological significance.

BACKGROUND: Transcription coregulator adapter protein FE65 is well known to play pivotal roles in pathogenesis of Alzheimer's disease by regulating amyloid precursor protein (APP) expression and processing. APP was recently reported to be also involved in development of human malignancies. Therefore, in this study, we studied FE65 status in different subtypes of human breast cancer and correlated the results with cell proliferation and migration of carcinoma cells and clinicopathological features of breast cancer patients to explore its biological and clinical significance in breast cancer. METHODS: We first immunolocalized FE65 and APP in 138 breast cancer patients and correlated the results with their tumor grade. Then, we did further exploration by proximity ligation assay, WST-8, and wound-healing assay. RESULTS: FE65 immunoreactivity in carcinoma cells was significantly associated with lymph-node metastasis, ERα, and high pathological N factor. APP immunoreactivity was significantly positively correlated with high pathological N factor. FE65, APP, and p-APP were all significantly correlated with shorter disease-free survival of breast cancer patients. In addition, the status of FE65 was significantly associated with overall survival. Results of in vitro analysis revealed that FE65 promoted the migration and proliferation of T-47D and ZR-75-1 breast carcinoma cells. In situ proximity ligation assay revealed that FE65 could bind to APP in the cytoplasm. FE65 was also associated with APP and ERα in carcinoma cells, suggesting their cooperativity in promoting carcinoma cell proliferation and migration. APP was also significantly associated with adverse clinical outcome of the patients. CONCLUSIONS: This is the first study to explore the clinical significance of FE65 in human breast cancer. The significant positive correlation of FE65 with poor clinical outcome, direct binding to APP, and promotion of carcinoma cell proliferation and migration indicated that FE65-APP pathway could serve as the potential candidate of therapeutic intervention in breast cancer patients.

SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

Facile Synthesis of Iron Oxide Nanozymes for Synergistically Colorimetric and Magnetic Resonance Detection Strategy.

Iron oxide nanomaterials with mimic enzymes activity have been paid more attention in the clinical diagnosis field. The modified surface molecules would influence the catalytic activity of nanozyme, which is worth studying. Furthermore, the traditional detection strategy is based on colorimetric change of substrates, however, the optical signal is easy to be interfered in complex biological applications. In our research, an efficient and facile preparation strategy was developed to obtain functional artificial nanozymes. Herein, three kinds of surfactants, including citrate acid, poly(ethylene glycol) bis (carboxymethyl) ether and tannic acid have been applied to modify these nanomaterials that showed uniform size, high soluble dispersity and stability. Furthermore, these nanozymes exhibited different peroxidase-like activity to catalyze the hydrogen peroxide and 3,3',5,5'-tetramethylbenzidine. More importantly, magnetic relaxation effect of iron oxide nanozymes was found to be changed during the catalytic reaction. In addition, the relationship between the magnetic signal of nanozymes and the substrate concentration showed a good linear dependence. Combined with the natural enzymes, the magnetic detection of iron oxide nanozymes also exhibited excellent substrate specificity. On these bases, a dual-function specific assay was constructed and further used for glucose detection. In conclusion, this study demonstrated an efficient iron oxide nanozymes preparation method and constructed a new synergistically colorimetric-magnetic diagnosis strategy.

Paradoxical embolism after surgery for breast cancer: a case report.

BACKGROUND: Paradoxical embolism (PDE) presented with concomitant pulmonary embolism (PE) and renal artery embolism (RAE) which occurred to breast cancer patient after breast-conserving therapy, has never been reported. CASE PRESENTATION: A 55-year-old female with breast cancer exhibited unexplained hypoxemia, followed with vomiting, diarrhea, unilateral flank pain and abdominal pain after lumpectomy 12 h. The urgent multi-detector row computed tomography (MDCT) confirmed the diagnosis of PE and RAE. Confusingly, the patient had no history of intracardiac defect, cardiac valvular diseases, atrial fibrillation or other cardiovascular disease and the definite cause was still unclear. However, after 10 days of prompt anticoagulant therapy in ICU, she was discharged in good condition. CONCLUSION: Breast cancer patients after surgery suffering from unexplained hypoxemia, abdominal pain, vomiting and diarrhea should be highly suspicious of PE or RAE, even PDE. Any clinical presentation on these postoperative patients should be given much more attention to make accurate diagnosis and appropriate interventions.

pH-Sensitive nanotheranostics for dual-modality imaging guided nanoenzyme catalysis therapy and phototherapy.

Triple-negative breast cancer shows resistance to conventional radiotherapies and chemotherapies, and few molecular targeted therapies are currently available for this malignancy in clinical settings. In this work, a theranostic nanosystem with a core-shell structure was synthesized through self-assembly of amphiphilic macromolecules, which can be used in effective catalysis therapy and phototherapy. Herein, we report that superparamagnetic iron oxide nanocrystals and IR780 dye were effectively loaded into the hydrophobic core of the nanosystem, which enabled dual-modality magnetic resonance imaging and near-infrared fluorescence imaging. Furthermore, on the hydrophilic crown, the neighboring carboxylic acid-based amide linkage showed charge conversion properties in the tumor acidic microenvironment and endowed the system with targeted diagnosis and delivery. Upon light excitation, this theranostic system exerted synergistic anti-cancer activity through the nano-enzyme catalysis effect enhanced phototherapy in a triple-negative 4T1 breast cancer model. Furthermore, there were no obvious side-effects. The results of our study demonstrate the great potential of this theranostic nanosystem in cancer diagnosis and therapy.

Efficacy and Safety of Sodium Tanshinone IIA Sulfonate Injection on Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.

Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy. Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy. Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. All studies were screened by two reviewers according to the inclusion and exclusion criteria independently. The Cochrane Collaboration's risk tool was used to assess the methodological quality of the included studies. Reviewer Manager 5.3 was employed for statistical analysis. Results: Sixteen trials involving 1,696 patients were included. The meta-analysis results indicated a combination of STS and angiotensin receptor blockers (ARBs) was more effective than ARB monotherapy in modulating hypertensive nephropathy, as represented by improved estimated glomerular filtration rate (eGFR) [mean difference (MD) = 6.87, 95% CI (4.47, 9.28), P < 0.00001] and reduced 24 h urinary protein [MD = -0.23, 95% CI (-0.27, -0.19), P < 0.00001], serum creatinine (SCr) [MD = -21.74, 95% CI (-24.11, -19.38), P < 0.00001], cystatin-C [MD = -0.16, 95% CI (-0.24, -0.07), P = 0.0003], urinary immunoglobulin G (IgG) [MD = -0.85, 95% CI (-1.11, -0.59), P < 0.00001], and urinary transferrin [MD = -0.61, 95% CI (-1.04, -0.17), P = 0.007]. In addition, the combination therapy had better control in systolic blood pressure (SBP) [MD = -6.53, 95% CI (-8.19, -4.87), P < 0.00001] and diastolic blood pressure (DBP) [MD = -4.14, 95% CI (-5.69, -2.59), P < 0.00001]. Only three trials reported adverse events, and no adverse drug reactions were observed. Conclusions: STS combined with ARBs had a stronger effect on improving renal function in patients with primary hypertensive nephropathy than ARB monotherapy. The combination therapy also provided auxiliary hypotensive effects. Further large-scale, multicenter, and rigorously designed randomized controlled trials (RCTs) should be conducted to confirm our findings.

PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K/Akt/GSK-3ß/Snail signaling.

Protein arginine methyltransferases (PRMT) catalyze protein arginine methylation and play an important role in many biological processes. Aberrant PRMT expression in tumor cells has been documented in several common cancer types; however, its precise contribution to hepatocellular carcinoma (HCC) cell invasion and metastasis is not fully understood. In this study, we identified a new oncogene, PRMT9, whose overexpression strongly promotes HCC invasion and metastasis. PRMT9 expression was detected more frequently in HCC tissues than in adjacent noncancerous tissues. PRMT9 overexpression was significantly correlated with hepatitis B virus antigen (HBsAg) status, vascular invasion, poor tumor differentiation and advanced TNM stage. Patients with higher PRMT9 expression had a shorter survival time and higher recurrence rate. PRMT9 expression was an independent and significant risk factor for survival after curative resection. Functional studies demonstrated that PRMT9 increased HCC cell invasion and lung metastasis. Knocking down PRMT9 with short hairpin RNA (shRNA) inhibited HCC cell invasion. Further investigations found that PRMT9 increased cell migration and invasion through epithelial-mesenchymal transition (EMT) by regulating Snail expression via activation of the PI3K/Akt/GSK-3ß/Snail signaling pathway. In clinical HCC samples, PRMT9 expression was positively associated with Snail expression and was negatively associated with E-cadherin expression. In conclusion, our study demonstrated that PRMT9 is an oncogene that plays an important role in HCC invasion and metastasis through EMT by regulating Snail expression via activation of the PI3K/Akt/GSK-3ß/Snail signaling pathway. Thus, PRMT9 may serve as a candidate prognostic biomarker and a potential therapeutic target.

PRMT5 promotes cell proliferation by inhibiting BTG2 expression via the ERK signaling pathway in hepatocellular carcinoma.

Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, has roles in cell growth regulation and cancer development. However, the role of PRMT5 in hepatocellular carcinoma (HCC) progression remains unclear. Here, we showed that PRMT5 expression was frequently upregulated in HCC tissues, and its expression was inversely correlated with overall survival in HCC patients. PRMT5 knockdown markedly inhibited in vitro HCC proliferation and in vivo tumorigenesis. We revealed that the mechanism of PRMT5-induced proliferation was partially mediated by BTG downregulation, leading to cell cycle arrest during the G1 phase in HCC cells. Ectopic BTG2 overexpression decreased HCC growth, caused cell cycle arrest at the G1 phase, and downregulated Cyclin D1 and Cyclin E1 protein expression. Furthermore, we found that PRMT5-induced ERK phosphorylation regulated BTG2 expression in HCC cells, whereas pretreatment with a selective ERK1/2 inhibitor (PD184352) significantly reversed the effect of PRMT5 on BTG2 expression. Our results indicated that PRMT5 promotes HCC proliferation by downregulating BTG2 expression via the ERK pathway.

Surgical Resection and Prognostic Analysis of 142 Cases of Hilar Cholangiocarcinoma.

Surgical resection for hilar cholangiocarcinoma is the only curative option, but low resectability rate and poor survival outcomes remain a challenge. This study was to assess the surgical resection for hilar cholangiocarcinoma and analyze the prognostic factors influencing postoperative survival. One hundred forty-two patients with hilar cholangiocarcinoma who underwent surgical resection between January 2006 and December 2014 were analyzed retrospectively based on clinicopathological and demographic data. Univariate and multivariate analysis against outcome were employed to identify potential factors affecting prognosis. Ninety-five patients were performed with R0 resection with median survival time of 22 months; whereas, 47 patients underwent non-R0 resection (R1 = 20, R2 = 27) with that of 10 months. Of these 95 patients, 19 underwent concomitant with vascular resection and reconstruction and 2 patients underwent pancreaticoduodenectomy. 64.8% patients (n = 92) underwent combined with hepatectomy. The one-year, three-year, and five-year survival rates after R0 resection were 76.3, 27.8, 11.3%, respectively, which was significantly better than that after non-curative resection (P = 0.000). Multivariate analysis revealed that non-curative resection (RR: 2.414, 95% CI 1.586-3.676, P = 0.000), pathological differentiation (P = 0.015) and preoperative serum total bilirubin above 10 mg/dL (RR: 1.844, 95% CI 1.235-2.752, P = 0.003) were independent prognostic factors. Aggressive curative resection remains to be the optimal option for hilar cholangiocarcinoma. Non-curative resection, pathological differentiation, and preoperative serum total bilirubin above 10 mg/ dL were associated with dismal prognosis.

Therapeutic significance and indications of pulmonary metastasectomy for hepatocellular carcinoma following liver resection.

BACKGROUND: To explore the therapeutic significance and indications of pulmonary metastasectomy (PMT) in hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) following liver resection (LR). PATIENTS AND METHODS: PM-HCC patients who underwent LR were retrospectively enrolled, and survival outcomes and prognostic factors were analyzed. Patients were divided into PMT and non-PMT group, and propensity score matching (PSM) analysis was used for survival comparison. Prognostic analysis and survival comparisons were performed specifically in PMT patients. RESULTS: Ninety-seven patients were enrolled, among which twenty-six underwent PMT while seventy-one did not. Survival outcome was superior in PMT group compared to non-PMT group (33.5 vs. 10.5 months) (p = 0.003), while no statistical difference was found after PSM analysis (33.5 vs. 11.2 months) (p = 0.138). Synchronous PM-HCC, serum alpha fetal protein≥400 ng/ml at PM diagnosis, no intrahepatic treatments (LR, ablation or transarterial chemoembolization) after LR, intrahepatic recurrence or metastasis at repeated PM diagnosis were inferior independent prognostic factors in PMT patients (p < 0.05). Superior survival outcomes were seen in candidate PMT patients when corresponding indications were satisfied (p = 0.014, p = 0.005). CONCLUSION: PMT might provide potential survival benefits in well selected PM-HCC patients who underwent LR. Well designed, multi-institutional studies with larger patient number were still to be required.

Isolated brain metastases prior to locoregional recurrence in hilar cholangiocarcinoma.

Isolated brain metastases prior to locoregional recurrence from hilar cholangiocarcinoma (HCCA) following curative resection are an extremely rare event. Very few reports regarding brain metastasis prior to locoregional recurrence following curative resection have been published due to the fact that to differentiate brain metastases from HCCA recurrence is challenging, particular in the early stages, since the neurological findings of brain metastasis are occult and subtle. Any patient with HCCA who has undergone radical resection and subsequently presented with a further onset of neurological symptoms should be evaluated for brain involvement. The present case study describes a patient with HCCA who underwent curative resection, and experienced isolated brain metastases prior to locoregional recurrence.

An Investigation on the Tribological Performances of the SiO2/MoS2 Hybrid Nanofluids for Magnesium Alloy-Steel Contacts.

Hybrid nano-materials offer potential scope for an increasing numerous novel applications when engineered to deliver availably functional properties. In the present study, the SiO2/MoS2 hybrid nanoparticles with different mass ratios were employed as lubricant additives in the base oil, and their tribological properties were evaluated using a reciprocating ball-on-plate tribometer for magnesium alloy-steel contacts. The results demonstrate that the SiO2/MoS2 hybrid nanoparticles exhibit superior lubrication performances than individual nano-SiO2 or nano-MoS2 even in high load and diverse velocity cases. The optimal SiO2/MoS2 mixing ratio and the concentration of SiO2/MoS2 hybrid nanoparticles in the base oil are 0.25:0.75 and 1.00-1.25 wt%, respectively. The excellent lubrication properties of the SiO2/MoS2 hybrid nanoparticles are attributed to the physical synergistic lubricating actions of nano-SiO2 and nano-MoS2 during the rubbing process.