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Supplementary Methods provide experimental details on bioinformatics analysis, standard assays using commercial reagents and kits; Supplementary Figures S1-8 describe additional data to support the function of MNX1-AS1, which promotes the tumorigenesis in both CRC cells and tissues; Supplementary tables S1-6 show clinical information of sequenced patients, detailed screening candidates for validation, regression analysis together with mass spectrometry data used in this study.

Long noncoding RNAs (lncRNA) are involved in tumorigenesis and drug resistance. However, the roles and underlying mechanisms of lncRNAs in colorectal cancer are still unknown. In this work, through transcriptomic profiling analysis of 21 paired tumor and normal samples, we identified a novel colorectal cancer–related lncRNA, MNX1-AS1. MNX1-AS1 expression was significantly upregulated in colorectal cancer and associated with poor prognosis. In vitro and in vivo gain- and loss-of-function experiments showed that MNX1-AS1 promotes the proliferation of colorectal cancer cells. MNX1-AS1 bound to and activated Y-box-binding protein 1 (YB1), a multifunctional RNA/DNA-binding protein, and prevented its ubiquitination and degradation. A marked overlap between genes that are differentially expressed in MNX1-AS1 knockdown cells and transcriptional targets of YB1 was observed. YB1 knockdown mimicked the loss of viability phenotype observed upon depletion of MNX1-AS1. In addition, MYC bound the promoter of the MNX1-AS1 locus and activated its transcription. In vivo experiments showed that ASO inhibited MNX1-AS1, which suppressed the proliferation of colorectal cancer cells in both cell-based and patient-derived xenograft models. Collectively, these findings suggest that the MYC–MNX1-AS1–YB1 axis might serve as a potential biomarker and therapeutic target in colorectal cancer.Significance:This study highlights the discovery of a novel colorectal cancer biomarker and therapeutic target, MNX1-AS1, a long noncoding RNA that drives proliferation via a MYC/MNX1-AS1/YB1 signaling pathway.

Long noncoding RNAs (lncRNA) are involved in tumorigenesis and drug resistance. However, the roles and underlying mechanisms of lncRNAs in colorectal cancer are still unknown. In this work, through transcriptomic profiling analysis of 21 paired tumor and normal samples, we identified a novel colorectal cancer–related lncRNA, MNX1-AS1. MNX1-AS1 expression was significantly upregulated in colorectal cancer and associated with poor prognosis. In vitro and in vivo gain- and loss-of-function experiments showed that MNX1-AS1 promotes the proliferation of colorectal cancer cells. MNX1-AS1 bound to and activated Y-box-binding protein 1 (YB1), a multifunctional RNA/DNA-binding protein, and prevented its ubiquitination and degradation. A marked overlap between genes that are differentially expressed in MNX1-AS1 knockdown cells and transcriptional targets of YB1 was observed. YB1 knockdown mimicked the loss of viability phenotype observed upon depletion of MNX1-AS1. In addition, MYC bound the promoter of the MNX1-AS1 locus and activated its transcription. In vivo experiments showed that ASO inhibited MNX1-AS1, which suppressed the proliferation of colorectal cancer cells in both cell-based and patient-derived xenograft models. Collectively, these findings suggest that the MYC–MNX1-AS1–YB1 axis might serve as a potential biomarker and therapeutic target in colorectal cancer. Significance: This study highlights the discovery of a novel colorectal cancer biomarker and therapeutic target, MNX1-AS1, a long noncoding RNA that drives proliferation via a MYC/MNX1-AS1/YB1 signaling pathway.

Background In patients with squamous cell carcinoma of the cervix (SCCC), a squamous cell carcinoma (SqCC) in the lung represents either a second primary tumor or metastasis. This distinction between second primary tumors and lung metastases in patients with SCCC significantly influences patient prognosis and therapy. Here, we aimed to differentiate second primary tumors from lung metastases in patients with SCCC by exploring the HPV status in SqCCs involving the lung within a large cohort. Methods P16 expression was assessed using immunohistochemistry on tissue microarrays including a total of 415 primary lung SqCCs and 21 lung SqCCs with prior SCCC. Following this, we performed HPV DNA typing and the sensitive RNAscope in situ method to screen all the cases for HPV E6/E7 expression, which is a more reliable indicator of transcriptively active HPV in tumor cells. Results The p16 positive expression rate was 13.7% (57/415) in primary lung SqCCs, but HPV DNA was not detected in any of the 57 primary lung SqCC cases that positively expressed p16. In contrast, HPV DNA was detected in all cases (21/21) with prior SCCC. Consistently, all 21 lung SqCCs with prior SCCC (21/21) showed extensive HPV16 E6/E7 expression. In striking contrast, none of the primary lung SqCCs (0/415) had a detectable RNAscope signal. Conclusions HPV does not seem to play a role in the development of primary lung SqCCs. HPV detection may be helpful in distinguishing second primary tumors from lung metastases in patients with SCCC., HPV does not seem to play a role in the development of primary lung SqCCs. HPV detection may be helpful in distinguishing second primary tumors from lung metastases in patients with SCCC.

Nasopharyngeal carcinoma is an Epstein–Barr virus (EBV)-related malignancy. Recently, we found that the EBV-encoded miRNA BART2-5p was increased in the serum of patients with preclinical nasopharyngeal carcinoma and that the copy number positively correlated with disease progression. In this study, we established its role in nasopharyngeal carcinoma progression and explored underlying mechanisms and clinical significance. BART2-5p was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of BART2-5p promoted migration and invasion of EBV-negative nasopharyngeal carcinoma cells, whereas genetic downregulation of BART2-5p in EBV-positive nasopharyngeal carcinoma cells decreased aggressiveness. Mechanistically, BART2-5p targeted RND3, a negative regulator of Rho signaling. Downregulation of RND3 phenocopied the effect of BART2-5p and reconstitution of RND3 rescued the phenotype. By suppressing RND3, BART2-5p activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV miRNA BART2-5p in promoting nasopharyngeal carcinoma metastasis and its potential value as a prognostic indicator or therapeutic target. Significance: This study shows that EBV-encoded BART2-5p miRNA suppresses expression of the RND3 Rho family GTPase, consequently promoting ROCK signaling, cell motility, and metastatic behavior of NPC cells.

Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P

Background: Dietary fat absorption involves the re-esterification of digested triacylglycerol in the enterocytes, it is a biological process catalyzed by monoacylglycerol O-acyltransferase 2 (MOGAT2, aka MGAT2), which is highly expressed in the small intestine. A previous study showed that the loss of the Mogat2 gene can prevent high-fat diet-induced obesity in mice. Obesity is associated with an increased risk of several types of cancer including postmenopausal breast cancer.Methods: We collected 147 patients with triple negative breast adenocarcinoma to explore the relationship between the expression of MOGAT2 and patient overall survival. And we generated a Mogat2-deficient mouse mammary tumor model by crossing Mogat2-deficient mice with MMTV-PyMT mice to examine the effect of losing MOGAT2 in vivo.Results: Our founding suggest that obesity was induced by a relatively high-fat diet (37% of calories from fat) in the mice with or without Mogat2 knockout. Mammary tumor development was deteriorated by a relatively high-fat diet regardless of Mogat2 deficiency. As a compensation mechanism, upregulation of diacylglycerol O-acyltransferases 1 and 2 (Dgat1 and Dgat2) in the Mogat2 deficient mice was found. Conclusions: Elevated expression of MOGAT2 in triple negative breast adenocarcinoma predicts poorer patient overall survival. With the compensation of Dgat1 and Dgat2, Mogat2 deficiency alone cannot prevent fat diet-induced obesity, nor prevent mammary tumor development in a mouse model.

Background: Differences between the features of primary cancer and matched metastatic cancer have recently drawn attention in research. This study investigated the concordance in microsatellite instability (MSI) and mismatch repair (MMR) status between primary and corresponding metastatic colorectal cancer (CRC). Methods: Consecutive patients with metastatic CRC who had both primary and metastatic tumors diagnosed at our institution in January 2008 through December 2016 were identified. Immunohistochemistry was used to test the MMR status of both primary and matched metastatic tumors, and PCR analysis was performed to test MSI in patients with deficient MMR (dMMR) status. Results: A total of 369 patients were included. Of the 46 patients with MSI-high primary tumors, 37 (80.4%) also had MSI-high metastatic tumors, whereas 9 (19.6%) had microsatellite stable (MSS) metastatic tumors. A high concordance was found in patients with liver, lung, or distant lymph node metastases. Interestingly, the discrepancy was more likely to be limited to peritoneal (5/20) or ovarian (4/4) metastasis (chi-square test, PP=.008). However, the change did not influence survival; the median overall survival of MSI-high and MSS metastatic tumors was 21.3 and 21.6 months, respectively (P=.774). The discrepancy rate was 1.6% for patients with proficient MMR primary tumors. Conclusions: For patients with dMMR primary tumors, the concordance of MSI and MMR status in primary CRC and corresponding metastatic cancer is potentially organ-specific. High concordance is found in liver, lung, and distant lymph node metastases, whereas discrepancy is more likely to occur in peritoneal or ovarian metastasis. Rebiopsy to evaluate MSI-high/dMMR status might be needed during the course of anti–PD-1 therapy in cases of peritoneal or ovarian metastasis.

Background: Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options. Methods: Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations EGFR/KRAS/BRAF mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan–Meier method with log-rank test was used for analyzing patient survival. Results: Major events, including EGFR, KRAS, and BRAF mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan–Meier analysis showed that patients with a KRAS mutation had ower 5-year overall survival than those with wild-type KRAS (25.4% vs 47.8%, P=0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, P=0.044). Conclusion: KRAS mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.

BACKGROUND Colorectal cancer (CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC (ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic. AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS. METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005, to October 1, 2015, were studied. Expression of autophagy-related proteins [Beclin1, microtubule-associated protein 1A/B-light chain 3 (LC3), and 4E-binding protein 1 (4E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed. RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients, immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3 (0.657, P < 0.001) and 4E-BP1 (0.211, P = 0.042) in ACRC tissues. LC3 was significantly overexpressed in tumor tissues compared to normal tissues (P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1 (P = 0.010) and 4E-BP1 (P = 0.005), pathological grade (P = 0.002), and T stage (P = 0.004) were independent prognostic factors for overall survival (OS). CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy. LC3 is overexpressed in tumor tissues, and Beclin1 and 4E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.

Background: Dietary fat absorption involves the re esterification of digested triacylglycerol in the enterocytes, it is a biological process catalyzed by monoacylglycerol O acyltransferase 2 (MOGAT2, aka MGAT2), which is highly expressed in the small intestine. A previous study showed that the loss of the Mogat2 gene can prevent high fat diet induced obesity in mice. Obesity is associated with an increased risk of several types of cancer including postmenopausal breast cancer.Methods: We collected 147 patients with triple negative breast adenocarcinoma to explore the relationship between the expression of MOGAT2 and patient overall survival. And we generated a Mogat2 deficient mouse mammary tumor model by crossing Mogat2 deficient mice with MMTV PyMT mice to examine the effect of losing MOGAT2 in vivo. Results: Our founding suggest that obesity was induced by a relatively high fat diet (37% of calories from fat) in the mice with or without Mogat2 knockout. Mammary tumor development was deteriorated by a relatively high fat diet regardless of Mogat2 deficiency. As a compensation mechanism, upregulation of diacylglycerol O acyltransferases 1 and 2 (Dgat1 and Dgat2) in the Mogat2 deficient mice was found. Conclusions: Elevated expression of MOGAT2 in triple negative breast adenocarcinoma predicts poorer patient overall survival. With the compensation of Dgat1 and Dgat2, Mogat2 deficiency alone cannot prevent fat diet induced obesity, nor prevent mammary tumor development in a mouse model.

ObjectiveTo evaluate the effectiveness of a novel computerized quantitative analysis based on histopathological and computed tomography (CT) images for predicting the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients.MethodsWe retrospectively reviewed the medical records of 153 ESCC patients who underwent esophagectomy alone and quantitatively analyzed digital histological specimens and diagnostic CT images. We cut pathological images (6000 × 6000) into 50 × 50 patches; each patient had 14,400 patches. Cluster analysis was used to process these patches. We used the pathological clusters to all patches ratio (PCPR) of each case for pathological features and we obtained 20 PCPR quantitative features. Totally, 125 computerized quantitative (20 PCPR and 105 CT) features were extracted. We used a recursive feature elimination approach to select features. A Cox hazard model with L1 penalization was used for prognostic indexing. We compared the following prognostic models: Model A: clinical features; Model B: quantitative CT and clinical features; Model C: quantitative histopathological and clinical features; and Model D: combined information of clinical, CT, and histopathology. Indices of concordance (C-index) and leave-one-out cross-validation (LOOCV) were used to assess prognostic model accuracy.ResultsFive PCPR and eight CT features were treated as significant indicators in ESCC prognosis. C-indices adjusted for LOOCV were comparable among four models, 0.596 (Model A) vs. 0.658 (Model B) vs. 0.651 (Model C), and improved to 0.711with Model D combining information of clinical, CT, and histopathology (all pConclusionQuantitative prognostic modeling using a combination of clinical data, histopathological, and CT images can stratify ESCC patients with surgery alone into high-risk and low-risk groups.

Circle of Willis (CoW) is the most critical collateral pathway that supports the redistribution of blood supply in the brain. The variation of CoW is closely correlated with cerebral hemodynamic and cerebral vessel-related diseases. But what is responsible for CoW variation remains unclear. Moreover, the visual evaluation for CoW variation is highly time-consuming. In the present study, based on the computer tomography angiography (CTA) dataset from 255 patients, the correlation between the CoW variations with age, gender, and cerebral or cervical artery stenosis was investigated. A multitask convolutional neural network (CNN) was used to segment cerebral arteries automatically. The results showed the prevalence of variation of the anterior communicating artery (Aco) was higher in the normal senior group than in the normal young group and in females than in males. The changes in the prevalence of variations of individual segments were not demonstrated in the population with stenosis of the afferent and efferent arteries, so the critical factors for variation are related to genetic or physiological factors rather than pathological lesions. Using the multitask CNN model, complete cerebral and cervical arteries could be segmented and reconstructed in 120 seconds, and an average Dice coefficient of 78.2% was achieved. The segmentation accuracy for precommunicating part of anterior cerebral artery and posterior cerebral artery, the posterior communicating arteries, and Aco in CoW was 100%, 99.2%, 94%, and 69%, respectively. Artificial intelligence (AI) can be considered as an adjunct tool for detecting the CoW, particularly related to reducing workload and improving the accuracy of the visual evaluation. The study will serve as a basis for the following research to determine an individual’s risk of stroke with the aid of AI.

Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6 (PRELID1P6) promotes glioma progression. Aberrant expression of genes was screened using The Cancer Genome Atlas database. We found that mRNA level of PRELID1P6 was highly upregulated in glioma and was associated with a shorter survival time. Functional studies showed that the knockdown of PRELID1P6 decreased cell proliferation, sphere formation, and clone formation ability and blocked the cell cycle transition at G0/G1, while overexpression of PRELID1P6 had the opposite effects. Mechanistically, knockdown of PRELID1P6 changed the cellular localization of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) from nucleus to cytoplasm, which promoted ubiquitin-mediated degradation of hnRNPH1. RNA-sequence and gene set enrichment analysis suggested that knockdown of PRELID1P6 regulates the apoptosis signaling pathway. Western blotting showed that PRELID1P6 increased TRF2 expression by hnRNPH1-mediated alternative splicing effect and activated the Akt/mTOR pathway. Furthermore, Akt inhibitor MK2206 treatment reversed the oncogenic function of PRELID1P6. PRELID1P6 was also found to be negatively regulated by miR-1825. Our result showed that PRELID1P6 promotes glioma progression through the hnHNPH1-Akt/mTOR pathway. These findings shed new light on the important role of PRELID1P6 as a novel oncogene for glioma.

The tumor immune microenvironment (TIME) plays an important role in penile squamous cell carcinoma (peSCC) pathogenesis. Here, the immunophenotype of the TIME in peSCC was determined by integrating the expression patterns of immune checkpoints (programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and Siglec-15) and the components of tumor-infiltrating lymphocytes, including CD8+ or Granzyme B+ T cells, FOXP3+ regulatory T cells, and CD68+ or CD206+ macrophages, in 178 patients. A high density of Granzyme B, FOXP3, CD68, CD206, PD-1, and CTLA-4 was associated with better disease-specific survival (DSS). The patients with diffuse PD-L1 tumor cell expression had worse prognoses than those with marginal or negative PD-L1 expression. Four immunophenotypes were identified by unsupervised clustering analysis, based on certain immune markers, which were associated with DSS and lymph node metastasis (LNM) in peSCC. There was no significant relationship between the immunophenotypes and high-risk human papillomavirus (hrHPV) infection. However, the hrHPV&ndash, positive peSCC exhibited a higher density of stromal Granzyme B and intratumoral PD-1 than the hrHPV&ndash, negative tumors (p = 0.049 and 0.002, respectively). In conclusion, the immunophenotypes of peSCC were of great value in predicting LNM and prognosis, and may provide support for clinical stratification management and immunotherapy intervention.

Jia-bin Lu,1,2,* Shao-hang Cai,1,3,* Ying-hua Pan,4,* Jing-ping Yun1,2 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; 2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 3Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 4Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510060, China *These authors contributed equally to this work Objective: Hepatocellular carcinoma (HCC) is a rapidly proliferating malignancy that requires large amounts of fatty acids to synthesize cellular membranes and provide energy. Epidermal fatty acid-binding protein (EFABP) is uniquely expressed in epidermal cells, but its role and expression in HCC are not clear. Subjects and methods: A total of 804 HCC specimens were collected to construct a tissue microarray (TMA) and for immunohistochemistry (IHC) analysis. The relationship between EFABP expression and clinical features of patients with HCC was analyzed. Results: The EFABP IHC score for HCC tissue was 0.76±0.69, being significantly higher than that for matched nontumorous tissue (0.48±0.55; P

Cystatin-C (Cys-C) has been studied as a valuable prognostic indicator in several malignancies. The goal of this study is to explore the expression and prognostic significance of Cys-C in clear cell renal cell carcinoma (CCRCC).Immunohistochemistry and western blot assays were performed to evaluate the level of Cys-C expression in CCRCC tissue. Expression levels of Cys-C in CCRCC tissue samples in relation to clinicopathological characteristics of the tumors were assessed. Their prognostic significance was analyzed by univariate and multivariate analyses. In addition, the expression of Cys-C in 786-O cell lines was inhibited by using CRISPR/Case9 and the effects of Cys-C knockout on 786-O cells in vitro were evaluated using MTT method, colony formation assay, cell cycle assay, and cell migration and invasive assay.The expression level of Cys-C was lower in CCRCC tissues (n = 253) than in paired adjacent non-cancerous tissues (n = 164) by immunohistochemistry (P 0.001). Among the 253 patients, the results showed that patients with low Cys-C expression level in cancer tissue has longer overall survival (OS) than that with high Cys-C level. Furthermore, knockout of Cys-C in 786-O cell line has ability to suppress cell proliferation, induce G0/G1 phase arrest, inhibited cell invasion, decreased phosphorylation of ERK1/2, STAT-3 and enhanced phosphorylated JNK expression.A decrease in serum Cys-C is a favorable prognostic indicator for CCRCC patients. Inhibition of Cys-C suppressed RCC 786-O cell proliferation and invasion. These results indicated that Cys-C could serve as an ideal prognostic biomarker in patients with CCRCC.

Background Non-small cell lung cancer (NSCLC) with different EGFR mutation types shows distinct sensitivity to tyrosine kinase inhibitors (TKIs). This study developed a patho-clinical profile-based prediction model of TKI-sensitive EGFR mutations. Methods The records of 1121 Chinese patients diagnosed with NSCLC from November 2008 to October 2014 (the development set) were reviewed. Multivariate logistic regression was conducted to identify any association between potential predictors and the classic sensitive EGFR mutations (exon 19 deletion and exon 21 L858R point mutation). A prediction index was created by assigning weighted scores to each factor proportional to a regression coefficient. Validation was made in an independent cohort consisting of 864 patients who were consecutively enrolled between November 2014 and January 2017 (the validation set). Results Seven independent predictors were identified: gender (female vs. male), adenocarcinoma (yes vs. no), smoking history (no vs. yes), N stage (N+ vs. N0), M stage (M1 vs. M0), brain metastasis (yes vs. no), and elevated Cyfra 21-1 (no vs. yes). Each was assigned a number of points. In the validation set, the area under curve of the prediction index appeared as 0.698 (95% confidence interval 0.663-0.733). The sensitivity, specificity, positive and negative predictive values, and concordance were 95.0%, 32.3%, 61.4%, 85.1%, and 65.6%, respectively. Conclusion We developed a patho-clinical profile-based model for predicting TKI-sensitive EGFR mutations. Our model may represent a noninvasive, economical choice for clinicians to inform TKI therapy.

Background: Programmed death ligand 1 (PD-L1) expression has been shown to predict benefit from anti-PD-1 treatment in several cancers. However, its predictive value in colorectal cancer seems limited. This study was aimed to explore the clinical and biomarker association of programmed death ligand 1 and its spatial heterogeneous expression in colorectal cancer. Methods: Tissue microarrays of 422 primary colorectal cancers from our hospital were used for the interpretation of PD-L1 and programmed death 1 (PD-1) expression, cluster of differentiation 4 (CD4) and CD8 density and microsatellite instability (MSI) status by immunohistochemistry. To assess the spatial heterogeneity of PD-L1 expression, Tissue microarrays of 383 paired intra-primary-tumor tissues, and 105 paired lymph node metastatic tumors and 64 paired distant metastatic tumors were also used. Results: PD-L1 was positive in 188 (44.5%) primary colorectal cancers. PD-L1 expression was associated with less advanced N category (P

Epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in a variety of epithelial carcinomas, and it is involved in cell adhesion and proliferation. However, its expression profile and biological function in nasopharyngeal carcinoma (NPC) remains unclear. In this study, higher expression of EpCAM was found in NPC samples compared with non-cancer nasopharyngeal mucosa by qRT-PCR. Additionally, immunohistochemistry (IHC) analysis of NPC specimens from 64 cases showed that high EpCAM expression was associated with metastasis and shorter survival. Multivariate survival analysis identified high EpCAM expression as an independent prognostic factor. Ectopic EpCAM expression in NPC cells promoted epithelial-mesenchymal transition (EMT), induced a cancer stem cell (CSC)-like phenotype, and enhanced metastasis in vitro and in vivo without an effect on cell proliferation. Notably, EpCAM overexpression reduced PTEN expression and increased the level of AKT, mTOR, p70S6K and 4EBP1 phosphorylation. Correspondingly, an AKT inhibitor and rapamycin blocked the effect of EpCAM on NPC cell invasion and stem-like phenotypes, and siRNA targeting PTEN rescued the oncogenic activities in EpCAM knockdown NPC cells. Our data demonstrate that EpCAM regulates EMT, stemness and metastasis of NPC cells via the PTEN/AKT/mTOR pathway.

Aim: Although immunohistochemistry (IHC) and reverse transcription-PCR can detect ALK rearrangements, the ALK break-apart FISH assay is currently considered the standard method. Materials & methods: Five patients with advanced non-small-cell lung cancer, who had an ALK-negative FISH result that was later confirmed as positive by the Ventana IHC assay, were studied. Four had previously received chemotherapy or radiotherapy. All five were subsequently treated with Crizoitinib 250 mg twice daily. Results & conclusion: Four patients had a partial response to Crizotinib and one had stable disease. IHC is an efficient technique for diagnosing ALK rearrangements in patients with non-small-cell lung cancer, and may serve as an alternative to FISH in clinical practice.

Experiment was performed to examine the plane polishing of SiC single crystal wafer by using the chemical magnetorheological finishing (CMRF) technique. The influence of some process parameters such as the concentration of diamond abrasive particles, the concentration of carbonyl iron powder and the machining gap in CMRF were studied comparing with the magnetorheological finishing (MRF) method. The results show that the surface roughness of polished SiC single crystal by the CMRF is slightly lower than that by the MRF. Polishing liquid with different components and processing parameters affects the coupling effect of mechanical removal and chemical removal in CMRF, and a better coupling effect can produce a better surface quality in CMRP. In the MRF, the surface roughness of SiC single crystal is lower for a higher concentration of carbonyl iron powder (CIP). However, in the CMRF, the CIP’s concentration may change the contact state between the catalyst and SiC, and the CIP’s concentration of about 20% can produce a better surface roughness of SiC. The machining gap between the polishing disk and the workpiece surface determines the processing effect, and the machining gap of 1.0 mm is suitable for the polishing of SiC in the MRF and CMRF.

The polishing experiments of anodic oxide film of aluminum were performed to research the influence of polishing parameters on the surface roughness and material removal rate in the cluster magnetorheological finishing (MRF). Experimental results demonstrate that a mirror effect can be reached when the anodic oxide film of aluminum is polished by the Cluster MRF. The roughness of the workpiece surface after polishing for 15 min is decreased from Ra 0.575μm to Ra 4.13nm and the material removal rate is 0.653mg/min. With the extension of the polishing time, the surface roughness rapidly declines at first and then slowly decreases. When the machining time is more than 15min, the anodic oxide film of aluminum is easily worn out, resulting in a sharp increase in the surface roughness. The machining gap between the workpiece and the polishing plate influences the polishing effect of anodic oxide film of aluminum. With the increase of the machining gap, the material removal rate decreases and the surface roughness increases. A good surface quality can be got at the machining gap of 1.1mm. The type and size of abrasive particles will directly affect the polishing effect of anodic oxide film of aluminum, and when using CeO2 abrasive with the particle size of W3, a higher material removal rate and a smaller surface roughness can be obtained.

Cancer patients are more susceptible to severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Angiotensin-converting enzyme 2 (ACE2) is the functional host receptor for SARS-CoV-2 entering into human cells. Bioinformatics’ analyses have revealed that ACE2 is upregulated in some cancer cells. In the present study, we evaluated ACE2 protein expression levels in several common malignancies compared to non-cancerous normal tissues. ACE2 expression was elevated in colorectal adenocarcinoma, pancreatic adenocarcinoma, gastric adenocarcinoma, and papillary renal cell carcinoma cancer. Yet, it was suppressed in chromophobe renal cell carcinoma, testicular germ cell tumors, and papillary thyroid carcinoma. Two tumor tissue microarrays were used to evaluate the prognostic value of ACE2 expression in patients with gastric adenocarcinoma, and colorectal adenocarcinoma without COVID-19. No significant survival benefit was found for patients with overexpression of ACE2 in the tumor. In the tumor vasculature, ACE2 expression was observed in only 54% of the tumor micro-vessels. Using an in vitro co-culture of endothelial cells and tumor cells overexpressing fusion protein ACE2-red fluorescent protein, we did not observe any clear and convincing intercellular transfer of ACE2 from cancer cells into endothelial cells. In summary, alteration of ACE2 expression was found in common malignancies, but there is no evidence of intercellular transfer of ACE2 from cancer cells to endothelial cells.

Ras-like without CAAX1 (RIT1) protein is a member of Ras family, which plays critical roles in signaling pathways and cellular process regulation. However, the role of RIT1 in esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we found that the expression of RIT1 is downregulated in ESCC compared to corresponding non-tumor tissues. The low-level expression of RIT1 was correlated with poorer prognosis. Then we showed that RIT1 inhibited proliferation, invasion, and migration of ESCC cells, and silencing RIT1 by shRNA promoted tumorigenicity and metastasis in nude mice. We further demonstrated that RIT1 inhibited the malignant behaviors of ESCC through inhibiting the PI3K/AKT and MAPK pathway and epithelial–mesenchymal transition in ESCC cells. Our study also revealed that RIT1 increased drug sensitivity to cisplatin (CDDP), and this function could be carried out through downregulating stemness of ESCC. In conclusion, our study indicates for the first time that RIT1 displays tumor-suppressing functions in ESCC, and these functions were carried out by inhibiting MAPK and PI3K/AKT signaling pathway, inhibiting EMT, and downregulating cancer stemness of ESCC cells.

Background Non‐small cell lung cancer (NSCLC) with different EGFR mutation types shows distinct sensitivity to tyrosine kinase inhibitors (TKIs). This study developed a patho‐clinical profile‐based prediction model of TKI‐sensitive EGFR mutations. Methods The records of 1121 Chinese patients diagnosed with NSCLC from November 2008 to October 2014 (the development set) were reviewed. Multivariate logistic regression was conducted to identify any association between potential predictors and the classic sensitive EGFR mutations (exon 19 deletion and exon 21 L858R point mutation). A prediction index was created by assigning weighted scores to each factor proportional to a regression coefficient. Validation was made in an independent cohort consisting of 864 patients who were consecutively enrolled between November 2014 and January 2017 (the validation set). Results Seven independent predictors were identified: gender (female vs. male), adenocarcinoma (yes vs. no), smoking history (no vs. yes), N stage (N+ vs. N0), M stage (M1 vs. M0), brain metastasis (yes vs. no), and elevated Cyfra 21‐1 (no vs. yes). Each was assigned a number of points. In the validation set, the area under curve of the prediction index appeared as 0.698 (95% confidence interval 0.663–0.733). The sensitivity, specificity, positive and negative predictive values, and concordance were 95.0%, 32.3%, 61.4%, 85.1%, and 65.6%, respectively. Conclusion We developed a patho‐clinical profile‐based model for predicting TKI‐sensitive EGFR mutations. Our model may represent a noninvasive, economical choice for clinicians to inform TKI therapy.

Yahui Yu,1–3,* Liangru Ke,1,4,* Xing Lv,1,2 Yi hong Ling,1,5 Jiabin Lu,1,5 Hu Liang,1,2 Wenze Qiu,1,2 Xinjun Huang,1,2 Guoying Liu,1,2 Wangzhong Li,1,2 Xiang Guo,1,2 Weixiong Xia,1,2 Yanqun Xiang1,2 1Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong, People’s Republic of China; 2Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Department of Radiation Oncology, Oncology Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Diagnostic Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 5Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic ofChina *These authors contributed equally to this work Purpose: Tumor stroma cells play an important role in the carcinogenesis and progression of cancer. The aim of the present investigation was to explore the predictive role of carcinoma-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) in nasopharyngeal carcinoma (NPC). Patients and methods: The densities of CAFs and TAMs were measured by immunohistochemistry staining for α-smooth muscle actin (α-SMA), CD68, and CD163 in two sets of tissue microarrays including 260 pretreatment NPC tissues, that is, a training test comprising of 152 patients and a validation set comprising of 108 patients. Chi-square tests were performed for comparisons among the groups. Survival rates were estimated by using the Kaplan–Meier method and compared with log-rank tests. Cox proportional hazards models were used to identify significant independent variables. Results: Patients older than 50 years showed a lower expression of CD68, and there was a positive relationship between the densities of CAFs and CD163+ TAMs (p=0.001). In the multivariate analysis of the training test, both α-SMA and CD163 were independent prognostic factors for overall survival and progression-free survival (all p

Background Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer. Method Altogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected. Result With a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5–8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS. Conclusion TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients.

// Pei-Yu Huang 1, 2, * , Shan-Shan Guo 1, 2, * , Yu Zhang 1, 3, * , Jia-Bin Lu 1, 3 , Qiu-Yan Chen 1, 2 , Lin-Quan Tang 1, 2 , Lu Zhang 1, 2 , Li-Ting Liu 1, 2 , Li Zhang 1, 4 , Hai-Qiang Mai 1, 2 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China 2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China 3 Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China 4 Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China * These authors contributed equally to this work Correspondence to: Li Zhang, e-mail: zhangli@sysucc.org.cn Hai-Qiang Mai, e-mail: maihq@sysucc.org.cn Keywords: CTLA-4, CD28, nasopharyngeal carcinoma, immunohistochemistry, prognostic factor Received: July 05, 2015 Accepted: January 26, 2016 Published: February 16, 2016 ABSTRACT The expression levels of CTLA-4 and CD28 were analyzed in 191 nasopharyngeal carcinoma (NPC) patients diagnosed and treated at our hospital between January 2010 and November 2011. The 3-year overall survival (OS) rate (91.4% vs. 81.2%, p = 0.043), failure-free survival (FFS) rate (82.8% vs. 68.0%, p = 0.009) and distant failure-free survival (D-FFS) rate (85.8% vs. 72.3%, p = 0.006) in the low tumor CTLA-4 expression group was higher than in the high tumor CTLA-4 group. There were no differences between the locoregional failure-free survival (LR-FFS) rates in the high and low tumor CTLA-4 expression groups. Moreover, no differences in the OS, FFS, D-FFS, or LR-FFS were observed between the groups with high and low lymphocyte CTLA-4 levels, high and low tumor CD28 levels, or high and low lymphocyte CD28 levels. Cox regression analysis confirmed the prognostic value of tumor CTLA-4 expression, particularly for D-FFS, in NPC patients ( p = 0.044). NPC patients with high tumor CTLA-4 expression had a poorer prognosis than those with low expression.

Monolayer brazed diamond wheel were used to grind AlSiC composite with different volume fraction of SiC. The effects of diamond mesh size of the grinding wheels and the volume fraction of SiC in AlSiC composite on the surface integrity of ground AlSiC composite were investigated. It is found that the surface roughness of ground AlSiC composite with 20% SiC is increased with the reduction of diamond grit’s size because of the clogging of diamond wheel. With the increasing of the volume fraction of SiC, there are more fractured and cracked SiC particles on the ground surface of AlSiC composite. On the other hand, the finer diamond grits (70/80) induce the finer fractured SiC particles on the ground surface of AlSiC with 50% and 70% SiC.

// Tao Qin 1,* , Yin-duo Zeng 1,2,* , Ge Qin 1,* , Fei Xu 1,* , Jia-bin Lu 1 , Wen-feng Fang 1 , Cong Xue 1 , Jian-hua Zhan 1 , Xin-ke Zhang 1 , Qiu-fan Zheng 1 , Rou-jun Peng 1 , Zhong-yu Yuan 1 , Li Zhang 1 and Shu-sen Wang 1 1 Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 2 Sun Yat-sen University Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China * These authors have contributed equally to this work Correspondence to: Shu-sen Wang, email: // Li Zhang, email: // Zhong-yu Yuan, email: // Keywords : PD-L1, breast cancer, ER, PR, prognosis, nomogram Received : July 07, 2015 Accepted : August 22, 2015 Published : September 10, 2015 Abstract Background: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer. Methods: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression. Results: The median follow-up time was 98 months(range, 17–265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis. Conclusions: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.

Purpose To explore the role of CD15 expression in the prognosis of clear cell renal cell carcinoma (ccRCC) in Chinese patients. Methods The study included 301 patients who had undergone surgery for localized ccRCC. All paraffin-embedded tumor sections were collected to make a set of tissue microarrays. CD15 expression was assessed by immunohistochemistry. The relationship between CD15 expression and survival parameters, clinicopathology features was assessed. Kaplan-Meier and Cox proportional hazards model were utilized to determine the correlation between CD15 expression and overall survival (OS). Results The median follow-up time was 54.6 months (range, 3-121 months). The positive rate of CD15 expression was 81.7% (246/301). The cut-off value of CD15 expression was defined as the maximum for Youden index by plotting the receiver operating characteristic curve for survival status. As the threshold was 0.5, all cases were divided into two groups: positive expression group and negative expression group. In correlation analysis, loss of CD15 expression was correlated with female gender, higher Fuhrman nuclear grade, with sarcomatoid differentiation, with necrosis, and with vascular invasion. Kaplan-Meier analysis indicated that the OS time of patients with loss of CD15 expression was shorter than that of patients with positive CD15 expression (P = 0.013). Conclusion CD15 is a significant prognostic factor in clear cell renal cell carcinoma.

Based on the principle of disc slitting process, a 3D model of the disc slitting process for galvanized sheet was established by using DEFORM-3D software, and the deformation, fracture and material effective stress of galvanized sheet were analyzed. The surface morphology of numerical simulation is in good agreement with the actual result. The curve of shearing force was obtained and well matched with the change rule of slitting process. Compared with the theoretical calculation result, the simulation result is reliable and can provide a reference for the calculation of shearing force.

Chemical reaction rate of SiC wafer surface usually determines the material removal rate (MRR) in chemical mechanical polishing (CMP). In this paper, systemic experiments are carried out to discover the relationship between Fe catalyst with different forms or valence and chemical reaction rate based on Fenton reaction. Experimental results show that the MRR changes little using Fe powder or hydrogen peroxide (H2O2) alone, but the MRR of SiC will increase largely by adding them both that will produce Fenton reaction. The MRR continues to increase slightly when Fe2+ ions is employ as catalyst, but that is much lower when utilizing Fe3+ ions. Moreover, SiC wafer with a smaller surface roughness and better quality can be obtained when using Fe powder as catalyst in Fenton reaction. The results indicate that the Fenton reaction can effectively improve the polishing efficiency of SiC substrate and Fe powder is more suitable for polishing of SiC than ferrous or ferric salt in CMP based on Fenton reaction.

This paper, taking the involute spur gear as a research object and using the LISP module embedded in AutoCAD, studies how to realize the drawing of two-dimensional graphics of the involute tooth profile and keyway of spur gear effectively and efficiently. The study, using the commands, such as stretch and Boolean operation of AutoCAD after programming, has realized the parametric modeling. By using this method, one can model them quickly, and lay the foundation of the assemble and analysis for the next step.

In recent years, floods and earthquakes occur frequently and cause great threats and harm to personal safety. On the basis of my patent named anti-seismic bed, which patent id is 200920287683.8, the flood control and anti-seismic bed is proposed. The anti-seismic bed doesn’t need external power supply and storage battery. When an earthquake occurs, the protection device starts and then an circular arch are formed by rotating protection boards. people are protected in bed body in 0.765s. When floods occur, flood protection airbag is filled with gas and launched by the Atmel89C52 microprocessor and YDE-WDT-P sensors. Bed body can float in the flood. Its functions are similar to the rescue boat and can protect human life’s safety.

As a new multifunctional material, strontium titanate (SrTiO3) ceramic has a wide application in grain boundary layer capacitor (GBLC) with the microstructure characteristics of semi-conductive crystalline grain and insulated boundary. An ultra-precision nanofishing technique is developed to lap and polish the brittle and thin SrTiO3 substrate with the cluster MR-effect plate where the abrasives are constrained by the cluster MR-effect chains, under the influence of a magnetic field, the carbonyl iron particles (CIPs) and non-magnetic abrasive particles remove material from the surface of workpiece being machined in this paper. Mahr XT20 roughmeter, Keyence VHX-600 and Olympus S4000 microscopes are used to investigate the characteristic of machined surface and the mechanism of material removal. An ultra-smooth planarization surface of SrTiO3 substrate with surface roughness Ra 3.8 nm (Mahr), RMS 0.973 nm (Veeco interferometer) is obtained under a high efficiency. It is found that the pore structures of the sintered substrate would weak the machinability of SrTiO3 and influence the further improvement of surface quality.

The growth of epitaxial layer of SiC wafer requires the surface of SiC substrate to reach an atomic scale accuracy. To solve the problems of low machining efficiency and low surface accuracy in the polishing process of SiC wafer, a novel ultra-precision machining method based on the synergistic effect of chemical reaction and flexible mechanical removal of the magnetorheological (MR) effect, the MR-chemical mechanical polishing (MRCMP) is proposed. In this technique, magnetic particles, abrasives and chemical additives are used as MR-chemical polishing fluid to form a cluster MR-effect flexible polishing platen under an applied magnetic field, and it is expected to realize an atomic scale ultra-smooth surface planarization with good controllability and high material removal rate by using the flexible polishing platen. Polishing experimental results of C surface of 6H-SiC crystal substrate indicate that an atomic scale zero-defect surface can be obtained. The surface roughness of C surface of SiC wafer decreased from 50.86nm to 0.42nm and the material removal rate was 98nm/min when SiC wafer was polished for 60 minutes.

In order to remove the cutting marks on the cutting surface of 6H-SiC single crystal wafer, experiments were conducted to investigate the effect of the abrasive characteristics (types, grain size, concentration and mixed abrasives) on the lapping performance of 6H-SiC single crystal wafer, then the removal mechanism of the abrasive grains in the lapping process was studied. Results indicate that the abrasives with larger grain size and higher hardness can result in a higher material removal rate while the abrasives with smaller grain size and lower hardness can achieve a lower surface roughness value. When the concentration of the abrasives is 7.69 wt%, a good lapping effect was obtained. Lower surface roughness value Ra can be obtained with a high material removal rate by using certain proportion mixed abrasives. Selecting appropriate abrasives can obtain a high surface quality of 6H-SiC wafer with a high efficiency.

Autophagy is an evolutionarily conserved process that involves lysosomal degradations of cellular organelles. Microtubule-associated protein 1 light chain 3A (LC3A), an autophagic gene, is differentially expressed in human cancers. However, the relationship between LC3A expression and hepatocellular carcinoma (HCC) has not been investigated. Tissue microarray-based immunohistochemistry was used to examine the expression patterns of LC3A in HCC. The resulting data were analyzed using receiver operating characteristic curves, Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression modeling. Two distinct patterns of LC3A expression were observed in HCC: "stone-like" structuring and diffuse cytoplasmic expression. High levels of LC3A expression were more frequently observed in HCC tissues compared to the adjacent non-tumorous tissue. Correlation analyses indicated that high expression of the "stone-like" LC3A was correlated with greater levels of serum AFP, poorer tumor differentiation and the presence of vascular invasion. Kaplan-Meier survival analysis showed a significant association between high expression of the "stone-like" LC3A and unfavorable prognosis (P0.001). Importantly, multivariate analysis (P0.05) identified the "stone-like" expression of LC3A in HCC as an independent prognostic factor. Collectively, our data provide compelling evidence that "stone-like" expression of LC3A plays an important role in HCC progression and may act as a biomarker of prognosis for patients with HCC.

A new planarization polishing method, based on the cluster magnetorheological (MR) effect and using MR fluid to form the flexible polishing pad, is presented in this paper to polish optical glass. To explore the machining characteristic of the viscid and flexible polishing pad based on the cluster MR-effect, some process experiments were conducted to reveal the influence of the machining gap, the speed of the polishing disc and the polishing time on the machining effect. The results indicate that the viscid and flexible polishing pad based on the cluster MR-effect under a strong magnetic field can reduce surface roughness effectively. When the strength of the magnetic field is 2000Gs, and the content of the carbonyl iron is 12%, the surface roughness can be reduced rapidly from the original Ra0.27μm to Ra1.4nm based on the cluster MR-effect.

Diffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. Although the International Prognostic Index (IPI) provides a clinical model for risk stratification of patients with DLBCL, notable variability in outcome is still observed within the same IPI category. Tumor-infiltrating macrophages (also called Tumor-associated macrophages) are the major component in the microenvironment of DLBCL. Their correlation with the prognosis of DLBCL remains controversial. Using a CD68 antibody in immunohistochemical analysis, we studied the expression of CD68 in 112 Chinese patients with DLBCL, with 65 patients (58%) categorized as low CD68 expression and 47 patients (42%) as high CD68 expression. The complete response (CR) rate of patients with low CD68 expression was higher than that with high CD68 expression (66.1% vs. 51.6%), but there was no statistical significance (P = 0.060). The median survival time of patients with low CD68 expression was not achieved and that of high expression was 41 months (P = 0.029). The results suggest that higher expression of CD68 tended to yield poor treatment outcome of DLBCL.

A new planarization grinding method based on the cluster magnetorheological (MR) effect is presented to grind optical glass in this paper. Some process experiments were conducted to reveal the influence of the speed of the grinding disc and grinding time and grinding pressure during the machining process. The results indicate that the speed of the grinding disc influences definitively on grinding effect of this planarization grinding method based on the cluster MR-effect. When the speed of the grinding disc is 110r/min, better machining effect can be achieved. Furthermore, the influence of the grinding time on machining effect is obviously, and the proper machining time is 6mins. However, under the experiment condition in this paper, the influence of grinding pressure on machining effect is unobvious.

Method of compound machining is used to process single crystal silicon and SrTiO3 ceramic substrates, and the factors on effects of compound machining are studied such as magnetic field intensity, processing time, rotating speed of lapping plate and lapping pressure. The results show that the roughness of work pieces processed by compound machining are smaller than that by lapping based on cluster MR effect and polyurethane pad polishing process, while the material removal rate is higher than polyurethane pad polishing process, therefore, compound machining shows its synergistic effect between lapping based on cluster MR effect and polyurethane pad polishing process. The type and properties of workpiece material, and machining parameters both have a significant impact on the roughness and material removal rate of compound machining process of polyurethane polishing pad and cluster abrasive brush based on MR effect.

Based on the electro-magneto-rheological (EMR) effect, the Fe3O4-based EMR fluid dispersed with micron-sized finishing abrasives is used as a polishing fluid to form a dynamical tiny-grinding wheel under an electro-magnetically coupled field. Using this EMR-effect-based tiny-grinding wheel, experiments were conducted to investigate the effect of the grain size, content and material of abrasive on material removal effect of normal glass. Results indicate that the abrasive can change the chain-like structure of the EMR-effect-based tiny-grinding wheel and influence the material removal ability of the tiny-grinding wheel remarkably. The material removal amount increases with the increase of the content of diamond abrasive in the EMR fluid, and grows slowly when the proportion of diamond abrasive exceeds to 6%. While the grain size of abrasive increases, the material removal amount increases at the beginning and decreases afterwards. The effect of abrasive on material removal depends on the hardness of abrasive, the greater the abrasive hardness, the higher the material removal efficiency. The machined area has a close relationship with both the density and grain size of abrasive.

A new planarization polishing method based on the cluster magnetorheological (MR) effect is presented to polish optical glass in this paper. Some process experiments were conducted to reveal the influence of the content of carbonyl iron and the abrasive materials in the MR fluid on the machining effect, and the machining characteristic of polished surface was studied. The results indicate that the surface roughness of the polished workpiece can be reduced rapidly when the strong magnetic field is applied, and ultra smooth surface with Ra 1.4 nm can be achieved while the CeO2 abrasives are used in the MR fluid. The content of carbonyl iron obviously influences the machining effect of this planarization polishing method based on cluster MR-effect. With the increase of the content of carbonyl iron in the MR fluid, the material removal rate improves and the surface roughness reduces rapidly. However, the difference of abrasive material results in various machining effects. As for the K9 optical glass, the CeO2 abrasive is better polishing abrasive than the SiC abrasive in the planarization polishing technique based on the cluster MR-effect.