A bioinspired tactile scanner for computer haptics.

Computer haptics (CH) is about integration of tactile sensation and rendering in Metaverse. However, unlike computer vision (CV) where both hardware infrastructure and software programs are well developed, a generic tactile data capturing device that serves the same role as what a camera does for CV, is missing. Bioinspired by electrophysiological processes in human tactile somatosensory nervous system, here we propose a tactile scanner along with a neuromorphically-engineered system, in which a closed-loop tactile acquisition and rendering (re-creation) are preliminarily achieved. Based on the architecture of afferent nerves and intelligent functions of mechano-gating and leaky integrate-and-fire models, such a tactile scanner is designed and developed by using piezoelectric transducers as axon neurons and thin film transistor (TFT)-based neuromorphic circuits to mimic synaptic behaviours and neural functions. As an example, the neuron-like tactile information of surface textures is captured and further used to render the texture friction of a virtual surface for "recreating" a "true" feeling of touch.

Emotion Recognition From Multimodal Physiological Signals via Discriminative Correlation Fusion With a Temporal Alignment Mechanism.

Modeling correlations between multimodal physiological signals [e.g., canonical correlation analysis (CCA)] for emotion recognition has attracted much attention. However, existing studies rarely consider the neural nature of emotional responses within physiological signals. Furthermore, during fusion space construction, the CCA method maximizes only the correlations between different modalities and neglects the discriminative information of different emotional states. Most importantly, temporal mismatches between different neural activities are often ignored; therefore, the theoretical assumptions that multimodal data should be aligned in time and space before fusion are not fulfilled. To address these issues, we propose a discriminative correlation fusion method coupled with a temporal alignment mechanism for multimodal physiological signals. We first use neural signal analysis techniques to construct neural representations of the central nervous system (CNS) and autonomic nervous system (ANS). respectively. Then, emotion class labels are introduced in CCA to obtain more discriminative fusion representations from multimodal neural responses, and the temporal alignment between the CNS and ANS is jointly optimized with a fusion procedure that applies the Bayesian algorithm. The experimental results demonstrate that our method significantly improves the emotion recognition performance. Additionally, we show that this fusion method can model the underlying mechanisms in human nervous systems during emotional responses, and our results are consistent with prior findings. This study may guide a new approach for exploring human cognitive function based on physiological signals at different time scales and promote the development of computational intelligence and harmonious human-computer interactions.

Comprehensive survival nomograms for locally advanced gastric cancer: a large population-based real-world study.

Background: This study aimed to construct and verify nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for locally advanced gastric cancer (LAGC) based on a therapeutic selection, demographic factors, and pathological features. Methods: The data used for the analysis were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed based on the Cox regression model. Results: The entire cohort comprised 21,757 patients with histologically confirmed LAGC, and was randomly distributed into training and verification groups at a ratio of 2:1 for building the prognostic predictive model. According to the multivariate analysis, 13 variables [i.e., age, marital status, race, tumor location, pathological grade, histological type, T and N stage, surgery, radiotherapy, chemotherapy, tumor size, and regional nodes examined (RNE)] were confirmed as independent predictors for both OS and CSS. All of the significant variables were used to create the nomograms for OS and CSS. Time-dependent receiver operating characteristic (ROC) curves, a decision curve analysis (DCA), the C-index, and calibration curves were applied to identify the discriminating superiority of the nomograms. Conclusions: The nomograms for OS and CSS in LAGC were built and validated based on the therapeutic selection and pathological and demographic variables using a national database. This study aims at helping clinicians make better clinical decisions and encouraging patients receive treatment actively.

CD142 promotes trophoblast cell migration by inhibiting BCL2-related autophagic degradation of IL-8.

The maintenance of migration of trophoblast cells is beneficial to pregnancy, and its weakening can lead to preeclampsia (PE). CD142 is considered as a classical motility-promoting factor. Our research aimed to explore the role of CD142 in trophoblast cell migration and potential mechanism. Through fluorescence-activated cell sorting (FACS) and gene transduction assays, CD142 expression levels of mouse trophoblast cell lines were upregulated and downregulated respectively. Then, the migratory level was detected through Transwell assays in different groups of trophoblast cells. The corresponding chemokines were screened by ELISA in different sorted trophoblast cells. Based on gene overexpression and knockdown assays, the production mode of identified valuable chemokine was analyzed by detecting gene and protein expression in trophoblast cells. Finally, the contribution of autophagy response to specific chemokine regulated by CD142 was explored by combining different groups of cells and autophagy regulators. Our results showed that both CD142 positive sorting and CD142 overexpression promoted the migratory ability of trophoblast cells, and trophoblast cells with the highest level of CD142 had the strongest migratory ability. In addition, CD142+ cells contained the highest level of IL-8. Consistently, CD142 overexpression promoted IL-8 protein expression in trophoblast cells while CD142 silencing was contrary. However, both CD142 overexpression and CD142 silencing did not affect IL-8 mRNA expression. Moreover, both CD142+ and CD142-overexpressed cells showed higher BCL2 protein expression and poorer autophagic activity. Importantly, autophagy activation with TAT-Beclin1 recovered the increased IL-8 protein expression in CD142+ cells. Obviously, the migratory ability of CD142+ cells inhibited by TAT-Beclin1 was recovered by the addition of IL-8 recombinant factor. In conclusion, CD142 inhibits the degradation of IL-8 through the inhibition of BCL2-Beclin1-autophagy signal transduction, thereby promoting the migration of trophoblast cells.

The new 'coN' staging system combining lymph node metastasis and tumour deposit provides a more accurate prognosis for TNM stage III colon cancer.

OBJECTIVE: Despite controversy over its origin and definition, the significance of tumour deposit (TD) has been underestimated in the tumour node metastasis (TNM) staging system for colon cancer, especially in stage III patients. We aimed to further confirm the prognostic value of TD in stage III colon cancer and to establish a more accurate 'coN' staging system combining TD and lymph node metastasis (LNM). METHODS: Information on stage III colon cancer patients with a definite TD status was retrospectively collected from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. The effect of TD on prognosis was estimated using Cox regression analysis. Maximally selected rank statistics were used to select the optimal cut-off value of TD counts. The predictive power of conventional N staging and the new coN staging was evaluated and compared by Akaike's information criterion (AIC), Harrell's concordance index (C-index) and time-dependent receiver operating characteristic (ROC) curves. Clinicopathological data of stage III colon cancer patients in the Xiangya database from 2014 to 2018 were collected to validate the coN staging system. RESULTS: A total of 39,185 patients with stage III colon cancer were included in our study: 38,446 in the SEER cohort and 739 in the Xiangya cohort. The incidence of TD in stage III colon cancer was approximately 30% (26% in SEER and 30% in the Xiangya database). TD was significantly associated with poorer overall survival (OS) (HR = 1.37, 95% CI 1.31-1.44, p < 0.001 in SEER). The optimal cut-off value of TD counts was 4, and the patients were classified into the TD0 (count = 0), TD1 (count = 1-3) and TD2 (count ≥ 4) groups accordingly. The estimated 5-year OS was significantly different among the three groups (69.4%, 95% CI 68.8%-70.0% in TD0; 60.5%, 95% CI 58.9%-62.2% in TD1 and 42.6%, 95% CI 39.2%-46.4% in TD2, respectively, p < 0.001). The coN system integrating LNM and TD was established, and patients with stage III colon cancer were reclassified into five subgroups (coN1a, coN1b, coN2a, coN2b and coN2c). Compared with conventional N staging, the coN staging Cox model had a smaller AIC (197097.581 vs. 197358.006) and a larger C-index (0.611 vs. 0.601). The AUCs of coN staging at 3, 5 and 7 years were also greater than those of conventional N staging (0.6305, 0.6326, 0.6314 vs. 0.6186, 0.6197, 0.6160). Concomitant with the SEER cohort results, the coN staging Cox model of the Xiangya cohort also had a smaller AIC (2883.856 vs. 2906.741) and a larger C-index (0.669 vs. 0.633). Greater AUCs at 3, 5 and 7 years for coN staging were also observed in the Xiangya cohort (0.6983, 0.6774, 0.6502 vs. 0.6512, 0.6368, 0.6199). CONCLUSIONS: Not only the presence but also the number of TDs is associated with poor prognosis in stage III colon cancer. A combined N staging system integrating LNM and TD provides more accurate prognostic prediction than the latest AJCC N staging in stage III colon cancer.

EPSTI1 as an immune biomarker predicts the prognosis of patients with stage III colon cancer.

Objective: The poor prognosis and heterogeneity of stage III colon cancer (CC) suggest the need for more prognostic biomarkers. The tumor microenvironment (TME) plays a crucial role in tumor progression. We aimed to explore novel immune infiltration-associated molecules that serve as potential prognostic and therapeutic targets. Methods: TME immune scores were calculated using "TMEscore" algorithm. Differentially expressed genes between the high and low TME immune score groups were identified and further investigated through a protein-protein interaction network and the Molecular Complex Detection algorithm. Cox regression, meta-analysis and immunohistochemistry were applied to identify genes significantly correlated with relapse-free survival (RFS). We estimated immune infiltration using three different algorithms (TIMER 2.0, CIBERSORTx, and TIDE). Single-cell sequencing data were processed by Seurat software. Results: Poor RFS was observed in the low TME immune score groups (log-rank P < 0.05). EPSTI1 was demonstrated to be significantly correlated with RFS (P < 0.05) in stage III CC. Meta-analysis comprising 547 patients revealed that EPSTI1 was a protective factor (HR = 0.79, 95% CI, 0.65-0. 96; P < 0.05)). More immune infiltrates were observed in the high EPSTI1 group, especially M1 macrophage and myeloid dendritic cell infiltration (P < 0.05). Conclusion: The TME immune score is positively associated with better survival outcomes. EPSTI1 could serve as a novel immune prognostic biomarker for stage III CC.

Prognostic factors and individualized nomograms predicting overall survival in stage IV rectal cancer patients with different metastatic status: a SEER-based study.

Background: The prognosis of rectal cancer patients with different metastatic status was significantly different. Our aim was to identify prognostic factors for metastatic rectal cancer (mRC) patients with different metastatic status and to construct specific nomograms to predict overall survival (OS). Methods: This study retrospectively analyzed mRC patients from 2010 to 2016 in the Surveillance, Epidemiology, and End Results Program database. All patients were ultimately divided into four groups: synchronous liver metastasis, synchronous lung metastasis, synchronous other organs metastasis and synchronous multiple metastases. Univariate and multivariate cox analyses were performed to screen out independent factors for each group. Individualized nomograms were constructed in different metastatic modes. The concordance index (C-index), decision curve analysis (DCA), time-dependent receiver operating characteristic (ROC) curve and calibration curve were performed to verify these nomograms. Results: Finally, 10,407 mRC patients were included in this study. Age, tumor grade, surgery of primary tumor, and chemotherapy were identified as common independent prognostic factors for each subgroup (all P<0.05). Other independent prognostic factors specific to each group included radiotherapy and marital status in the liver metastasis group, race, N stage, and the presence or absence of site-specific metastases in the multiple metastases group (all P<0.05). Higher T staging suggested worse OS in the group with liver, lung, and multiple site metastases. Individualized nomograms predicting 1-, 2-, and 3-year OS for each group were constructed by combining all independently significant risk factors in each group. The area under the curve (AUC) values and C-indexes of these nomograms created by each subgroup were greater than 0.7. All calibration curves and DCA curves showed that these nomograms had good clinical application significance. Conclusions: Individualized prognostic nomograms were constructed for mRC patients with different metastatic status based on different prognostic factors. These nomograms presented satisfactory predictive effects, which helps to provide survival assessment and individualized treatment decision-making for mRC patients with different metastatic status.

m6A Methyltransferase KIAA1429 Regulates the Cisplatin Sensitivity of Gastric Cancer Cells via Stabilizing FOXM1 mRNA.

Although cisplatin is frequently used to treat gastric cancer, the resistance is the main obstacle for effective treatment. mRNA modification, N6-methyladenosine (m6A), is involved in the tumorigenesis of many types of cancer. As one of the largest m6A methyltransferase complex components, KIAA1429 bridges the catalytic m6A methyltransferase components, such as METTL3. In gastric cancer, KIAA1429 was reported to promote cell proliferation. However, whether KIAA1429 is involved in the resistance of gastric cancer to cisplatin remains unclear. Here, we generated cisplatin resistant gastric cancer cell lines, and compared the m6A content between resistant cells and wild type cells. The m6A content as well as KIAA1429 expression are higher in resistant cells. Interestingly, the expression of KIAA1429 was significantly increased after cisplatin treatment. We then used shRNA to knockdown KIAA1429 and found that resistant cells responded more to cisplatin treatment after KIAA1429 depletion, while overexpression of KIAA1429 decreased the sensitivity. Moreover, we identified a putative p65 binding site on the promoter area of KIAA1429 and ChIP assay confirmed the binding. p65 depletion decreased the expression of KIAA1429. YTHDF1 is the most abundant m6A "reader" that interacts with m6A modified mRNA. Mechanistically, YTHDF1 was recruited to the 3'-untranslated Region (3'-UTR) of transcriptional factor, FOXM1 by KIAA1429 and stabilized FOXM1 mRNA. More importantly, KIAA1429 knockdown increased the sensitivity of resistant cells to cisplatin in vivo. In conclusion, our results demonstrated that KIAA1429 facilitated cisplatin resistance by stabilizing FOXM1 mRNA in gastric cancer cells.

Survival effects of primary and metastatic surgical treatment in metastatic small intestinal tumors: A propensity score-matching study.

OBJECTIVE: To analyze the effects of primary tumor resection and metastatic lesion resection on the survival of metastatic small intestinal tumors. METHODS: The research subjects were patients with metastatic small bowel tumors identified from 2004 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching and Kaplan-Meier analyses were performed to analyze the effect of surgery on the prognosis. RESULTS: A total of 4,034 patients from the SEER database were analyzed. Both before and after the propensity score-matching analysis, the prognosis of patients who underwent primary tumor surgery and metastatic surgery was better than that of patients who did not undergo surgery; all were patients with metastatic small bowel adenocarcinoma (mSIA) or metastatic small intestinal neuroendocrine tumors (mSI-NETs) (all p < .005). Patients with mSIA and adequate lymph node dissection had a longer prognosis than mSIA patients with inadequate lymph node dissection, but this survival benefit was not present in mSI-NET patients. It made no difference in the prognosis of mSIA and mSI-NETs whether localized surgery or intestine-ectomy was performed. Patients with mSIA who underwent primary and metastatic excision plus chemotherapy had the best overall survival and cancer-specific survival rates, whereas mSI-NET patients who underwent primary and metastatic excision had the best overall survival and cancer-specific survival rates (all p < .001). CONCLUSION: In these carefully selected patients, primary tumor resection and/or metastatic lesion resection significantly improved the survival rates for patients with mSIA and mSI-NETs. The mSIA patients with resectable primary tumors seemed to require a sufficient number of lymph node dissections more than the patients with well-differentiated mSI-NETs.

The survival impact of radiotherapy on synchronous metastatic rectal cancer: metastatic site can serve for radiotherapy-decision.

Purpose: The metastatic site seems to represent a malignancy with a different biological characteristic. Radiotherapy, as a successful, well-tolerated, cost-effective and time-efficient intervention, is able to provide clear benefits for the treatment of locally advanced rectal cancer and has become an essential component of palliative oncology care. The real-world effect of radiotherapy on the survival outcomes of metastatic rectal cancer (mRC) patients might do exist and was worth exploring. Patients and methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database in this retrospective analysis. The statistical methods included Pearson's chi-square test, Log-rank test, Cox regression model and propensity score matching (PSM). Results: The multivariable Cox regression displayed that radiotherapy may not be used as a prognostic factor for mRC (p=0.057). However, radiotherapy may be associated with the prognosis if the metastatic site was excluded from the multivariate analysis (p<0.001). Radiotherapy seemed to fail to improve OS before PSM (p<0.001) and after PSM without the metastatic site as a matching factor (p<0.001). Nevertheless, there was no significant survival difference between radiotherapy and non-radiotherapy cohort after PSM with the metastatic site as a matching factor (p=0.057). All of M1a rectal cancer patients appear to obtain survival benefit from radiotherapy without the impact of PSM (p<0.001). Notwithstanding, radiotherapy was associated with improved OS of patients with rectal liver-limited metastasis (p=0.023) and did not appear to provide survival benefit for rectal lung-limited (p=0.386) and other-limited metastasis (p=0.385). Both of M1b mRC with and without liver metastasis did not seem to obtain survival benefit from radiotherapy. Conclusions: Carefully selected data from the SEER database suggested that radiotherapy appears to improve overall survival only in patients with rectal liver-limited metastasis.

A thrombin-triggered self-regulating anticoagulant strategy combined with anti-inflammatory capacity for blood-contacting implants.

Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the long-term function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings.

A novel surgical technique of internal limiting membrane peeling for high myopic foveoschisis: a wide range of whole piece consecutive peeling without preservation of epi-fovea.

AIM: To demonstrate an improved surgical technique of whole piece consecutive internal limiting membrane (ILM) peeling without preservation of the epi-fovea to treat high myopic foveoschisis (MF). METHODS: A 23-gauge 3-port pars plana vitrectomy was performed on 16 patients with high MF. A parallel arc line along the vascular arcades was scraped out with a curved membrane scraper DSP. Next, an ILM forceps was used to catch hold of the incisal edge of the ILM flap, and the action of releasing and separating was subsequently taken toward the direction of the macular fovea. Next, the ILM forceps was used to grasp the released area, and the whole area coherent ILM peeling covering the macular fovea was implemented thereafter. Finally, the ILM was folded backwards and peeled off in the arc direction. RESULTS: At the final visit, the average central macular thickness decreased remarkably from 423.76±177.67 to 178.24±66.21 µm. The mean logarithm of the minimum angle of resolution best-corrected visual acuity of 1.37±0.59 was significantly alleviated to 0.74±0.59. CONCLUSION: The wide range of whole piece consecutive ILM peeling without preservation of the epi-fovea is proven to be effective and significantly reduced the occurrence of retinal tear and macular hole.

Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy.

Atherosclerosis, the principle cause of cardiovascular disease (CVD) worldwide, is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Atherogenesis is associated with the upregulation of CD47, a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or "efferocytosis." Here, we have developed platelet membrane-coated mesoporous silicon nanoparticles (PMSN) as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody. Briefly, the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an affinity to plaques and atherosclerotic sites. The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47. In an atherosclerosis model established in ApoE-/- mice, PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques. Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis. Overall, this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy, which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis.

m6A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m6A-dependent manner.

N6-methyladenosine (m6A) modifications of RNAs are involved in various aspects of colorectal carcinogenesis via regulation of mRNA stability, splicing, and translation. KIAA1429, an m6A methyltransferase, was found deregulated in multiple cancer types. However, its role in colorectal cancer remains elusive. By analyzing TCGA and GEPIA database, we found that KIAA1429 in colorectal cancer was highly expressed. In addition, we used immunohistochemistry, western blotting, and QRT-PCR to detect the expression of KIAA1429 in colorectal cancer samples and cell lines, and we found that KIAA1429 was overexpressed in colorectal cancer sample and cell line. Functionally, silencing of KIAA1429 by shRNA in colorectal cancer cell lines resulted in decreased cell proliferation, colony formation, and migration. On the contrary, overexpression of KIAA1429 increased cell proliferation, colony formation, and migration. Further mechanism analysis demonstrated that KIAA1429 increased the expression of SIRT1 via regulating its mRNA stability in an m6A-dependent manner. More importantly, in vivo experiment showed that depletion of KIAA1429 significantly inhibited colorectal tumor growth. In conclusion, our results suggested that the m6A methyltransferase KIAA1429 promotes the growth and motility of colorectal cancer and could be a potent therapeutic target.

The survival impact of palliative radiotherapy on synchronous metastatic pancreatic ductal adenocarcinoma: metastatic site can serve for radiotherapy-decision.

Background: The metastatic site seems to represent a malignancy with a different biological characteristic and is an important prognostic factor in metastatic pancreatic ductal adenocarcinoma (mPDAC). Palliative radiotherapy is a therapeutic option, and usually used for pain management in the treatment of mPDAC. The real-world effect of radiotherapy on the survival outcomes of mPDAC patients might do exist and is worth exploring. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) was extracted to identify mPDAC diagnosed in the periods of 2010-2016. The statistical methods included Pearson's chi-square test, Log-rank test, Cox regression model and propensity score matching (PSM). Results: Radiotherapy was able to improve the overall survival of PDAC with liver metastasis (p<0.001), but not for PDAC patients with lung (p=0.130), bone (p=0.451) and brain metastasis (p=0.226) before PSM. Radiotherapy can only a prognostic factor for PDAC liver metastasis (p=0.001) in the cox regression analysis. The survival curves provided consistent results with cox regression analysis (PDAC with liver metastasis: p=0.023, PDAC with lung metastasis: p=0.528, PDAC with bone metastasis: p=0.210, PDAC with brain metastasis: p=0.106) after PSM. We continue to divided PDAC liver patients into PDAC-liver-metastasis with and without lung, bone, and/or brain (LBB) metastasis. Finally, radiotherapy can be used as a feasible treatment to prolong the overall survival of patients with PDAC liver metastasis without LBB metastasis. Conclusions: Radiotherapy can be used as a feasible treatment to prolong the overall survival of patients with PDAC liver metastasis without LBB metastasis.

Web-Based Dynamic Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Breast Cancer Patients with Lung Metastases.

BACKGROUND: 60-70% of patients who die from breast cancer have lung metastases. However, there is a lack of readily available tools for accurate risk stratification in patients with breast cancer lung metastases (BCLM). Therefore, a web-based dynamic nomogram was developed for BCLM to quickly, accurately, and intuitively assess overall and cancer-specific survival rates. METHODS: Patients diagnosed with BCLM between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and Final Results (SEER) database. After excluding incomplete data, all patients were randomly assigned to training and validation cohorts (2:1). Patients' basic clinical information, detailed pathological staging and treatment information, and sociological information were included in further analysis. Nomograms were constructed following the evaluations of the Cox regression model and verified using the concordance index (C-index), calibration curves, time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Web-based dynamic nomograms were published online. RESULTS: 3916 breast cancer patients with lung metastases were identified from the SEER database. Based on multivariate Cox regression analysis, overall survival (OS) and cancer-specific survival (CSS) are significantly correlated with 13 variables: age, marital status, race, grade, T stage, surgery, chemotherapy, bone metastatic, brain metastatic, liver metastatic, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). These are included in the construction of the nomogram of OS and CSS. The time-dependent receiver operating characteristic curve, decision curve analysis, consistency index, and calibration curve prove the distinct advantages of the nomogram. CONCLUSIONS: Our web-based dynamic nomogram effectively integrates patient molecular subtype and sociodemographic characteristics with clinical characteristics and guidance and can be easily used. ER-Negative should receive attention in diagnosing and treating BCLM.

Chemotherapy exacerbates the survival paradox of colon cancer: a propensity score matching analysis.

Background: Colon cancer is one of the most common tumor diseases in the world. Currently, clinicians usually evaluate the survival and prognosis of patients according to their tumor-node-metastasis (TNM) stage. However, current studies have found that there is a certain survival paradox in TNM staging. Methods: In the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with colon cancer by surgical pathology from 2004 to 2011 were selected for analysis of 5-year overall survival (OS). Propensity score matching (PSM) was performed to analyze the difference in survival between different stages and the effect of chemotherapy on prognosis. Results: The OS of stage IIIA colon cancer sufferers was significantly superior to stage IIB/IIC and separate stage IIB or IIC colon cancer patients before and after PSM analysis (P<0.05 for all). Moreover, the difference in survival was more significant when stage IIB/IIC patients were compared with stage IIIA patients with chemotherapy. Conclusions: The survival paradox existed both in all stage IIB/IIC patients, or individual stage IIB or IIC patients compared with stage IIIA sufferers, and the survival paradox between stage IIIA and stage IIC was more obvious. Moreover, chemotherapy had a positive effect on the prognosis of patients with stage IIIA, IIC and IIB in this study. Chemotherapy exacerbates the survival paradox of colon cancer, even if it is not the cause of the survival paradox.

The Survival Effect of Radiotherapy on Stage II/III Rectal Cancer in Different Age Groups: Formulating Radiotherapy Decision-Making Based on Age.

INTRODUCTION: Total mesorectal excision (TME), chemotherapy (CT), and radiotherapy (RT) are usually integrated into the comprehensive treatment of stage II/III rectal cancer (RC). Neoadjuvant radiotherapy (nRT) has become the standard treatment for stage II/III RC patients to help reduce the size of a tumor or kill cancer cells that have spread. Adjuvant RT is delivered after the resection to destroy remaining cancer cells and used mainly in stage II/III RC patients who have not received preoperative radiotherapy, such as those who suffered from a bowel obstruction before surgery. It is controversial whether radiotherapy can improve the survival of stage II/III RC patients. An increasing number of studies have reported that rectal cancer exhibited mismatched biology, epidemiology, and therapeutic response to current treatment strategy in different age groups. It is necessary to investigate whether radiotherapy exhibits disparate effects in different age groups of patients with stage II/III RC. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) Program was extracted to identify stage II/III RC diagnosed in the periods of 2004-2016. The statistical methods included Pearson's chi-square test, log-rank test, Cox regression model, and propensity score matching. RESULTS: Neoadjuvant radiotherapy (nRT) cannot improve the prognosis, and postoperative RT may even reduce the survival time for early onset stage II/III RC. Postoperative RT was not able to improve the overall survival (OS), while nRT may provide limited survival improvement for middle-aged stage II/III RC patients. In addition, radiotherapy can significantly improve the prognosis for elderly stage II/III RC. CONCLUSIONS: This study indicated the inconsistent survival effect of radiotherapy on stage II/III rectal cancer patients in different age groups. Hence, we formulated a novel flow chart of radiotherapy decision-making based on age in stage II/III RC patients.

Follistatin-Like 3 Enhances Invasion and Metastasis via ß-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer.

Previous studies reported that Follistatin-like 3 (FSTL3) is abundantly expressed in several solid tumors and participate in the regulation of cell metabolism. However, the clinico-pathological significance, biological role and molecular mechanism of FSTL3 in colorectal cancer (CRC) is still unclear. Here we report that the expression level of FSTL3 in colon cancer specimens was significantly higher, compared to normal tissue and interestingly, the expression of FSTL3 was related to lymph node metastasis, tumor stage, tumor size, and intravascular emboli (IVE). As an upstream molecular event, we found that transcriptional regulation of FSTL3 was highly dependent on YAP1 de-phosphorylation events and that increased FSTL3 expression readily activated the ß-Catenin pathway, which is a well-known signaling hub that promotes EMT processes and aerobic glycolysis in cancer cells. We found that elevated FSTL3 expression strongly promotes migration, invasion and metastatic formation of CRC cells by directly activating ß-Catenin -mediated EMT and aerobic glycolysis. In the xenograft mouse model, FSTL3 expression was linked to increased metastatic formation of CRC cells. Together, the activation of YAP1 induces FSTL3 expression. FSTL3-mediated ß-Catenin pathway activation promotes EMT and aerobic glycolysis and therefore affecting the invasive and metastatic capacity of CRC cells. The abundant FSTL3 expression is a poor prognostic factor and pharmacological targeting of YAP1 can counteract FSTL3 expression, suggesting a promising therapeutic target for anti-metastatic strategies in patients suffering from CRC.