Repetition rate tuning and locking of solitons in a microrod resonator.

Recently, there has been significant interest in the generation of coherent temporal solitons in optical microresonators. In this Letter, we present a demonstration of dissipative Kerr soliton generation in a microrod resonator using an auxiliary-laser-assisted thermal response control method. In addition, we are able to control the repetition rate of the soliton over a range of 200 kHz while maintaining the pump laser frequency, by applying external stress tuning. Through the precise control of the PZT voltage, we achieve a stability level of 3.9 × 10-10 for residual fluctuation of the repetition rate when averaged 1 s. Our platform offers precise tuning and locking capabilities for the repetition frequency of coherent mode-locked combs in microresonators. This advancement holds great potential for applications in spectroscopy and precision measurements.

Bone metastasis is a late-onset and unfavorable event in survivors of gastric cancer after radical gastrectomy: Results from a clinical observational cohort.

Background: The timing and incidence of recurrent bone metastasis (BM) after radical gastrectomy in patients with gastric cancer (GC) as well as the survival of these patients were not fully understood. The aim of this study was to analyze the data of an observational GC cohort and identify patients who underwent curative gastrectomy and had recurrent BM to describe and clarify the pattern and profile of BM evolution after surgery. Methods: Data were retrieved from a hospital-based GC cohort, and patients who underwent upfront radical gastrectomy were selected. The time points of specific organ metastatic events were recorded, and the person-year incidence rate of metastatic events was calculated. The latency period of BM events after gastrectomy was measured and compared with that of the other two most common metastatic events, liver metastasis (LM) and distant lymph node metastasis (LNM), using analysis of variance. Propensity score matching and subgroup analysis were used for sensitivity analysis. Results: A total of 1324 GC cases underwent radical gastrectomy between January 2011 and December 2021. Of these, 67 BM, 218 LM, and 248 LNM occurred before the last follow-up. The incidence of BM events was 1.7/100 person-years, which was approximately 3-fold lower than that of LM and distant LNM events (5.5 and 6.3 per 100 person-years, respectively). BM events had a significantly longer latency (median time, 16.5 months) than LM and LNM events (11.1 and 12.0 months, respectively). Recurrent BM led to a worse prognosis (median survival, 4.5 months) than those of LM and LNM events (median survival, 7.7 and 7.1 months, respectively). However, no difference in overall survival after gastrectomy was observed among the groups. Conclusions: Compared with other common metastatic events, BM in GC after gastrectomy is a late-onset event indicating poor survival. Trial registration: No. ChiCTR1800019978; http://www.chictr.org.cn/.

Prediction of common labels for universal domain adaptation.

Universal domain adaptation (UniDA) is an unsupervised domain adaptation that selectively transfers the knowledge between different domains containing different label sets. However, the existing methods do not predict the common labels of different domains and manually set a threshold to discriminate private samples, so they rely on the target domain to finely select the threshold and ignore the problem of negative transfer. In this paper, to address the above problems, we propose a novel classification model named Prediction of Common Labels (PCL) for UniDA, in which the common labels are predicted by Category Separation via Clustering (CSC). It is noted that we devise a new evaluation metric called category separation accuracy to measure the performance of category separation. To weaken negative transfer, we select source samples by the predicted common labels to fine-tune model for better domain alignment. In the test process, the target samples are discriminated by the predicted common labels and the results of clustering. Experimental results on three widely used benchmark datasets indicate the effectiveness of the proposed method.

Incorporation of liver chemistry score in predicting survival of liver-involved advanced gastric cancer patients who received palliative chemotherapy.

BACKGROUND: Gastric cancer liver metastasis (GCLM) patients usually accompany by abnormal serum liver function tests (LFTs) more or less; however, the prognostic value of LFTs is not fully understood. This study aimed to develop a liver chemistry score (LCS) based on LFTs and incorporate it into prognosis determination for GCLM patients who received palliative chemotherapy. METHODS: Data were derived from hospitalized GCLM patients in two general hospitals in China. LCS was generated based on the results of LFTs by LASSO regression. Cutoff value of the score was determined by restricted cubic spline. The score was then incorporated into Cox regression analysis to construct a predictive nomogram; the model was then evaluated internally and externally by AUC of time-dependent receiver operating characteristic curves (ROC) and calibration curves. RESULTS: Three hundred and thirty-six and 72 patients were included in development and validation cohort, respectively. LASSO regression analysis in development cohort finally reached a two-parametric LCS calculated on AST and ALP levels as 0.03343515 × ln (AST, U/L) + 0.02687997 × ln (ALP, U/L), and 0.232 was set as optimal cutoff value. Patients in low (LCS < 0.232) or high (LCS ≥ 0.232) score group experienced different survival times; median OS was 13.54 (95% CI: 11.1-15.6) months in the low LCS group and 7.3 (6.6-9.3) months in the high LCS group (p < 0.001). A nomogram including LCS and other clinical parameters was constructed and showed superior performance than model not including LCS. AUC of 6-month ROC improved from 0.647 (95% CI: 0.584-0.711) to 0.699 (0.638-0.759) in internal validation, and 0.837 (0.734-0.940) to 0.875 (0.784-0.966) in external validation. CONCLUSIONS: Liver chemistry score is useful in determining the prognosis of gastric cancer patients with liver metastasis and may be helpful to clinicians in decision-making.

Machine learning models for predicting one-year survival in patients with metastatic gastric cancer who experienced upfront radical gastrectomy.

Tumor metastasis is a common event in patients with gastric cancer (GC) who previously underwent curative gastrectomy. It is meaningful to employ high-volume clinical data for predicting the survival of metastatic GC patients. We aim to establish an improved machine learning (ML) classifier for predicting if a patient with metastatic GC would die within 12 months. Eligible patients were enrolled from a Chinese GC cohort, and the complete detailed information from medical records was extracted to generate a high-dimensional dataset. Appropriate feature engineering and feature filter were conducted before modeling with eight algorithms. A 10-fold cross validation (CV) nested in a holdout CV (8:2) was employed for hyperparameter tuning and model evaluation. Model selection was based on the area under the receiver operating characteristic (AUROC) curve, recall, and precision. The selected model was globally explained using interpretable surrogate models. Of the total 399 cases (median survival of 8.2 months), 242 patients survived less than 12 months. The linear discriminant analysis (LDA), support vector machine (SVM), and random forest (RF) model had the highest AUROC (0.78 ± 0.021), recall (0.93 ± 0.031), and precision (0.80 ± 0.026), respectively. The LDA model created a new function that generally separated the two classes. The predicted probability of the SVM model was interpreted using a linear regression model visualized by a nomogram. The predicted class of the RF model was explained using a decision tree model. In summary, analyzing high-volume medical data by ML is helpful to produce an improved model for predicting the survival in patients with metastatic GC. The algorithm should be carefully selected in different practical scenarios.

Determination of Survival of Gastric Cancer Patients With Distant Lymph Node Metastasis Using Prealbumin Level and Prothrombin Time: Contour Plots Based on Random Survival Forest Algorithm on High-Dimensionality Clinical and Laboratory Datasets.

PURPOSE: This study aimed to identify prognostic factors for patients with distant lymph node-involved gastric cancer (GC) using a machine learning algorithm, a method that offers considerable advantages and new prospects for high-dimensional biomedical data exploration. MATERIALS AND METHODS: This study employed 79 features of clinical pathology, laboratory tests, and therapeutic details from 289 GC patients whose distant lymphadenopathy was presented as the first episode of recurrence or metastasis. Outcomes were measured as any-cause death events and survival months after distant lymph node metastasis. A prediction model was built based on possible outcome predictors using a random survival forest algorithm and confirmed by 5×5 nested cross-validation. The effects of single variables were interpreted using partial dependence plots. A contour plot was used to visually represent survival prediction based on 2 predictive features. RESULTS: The median survival time of patients with GC with distant nodal metastasis was 9.2 months. The optimal model incorporated the prealbumin level and the prothrombin time (PT), and yielded a prediction error of 0.353. The inclusion of other variables resulted in poorer model performance. Patients with higher serum prealbumin levels or shorter PTs had a significantly better prognosis. The predicted one-year survival rate was stratified and illustrated as a contour plot based on the combined effect the prealbumin level and the PT. CONCLUSIONS: Machine learning is useful for identifying the important determinants of cancer survival using high-dimensional datasets. The prealbumin level and the PT on distant lymph node metastasis are the 2 most crucial factors in predicting the subsequent survival time of advanced GC. TRIAL REGISTRATION: ChiCTR Identifier: ChiCTR1800019978.

Development and validation of a prognostic scoring model for mortality risk stratification in patients with recurrent or metastatic gastric carcinoma.

BACKGROUND: Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma. METHODS: Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts. RESULTS: Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts. CONCLUSION: The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

Performances of Prognostic Models in Stratifying Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy: a Validation Study in a Chinese Cohort.

PURPOSE: While several prognostic models for the stratification of death risk have been developed for patients with advanced gastric cancer receiving first-line chemotherapy, they have seldom been tested in the Chinese population. This study investigated the performance of these models and identified the optimal tools for Chinese patients. MATERIALS AND METHODS: Patients diagnosed with metastatic or recurrent gastric adenocarcinoma who received first-line chemotherapy were eligible for inclusion in the validation cohort. Their clinical data and survival outcomes were retrieved and documented. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive ability of the models. Kaplan-Meier curves were plotted for patients in different risk groups divided by 7 published stratification tools. Log-rank tests with pairwise comparisons were used to compare survival differences. RESULTS: The analysis included a total of 346 patients with metastatic or recurrent disease. The median overall survival time was 11.9 months. The patients were different into different risk groups according to the prognostic stratification models, which showed variability in distinguishing mortality risk in these patients. The model proposed by Kim et al. showed relative higher predicting abilities compared to the other models, with the highest χ2 (25.8) value in log-rank tests across subgroups, and areas under the curve values at 6, 12, and 24 months of 0.65 (95% confidence interval [CI]: 0.59-0.72), 0.60 (0.54-0.65), and 0.63 (0.56-0.69), respectively. CONCLUSIONS: Among existing prognostic tools, the models constructed by Kim et al., which incorporated performance status score, neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, and tumor differentiation, were more effective in stratifying Chinese patients with gastric cancer receiving first-line chemotherapy.

Survival outcomes of adjuvant taxanes, platinum plus fluoropyrimidines versus platinum and fluoropyrimidines for gastric cancer patients after D2 gastrectomy: a retrospective propensity score-matched analysis.

BACKGROUND: To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. METHODS: Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. RESULTS: Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). CONCLUSIONS: For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. TRIAL REGISTRATION: This project has been registered in the Chinese Clinical Trial Registry ( ChiCTR1800019978 ).

Identification of Key Genes for Hepatitis Delta Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.

BACKGROUND: It has been proposed that hepatitis delta virus (HDV) induces hepatic carcinogenesis by distinct molecular events compared with hepatocellular carcinoma (HCC) that is commonly induced by other hepatitis viruses. This study aimed to explore the underlying mechanism by identifying the key genes for HDV-HCC using bioinformatics analysis. METHODS: The GSE107170 dataset was downloaded and the differentially expressed genes (DEGs) were obtained by the online tool GEO2R. Gene otology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using R packages. The protein-protein interaction (PPI) network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Hub genes were selected by Cytoscape software according to degree algorithm. The hub genes were further validated in terms of expression and survival analysis based on public databases. RESULTS: A total of 93 commonly upregulated genes and 36 commonly downregulated genes were found. The top 5 upregulated hub genes were TFRC, ACTR2, ARPC1A, ARPC3, and ARPC2. The top 5 downregulated hub genes were CTNNB1, CCND1, CDKN1B, CDK4, and CDKN1A. In the validation analysis, the expressions of ARPC1A, ARPC3, and CDK4 were promoted in general liver cancer samples. Higher expressions of ARPC2 and CDK4 and lower expressions of CDKN1A, CCND1, and CDKN1B were associated with worse prognosis in general HCC patients. CONCLUSION: The present study identifies a series of key genes that may be involved in the carcinogenesis of HDV-HCC and used as prognostic factors.

Two-stage battery recharge scheduling and vehicle-charger assignment policy for dynamic electric dial-a-ride services.

Coordinating the charging scheduling of electric vehicles for dynamic dial-a-ride services is challenging considering charging queuing delays and stochastic customer demand. We propose a new two-stage solution approach to handle dynamic vehicle charging scheduling to minimize the costs of daily charging operations of the fleet. The approach comprises two components: daily vehicle charging scheduling and online vehicle-charger assignment. A new battery replenishment model is proposed to obtain the vehicle charging schedules by minimizing the costs of vehicle daily charging operations while satisfying vehicle driving needs to serve customers. In the second stage, an online vehicle-charger assignment model is developed to minimize the total vehicle idle time for charges by considering queuing delays at the level of chargers. An efficient Lagrangian relaxation algorithm is proposed to solve the large-scale vehicle-charger assignment problem with small optimality gaps. The approach is applied to a realistic dynamic dial-a-ride service case study in Luxembourg and compared with the nearest charging station charging policy and first-come-first-served minimum charging delay policy under different charging infrastructure scenarios. Our computational results show that the approach can achieve significant savings for the operator in terms of charging waiting times (-74.9%), charging times (-38.6%), and charged energy costs (-27.4%). A sensitivity analysis is conducted to evaluate the impact of the different model parameters, showing the scalability and robustness of the approach in a stochastic environment.

Absence of MHC class â ¡ molecules promotes natural killer cells activation in mice.

The development and immune recognition of natural killer (NK) cell are regulated critically by major histocompatibility complex (MHC) class I molecules. However, it remains unclear whether the function of NK cells is regulated by MHC class II molecules. To test this, we monitored the development, phenotype and function of NK cells by using MHC class II deficient (H2-/-) mice. The numbers and development of NK cells keep unaltered in H2-/- mice, compared with those in wide type (H2+/+) mice. A part of Ly49 family receptors on NK cells are down-regulated both in mRNA and protein expression in absence of MHC class II molecules. Furthermore, NK cells obtained from H2-/- mice exhibit more expression of CD69 and IFN-γ after cross-linking with NK1.1. Also, the cytotoxicity against tumor cell lines of NK cells from H2-/- mice was increased significantly. Taken together, our study indicates that the absence of MHC class II molecules promotes the activation and function of NK cells in mice.

NK cells contribute to hepatic CD8+ T cell failure in hepatitis B virus-carrier mice after alcohol consumption.

Despite the fact that both Hepatitis B virus (HBV) infection and excessive alcohol consumption represent health problems worldwide, the mechanism by which alcohol affected the progression of HBV-associated liver disease are not completely understood. Therefore, we studied how alcohol affects the development of HBV infection and the role of T cells and NK cells in the antiviral response. Mononuclear cells (MNCs) derived from HBV-carrier mice and wild type (WT) mice were characterized for phenotype by flow cytometry, HBV antigen and gene expression were detected by Radio Immunoassay (RIA), immunohistochemistry and quantitative real-time (qRT)-PCR. Metabolomics changes were detected in mice liver tissue based on ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS). The mice after ethanol consumption shows higher levels of HBV surface Ag (HBsAg), HBV core antigen (HBcAg) and HBV 3.5 kb RNA expression, and a lower level of CD8+ T cells during HBV persistence, with an increased lymphocyte activation gene-3 (LAG-3) expression on CD8+ T cell. In addition, the energy metabolism was downregulated and the oxidative stress was upregulated in the liver tissue. Furthermore, NK cells depletion results in a lower levels of HBV surface Ag (HBsAg) and HBV 3.5 kb RNA expression, and a higher level of CD8+ T cells with reduced expression of LAG-3. In conclusion, alcohol abuse induces CD8+ T cells failure after acute HBV infection, but depletion of NK cells could retore CD8+ T cell activity. Moreover, downregulation of energy metabolism and upregulation of oxidative stress may also contribute to CD8+ T cell failure.

Poorer prognosis of ovarian squamous cell carcinoma than serous carcinoma: a propensity score matching analysis based on the SEER database.

BACKGROUND: Ovarian squamous cell carcinoma (SCC) is a rare cancer with possible poor survival, however no direct evidence supports this viewpoint and the independent prognostic factors are controversial. Patients with ovarian SCC and serous carcinoma (SC) who were diagnosed between 2004 and 2016 were selected using the recent released SEER database. Propensity score matching was used to balance the characteristics of the two groups. The difference of survival between patients with ovarian SCC and SC was explored using Kaplan-Meier method. Cox regression analyses were performed to further identify the independent prognostic factors among patients with ovarian SCC. RESULTS: Of 15,286 patients (15,106 SC cases and 180 SCC cases), 304 were identified in the matched cohort (200 SC cases and 104 SCC cases). The overall survival and cause-specific survival for patients with SCC were significantly poorer (Plog-rank < 0.001). The median survival time was 21 months for SCC and 95 months for SC. Patients who underwent bilateral salpingo-oophorectomy with hysterectomy and omentectomy seemed to have a better outcome. In multivariate analysis, older age at diagnosis, larger tumor size, bilateral and FIGO stage IV malignancy were the independent risk factors for poor disease outcome. CONCLUSIONS: The prognosis of ovarian SCC is worse than ovarian SC. Older age at diagnosis, advanced disease stage, larger tumor size and bilateral malignancy are the independent risk factors for poor survival.

High Preoperative Fibrinogen and Systemic Inflammation Response Index (F-SIRI) Predict Unfavorable Survival of Resectable Gastric Cancer Patients.

PURPOSE: This study was to investigate the prognostic significance of the preoperative fibrinogen and systemic inflammation response index (F-SIRI) in a Chinese cohort of resectable gastric cancer. MATERIALS AND METHODS: Baseline characteristics, preoperative fibrinogen levels and peripheral neutrophil, monocyte, and lymphocyte counts were retrospectively reviewed in 240 patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and SIRI were defined as 4.0 g/L and 1.2. Then patients with hyperfibrinogenemia (≥4.0 g/L) and high SIRI (≥1.2) were assigned with an F-SIRI of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), and 0 (neither abnormality), respectively. The prognostic value was examined by univariate and multivariate survival analysis. RESULTS: Preoperative F-SIRI was significantly correlated with tumor size, fibrinogen level, and adjuvant chemotherapy. Whereas there was no significant difference in age, gender, tumor location or other characteristics between groups. In addition, high preoperative F-SIRI was significantly associated with worse disease-free survival (DFS) (hazard ratio [HR], 2.299; 95% confidence interval [CI], 1.482-3.566; P<0.001) and overall survival (OS) (HR, 2.461; 95% CI, 1.584-3.824; P<0.001) by univariate survival analysis. Moreover, it remained an independent predictor for impaired DFS (HR, 2.023; 95% CI, 1.273-3.215; P=0.003) and OS (HR, 2.341; 95% CI, 1.480-3.705; P<0.001) in multivariate Cox regression analysis. CONCLUSIONS: Preoperative F-SIRI could serve as a significantly prognostic marker for long-term survival in Chinese patients who underwent radical gastrectomy.

Suberoylanilide hydroxamic acid overcomes erlotinib-acquired resistance via phosphatase and tensin homolog deleted on chromosome 10-mediated apoptosis in non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear. METHODS: An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting. RESULTS: The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone. CONCLUSIONS: PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

Survival benefits of palliative gastrectomy in stage IV gastric cancer: a propensity score matched analysis.

BACKGROUND: This study aimed to investigate the effect of palliative gastrectomy on survival in stage IV gastric cancer. METHODS: Patients diagnosed with stage IV gastric cancer between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were estimated by the Kaplan-Meier method before and after propensity score matching (PSM). Univariate and multivariate Cox analyses were performed to evaluate risk factors for survival in patients who underwent palliative gastrectomy. RESULTS: We examined 6,529 patients with stage IV gastric cancer, of which 625 underwent palliative gastrectomy. Using a 1:2 PSM, the 625 patients were matched with 1,250 patients from the no gastrectomy group. The overall survival was higher in the gastrectomy group before [hazard ratio (HR) =0.57, 95% confidence interval (CI): 0.53-0.62, P<0.0001] and after PSM (HR =0.51, 95% CI: 0.46-0.57, P<0.0001). Multivariate Cox analysis confirmed the survival benefits of palliative gastrectomy and chemotherapy. Older age, over-lapping lesions, non-adenocarcinomas, higher tumor grade, and lung metastasis significantly increased the risk of mortality. In the gastrectomy group, patients aged ≥80 years, diagnosed with grades 3/4 non-adenocarcinomas, or with lung metastasis showed poorer prognosis. However, chemotherapy could improve the survival of these patients. CONCLUSIONS: Palliative gastrectomy provides survival benefits to stage IV gastric cancer patients. However, age, tumor grade, tumor histology, and lung metastasis status should be considered while making a decision regarding gastrectomy. Chemotherapy should also be recommended for these patients.

Differential Metabolic Pathways and Metabolites in a C57BL/6J Mouse Model of Alcoholic Liver Disease.

BACKGROUND Alcoholic liver disease (ALD), an important cause of acute or chronic liver injury, results from binge drinking or long-term alcohol consumption. To date, there is no well-established mouse model with a comprehensive metabolic profile that mimics ALD in humans. This study aimed to explore the differential metabolic pathways and related differential metabolites in the liver of an ALD mouse model. MATERIAL AND METHODS A C57BL/6J mouse model of ALD was induced by alcohol feeding for 10 days plus binge alcohol feeding. The metabolomic profiles in the liver of the ALD mouse model was detected through ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS). RESULTS A total 35 metabolites were significantly altered during the development of ALD. These metabolites were correlated to multiple metabolic pathways, including purine metabolism, the pentose phosphate pathway, cysteine and methionine metabolism, D-glutamine and D-glutamate metabolism, pyrimidine metabolism, and vitamin B6 metabolism. CONCLUSIONS The findings of the present study reveal potential biomarkers of ALD, and provide further insights into the pathogenesis of ALD.

Surgery on primary tumor shows survival benefit in selected stage IV colon cancer patients: A real-world study based on SEER database.

Objectives: Most patients with stage IV colon cancer did not have the opportunity for curative surgery, only selected patients could benefit from surgery. This study aimed to determine whether surgery on the primary tumor (SPT) should be performed in patients with stage IV colon cancer and how to select patients for SPT. Methods: This study included 48,933 patients with stage IV colon cancer who were identified in the Surveillance, Epidemiology and End Results (SEER) database between 1998 and 2015. Propensity score matching (PSM) analysis was adopted to balance baseline differences between SPT and non-surgery groups. Kaplan-Meier (K-M) curves were utilized to compare the overall survival (OS). Prognostic nomograms were generated to predict survival based on pre- and post-operative risk factors. Patients were divided into low, middle, and high mortality risk subsets for OS by X-tile analyses based on scores derived from above nomograms. Results: Patients with SPT had a significantly longer OS than those without surgery, regardless of the metastatic sites and diagnostic years. Nomograms, according to the pre- and post-operative risk factors, showed moderate discrimination (all C-indexes above 0.7). Based on X-tile analyses, low mortality risk subset (post-operative score ≤ 22.3, preoperative score ≤ 9.7) recommended for SPT, and high mortality risk was not. Conclusions: SPT led to prolonged survival in stage IV colon cancer. Our nomograms would help to select suitable patients for SPT.

Correlation between miR-138-5p expression and efficacy of platinum-based chemotherapy in advanced gastric cancer patients.

BACKGROUND: We investigated the relationship between levels of microRNA (miR)-138-5p in plasma and tumor tissues from advanced gastric cancer patients, and the efficacy of first-line platinum-based chemotherapy. METHODS: MiR-138-5p expression was measured by qRT-PCR in cancerous tissues and plasma from 51 advanced gastric cancer patients, in paracancerous tissues and in plasma from healthy volunteers as control. All patients received first-line platinum-based chemotherapy. Correlations between miR-138-5p expression and the treatment efficacy, progression-free survival (PFS), and overall survival (OS) of first-line chemotherapy were evaluated. RESULTS: Significantly lower levels of miR-138-5p were detected in gastric cancer tissues compared with paracancerous tissues and in the plasma of patients compared with control subjects (both P<0.05). A positive correlation was detected between the treatment efficacy and miR-138-5p expression in both cancer tissues and plasma (P<0.05). Receiver-operating characteristic (ROC) curves were constructed to determine the optimal miR-138-5p cutoff value for predicting the efficacy of platinum-based chemotherapy. Patients with high miR-138-5p expression in either tissues (≥0.081) or plasma (≥0.047) had better treatment responses and longer PFS and OS than patients with low miR-138-5p expression (P<0.05), and multivariate analyses confirmed miR-138-5p expression as a promising prognostic biomarkers. CONCLUSIONS: Our study suggested that miR-138-5p expression in cancer tissues or plasma could be a useful predictive biomarker for the efficacy of platinum-based chemotherapy and prognoses in advanced gastric cancer patients.