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Abstract CD44 plays a key role in the communication of CSCs with the microenvironment and the regulation of stem cell properties. UALCAN was used to analyze the expression of CD44 in bladder cancer (BLCA) and normal tissue. The UALCAN was utilized to analyze the prognostic value of CD44 in BLCA. The TIMER database was used to explore the relationship between CD44 and PD-L1; CD44 and tumor-infiltrating immune cells. The regulatory effect of CD44 on PD-L1 was verified by cell experiments in vitro. IHC confirmed the results of the bioinformatics analysis. GeneMania and Metascape were used to analyze protein–protein interaction (PPI) investigations and functional enrichment analysis. We found that BLCA patients with high CD44 expression had worse survival than those with low CD44 expression (P

In order to meet the rapid growth of railway transportation demand, the technology that can improve its capacity has been widely concerned. Virtual Coupling (VC) is a new technology to improve capacity by decreasing headways between successive trains. Its basic principle is to control the train formation operation in coordination with the goal of keeping the same speed under the support of data transmission technology such as train-to-train communication. Our paper first reviews the existing theoretical research on train formation operation control, which is divided into four categories: train following, feedback control, optimal control and computational intelligent method. Secondly, by reviewing the related projects in Europe and China, based on the scenario analysis method, five general scenarios and two emergency scenarios in the whole process of VC operation are sorted out. Then, an original, complete list of performance indicators (PIs) is proposed for evaluating the performance of VC in different scenarios. Additionally, the paper gives a brief insight into VC operation by providing an adequate context to understand the proposed PIs.

ObjectiveTo construct a reliable nomogram available online to predict the postoperative survival of patients with perihilar cholangiocarcinoma.MethodsData from 1808 patients diagnosed with perihilar cholangiocarcinoma between 2004 and 2015 were extracted from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into training and validation sets. The nomogram was established by machine learning and Cox model. The discriminant ability and prediction accuracy of the nomogram were evaluated by concordance index (C-index), receiver operator characteristic (ROC) curve and calibration curve. Kaplan-Meier curves show the prognostic value of the associated risk factors and classification system.ResultsMachine learning and multivariate Cox risk regression model showed that sex, age, tumor differentiation, primary tumor stage(T), lymph node metastasis(N), TNM stage, surgery, radiation, chemotherapy, lymph node dissection were associated with the prognosis of perihilar cholangiocarcinoma patients relevant factors (P

With the continuous development of the Automatic Train Operation (ATO) system in high-speed railways, automatic driving is progressively supplanting manual operations, ushering in a new era of predictability and reliability for high-speed railway transport. Concurrently, the advent of the ATO system provides a notable impact on real-time rescheduling during disruptions, as it equips dispatchers with precise insights into train operation statuses. This paper is dedicated to a thorough analysis of how the transition to automatic driving in train operations influences the real-time rescheduling model. Based on the distinctive impact of the ATO system on real-time rescheduling, we have proposed a mixed-integer linear programming model that combines train re-timing, reordering, and the minimization of passenger delays. To validate the effectiveness of our model, we present several experiments conducted using data from the Beijing–Shanghai high-speed railway line. The results unequivocally demonstrate that our ATO-based model significantly mitigates train delay time, demonstrating its practical value in optimizing high-speed railway operations.

The arrival interval at high-speed railway stations is one of the key factors that restrict the improvement of the train following intervals. In the process of practical railway operation, sudden conflicts occur sometimes. Especially when the conflict arises at the station, because the home signal cannot be opened in time, the emergency may affect the adjustment of the train operation under the scheduled timetable, resulting in a longer train following interval or even delay. With the development of artificial intelligence and the deep integration of big data, the architecture of train operation control and dispatch integration is gradually improving from the theoretical point. Based on this and inspired by the Green Wave policy, we propose an integrated operation method that reduces the arrival interval by avoiding unnecessary stops in front of the home signal and increasing the running speed of trains through the throat area. It is a two-step optimization method combining both intelligent optimization and mathematical–theoretical analysis algorithms. In the first step, the recommended approaching speed and position are obtained by analytical calculation. In the second step, the speed profile from the current position to the position corresponding to the recommended approaching speed is optimized by intelligent optimization algorithms. Finally, the integrated method is verified through the analysis of two distinct case studies. The first case study utilizes data from the Beijing–Shanghai high-speed railway line, while the second one is based on the field test. The numerical result shows that the proposed method could save the entry running time effectively, compared with the normal strategy given by the train driver. The method can mitigate controllable conflict events occurring at the station and provides theoretical support for practical operation.

Abstract Background Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer. Methods The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed. Results In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells. Conclusion Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer.

Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer.

Tumor metastasis remains a major challenge for patients with breast cancer. Aberrant epigenetic factor lysine‐specific demethylase 6B (KDM6B) has been associated with tumor progression. Here, we show that KDM6B is significantly down‐regulated in human breast cancer tissues, and its low expression is associated with poor prognosis of patients with breast cancer. Furthermore, overexpression of KDM6B remarkably inhibited cell proliferation, invasion, migration and epithelial–mesenchymal transition markers of breast cancer cells in vitro and tumor growth and lung metastasis in vivo. Notably, the expression of KDM6B in breast cancer tissues was negatively correlated with that of β‐catenin, and overexpression of KDM6B decreased the expression of β‐catenin and its accumulation in the nucleus of breast cancer cells. Overall, our findings provide novel insights into suppression of metastasis of breast cancer cells by KDM6B via β‐catenin and suggest involvement of the KDM6B‐Wnt/β‐catenin axis in breast cancer progression.

APAP is one of the most commonly used antipyretic and pain medications, but excessive use can cause liver toxicity and damage. 3,4-dihydroxyphenylethyl alcohol glycoside (DAG) is a component isolated from Sargentodoxa cuneata known to have anti-apoptotic, anti-oxidation and anti-inflammatory effects. However, the effects of DAG on acute liver failure (ALF) are largely unknown. The purpose of this study is to study the protective effects and mechanism of DAG on APAP-induced ALF in mice. We established an ALF model in adult male pathogen-free C57BL/6 mice treated with APAP (300 mg/kg) by intraperitoneal injection and resolved by 24 h. Hematoxylin and eosin (HE) staining was used to evaluate the pathological changes in mouse liver tissue. The infiltration of neutrophils in liver tissue and reactive oxygen species (ROS) in AML12 cells were analyzed by flow cytometry. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were analyzed using relevant kits. Our results show that DAG reduced APAP-induced serum ALT and AST levels, histopathological changes, liver neutrophil infiltration and proinflammatory cytokines production, also attenuated the accumulation of MDA and the exhaustion of GSH, CAT and SOD. In vitro experiment indicated that DAG dose-dependently inhibited APAP-induced the levels of pro-inflammatory factors (IL-1β and IL18), and reactive oxygen species (ROS) and preventing GSH depletion in mouse AML12 hepatocytes. More interestingly, DAG inhibited the expression of ERK, HO-1, NLRP3, Caspase1 (p20) and Gasdermin-D and upregulated the expression of GPX4 in liver tissues and AML12hepatocytes. Therefore, our results indicate that DAG may act as a potential agent to treat ALF induced by APAP by inhibiting hepatocyte ferroptosis and pyroptosis.

The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer remains controversial. Here, we evaluated the inhibitory effect of HT on mouse pancreatic cancer, and the effect of HT on the immune microenvironment. We found that HT can inhibit the proliferation of Panc 02 cells through signal transducer and activator of transcription (STAT) 3/Cyclin D1 signaling pathway. In the tumor-bearing mice treated with HT, the orthotopic pancreatic tumors were suppressed, accompanied by a decrease in the proportion of myeloid-derived suppressor cells (MDSCs) and an increase in the proportion of M1 macrophages. In addition, we found that HT inhibited the expression of immunosuppressive molecules in bone marrow (BM)-derived MDSCs, as well as down-regulated CCAAT/enhancer-binding protein beta (C/EBPβ) and phosphorylation of STAT3. Moreover, HT enhanced the anti-tumor effect of anti-CD47 antibody in vivo. HT combined with plumbagin (PLB) induced more Panc 02 cells death than HT or PLB alone. This combination therapy not only inhibited the accumulation of MDSCs, but also promoted the infiltration of CD4+ and CD8+ T cells in the tumors. In summary, HT is a potential immunomodulatory drug for the treatment of pancreatic cancer.

In this paper, we propose the motion recurring pattern analysis (MRPA) method for the lossless representation of a motion database at the segment level instead of the motion degree of freedom (DOF) level. First, we concatenate all the motions into a long sequence in the motion database, and we discover similar posture paths by building a matching trellis structure based on the randomized k-d tree. Second, horizontal segments of paths are suitably refined, based on a self-organizing map, to obtain the optimized segmentation for maximum compression gains. Third, by using the path as a connection agent, these segments are clustered into a forest of trees. With this forest structure, we obtain the prediction residuals (the differences between the nonroot branches and their parents), and the differences between neighboring residuals are encoded under floating-point compression. Relative to previous lossless compression methods, our approach can achieve a higher compression ratio with comparable decompression time costs.

As a new technology to improve transportation capacity by compressing train tracking interval, virtual coupling (VC) has attracted significant attention from both industry and academia. The traditional overspeed protection mechanism cannot guarantee the safe running for a train fleet. Therefore, in this article, we study two key problems of the overspeed protection mechanism: the limit speed calculation and the safe control for the protection of train in the formation when overspeed occurs. This article describes the calculation methods of limit speed difference (LSD) based on relative coordinates and a collision mitigation approach by minimizing the relative kinetic energy, respectively. Finally, the effectiveness of the proposed method is verified through numerical analysis. The proposed calculation method of limit speed can realize large headway at low speed and small headway at high speed, which can meet the time requirement of switch and route arrangement in station areas. The performance of the model predictive control (MPC) based approach is compared with other two control strategies, i.e. basic adaptive cruise control (ACC) and directly maximum braking control (DBC). The simulation results show that the MPC strategy has the best performance among these three strategies in reducing the total relative kinetic energy of virtually-coupled train formation, followed by the DBC control strategy, and the basic ACC control strategy needs to be improved.

In recent years, urban rail transit has been developing rapidly, which provides great convenience for passengers. Consequently more and more wireless hot spots are set up along the track. In our paper, the advantages of wireless positioning in urban rail transit are discussed firstly. Then a fingerprinting train positioning algorithm for metro based on deep learning is proposed. The model of fingerprinting positioning and the simulation environment are established to verify the effectiveness of the algorithm. Finally, the results satisfy the accuracy requirements for train positioning in the research on the energy-efficient operation of metro train and it can be used to provide position information for the energy-saving analysis.

Background/Aims: The bi-functional enzyme 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase-4 (PFKFB4) is highly expressed in many types of cancer and its requirement for tumor survival has been demonstrated in glioma, lung, and prostate cancers. However, whether PFKFB4 plays a role in the tumor metastasis remains uncertain. This study explores the role of PFKFB4 in tumor metastasis and its underlying mechanisms in breast cancer cells. Methods: The expression of PFKFB4 was first analyzed using the Cancer Genome Atlas (TCGA) dataset, and confirmed by immunohistochemical staining of tissue microarray and breast cancer tissues from patient samples. Gain- and loss-of- function approaches were used to investigate the effects of PFKFB4 on breast cancer cell migration in vitro. Orthotopic xenograft model and experimental metastasis model were used to assess the effects of PFKFB4 on breast cancer cell metastasis in vivo. ELISA and immunofluorescence staining were used to examine HA production. Quantitative RT-PCR and western blotting were used to explore the mRNA and protein levels of HAS2, respectively. Results: We found that PFKFB4 enhances the migration/invasiveness of breast cancer cells in vitro as well as in vivo. Notably, the effects of PFKFB4 on migration are mediated by induction of HAS2 expression and HA production. Moreover, PFKFB4-induced HAS2 up-regulation depends upon the activation of p38 signaling. Conclusion: PFKFB4 promotes the metastasis of breast cancer cells via induction of HAS2 expression and HA production in a p38-dependent manner. Therefore, the PFKFB4/p38/HAS2 signaling pathway may serve as a potential therapeutic target for metastatic breast cancer.

In this article, we consider the identification problem of a class of nonlinear multiple-input single-output output-error autoregressive systems. First, a recursive generalized least squares algorithm using the auxiliary model identification idea is developed. Then, using the filtering technique, the identification model is decomposed into a filtered sub-identification model and a noise sub-identification model. For solving the difficulties that the filter is unknown and the information vectors contain the unknown variables, the interactive estimation theory and the the idea of replacing the unknown variables with their corresponding estimates are employed: the recursive least squares method is again used for identifying the system and noise model parameters, and the parameter estimates of the noise model are used to construct the estimated filter. Finally, a nonlinear example is given to verify the effectiveness of the algorithms, and the simulation results show that the recursive least squares algorithm using the filtering technique can produce more accurate parameter estimates under larger noise variances.

Background: Ovarian cancer is a difficult and lethal illness that requires early detection and precise classification for effective therapy. Microarray technology has permitted the simultaneous assessment of hundreds of genes' expression levels, yielding important insights into the molecular pathways driving ovarian cancer. To reduce computational complexity and improve accuracy, choosing the most likely differential genes to explain the impacts of ovarian cancer is necessary. Medical datasets, including those related to ovarian cancer, are often limited in size due to privacy concerns, data collection challenges, and the rarity of certain conditions. Data augmentation allows researchers to expand the dataset, providing a larger and more diverse set of examples for model training. Recent advances in machine learning and bioinformatics have shown promise in improving ovarian cancer classification based on gene information. Methods: In this paper, we present an ensemble algorithm based on gene selection, data augmentation, and boosting approaches for ovarian cancer classification. In the proposed approach, the initial genetic data were first subjected to feature selection. Results: The target genes were screened and combined with data augmentation and ensemble boosting algorithms. From the results, the chosen ten genes could accurately classify ovarian cancer at 98.21%. Conclusions: We further show that the proposed algorithm based on clustering approaches is effective for real-world ovarian cancer data, with 100% accuracy and strong performance in distinguishing between distinct ovarian cancer subtypes. The proposed algorithm may help doctors identify ovarian cancer patients early and develop individualized treatment plans. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the potential bioactive compounds from Phyllanthus emblica L. fruit. Methods: Acetone extracts (60%) of P emblica fruit were dissolved in water and fractionated sequentially with light petroleum and ethyl acetate (EtOAc). The water fraction was separated using Sephadex LH-20 and the isolated compounds were purified by preparative high-performance liquid chromatography. The structures of the isolated compounds were determined through HR-ESI-MS and spectroscopic methods, including 1D- and 2D-NMR, and the antioxidant abilities of the isolates were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Results: Three new phenolic compounds, mucic acid 1-ethyl ester 3- O -gallate (1), mucic acid 6-methyl ester 3- O -gallate (2), and mucic acid 6-ethyl ester 2- O -gallate (3), together with 4 known compounds (4 - 7), were isolated from P emblica fruit. All phenolics exhibited potent antioxidant abilities (DPPH: IC50 7.5-13.2 µM; ABTS: 1.12-2.84 µM Trolox/µM; FRAP: 1.11-2.26 µM Fe2+/µM). Conclusions: Our research contributes to the growing body of evidence demonstrating the benefits of P emblica for health and supports the functional food and nutraceutical applications of the fruit. [ABSTRACT FROM AUTHOR]

Pulmonary sarcomatoid carcinoma (PSC) is an aggressive and poorly differentiated type of non-small cell lung carcinoma. Because of the rarity of PSC, the efficacy and toxicity of immunotherapy remain unclear. Hence, the aim of this study was to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) for the treatment of advanced PSC. The study cohort was limited to 33 patients with pathologically confirmed PSC treated with ICIs in four hospitals in China from March 2018 to March 2022. Expression of programmed death ligand 1 (PD-L1) was detected by immunohistochemical analysis. Categorical variables were compared with the Fisher exact test and survival analysis was conducted with the Kaplan-Meier method. Of the 33 PSC patients, 8 (24.2%) received monotherapy with ICIs and 25 (75.8%) received combination therapy with ICIs. The objective response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8%, respectively. The median durations of progression-free survival (PFS) and overall survival (OS) were 6.07 and 21.33 months, respectively. PD-L1 status in 16 available samples was assessed, which included 30.3% PD-L1-positive patients. The ORRs for PD-L1-positive vs. -negative patients were 50.0% and 90.0%, the DCR was 33.3% and 83.3%, and the median PFS was 17.50 and 6.07 months, respectively (p=0.812). The median OS was not reached in PD-L1-positive and -negative patients (p=0.655). The incidence of immune-related adverse (irAEs) was 48.5% and mainly included grade 1 or 2 (39.4%), while the incidence of grade 3 or 4 was 9.1%. Pneumonia (9.1%) and skin rash (9.1%) were the most frequent irAEs. Immunotherapy with ICIs was a promising regimen to improve the prognosis of patients with advanced PSC. [ABSTRACT FROM AUTHOR]

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD. [ABSTRACT FROM AUTHOR]

Purpose: The great efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been identified in patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, it has not yet been established in postoperative adjuvant therapy. Patients and methods: To compare the prognosis and toxicity of EGFR-TKI-based adjuvant therapy and non-EGFR-TKI-based adjuvant therapy in resected NSCLC with sensitive EGFR mutations, we performed this meta-analysis of all eligible randomized controlled trials (RCTs). Results: A comprehensive literature search of electronic databases (from inception to December 31, 2017) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology conferences and World Conference on Lung Cancer held between January 2000 and November 2017 were searched to identify relevant trials. Disease-free survival (DFS), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Five RCTs were selected, and 560 participants were included. This meta-analysis demonstrated that EGFR-TKI-based adjuvant therapy was associated with better DFS compared with non-EGFR-TKI-based therapy (HR =0.52, 95% CI 0.34–0.78, P=0.002). Pooled estimate has showed the trend of superiority of EGFR-TKI-based therapy in the aspect of OS (HR =0.65, 95% CI 0.22–1.91, P=0.43); however, the difference was not significant. The incidence rate of grade 3–4 toxicities of EGFR-TKI-based regimens was significantly higher for rash (OR =10.17, 95% CI 2.37–43.63, P=0.002) but lower for vomiting (OR =0.08, 95% CI 0.01–0.61, P=0.02). Conclusion: EGFR-TKI-based therapy was associated with better DFS compared with non-EGFR-TKI-based adjuvant therapy in patients with NSCLC harboring EGFR mutations. A trend was found that EGFR-TKI-based regimen improved the OS, though the difference was not significant. Although more OS data are needed, EGFR-TKI-based treatment has the potential to be an alternative of adjuvant therapy for NSCLC with a sensitive EGFR mutation. [ABSTRACT FROM AUTHOR]

The article focuses on the decision of the U.S. Supreme Court in the case Elonis v. United States wherein the Court reversed a conviction for making online threats over the social media platform Facebook. It mentions that ambiguity in the intent requirement with the ease with which true threats can be made in the Internet age.

Objective: The prognostic significance of CD24 expression for survival in patients with gastric cancer remains controversial. We conducted a meta-analysis to investigate the impact of CD24 expression on clinicopathological features and survival outcomes in gastric cancer. Methods: A comprehensive literature search of the electronic databases PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI; up to April 8, 2014) was performed for relevant studies using multiple search strategies. Correlations between CD24 expression and clinicopathological features and overall survival (OS) were analyzed. Results: A total of 1,041 patients with gastric cancer from 9 studies were included. The pooled odds ratios (ORs) indicated CD24 expression was associated with tumor depth (OR = 0.45, 95% confidence interval [CI]  = 0.32–0.63; P<0.00001), status of lymph nodes (OR = 0.40, 95% CI = 0.25–0.64; P = 0.0001) and tumor node metastasis (TNM) stage (OR = 0.56, 95% CI = 0.41–0.77; P = 0.0003). The pooled hazard ratio (HR) for OS showed overexpression of CD24 reduced OS in gastric cancer (HR = 1.99, 95% CI = 1.29–3.07, P = 0.002). Whereas, combined ORs showed that CD24 expression had no correlation with tumor differentiation or Lauren classifications. Conclusion: CD24 overexpression in patients with gastric cancer indicated worse survival outcomes and was associated with common clinicopathological poor prognostic factors. [ABSTRACT FROM AUTHOR]

Background: The management of limited-disease esophageal small cell carcinoma is not well defined, and the role of surgery is still controversial. We aim to determine the optimal treatment strategy in limited-disease of esophageal small cell carcinoma. Methods and Findings: We conducted a retrospective review of 141 patients with limited-disease esophageal small cell carcinoma from 3 institutions in China who underwent treatment between July 1994 and September 2008, July 1994 and July 2011, and June 2004 and December 2010, respectively. The survival rate was calculated by the Kaplan-Meier method, and the log-rank test was used to assess the survival differences between the groups. Cox proportional hazards model were used to further determine the independent factors impacting overall survival. The median survival time was 16.1 months for the entire cohort of patients, with a 5-year survival rate of 6.7%. The median survival times for surgery alone, surgery combined with chemotherapy, surgery combined with radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0 months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding 5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For the 105 patients who underwent R0 resection, the median disease-free survival time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5 months. The multivariate Cox regression analysis demonstrated that advanced pathological staging (p = 0.003), and pure esophageal small cell carcinoma (p = 0.035) were independent factors decreasing overall survival. Conclusions: Our data suggested that multidisciplinary modalities achieved encouraging long-term survival in patients with resectable limited-disease of esophageal small cell carcinoma. [ABSTRACT FROM AUTHOR]

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD.

Objective: To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics., Methods: Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis., Results: Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway., Conclusion: Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Pulmonary sarcomatoid carcinoma (PSC) is an aggressive and poorly differentiated type of non-small cell lung carcinoma. Because of the rarity of PSC, the efficacy and toxicity of immunotherapy remain unclear. Hence, the aim of this study was to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) for the treatment of advanced PSC. The study cohort was limited to 33 patients with pathologically confirmed PSC treated with ICIs in four hospitals in China from March 2018 to March 2022. Expression of programmed death ligand 1 (PD-L1) was detected by immunohistochemical analysis. Categorical variables were compared with the Fisher exact test and survival analysis was conducted with the Kaplan-Meier method. Of the 33 PSC patients, 8 (24.2%) received monotherapy with ICIs and 25 (75.8%) received combination therapy with ICIs. The objective response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8%, respectively. The median durations of progression-free survival (PFS) and overall survival (OS) were 6.07 and 21.33 months, respectively. PD-L1 status in 16 available samples was assessed, which included 30.3% PD-L1-positive patients. The ORRs for PD-L1-positive vs. -negative patients were 50.0% and 90.0%, the DCR was 33.3% and 83.3%, and the median PFS was 17.50 and 6.07 months, respectively (p=0.812). The median OS was not reached in PD-L1-positive and -negative patients (p=0.655). The incidence of immune-related adverse (irAEs) was 48.5% and mainly included grade 1 or 2 (39.4%), while the incidence of grade 3 or 4 was 9.1%. Pneumonia (9.1%) and skin rash (9.1%) were the most frequent irAEs. Immunotherapy with ICIs was a promising regimen to improve the prognosis of patients with advanced PSC.

Objective: Programmed cell death 1 (PD-1) and one of its ligands, PD-L1, are key immune checkpoint proteins. Evidences showed PD-L1 is an emerging biomarker for immunotherapy by anti-PD-1 and anti-PD-L1 antibody in non-small cell lung cancer (NSCLC). To investigate the association of PD-L1 protein expression with clinicopathological features and its impact on survival outcome, we conducted a meta-analysis., Methods: A comprehensive literature search of electronic databases (up to July 10, 2014) was performed. Correlation between PD-L1 expression and clinicopathological features and overall survival (OS) was analyzed by synthesizing the qualified data. Publication biases were examined., Results: A total of 1,550 NSCLC patients from 9 studies were included. The pooled odds ratios (ORs) indicated high PD-L1 expression was associated with poor tumor differentiation [OR =0.53, 95% confidence interval (CI): 0.39-0.72, P<0.0001]. Whereas, none of other clinicopathological characteristics [gender, smoking status, histological type, invasive depth of tumor, status of lymph node metastasis and tumor node metastasis (TNM) stage] were correlated with PD-L1 expression in current analysis. The combined hazard ratio (HR) for OS showed high expression of PD-L1 impaired the OS in NSCLC (HRpositive/negative =1.47, 95% CI: 1.19-1.83, P=0.0004)., Conclusions: Our meta-analysis indicated PD-L1 protein expression in NSCLC was not associated with common clinicopathological characteristics, except tumor differentiation. It was a poor prognostic biomarker for NSCLC. Further research should be performed to investigate the precise clinicopathological and prognostic significance of PD-L1 in NSCLC under uniform testing standard.

Background and Objective: Clinical factors and molecular markers can be used to predict the prognosis of gefitinib-treated locally advanced or metastatic non-small cell lung cancer (NSCLC). This study was to identify predictive factors for the response and survival of gefitinib-treated locally advanced or metastatic NSCLC patients in China., Methods: Clinical data of 256 gefitinib-treated Chinese NSCLC patients from two existing clinical trials were analyzed. Univariate and multivariate analyses were performed to determine predictive factors of response and survival., Results: The objective response rate was 24.6%; the disease control rate was 54.7%. Median survival time was 11.43 months (95% CI, 8.64-14.22 months). The 1-year survival rate was 48.0% (95% CI, 41.0%-55.0%). Adenocarcinoma and skin rash were associated with better response. The patients with lower performance status (PS) score (0-1) and those with disease control (complete remission, partial remission, and stable disease) had longer survival when compared with their counterparts., Conclusions: Adenocarcinoma and skin rash are predictors of better response to gefitinib. Low PS score and disease control are predictors of longer survival after treatment of gefitinib.