Impact of chemotherapy on prognosis of resectable pathological T3N0M0 esophageal cancer patients: a population-based study.

Aims: This study aimed to retrospectively determine the influence factors and survival effects of chemotherapy in pathological T3N0M0 esophageal cancer (EC) patients based on histological type. Methods: A total of 1136 pathological T3N0M0 EC patients who had surgery were chosen from the Surveillance, Epidemiology and End Results database. The patients were divided into subgroups based on histological type and chemotherapy status. Multivariate logistic regression, log-rank test and Cox regression were used to identify prognostic risk factors and survival differences. A propensity score matching analysis was applied to adjust the covariates. The impact of additional chemotherapy was also assessed in patients who had postoperative radiotherapy. Results: The 5-year overall survival was 36.4% for all patients. Chemotherapy was an independent protective factor of survival in both adenocarcinoma and squamous cell carcinoma patients. In the survival analysis, chemotherapy significantly improved the prognosis of EC patients, both for adenocarcinoma and squamous cell carcinoma. Propensity score matching analysis validated these results. Conclusion: Chemotherapy is recommended for pathological T3N0M0 EC patients regardless of histological type.

Lay abstract The prognosis of patients with different histological types of esophageal cancer varies. Chemotherapy is important treatment for these patients. However, the survival benefits of chemotherapy with regard to histological type and clinical stage are unclear. Here the authors used a public database to explore the prognostic value of chemotherapy and survival influence factors in these patients.

CXXC finger protein 4 inhibits the CDK18-ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway.

Gastric cancer, is the fourth most common tumour type yet, ranks second in terms of the prevalence of cancer-related deaths worldwide. CXXC finger protein 4 (CXXC4) has been considered as a novel cancer suppressive factor, including gastric cancer. This study attempted to investigate the possible function of CXXC4 in gastric cancer and the underlying mechanism. The binding of the ETS domain-containing protein-1 (ELK1) to the long non-coding RNA MIR100HG promoter region was identified. Then, their expression patterns in gastric cancer tissues and cells (SGC7901) were detected. A CCK-8 assay was used to detect SGC7901 cell proliferation. Subsequently, SGC7901 cells were co-cultured with CD3+ T cells, followed by measurement of CD3+ T cell proliferation, magnitude of IFN-γ+ T cell population and IFN-γ secretion. A nude mouse model was subsequently developed for in vivo validation of the in vitro results. Low CXXC4 expression was found in SGC7901 cells. Nuclear entry of ELK1 can be inhibited by suppression of the extent of ELK1 phosphorylation. Furthermore, ELK1 is able to bind the MIR100HG promoter. Overexpression of CXXC4 resulted in weakened binding of ELK1 to the MIR100HG promoter, leading to a reduced proliferative potential of SGC7901 cells, and an increase in IFN-γ secretion from CD3+ T cells. Moreover, in vivo experiments revealed that CXXC4 inhibited immune escape of gastric cancer cells through the ERK1/2 axis. Inhibition of the CXXC4/ELK1/MIR100HG pathway suppressed the immune escape of gastric cancer cells, highlighting a possible therapeutic target for the treatment of gastric cancer.

Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer.

Colorectal Cancer (CRC) is the third most common cancer worldwide, and the occurrence and development of CRC are influenced by the molecular biology characteristics of CRC, especially alterations in key signaling pathways. The transforming growth factor-ß (TGF-ß) plays a crucial role in cellular growth, differentiation, migration, and apoptosis, with SMAD4 protein serving as a key transcription factor in the TGF-ß signaling pathway, thus playing a significant role in the onset and progression of CRC. CRC is one of the malignancies with a high mortality rate worldwide. Despite significant research progress in recent years, especially regarding the role of SMAD4, its dual role in the early and late stages of tumor progression has promoted further discussion on its complexity as a therapeutic target, highlighting the urgent need for a deeper analysis of its role in CRC. This review aims to explore the function of SMAD4 protein in CRC and its potential as a therapeutic target.

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia: Based on serum pharmacochemistry and network pharmacology.

BACKGROUND: YangshenDingzhi granules (YSDZ) are clinically effective in preventing and treating COVID-19. The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology. METHODS: The chemical constituents of YSDZ in the blood were examined using ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive Orbitrap MS). Potential protein targets were obtained from the SwissTargetPrediction database, and the target genes associated with viral pneumonia were identified using GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1. Protein-protein interaction networks were constructed using the STRING database. The Metascape database was employed to perform enrichment analyses of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways for the targets, while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks. Further, in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia. RESULTS: Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum. Among these, MAPK1, MAPK3, AKT1, EGFR, and TNF play significant roles. In vitro tests revealed that the medicated serum suppressed the replication of H1N1, RSV, and SARS-CoV-2 replicon. Further, in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1. CONCLUSION: The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

[Responses of radial growth of Fraxinus mandshurica from different provenances to climate at Maoershan in Northeast China]. / 东北地区帽儿山种源实验林区不同种源水曲柳径向生长对气候的响应.

To understand the responses of radial growth of Fraxinus mandshurica from different provenances to climatic factors, we used the dendrochronological method to establish the standard chronologies of F. mandshurica from 20 provenances in Maoershan provenance test forest, and analyzed the differences in radial growth and their correlation with climate factors. The results showed that the overall trend of F. mandshurica chronologies from 20 provenances was generally similar. There were differences in growth amplitude, with the average radial growth of F. mandshurica from Dailing, Lushuihe and Sanchazi being the highest. The radial growth of F. mandshurica from 20 provenances was significantly positively correlated with the highest temperature in July and the average temperature in July except for Huinan. The radial growth of F. mandshurica from 14 provenances was significantly positively correlated with the precipitation in August. The radial growth of F. mandshurica was constrained by temperature and precipitation during the growing season. There was difference in radial growth among F. mandshurica from different provenances under drought stress. F. mandshurica from Wangqing, Dailing, and Hailin had stronger resistance to drought, while that from Wandianzi, Zhanhe, and Xinglong had better recovery ability after drought.

Plasma GPI and PGD are associated with vascular normalization and may serve as novel prognostic biomarkers for lung adenocarcinoma: Multi-omics and multi-dimensional analysis.

The aim of this study was to explore potential novel plasma protein biomarkers for lung adenocarcinoma (LUAD). A plasma proteomics analysis was carried out and candidate protein biomarkers were validated in 102 LUAD cases and 102 matched healthy controls. The same LUAD tumor tissues were detected to explore the correlation between the expression of candidate proteins in tissues and plasma and vascular normalization. A LUAD active metastasis mice model was constructed to explore the role of candidate proteins for lung metastasis. GPI and PGD were verified to be upregulated in plasma from LUAD patients, and the expression of GPI in tumor tissue was positively correlated with the expression of GPI in plasma and negatively correlated with the normalization of tumor blood vessels. Meanwhile, a negative correlation between the expression of GPI and PGD in plasma and tumor vascular normalization was discovered. In the LUAD active metastasis model, the lowest levels of vascular normalization and the highest expression of GPI and PGD were found in mice with lung metastases. This study found that GPI and PGD may be potential plasma biomarkers for LUAD, and monitoring those may infer the risk of metastasis and malignancy of the tumor. SIGNIFICANT: We identified GPI and PGD as potential novel diagnostic and prognostic biomarkers for LUAD. PGD and GPI can be used as diagnostic biomarkers in combination with other available strategies to assist in the screening and diagnosis of LUAD, and as prognostic biomarkers aid in predict the risk of tumor metastasis and malignancy in patients with LUAD.

Identification of novel pQTL-SNPs associated with lung adenocarcinoma risk: A multi-stage study.

BACKGROUND AND OBJECTIVE: To explore the association between protein quantitative trait loci (pQTL-SNPs) and the risk of LUAD. METHODS: "Blood +" high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non-tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL-SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL-SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. RESULTS: A total of 7 pQTL-SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL-SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL-SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients. CONCLUSION: A total of 4 pQTL-SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation.

Meta-analysis of the efficacy and safety of Xihuang Pills/capsules in adjuvant treatment of uterine cervical neoplasms.

BACKGROUND: Xihuang Pills/Capsules have a longstanding history of utilization in traditional Chinese medicine (TCM) for treating cancer. Nevertheless, a comprehensive investigation is required regarding the specific impacts and safety of Xihuang Pills/Capsules in individuals with uterine cervical neoplasms. Thus, conducting a meta-analysis is essential to evaluate the clinical effectiveness of combining Xihuang Pills/Capsules with Western medicine in patients with cervical neoplasms. METHODS: The research involved searching 5 English and 4 Chinese databases for randomized controlled trials (RCTs) investigating the use of Xihuang Pills/Capsules in conjunction with Western medicine for treating uterine cervical neoplasms. Subsequently, statistical analysis was carried out using Review Manager software (version 5.3). RESULTS: This research encompassed 10 RCTs involving 937 patients. The findings revealed that the combination of Xihuang Pills/Capsules with Western medicine treatment led to improvements in various aspects of the patients' condition. Specifically, there was an enhancement in the short-term efficacy rate (risk ratio [RR] = 1.14, 95% confidence interval [CI]: 1.06-1.22, P = .0003), Karnofsky performance score (KPS) (mean difference [MD] = 5.90, 95% CI: 0.54-11.26, P = .03), survival rates, CD3+, CD3 + CD4+, CD3 + CD8+, CD3-CD56 + cells, and immunoglobulin M in patients with uterine cervical neoplasms. Moreover, the combination treatment resulted in a reduction of adverse reactions, including gastrointestinal reactions (RR = 0.52, 95% CI: 0.42-0.64, P < .00001), radiation proctitis (RR = 0.47, 95% CI: 0.33-0.68, P < .0001), myelosuppression (RR = 0.41, 95% CI: 0.26-0.64, P < .0001), as well as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) levels. Additionally, the treatment exhibited an inhibitory effect on white blood cells (WBCs) and platelets (PLTs). CONCLUSION: The amalgamation of Xihuang Pills/Capsules with conventional anti-tumor therapy proves to be both effective and safe in the treatment of cervical neoplasms. However, further validation through high-quality RCTs is necessary to substantiate these findings.

Expression of p53 as a biomarker in determining response to apatinib for advanced gastric cancer.

Background: Apatinib has shown outstanding value in the treatment of advanced gastric cancer (AGC). However, no biomarkers are available to select AGC patients who will benefit from apatinib. The aim of the present study was to investigate the association between p53 and Ki67 expression of and the outcome in AGC patients treated with apatinib. Methods: From December 2015 to December 2020, 92 AGC patients were enrolled and was retrospectively evaluated. They were given apatinib at a daily dose of 500 or 250 mg every 4 weeks to monitor clinical efficacy and adverse events (AEs). Kaplan-Meier method was used for survival analysis. Expression of p53 and Ki67 was detected by immunohistochemistry (IHC) and correlated with survival. Results: Among 92 evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 17.4% and 79.3%, respectively, and none of them achieved a CR, 16 achieved a PR (17.4%) (95% CI 9.8%-26.1%). Stable disease (SD) was observed in 57.6% of patients (95% CI 49.2%-69.9%) and PD in 21.7% of patients (95% CI 13.6%-31.3%). The median progression free survival (mPFS) was 122.7 ± 8.2 days, and the median overall survival (mOS) was 203.4 ± 11.9 days. P53 expression was observed in 35 patients (38.0%) and high expression of Ki67 was detected in 34 patients (37.0%). There was a statistically significant inverse relationship between p53 and Ki67 expression (P=0.014). Moreover, p53 was significantly correlated with the OS (P=0.018), but Ki67 had no significant influence on OS. Conclusions: Apatinib showed promising efficiency and was well tolerated as a second-line treatment for AGC patients. AGC patients with p53-negative were likely to benefit from apatinib treatment; however, the expression of Ki67 proteins has no significant impact on the outcome of AGC patients.

A Novel Deep Learning Network and Its Application for Pulmonary Nodule Segmentation.

Pulmonary nodules are the early manifestation of lung cancer, which appear as circular shadow of no more than 3 cm on the computed tomography (CT) image. Accurate segmentation of the contours of pulmonary nodules can help doctors improve the efficiency of diagnosis. Deep learning has achieved great success in computer vision. In this study, we propose a novel network for pulmonary nodule segmentation from CT images based on U-NET. The proposed network has two merits: one is that it introduces dense connection to transfer and utilize features. Additionally, the problem of gradient disappearance can be avoided. The second is that it introduces a new loss function which is tolerance on the pixels near the borders of the nodule. Experimental results show that the proposed network at least achieves 1% improvement compared with other state-of-art networks in terms of different criteria.

KIF11 manipulates SREBP2-dependent mevalonate cross talk to promote tumor progression in pancreatic ductal adenocarcinoma.

Cholesterol metabolism is highly correlated with risks of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the underlying mechanisms of activation of cholesterol biogenesis remain inconclusive. KIF11 is a key component of the bipolar spindle and expresses highly in various malignancies. However, its functional role in PDAC tumorigenesis is still unclear. This study aims to elucidate the oncogenic functions of KIF11 in stimulating cholesterol metabolism, thereby driving PDAC progression. We utilized bioinformatics analysis to identify that KIF11 expressed highly in tumor samples versus paired normal tissues and high KIF11 correlated with high clinical stages of patients. Patients with high KIF11 had worse survival outcomes relative to those with low KIF11. Gene set enrichment analysis (GSEA) revealed that KIF11 correlated intensively with the mevalonate (MVA) metabolic pathway. Positive associations were observed between KIF11 and MVA-signature (HMGCR, FDFT1, SQLE, and MSMO1). KIF11 could elevate the free cholesterol content of PDAC cells and targeting MVA inhibited the in vitro growth of KIF11-overexpressing cells. Mechanistically, we found KIF11 could interact with SREBP2, the master regulator of MVA. High KIF11 could increase SREBP2 proteins, but not alter their mRNA levels. KIF11 could attenuate the ubiquitination-mediated degradation of SREBP2, thereby enhancing its stability and accumulation. Accordingly, KIF11 stimulated the expressions of MVA-signature and free cholesterol contents depending on SREBP2. In addition, KIF11 depended on SREBP2 to promote cell growth, migration, stemness, and colony formation abilities. The subcutaneous xenograft models indicated that targeting MVA biogenesis (atorvastatin) is effective to restrict the in vivo growth of KIF11high PDAC. Taken together, our study identified that KIF11 could activate the MVA cross talk to drive PDAC progression and inhibiting the KIF11/MVA axis provided a therapeutic vulnerability in the treatment of PDAC.

Roles of intercellular cell adhesion molecule-1 (ICAM-1) in colorectal cancer: expression, functions, prognosis, tumorigenesis, polymorphisms and therapeutic implications.

Colorectal cancer (CRC) is a major global health problem and one of the major causes of cancer-related death worldwide. It is very important to understand the pathogenesis of CRC for early diagnosis, prevention strategies and identification of new therapeutic targets. Intercellular adhesion molecule-1 (ICAM-1, CD54) displays an important role in the the pathogenesis of CRC. It is a cell surface glycoprotein of the immunoglobulin (Ig) superfamily and plays an essential role in cell-cell, cell-extracellular matrix interaction, cell signaling and immune process. It is also expressed by tumor cells and modulates their functions, including apoptosis, cell motility, invasion and angiogenesis. The interaction between ICAM-1 and its ligand may facilitate adhesion of tumor cells to the vascular endothelium and subsequently in the promotion of metastasis. ICAM-1 expression determines malignant potential of cancer. In this review, we will discuss the expression, function, prognosis, tumorigenesis, polymorphisms and therapeutic implications of ICAM-1 in CRC.

Association between long noncoding RNA rs944289 and rs7990916 polymorphisms and the risk of colorectal cancer in a Chinese population.

Long non-coding RNAs (LncRNAs) play vital roles in the tumorigenesis of many cancers. Single nucleotide polymorphisms (SNPs) of the lncRNA also play vital roles in tumorigenesis. We explored lncRNA rs944289 and rs7990916 polymorphisms and analyzed the relationship between these lncRNA polymorphisms with the colorectal cancer (CRC) risk in a Chinese population. We recruited 1003 CRC patients from the Affiliated People's Hospital of Jiangsu University and the Fujian Medical University Union Hospital from October 2014 to August 2017. Genomic DNA was extracted using a DNA Kit from lymphocytes of peripheral blood and the genotyping was performed with a SNPscan method. We found that the rs944289 TT homozygote was associated with the decreased CRC risk in the overall population. LncRNA rs944289 TT decreased the CRC risk in the subgroup of female, male, age ≥ 61, without alcohol intake, smoking and BMI ≥ 24 by logistic regression. The subgroup analysis revealed that lncRNA rs7990916 was not associated with CRC risk except for age < 61. Logistic regression analysis revealed that lncRNA rs944289 TT homozygote was associated with the increased risk of rectum cancer (TT vs. CC + CT: adjusted OR = 1.29, 95% CI 1.10-1.66, P = 0.041) or colon cancer. In summary, we proved that lncRNA rs944289 might be significantly related to the decreased CRC risk in the Chinese Han populations and lncRNA rs7990916 was not associated with the CRC risk except for patients of age < 61. In the future, studies with larger samples should be conducted to validate our results.

A Novel apaQTL-SNP for the Modification of Non-Small-Cell Lung Cancer Susceptibility across Histological Subtypes.

Background: Alternative polyadenylation (APA) events may be modulated by single nucleotide polymorphisms (SNPs). Therefore, this study aims to evaluate the association between APA quantitative trait loci (apaQTLs)-related SNPs (apaQTL-SNPs) and non-small-cell lung cancer (NSCLC) risk. Methods: APA-related genes associated with NSCLC (LUAD and LUSC) were first identified, and the respective apaQTL-SNPs of those genes were selected. Then, a two-phase case-control study was performed to evaluate the association between candidate apaQTL-SNPs and NSCLC risk. Results: A total of 7 LUAD- and 21 LUSC-associated apaQTL-SNPs were selected. In the first phase, the apaQTL-SNP rs10138506 was significantly associated with LUAD risk (p < 0.05), whereas the other two apaQTL-SNPs (rs1130698 and rs1130719) were significantly associated with LUSC risk (p < 0.05). In the second phase, the variant G allele of rs10138506 was still significantly associated with an increased risk of LUAD (OR = 1.42, 95%CI = 1.02−1.98, p = 0.038). Functional annotation indicated that the variant G allele of rs10138506 was significantly associated with a higher PDUI value of CHURC1. Meanwhile, 3'RACE experiments verified the presence of two poly(A) sites (proximal and distal) in CHURC1, while qRT-PCR results indicated that different genotypes of rs1127968 which, in perfect LD with rs10138506, can mediate changes in the lengths of the 3'UTR of CHURC1 isoforms. Conclusion: The variant G allele of rs10138506 in CHURC1 was correlated with a longer 3'UTR of CHURC1 mRNA and an increased LUAD risk. Further studies should evaluate the interaction between rs10138506 and different 3'UTR lengths of CHURC1 that regulate LUAD development.

LINC01224 accelerates malignant transformation via MiR-193a-5p/CDK8 axis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with a significantly high mortality rate, yet, its pathogenesis is not fully understood. Bioinformatics predicted that LINC01224 is highly expressed in stomach adenocarcinoma (STAD), and showed that LINC01224 adsorbed miR-193a-5p to target CDK8. Therefore, this study intended to verify the effect of the LINC01224/miR-193a-5p/CDK8 axis on the biological behavior of gastric cancer. METHODS: Expressions of LINC01224, miR-193a-5p, CDK8, apoptosis-, and EMT-related genes were analyzed using the GEPIA website, RT-qPCR, in situ hybridization, and Western blot as needed. Bioinformatics and dual luciferase assay were used to evaluate the relationship between LINC01224, miR-193a-5p, and CDK8. Functional experiments and rescue experiments (MTT assay, flow cytometry, wound healing assay, and Transwell) were conducted to detect the effects of the above genes on the biological characteristics of GC cells. Tumorigenesis assay was used to verify the results of in vitro experiments. RESULTS: LINC01224 adsorbed miR-193a-5p to target and upregulate CDK8. The expressions of LINC01224 and CDK8 were increased, while the expression of miR-193a-5p was decreased in GC. Overexpressed LINC01224 promoted cell viability, migration and invasion, accelerated tumor formation, attenuated apoptosis, inhibited the expressions of apoptosis-related proteins, and promoted the expressions of EMT-related proteins, whereas silenced LINC01224 led to the opposite effect. MiR-193a-5p inhibitor partially offset the effect of silenced LINC01224; interestingly, siCDK8 significantly reversed the effect of miR-193a-5p inhibitor on GC cells. CONCLUSION: LINC01224 affects the biological behavior of gastric cancer by mediating miR-193a-5p to regulate CDK8.

Apatinib combined with S-1 as second-line therapy in advanced gastric cancer.

ABSTRACT: Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of the present study is to evaluate the efficacy and safety of apatinib combined with S-1 as the second-line therapy for AGC patients.Patients with AGC were enrolled in this study. Patients received oral apatinib (250 mg to 500 mg once daily) and S-1(40 mg/m2 twice daily) on days 1-14. Each cycle was 28 days and one course of treatment consisted of 2 cycles. Clinical efficacy and adverse events (AEs) were observed. Kaplan-Meier method was used for survival analysis.From November 2015 to December 2017, 58 AGC patients who failed first-line chemotherapy were enrolled and assessed retrospectively. According to the Response Evaluation Criteria in Solid Tumors (RECIST) standard, all patients were evaluable for response. None achieved CR, and 10 (17.2%) achieved PR (95% CI 7.2%-27.3%). SD was observed in 58.6% (34/58) of patients (95% CI 45.6%-71.7%) and NR in 24.1% (14/58) of patients (95% CI 12.8%-35.5%). The objective response rate (ORR) and the disease control rate (DCR) were 17.2% and 75.8% respectively. The median progression-free survival (PFS) and median overall survival (OS) were 143.1 days (95% CI 121.7-164.5) and 211.6 days (95% CI 162.9-219.7) respectively. The multivariate analysis showed that the ECOG PS was the independent factor of PFS and OS for AGC patients (PFS: HR = 3.565, 95% CI: 2.25-5.65, P < .001; OS: HR = 3.676, 95% CI: 2.29-5.89, P < .001). The main AEs were fatigue (72.4%), hypertension (46.6%), and leukopenia (48.3%).Apatinib combined with S-1 showed promising efficiency and was well tolerated as the second-line therapy for AGC patients. ECOG PS was the independent factor of PFS and OS for AGC patients. AEs were moderate and controllable, and leukopenia or hypertension was predictable factors for the PFS and OS of AGC patients.

High expression of WSB1 is associated with poor prognosis in hepatocellular carcinoma and affects epithelial-mesenchymal transition.

PURPOSE: To explore the expression of WD-40 repeat and SOCS box containing 1 (WSB1) and its clinical significance in hepatocellular carcinoma (HCC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of WSB1 in clinical tissues. Survival curves were platted using the Kaplan-Meier method and log rank test was used to compare survival between groups. The influencing factors for the long-term survival were analysed using Cox univariate and multivariate analysis. In in vitro study, Western blot was used to evaluate the effects of WSB1 on epithelial-mesenchymal transition (EMT) of tumor cells. RESULTS: The expression of WSB1 was much higher in cancer tissues than that in para-normal tissues, and the WSB1 expression was correlated with tumor differentiation, lymph node metastasis and clinical stage. In addition, HCC patients with higher WSB1 expression had significantly poorer progression-free survival (PFS) and overall survival (OS). Both univariate analysis and multivariate analyses indicated that high expression of WSB1 was an independent predictor of poor prognosis in HCC. Further in in vitro study, downregulation of WSB1 in HCC cell line could reduce the expression of epithelial phenotype protein (E-cadherin) while increase the expression of mesenchymal phenotype protein (N-cadherin and Vimentin). CONCLUSIONS: WSB1 might contribute into the development of HCC and serve as a clinical biomarker and a therapeutic target for HCC patients.

A Facile Approach to High Precision Detection of Cell-to-Cell Variation for Li-ion Batteries.

Over the past decade, it has been repeatedly demonstrated that homogeneity in electrochemical performance of lithium-ion cells plays a major role in determining the life and safety of lithium-ion battery modules or packs. Generally, the homogeneity of a battery pack is evaluated by characterizing the cells individually in terms of capacity, mass, impedance. Particularly, high quality electrochemical data heavily relies on the availability of high precision current source to minimize the discrepancy induced by the channel-to-channel variation. Here, a facile and precise measurement method is reported for screening cell-to-cell variations, in which voltage is the only indicator parameter independent of high precision current source. In detail, by connecting the cells in series (CiS), the measurement error of electrochemical data caused by stability and discrepancy of current sources among different charge/discharge equipment can be effectively avoided. The findings of this work showed that the cell-to-cell variations can be simply and sensitively detected with CiS configuration. For example, the relative standard deviation, which is the evaluation criterion of battery homogeneity, was 2.14% based on CiS while it was 0.43% based on individual measurements. The simple and precise CiS measurement is promising for evaluation of cell quality or module integration quality. In addition, this work can also provide a solid foundation for the development of detection algorithms for battery management systems to rapidly monitor battery homogeneity.

Fuling-Guizhi Herb Pair in Coronary Heart Disease: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation.

The Fuling (Poria cocos)-Guizhi (Cinnamomi ramulus) herb pair (FGHP) is a commonly used traditional Chinese herbal formula with coronary heart disease (CHD) treatment potential. However, the mechanism of FGHP in the treatment of CHD was still unclear. In this study, the action targets and underlying mechanism of FGHP against CHD were successfully achieved by combined network pharmacology prediction with experimental verification. 76 common targets were screened out by overlapping the chemical-protein data of FGHP and CHD-related targets. Then, two key targets were further selected for verification by using western blot analysis after analyzing PPI, GO function, and KEGG pathway. Results indicated FGHP could alleviate CHD syndromes and regulate inflammatory responses in acute myocardial ischemia rats, and the reduction of expression of TNF-α and IL-6 in myocardial tissue would be one of its possible underlying mechanisms. Our work demonstrated that network pharmacology combined with experimental verification provides a credible method to elucidate the pharmacological mechanism of FGHP against CHD.

A polymeric composite protective layer for stable Li metal anodes.

Lithium (Li) metal is a promising anode for high-performance secondary lithium batteries with high energy density due to its highest theoretical specific capacity and lowest electrochemical potential among anode materials. However, the dendritic growth and detrimental reactions with electrolyte during Li plating raise safety concerns and lead to premature failure. Herein, we report that a homogeneous nanocomposite protective layer, prepared by uniformly dispersing AlPO4 nanoparticles into the vinylidene fluoride-co-hexafluoropropylene matrix, can effectively prevent dendrite growth and lead to superior cycling performance due to synergistic influence of homogeneous Li plating and electronic insulation of polymeric layer. The results reveal that the protected Li anode is able to sustain repeated Li plating/stripping for > 750 cycles under a high current density of 3 mA cm-2 and a renders a practical specific capacity of 2 mAh cm-2. Moreover, full-cell Li-ion battery is constructed by using LiFePO4 and protected Li as a cathode and anode, respectively, rendering a stable capacity after 400 charge/discharge cycles. The current work presents a promising approach to stabilize Li metal anodes for next-generation Li secondary batteries.