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Abstract Gastric adenocarcinoma (STAD) is the most prevalent malignancy of the human digestive system and the fourth leading cause of cancer-related death. Calcium pools, especially Ca2+ entry (SOCE) for storage operations, play a crucial role in maintaining intracellular and extracellular calcium balance, influencing cell activity, and facilitating tumor progression. Nevertheless, the prognostic and immunological value of SOCE in STAD has not been systematically studied. The objective of this study was to develop a risk model for SOCE signature and to explore its correlation with clinical characteristics, prognosis, tumor microenvironment (TME), as well as response to immunotherapy, chemotherapy, and targeted drugs. We used the TCGA, GEO (GSE84437 and GSE159929), cBioPortal and TIMER databases to acquire mRNA expression data for STAD, along with patient clinical indicators, single-cell sequencing data, genomic variation information, and correlations of immune cell infiltration. An analysis of SOCE genes based on tumor vs. normal tissue comparisons, pan-cancer dimension, single-cell sequencing, DNA mutation, and copy number variation revealed that SOCE genes significantly impact the survival of STAD patients and are differentially involved in the immune response. SOCE co-expressed genes were identified by Pearson analysis, and subsequently protein-protein interaction (PPI) and gene function enrichment analysis indicated that coexpressed genes were associated with multicellular pathways. Based on TCGA and GSE84437 datasets, a multifactor Cox proportional hazard regression analysis was conducted to identify SOCE co-expressed genes associated with overall survival in STAD patients. Several mRNA prognostic genes, including PTPRJ, GPR146, LTBP3, FBLN1, EFEMP2, ADAMTS7 and LBH, were identified, which could be used as effective prognostic predictors for STAD patients. In both training and test datasets, receiver operating characteristic (ROC) curves were utilized to evaluate and illustrate the predictive capability of this characteristic in forecasting overall survival of STAD patients. The qPCR and human protein atlas (HPA) were employed to assess mRNA expression and protein levels. Furthermore, the ESTIMATE, TIMER, CIBERSORT, QUANTISEQ, MCPCOUNTER, xCell and EPIC algorithms were utilized to perform immune score and analyze immune cell infiltration. It effectively revealed the difference in prognosis and immune cell infiltration in TME between high-risk and low-risk groups based on the risk signature associated with SOCE. Notably, significant differences in tumor immune dysfunction and rejection (TIDE) scores between the two groups, suggesting that patients in the low-risk group may exhibit a more favorable response to ICIS treatment. The GDSC database and R packages for predictive analysis were utilized to analyze responses to chemotherapy and targeted drugs in high-risk and low-risk groups. In summary, the 7-gene signature associated with SOCE serves as a significant biomarker for evaluating the TME and predicting the prognosis of STAD patients. In addition, it may provide valuable insights for developing effective immunotherapy and chemotherapy regiments for patients with STAD.

Abstract Background: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S‐1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. Methods: A non‐inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. Results: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent‐to‐treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3‐year overall survival (OS) and disease‐free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153–1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064–0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076–0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110–1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. Conclusion: Adjuvant SOX was non‐inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.

Abstract Background This retrospective study aimed to assess the suitability of POSSUM and its modified versions, E-PASS and its modified score, SRS, and SORT scores for predicting postoperative complications and mortality in patients undergoing laparoscopic radical gastrectomy for gastric cancer. Materials and methods Data analysis was performed on 349 patients who underwent laparoscopic radical gastrectomy at Tianjin Medical University General Hospital between January 2016 and December 2021. The discriminative ability of the scoring systems was evaluated using the area under the receiver operating characteristic curve (AUC). The primary endpoint focused on the prediction of postoperative complications, while the secondary endpoint assessed the prediction of postoperative mortality. Results Among the scoring systems evaluated, the modified E-PASS (mE-PASS) score exhibited the highest AUC (0.846) and demonstrated the highest sensitivity (81%) and specificity (79%) for predicting postoperative complications. All other scores, except for POSSUM, showed moderate discriminative ability in predicting complications. In terms of predicting postoperative mortality, the E-PASS score had the highest AUC (0.978), while the mE-PASS score displayed the highest sensitivity (76%) and specificity (90%). Notably, both E-PASS and mE-PASS scores exhibited excellent discriminative ability. Conclusions The P-POSSUM, O-POSSUM, E-PASS, mE-PASS, SRS, and SORT scoring systems are useful tools for predicting postoperative outcomes in laparoscopic radical gastrectomy. Among them, the mE-PASS score demonstrated the best predictive power. However, the POSSUM system could only be applicable to predict postoperative mortality.

BackgroundAutism spectrum disorder (ASD) is associated with alterations in the gut microbiome. However, there are few studies on gut microbiota of children with ASD in China, and there is a lack of consensus on the changes of bacterial species.PurposeAutism spectrum disorder (ASD) is associated with alterations in the gut microbiome. However, there are few studies on gut microbiota of children with ASD in China, and there is a lack of consensus on the changes of bacterial species.MethodsWe used 16S rRNA sequencing to analyze ASD children (2 to 12 years), HC (2 to 12 years).ResultsOur findings showed that the α-diversity, composition, and relative abundance of gut microbiota in the ASD group were significantly different from those in the HC groups. Compared with the HC group, the α-diversity in the ASD group was significantly decreased. At the genus level, the relative abundance of g_Faecalibacterium, g_Blautia, g_Eubacterium_eligens_group, g_Parasutterella, g_Lachnospiraceae_NK4A136_group and g_Veillonella in ASD group was significantly increased than that in HC groups, while the relative abundance of g_Prevotella 9 and g_Agathobacter was significantly decreased than that in HC groups. In addition, KEGG pathway analysis showed that the microbial functional abnormalities in ASD patients were mainly concentrated in metabolic pathways related to fatty acid, amino acid metabolism and aromatic compound metabolism, and were partially involved in neurotransmitter metabolism.ConclusionThis study revealed the characteristics of gut microbiota of Chinese children with ASD and provided further evidence of gut microbial dysbiosis in ASD.

BackgroundAnastomotic leakage is a serious complication after colorectal cancer surgery, which affects the quality of life and the prognosis. This study aims to create a novel nomogram to predict the risk of anastomotic leakage for patients with colorectal cancer based on the preoperative inflammatory-nutritional index and abdominal aorta calcium index.Methods292 patients at Tianjin Medical University General Hospital (Tianjin, China) from January 2018 to October 2021 who underwent colorectal cancer surgery with a primary anastomosis were retrospectively reviewed. A nomogram was constructed based on the results of multivariate logistic regression model. The calibration curves and receiver operating characteristic curves were used to verify the efficacy of the nomogram.ResultsUnivariate and multivariate analyses showed that tumor location (P = 0.002), preoperative albumin (P = 0.006), preoperative lymphocyte (P = 0.035), preoperative neutrophil to lymphocyte ratio (P = 0.024), and superior mesenteric artery calcium volumes score (P = 0.004) were identified as the independent risk factors for postoperative anastomotic leakage in patients with colorectal carcinoma. A nomogram was constructed based on the results of the multivariate analysis, and the C-index of the calibration curves was 0.913 (95%CI: 0.870–0.957) in the training cohort and 0.840 (95%CI: 0.753–0.927) in the validation cohort.ConclusionThe nomogram, combining basic variables, inflammatory-nutritional index and abdominal aorta calcium index, could effectively predict the possibility of postoperative anastomotic leakage for patients with colorectal cancer, which could guide surgeons to carry out the appropriate treatment for the prevention of anastomotic leakage.

Studies have indicated that the ethanol exposure impairs the gut microbiota, At the same time, high levels of alcohol exposure damage sperm in mice. However, whether the gut microbiota is involved in mediating the effects of alcohol on sperm quality remains unclear. This study aimed to assess the effect of chronic alcohol consumption on intestinal microbiota in mice and analyze the potential pathophysiological effect of altered intestinal microbiota on sperm quality. We established a mouse model of chronic alcohol consumption by allowing male C57 mice to freely ingest 10% ethanol for 10 weeks, and collected the fecal microbiota of the male mice in the chronic drinking group (alcohol) and the control group (control) and transplanted the specimens into the transplant groups (the alcohol-fecal microbiota transplantation [FMT] group and the control-FMT group). Sperm quality was significantly decreased in the alcohol-FMT group compared with the control-FMT group. Gut microbiota analysis revealed that the abundance of 11 operational taxonomic units (OTUs) was altered in the alcohol-FMT group. Nontargeted metabolomics identified 105 differentially altered metabolites, which were mainly annotated to amino acids, lipids, glycerophosphoethanolamine, organic oxygenic compounds, organic acids and their derivatives, steroids, and flavonoids. In particular, the oxidative phosphorylation pathway, which is the key to spermatogenesis, was significantly enriched in the alcohol-FMT group. Moreover, compared with the control-FMT group, the alcohol-FMT group presented significantly higher serum endotoxin and inflammatory cytokine levels, with more pronounced T cell and macrophage infiltration in the intestinal lamina propria and elevated levels of testicular inflammatory cytokines. In addition, RNA sequencing showed significant differences in the expression of testis-related genes between the alcohol-FMT group and the control-FMT group. In particular, the expression of genes involved in gamete meiosis, testicular mitochondrial function, and the cell division cycle was significantly reduced in alcohol-FMT mice. In conclusion, these findings indicated that intestinal dysbiosis induced by chronic alcohol consumption may be an important factor contributing to impaired sperm quality. Chronic alcohol consumption induces intestinal dysbiosis, which then leads to metabolic disorders, elevated serum endotoxin and inflammatory cytokine levels, testicular inflammation, abnormal expression of related genes, and ultimately, impaired sperm quality. These findings are potentially useful for the treatment of male infertility.

Abstract Background Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal malignancy, which produces osteoid, bone, or chondroid material and is located in the soft tissue without attachment to skeletal bones and periosteum. One of the things that ESOS originated from mesentery is much rarer. Case presentation A 75-year female had a history of pain in the left lower abdomen for more than 4 months. Abdominal computerized tomography (CT) and magnetic resonance imaging revealed a large, irregular, and solid-cystic mass (largest diameter was 11.5 cm). The tumor was radically removed during an open operation. It was composed of abundant osteoid and polyhedral-shaped tumor cells with high atypia and high mitotic activity microscopically. The final pathological diagnosis was osteoblastic osteosarcoma, arising from the sigmoid mesocolon with negative margins. A 9-month follow-up by CT exhibited signs of peritoneal metastasis. Conclusions Given the rarity of cases of mesenteric ESOS, diagnosis mainly depended on pathology findings or should be taken into consideration when the mesenteric mass was found. Its most effective treatment had not been determined, with surgical excision being generally accepted. Ensuring negative surgical margins may be an important factor affecting prognosis.

Abstract Background Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. Methods The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. Results CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P

Background: Piezo2 is a transmembrane-spanning ion channel protein implicated in multiple physiological processes, including cell proliferation and angiogenesis in many cell types. However, Piezo2 was recognized as representing a double-edged sword in terms of tumor growth. The prognostic and immunotherapeutic roles of Piezo2 in pan-cancer have not been reported.Methods: In this study, several databases available including the UCSC Xena database, HPA, TIDE, GSEA, and cBioportal were used to investigate the expression, alterations, associations with immune indicators, and prognostic roles of Piezo2 across pan-cancer. R software and Perl scripts were used to process the raw data acquired from the UCSC Xena database.Results: Based on processed data, our results suggested that Piezo2 expression levels were tissue-dependent in different tumor tissues. Meanwhile, the survival analysis reflected that patients suffering from KIRC, LUAD, and USC with high Piezo2 expression had good OS, while those suffering from KIRP and SARC with high Piezo2 expression had poor OS. In addition, our results showed that Piezo2 expression was associated with the infiltration of CD4+ T memory cells, mast cells, and dendritic cells. These results suggested that Piezo2 may involve tumor progression by influencing immune infiltration or regulating immune cell function. Further analysis indicated that Piezo2 could influence TME by regulating T-cell dysfunction. We also found that gene mutation was the most common genetic alteration of Piezo2. The GSEA analysis revealed that Piezo2 was associated with calcium ion transport, the activation of the immune response, antigen processing and presentation pathways.Conclusion: Our study showed the expression and prognostic features of Piezo2 and highlighted its associations with genetic alterations and immune signatures in pan-cancer. Moreover, we provided several novel insights for further research on the therapeutic potential of Piezo2.

Abstract Background Long non-coding RNAs exert vital roles in several types of cancer. The objective of this study was to explore the role of LINC_00355 in gastric cancer (GC) progression and its potential mechanism. Methods The expression levels of LINC_00355 in GC tissues and cells were detected by quantitative real-time PCR, followed by assessing the effects of LINC_00355 knockdown or overexpression on cell properties. Dual-luciferase reporter assay was utilized to identify the relationship between LINC_00355 and microRNA (miR)-15a-5p and miR-15a-5p and PHD finger protein 19 (PHF19), followed by the rescue experiments. Results The results showed that LINC_00355 was highly expressed in GC tissues and cells compared with the corresponding control. LINC_00355 knockdown decreased the viability, migration, and invasion and increased the accumulation of GC cells in G1 phase and apoptosis. Meanwhile, LINC_00355 downregulation markedly increased cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase protein levels, whereas decreased cyclin D1, cyclin E, matrix metalloproteinase (MMP) 9, MMP2, and N-cadherin protein levels in GC cells. However, LINC_00355 overexpression had the opposite effects. It was verified that LINC_00355 upregulated the expression of PHF19 through sponging miR-15a-5p. Furthermore, PHF19 overexpression reversed the effect of LINC_00355 knockdown on GC cell properties, including cell viability, migration, invasion, and apoptosis. Conclusions Collectively, these results suggest that LINC_00355 promotes GC progression by up-regulating PHF19 through sponging miR-15a-5p. Our findings may provide an important clinical basis for reversing the malignant phenotype of GC.

Background There was much hard work to study the trastuzumab resistance in HER2-positive gastric cancer (GC), but the information which would reveal this abstruse mechanism is little. In this study, we aimed to investigate the roles of tumor cell-derived CCL2 on trastuzumab resistance and overcome the resistance by treatment with the anti-CD40-scFv-linked anti-HER2 (CD40 ×HER2) bispecific antibody (bsAb).Methods We measured the levels of CCL2 expression in HER2-positive GC tissues, and revealed biological functions of tumor cell-derived CCL2 on tumor-associated macrophages (TAMs) and the trastuzumab resistance. Then, we developed CD40 ×HER2 bsAb, and examined the targeting roles on HER2 and CD40, to overcome the trastuzumab resistance without systemic toxicity.Results We found the level of CCL2 expression in HER2-postive GC was correlated with infiltration of TAMs, polarization status of infiltrated TAMs, trastuzumab resistance and survival outcomes of GC patients. On exposure to CCL2, TAMs decreased the M1-like phenotype, thereby eliciting the trastuzumab resistance. CCL2 activated the transcription of ZC3H12A, which increased K63-linked deubiquitination and K48-linked auto-ubiquitination of TRAF6/3 to inactivate NF-κB signaling in TAMs. CD40 ×HER2 bsAb, which targeted the CD40 to restore the ubiquitination level of TRAF6/3, increased the M1-like phenotypic transformation of TAMs, and overcame trastuzumab resistance without immune-related adversary effects (irAEs).Conclusions We revealed a novel mechanism of trastuzumab resistance in HER2-positive GC via the CCL2-ZC3H12A-TRAF6/3 signaling axis, and presented a CD40 ×HER2 bsAb which showed great antitumor efficacy with few irAEs.

Objective: Natural extracts, including nobiletin, have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs. However, whether and how nobiletin affects tumor growth and progression in renal cell carcinoma (RCC) are still unclear. Methods: Cell proliferation, cell cycle and apoptosis analyses, colony-formation assays, immunoblotting analysis, and qRT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro. The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib. Results: Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells. Mechanistically, nobiletin decreased SKP2 protein expression by reducing its transcriptional level. The downregulated SKP2 caused accumulation of its substrates, p27 and p21, which further inhibited the activity of the G1 phase-related protein, CDK2, leading to inhibition of cell proliferation and tumor formation. A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor, palbociclib. A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model. Conclusions: Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor, palbociclib, on RCC, which indicates a potential new therapeutic strategy.

Abstract Background Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. Methods RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. Discussion This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. Trial registration Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

Objectives Although laparoscopic distal gastrectomy has been widely used for distal gastric cancer, the best functional reconstruction type has not yet been established. Based on previous experience, we propose a modified uncut Roux-en-Y anastomosis. This study aimed to compare the outcomes of different intracorporeal anastomoses after laparoscopic distal gastrectomy. Methods From April 2015 to August 2020, the data of 215 patients who underwent laparoscopic distal gastrectomy was collected. The patients were divided into 4 groups according to the digestive tract reconstruction method, Billroth-I, Billroth-II, Roux-en-Y, and the modified uncut Roux-en-Y. Clinicopathologic characteristics, surgery details, short-term outcomes, and postoperative nutritional status were analyzed. Results The operation time of Billroth-I anastomosis was significantly shorter (216.2 ± 25.8 min, P < .001) than that of other methods. There was no difference in postoperative complications and OS among the 4 reconstruction methods. The incidences of esophagitis, gastritis, and bile reflux were significantly lower in the Roux-en-Y and uncut Roux-en-Y group (P < .001) 1 year after surgery. And the postoperative albumin and PNI levels in uncut Roux-en-Y group were higher than those in other groups(P < .05). On multivariate analysis, age and reconstruction type were independently related to esophagitis, gastritis, and bile reflux. Serum albumin and the prognostic nutritional index were significantly higher in the uncut Roux-en-Y group than other groups (P < .05). Conclusions All 4 reconstruction techniques are feasible and safe. The Roux-en-Y and uncut Roux-en-Y are superior to Billroth-Ⅰ and Billroth-Ⅱ+Braun in terms of reflux esophagitis, gastritis, and bile reflux. Uncut Roux-en-Y may result in better PNI than the others.

The clinical application of anastomotic instruments improves the efficiency of the digestive tract surgery. However, the stapler with titanium nails implanted is still controversial in terms of anastomotic complications, and further improvement and optimization are needed. The purpose of this study was to explore the optimal microtextured parameters that could enhance the bioactivity of titanium implants in vitro. Laser microtexturing technology was used to construct the groove-type microstructural surfaces with different parameters, and human gastric mucosal epithelial cells (GES-1 cells) and mouse fibroblasts (3T3 cells) were cultured on the surface of the titanium plates in vitro. The data of cell adhesion, cell proliferation and cell activity were obtained and statistically analyzed. The textured titanium plates meet the expected design. GES-1 and 3T3 cell adhesion were better in the surface of titanium plates in microstructural group than that in the polished group. GES-1 and 3T3 cells also showed higher proliferative activity in the microstructural group compared with the polished group. The laser textured titanium plates have good groove-type microstructure, which increase the surface roughness, change the surface wettability, promote the adhesion, proliferating and orderly growth of GES-1 and 3T3 cells, and show good biological properties.

Background: Increasing evidence indicated that the tumor microenvironment (TME) plays a critical role in tumor progression. This study aimed to identify and evaluate mRNA signature involved in lymph node metastasis (LNM) in TME for gastric cancer (GC). Methods: Gene expression and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to evaluate the TME of GC. The heatmap and Venn plots were applied for visualizing and screening out intersect differentially expressed genes (DEGs) involved in LNM in TME. Functional enrichment analysis, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were also conducted. Furthermore, binary logistic regression analysis were employed to develop a 4-mRNAs signature for the LNM prediction. ROC curves were applied to validate the LNM predictive ability of the riskscore. Nomogram was constructed and calibration curve was plotted to verify the predictive power of nomogram. Results: A total of 88 LNM related DEGs were identified. Functional enrichment analysis and GSEA implied that those genes were associated with some biological processes, such as ion transportation, lipid metabolism and thiolester hydrolase activity. After univariate and multivariate logistic regression analysis, 4 mRNAs (RASSF2, MS4A2, ANKRD33B and ADH1B) were eventually screened out to develop a predictive model. ROC curves manifested the good performance of the 4-mRNAs signature. The proportion of patients with LNM in high-risk group was significantly higher than that in low-risk group. The C-index of nomogram from training and test cohorts were 0.865 and 0.765, and the nomogram was well calibrated. Conclusions: In general, we identified a 4-mRNAs signature that effectively predicted LNM in GC patients. Moreover, the 4-mRNAs signature and nomogram provide a guidance for the preoperative evaluation and postoperative treatment of GC patients.

Owing to the localized surface plasmon resonance (LSPR), dynamic manipulation of optical properties through the structure evolution of plasmonic nanoparticles has been intensively studied for practical applications. This paper describes a novel method for direct reversible self-assembly and dis-assembly of Au nanoparticles (AuNPs) in water driven by pH stimuli. Using 3-aminopropyltriethoxysilane (APTES) as the capping ligand and pH-responsive agent, the APTES hydrolyzes rapidly in response to acid and then condenses into silicon. On the contrary, the condensed silicon can be broken down into silicate by base, which subsequently deprotonates the APTES on AuNPs. By controlling condensation and decomposition of APTES, the plasmonic coupling among adjacent AuNPs could be reversible tuned to display the plasmonic color switching. This study provides a facile and distinctive strategy to regulate the reversible self-assembly of AuNPs, and it also offers a new avenue for other plasmonic nanoparticles to adjust plasmonic properties via reversible self-assembly.

BackgroundGastrointestinal stromal tumor (GIST) is the most common type of mesenchymal tumors in the digestive tract, often recrudescing even after R0 resection. Adjuvant tyrosine kinase inhibitor therapy prolonged recurrence-free survival (RFS). This study aimed to develop a novel nomogram for predicting the RFS of patients following surgical resection of GISTs.MethodsClinicopathologic data of patients with GISTs at Tianjin Medical University General Hospital (Tianjin, China) from January 2000 to October 2019 were retrospectively reviewed. Univariate and multivariate Cox regression analyses were used to select the suitable variables from the training cohort to construct a nomogram for 2- and 5-year RFS. The 1,000 bootstrap samples and calibration curves were used to validate the discrimination of the nomogram. The receiver operating characteristic analysis(ROC) was used to compare the predictive ability of the nomogram and present four commonly used risk stratification systems: National Institutes of Health (NIH)–Fletcher staging system; NIH–Miettinen criteria; Modified NIH criteria; and Air Forces Institute of Pathology risk criteria (AFIP).ResultsUnivariate and multivariate analyses showed that the tumor site, tumor size, mitotic index, tumor rupture, and prognostic nutritional index were significant factors associated with RFS. These variables were selected to create the nomogram for 2- and 5-year RFS (all P

Prostate cancer is the second leading cause of cancer-related death in men. Early prostate cancer has a high 5-year survival rate. However, the five-year survival rate is low in progressive prostate cancer, which manifests as bone metastasis. The EGF receptor overexpression increases during disease progression and in the development of castration-resistant disease, and may be a potential therapeutic target. Liver X receptors (LXRs) are ligand-dependent nuclear receptor transcription factors and consist of two subtypes, LXR-α and LXR-β, which can inhibit tumor growth in various cancer cells. We revealed that LXR-α, but not LXR-β, was reduced in prostate cancer tissues compared with adjacent normal tissues. LXRs’ agonist GW3965 enhanced the inhibitory action of LXR-α on the proliferation and metastasis of prostate cancer cells. Furthermore, our results support the notion that LXR-α is regulated by the EGFR/AKT/FOXO3A pathway. As an EGFR inhibitor, Afatinib could weaken AKT activation and increase the expression level of FOXO3A in prostate cancer. In addition, we indicated that the combination of Afatinib and GW3965 simultaneously increased and activated LXR-α, which led to an increase of tumor suppressors, and eventually inhibited tumor progression. Therefore, the combination of EGFR inhibitor and LXRs agonist may become a potential treatment strategy for prostate cancer, especially metastatic prostate cancer.

BackgroundColorectal cancer (CRC) is the third most lethal and malignant type of cancer in the world. Abnormal expression of human microRNA-200a (hsa-miRNA-200a or miR-200a) has previously been characterized as a clinically noticeable biomarker in several cancers, but its role in CRC is still unclear.MethodsThree CRC miRNA expression datasets were integratively analyzed by Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Nine candidate miRNAs were identified and validated for diagnostic and prognostic capability with the prediction model. The potential roles of the tumor suppressor miR-200a-3p in invasion, migration, and epithelial-mesenchymal transition of CRC cells were elaborated by in vitro studies.ResultsNine miRNAs (miR-492, miR-200a, miR-338, miR-29c, miR-101, miR-148a, miR-92a, miR-424, and miR-210) were identified as potentially useful diagnostic biomarkers in the clinic. The overall accuracy rate of the nine miRNAs in the diagnostic model was 0.94, 0.89, and 0.978 in the testing, validation, and independent validation dataset, respectively. CRC patients in the GSE29622 cohort were separated by the prognostic model into the low-risk score group and the high-risk score group. The area under the receiver operating characteristic curve (AUC) was 0.872 and 0.783 for predicting the 1- to 10-year survival of CRC patients. The performance of the prognostic model was validated by an independent TCGA-Colon Adenocarcinoma (COAD) dataset with AUC values between 0.911 and 0.796 in predicting 1- to 10-year survival. Nomograms comprising risk scores, tumor stage, and TNM staging were generated for predicting 1-, 3-, and 5-year overall survival (OS) in the GSE29622 and TCGA-COAD datasets. Colony formation, invasion, and migration in DLD1 and SW480 cells were suppressed by overexpression of miR-200a-3p. Inhibition of miR-200a-3p function contributed to abnormal colony formation, migration, invasion, and epithelial–mesenchymal transition (EMT). miR-200a-3p binding sites were located within the 3′-untranslated region (3′-UTR) of the Forkhead box protein A1 (FOXA1) mRNA.ConclusionWe developed and validated a diagnostic and prognostic prediction model for CRC. miR-200a-3p was determined to be a potential diagnostic and prognostic biomarker for CRC.

Modal parameters can reflect the dynamic characteristics of the structure and can be used to control vibration. To identify the operational modal parameters of linear slow-time-varying structures only from non-stationary vibration response signals, a method based on moving window locality preserving projections (MWLPP) algorithm is proposed. Based on the theory of “time freeze”, the method selects a fixed length window and takes the displacement response signal in each window as a stationary random sequence. The locality preserving projections algorithm is used to identify the transient modal frequency and modal shape of the structure at this window. The low-dimensional embedding of the displacement response data set calculated by locality preserving projections (LPP) corresponds to the modal coordinate response matrix, and the transformation matrix corresponds to the modal shape matrix. The simulation results of the mass slow-time-varying three degree of freedom (DOF) and the density slow-time-varying cantilever beam show that the new method can effectively identify the modal shape and modal natural frequency of the linear slow-time-varying only from the non-stationary vibration response signal, and the performance is better than the moving window principal component analysis (MWPCA).

Background: Down-regulation of suppressor of cytokine signaling 3 (SOCS3) inhibits prostate cancer (PCa) cell growth. Liver X receptors (LXRs) agonists have been recently introduced for PCa treatment. We postulated that LXR may inhibit the carcinogenesis of PCa via the SOCS3 pathway. Methods: LNCaP cells were cultured and transfected with SOCS3 small-interfering RNA (SOCS3-siRNA) and control small-interfering RNA (control-siRNA). Then cells were treated with LXR activator (GW3965). The expressions of PCa related transcript factors, e.g. transcription 3 (STAT3), nuclear factor kappa B (NF-κB) and activation protein 1(AP1) were detected by western blot assay. In vitro cell proliferation, cell migration, cell invasion and apoptosis were analysed. Nude mice were used for in vivo tumorgenesis. Results: In cells treated with control-siRNA, GW3965 enhanced SOCS3 expression and significantly inhibited the phosphorylation of STAT3, NF-κB and AP1 expressions, accompanied by dramatically reduced cellular proliferation rate, immigration and invasion of cultured cells. In cells treated with SOCS3-siRNA, the inhibitory effects of LXR activator on the phosphorylation of STAT3 and expressions of NF-κB and AP1 were totally abolished. The cell proliferation rate, immigration and invasion were markedly elevated by SOCS3 gene mutation, even with GW3965 treatment. The in vivo tumorgenesis assay showed that GW3965 significantly reduced the tumor volumes in tumor-bearing nude mice receiving saline injection, but failed to limit the tumor volume in tumor-bearing nude mice receiving SOCS3 antibody injection. Conclusion: Our results provide evidence in support of the notion that LXR agonist may regulate the carcinogenesis of PCa via the SOCS3 pathway.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the risk factors of impaired male fertility potential. Studies have investigated the effect of CP/CPPS on several semen parameters but have shown inconsistent results. Hence, we performed a systematic literature review and meta-analysis to assess the association between CP/CPPS and basic semen parameters in adult men. METHODS: Systematic literature searches were conducted with PubMed, EMBASE and the Cochrane Library up to August 2013 for case-control studies that involved the impact of CP/CPSS on semen parameters. Meta-analysis was performed with Review Manager and Stata software. Standard mean differences (SMD) of semen parameters were identified with 95% confidence intervals (95% CI) in a random effects model. RESULTS: Twelve studies were identified, including 999 cases of CP/CPPS and 455 controls. Our results illustrated that the sperm concentration and the percentage of progressively motile sperm and morphologically normal sperm from patients with CP/CPPS were significantly lower than controls (SMD (95% CI) -14.12 (-21.69, -6.63), -5.94 (-8.63, -3.25) and -8.26 (-11.83, -4.66), respectively). However, semen volume in the CP/CPPS group was higher than in the control group (SMD (95% CI) 0.50 (0.11, 0.89)). There was no significant effect of CP/CPPS on the total sperm count, sperm total motility, and sperm vitality. CONCLUSIONS: The present study illustrates that there was a significant negative effect of CP/CPPS on sperm concentration, sperm progressive motility, and normal sperm morphology. Further studies with larger sample sizes are needed to better illuminate the negative impact of CP/CPPS on semen parameters.

Gastric cancer (GC) remains a global healthcare challenge because of its high incidence and poor prognosis. The efficacy of current chemotherapy regimens for advanced GC is limited. T cells, which have been implicated in the progression of GC, have a significant impact in the tumor microenvironment. With a more detailed understanding of the mechanisms underlying the cancer immunoediting process, immunotherapy may become a promising treatment option for patients with GC. Several clinical trials are currently investigating different mechanisms targeting the tumor immune response. The present review summarized T cell-involved immune responses and various immunotherapy strategies for GC. [ABSTRACT FROM AUTHOR]