Predictive nomogram for lymph node metastasis and survival in gastric cancer using contrast-enhanced computed tomography-based radiomics: a retrospective study.

Background: Lymph node involvement significantly impacts the survival of gastric cancer patients and is a crucial factor in determining the appropriate treatment. This study aimed to evaluate the potential of enhanced computed tomography (CT)-based radiomics in predicting lymph node metastasis (LNM) and survival in patients with gastric cancer before surgery. Methods: Retrospective analysis of clinical data from 192 patients diagnosed with gastric carcinoma was conducted. The patients were randomly divided into a training cohort (n = 128) and a validation cohort (n = 64). Radiomic features of CT images were extracted using the Pyradiomics software platform, and distinctive features were further selected using a Lasso Cox regression model. Features significantly associated with LNM were identified through univariate and multivariate analyses and combined with radiomic scores to create a nomogram model for predicting lymph node involvement before surgery. The predictive performance of radiomics features, CT-reported lymph node status, and the nomogram model for LNM were compared in the training and validation cohorts by plotting receiver operating characteristic (ROC) curves. High-risk and low-risk groups were identified in both cohorts based on the cut-off value of 0.582 within the radiomics evaluation scheme, and survival rates were compared. Results: Seven radiomic features were identified and selected, and patients were stratified into high-risk and low-risk groups using a 0.582 cut-off radiomics score. Univariate and multivariate analyses revealed that radiomics features, diabetes mellitus, Nutrition Risk Screening (NRS) 2002 score, and CT-reported lymph node status were significant predictors of LNM in patients with gastric cancer. A predictive nomogram model was developed by combining these predictors with the radiomics score, which accurately predicted LNM in gastric cancer patients before surgery and outperformed other models in terms of accuracy and sensitivity. The AUC values for the training and validation cohorts were 0.82 and 0.722, respectively. The high-risk and low-risk groups in both the training and validation cohorts showed significant differences in survival rates. Conclusion: The radiomics nomogram, based on contrast-enhanced computed tomography (CECT ), is a promising non-invasive tool for preoperatively predicting LNM in gastric cancer patients and postoperative survival.

Novel affibody molecules as potential agents in molecular imaging for MAGE-A3-positive tumor diagnosis.

BACKGROUND: The cancer-testis protein melanoma antigen A3 (MAGE-A3) is highly expressed in a broad range of malignant tumor forms. It has been confirmed that affibody molecules, a novel family of small (∼6.5 kDa) targeting proteins, are useful agents for molecular imaging and targeted tumor treatment. As a novel agent for in vivo molecular imaging detection of MAGE-A3-positive tumors, the efficacy of affibody molecules was assessed in this research. METHODS: In this study, three cycles of phage display library screening resulted in the isolation of two new affibody molecules (ZMAGE-A3:172 and ZMAGE-A3:770) that attach to MAGE-A3. These molecules were then expressed in bacteria and purified. The affibody molecules with high affinity and specificity were evaluated using western blotting, immunohistochemistry, indirect immunofluorescence, surface plasmon resonance, and near-infrared optical imaging of tumor-bearing nude mice. RESULTS: The selected ZMAGE-A3 affibodies can precisely bind to the MAGE-A3 protein in living cells and display high-affinity binding to the MAGE-A3 protein at the molecular level. Furthermore, the accumulation of DyLight755-labeled ZMAGE-A3:172 or ZMAGE-A3:770 in MAGE-A3-positive tumors was achieved as early as 30 min and disappeared at 48 h post-injection. CONCLUSION: Our findings support the potential of the two MAGE-A3 protein-binding affibody molecules for their use as molecular imaging agents.

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo.

Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound----colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model in vitro and established a well-recognized rat model of BLM-induced lung injury in vivo. The results demonstrated that colchicine-myricetin hybrid protected BEAS-2B cells against BLM-induced cell injury in an increased dose manner, and reduced wet/dry weight ratio, histological scoring, and inflammation cytokines IL-1ß, IL-6, IL-18, and TNF-α levels of lung tissue of the rats. Furthermore, we found colchicine-myricetin hybrid inhibited caspase-1, ASC, GSDMD, and NLRP-3 expression in vivo. Meanwhile, we used molecular docking to analyze the binding mode of colchicine-myricetin hybrid and human neutrophil elastase (HNE), it revealed that colchicine-myricetin hybrid showed strong binding affinity toward human neutrophil elastase when compared to its parent molecules. In conclusion, It is suggested that colchicine-myricetin hybrid antagonized acute lung injury by focusing on multi-targets via multi-mechanisms, and might be served as a potential therapeutic agent for acute lung injury.

Design, synthesis and evaluation of a myricetin and nobiletin hybrid compound for alleviating hyperuricemia based on metabolomics and gut microbiota.

Hyperuricemia (HUA) is the fourth most common basic metabolic disease that can cause damage to multiple organs throughout the body. In this study, a hybrid compound consisting of myricetin and nobiletin was synthesized and its biological activity was evaluated. We named the hybrid compound MNH, and its structure was confirmed by spectroscopy. This study used serum metabolomics profiling with LC/MS and 16S rRNA gene sequencing analysis to explore the anti-HUA efficacy of MNH on a yeast paste-induced mouse model. The results showed that serum uric acid (UA), creatinine (CRE) and urea nitrogen (BUN) levels were significantly decreased after the intervention of MNH. The efficacy of MNH in lowering UA was somewhat greater than that of myricetin and nobiletin. In addition, MNH could repair the renal histopathological damage. Moreover, serum metabolomics demonstrated that MNH regulated the metabolic pathways involved in glycerophospholipid metabolism, arachidonic acid metabolism and alanine etc. Furthermore, MNH supplementation restored the composition of gut microbiota with remarkable reductions in Lactobacillus and Limosilactobacillus and significant elevations in norank_f_Muribaculaceae and Bacteroides at the genus level. Taken together, these results indicated that MNH might represent a protective effect against HUA via modulating gut microbiota and metabolomics.

Lactate Dehydrogenase and Risk of Readmission with Gastric Cancer: A Propensity Score Matching Analysis.

PURPOSE: Readmission is one of the measures of quality of care and potential costs. This study aimed to determine whether lactate dehydrogenase (LDH) is associated with an increased risk of 30-day readmission in gastric cancer. METHODS: We performed a retrospective study of patients who underwent radical gastrectomy for gastric cancer at our institution between July 2014 and May 2018. Balanced cohorts were created by propensity score matching (PSM) with a 1:1 ratio to generate the elevated LDH (ELDH) group (n = 151) and the low LDH group (Control) (n = 302). To determine the incidence, causes, and risk factors of 30-day readmission, subgroup analyzes were performed and used to develop an efficient prediction model. RESULTS: A total of 788 patients met the criteria to be included in the study. The cutoff value for serum LDH was 215.5. After PSM, a total of 302 patients were matched in pairs (ELDH group, n = 151, Control group, n = 151). ELDH levels had a higher risk of readmission (p = 0.005, Odds ratio 3.768, 95% confidence interval 1.493-9.510). The pre-match 30-day readmission rate was 7.2 percent, and common causes of post-match readmission included infection-related symptoms, gastrointestinal symptoms, and gastrointestinal bleeding. CONCLUSIONS: Patients with preoperative ELDH levels, postoperative complications, and high preoperative American Society of Anesthesiologists Scores had a higher risk of readmission 30 days after surgery.

Perturbations in gastrointestinal tract microbiota composition and function in individuals with yellow-greasy tongue coating / 数字中医药（英文）

@#【Objective】  To study the composition and function of tongue coating (TC) and gastrointestinal tract (GIT) microbiota in participants with yellow-greasy tongue coating (YGTC), and to explore the representative metabolite markers and pathways in this group. 【Methods】  Subjects with YGTC or thin-white tongue coating (TWTC) were recruited from December 1, 2021 to October 30, 2022, and the TC and fecal samples were collected. Samples were subjected to both whole-genome shotgun (WGS), and 16S rRNA gene sequencing. The α-diversity analysis, principal component analysis (PCA), and Spearman correlation analysis were performed for two groups. Ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC–MS/MS) analysis was used to analyze metabolomics and enrichment of metabolic pathways. 【Results】  The results revealed 20 YGTC participates and 19 TWTC participates. At the genus level, the dominant bacterial species of TC flora and intestinal flora in the two groups were roughly the same, but the relative kurtosis difference was marked, and the abundance of potentially pathogenic bacteria in TC and fecal samples of YGTC subjects was higher. There were 9 down-regulated microorganisms in the TC samples, 26 down-regulated microorganisms, and 6 up-regulated microorganisms in YGTC subjects. The α-diversity analysis indicated that the Chao and abundance-based coverage estimator (ACE) indices of TC bacteria in the YGTC subjects showed a decreasing trend, but the difference was not statistically significant (P > 0.05). The α-diversity of fecal samples and the Chao and ACE indices decreased significantly (P < 0.05). PCA showed that the microflora structure of TC and fecal samples were significantly different between the two groups. Spearman correlation analysis showed that there was no correlation between TC and fecal microorganisms at phyla and genus levels in the same subjects (P > 0.05). The metabolomics results demonstrated that fumarate reductase, V/A ATPase, and phosphatidylethanolamine were increased, and glycerate-3p, UDP-glucose, and quinone oxidoreductase metabolites were decreased in YGTC TC samples. Inosine monophosphate (IMP), uridine monophosphate (UMP), and gamma-aminobutyric acid(GABA) were increased in YGTC fecal samples, while the contents of ribo-5P, histidine, biotin,and cobalamin were decreased. Metabolic pathway analysis indicated that the abundance of the TC and fecal samples of the YGTC subjects was relatively low in various metabolic pathways, including amino acid metabolism, carbohydrate metabolism, nitrogen metabolism, and energy metabolism. 【Conclusion】  Structural and functional changes in TC and GIT microbiota or metabolite markers could be potential biological bases of YGTC formation.

Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo.

Colchicine is a bioactive alkaloid originally from Colchicum autumnale and possesses excellent antiproliferative activity. However, colchicine-associated severe toxicity, gastrointestinal side effects in particular, limits its further therapeutic use. In the current study, we thus designed and synthesized a novel hybrid (CMH) by splicing colchicine and magnolol, a multifunctional polyphenol showing favorable gastrointestinal protection. The antitumor activity of CMH in Lewis lung carcinoma (LLC) was then evaluated in vitro and in vivo. Biologically, CMH inhibited the growth of LLC cells with an IC50 of 0.26 µM, 100 times more potently than cisplatin (26.05 µM) did. Meanwhile, the cytotoxicity of CMH was 10-fold lower than that of colchicine in normal human lung cells (BEAS-2B). In C57BL/6 mice xenograft model, CMH (0.5 mg/kg) worked as efficacious as colchicine (0.5 mg/kg) to inhibit tumor growth and 2 times more potently than cisplatin (1 mg/kg). In terms of mortality, 7 out of 10 mice died in colchicine group (0.75 mg/kg), while no death was observed in groups receiving CMH or cisplatin at 0.75 mg/kg. Mechanistic studies using Western blot revealed that CMH dose-dependently suppressed the protein expression of phosphorylated ERK. Molecular docking analysis further indicated that CMH was well fitted in the colchicine binding site of tubulin and formed several hydrogen bonds with tubulin protein. These results enable our novel hybrid CMH as a potential antineoplastic agent with lower toxicity, and provide perquisites for further investigation to confirm the therapeutic potentiality of this novel hybrid.

Risk Factors and Prognostic Analysis of Gastrointestinal Stromal Tumor Recurrence-Metastasis.

Objective: Gastrointestinal stromal tumors (GISTs) are potential malignancies that occur in the digestive tract. This study aimed to investigate the risk factors and prognosis of recurrence and metastasis of gastrointestinal stromal tumor (GIST). Methods: From January 2018 to December 2019, 422 patients with GIST who received surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Their clinical data were retrospectively analyzed, and their follow-ups were continued until March 31, 2022. Subsequently, univariate and multivariate Cox analyses, survival curves, and nomograms were adopted to explore the relationship between clinicopathological characteristics and recurrence or metastasis in patients with GIST. Results: Univariate and multivariate Cox analysis exhibited that the prognosis of patients was affected by tumor rupture (P = 0.040), tumor location (P < 0.001), tumor diameter (P = 0.016), mitotic figures (P < 0.001), and risk grade (P < 0.009). The above variables were selected to create the nomogram for 3-year disease-free survival (DFS). The 3-year the ROC (receiver operating characteristic) curves of the nomogram were (0.878 95% confidence interval [CI]: 0.871-0.939). Conclusion: Collectively, risk factors affecting postoperative recurrence or metastasis of GIST consist of primary site of tumors, tumor rupture, tumor diameter >10 cm, high-risk tumor classification, and mitotic figures ≥10 per 50 HPFs. And the application of nomogram may help physicians provide individualized diagnosis and treatment for patients with GISTs following surgical resection.

Association of Sarcopenia and Low Nutritional Status with Unplanned Hospital Readmission after Radical Gastrectomy in Patients with Gastric Cancer: A Case-Control Study.

Objective: Sarcopenia is one of the influencing factors of poor prognosis in patients with gastric cancer but the association with readmission are unknown. We aimed to explore factors associated with readmission after gastrectomy and to determine whether preoperative sarcopenia is a common outcome in readmitted patients. Methods: In this case-control study, patients who underwent gastric resection in the First Affiliated Hospital of Wenzhou Medical University between April 2016 and September 2017 were included. The reasons of readmission patients were described. The readmission patients and non-readmission patients were matched by propensity score matching (PSM). The univariate analysis was applied for the baseline characteristics, operative details, postoperative prognosis and discharge disposition, and multiple logistic regression analysis for the independent risk factors of readmission. Results: The unplanned readmission rate within 30 days of radical gastrectomy for gastric cancer was 6.5% (43/657). The average time interval from discharge to readmission was 13 days. Delayed gastric evacuation was the main cause of readmission (18.6%, 8/43). Body mass index (BMI), nutritional risk screening (NRS) 2002 score, history of abdominal surgery, sarcopenia, and preoperative albumin were included in the multivariate logistic regression analysis. NRS 2002 (OR = 3.43, 95% CI: 1.10-10.72, P=0.034) and sarcopenia (OR = 4.25, 95% CI: 1.13-16.02, P=0.033) were found to be independently associated with unplanned readmission within 30 days of radical gastrectomy for cancer. Other factors such as age, sex, BMI, American Society of Anesthesiologists grade, surgical method, operation and reconstruction type, TNM stage, surgical duration, previous abdominal surgery, and preoperative albumin and hemoglobin level were not associated with unplanned readmission after radical gastrectomy for cancer. Conclusions: Sarcopenia and low nutritional status are independently associated with unplanned readmission within 30 days of radical gastrectomy for cancer.

Effect of Short-Term Preoperative Parenteral Nutrition Support for Gastric Cancer Patients with Sarcopenia: a Propensity Score Matching Analysis.

INTRODUCTION: Sarcopenia is well recognized as an unfavorable prognostic marker for gastric cancer (GC) patients. Currently, few nutritional interventions-such as parenteral nutrition-exist for the treatment of patients with sarcopenia. This study aimed to estimate the effectiveness of short-term preoperative parenteral nutrition (PN) in GC patients with sarcopenia. MATERIALS AND METHODS: We collected data on GC patients with sarcopenia who underwent radical gastrectomy at our hospital from 2010 to 2018. A 1:1 ratio propensity score matching (PSM) was applied to establish the PN and control groups. Data were analyzed using the chi-squared, Mann-Whitney U, and Fisher's exact tests. RESULTS: In total, 428 patients met the inclusion criteria, and the propensity scores identified 166 matched pairs of patients with sarcopenia. The overall incidence of postoperative complications between both groups was not significantly different (P = 0.728). The PN group had a lower rate of intra-abdominal infection (P = 0.032) and higher hospitalization costs (P < 0.001) than the control group. Multivariate analysis demonstrated that age, Charlson score, and TNM stage were independent risk factors for postoperative complications. Additionally, subgroup analysis revealed that short-term preoperative PN support is associated with decreased postoperative surgical complications in patients with albumin levels < 35 g/L (P = 0.025). CONCLUSION: Short-term preoperative PN support is not associated with reduction of overall complication rate in patients with GC and sarcopenia. However, those with sarcopenia and hypoalbuminemia benefited from preoperative PN support.

Comprehensive Analysis to Identify MAGEA3 Expression Correlated With Immune Infiltrates and Lymph Node Metastasis in Gastric Cancer.

Gastric cancer (GC) is an aggressive malignant tumor and causes a significant number of deaths every year. With the coming of the age of cancer immunotherapy, search for a new target in gastric cancer may benefit more advanced patients. Melanoma-associated antigen-A3 (MAGEA3), one of the members of the cancer-testis antigen (CTA) family, was considered an important part of cancer immunotherapy. We evaluate the potential role of MAGEA3 in GC through the TCGA database. The result revealed that MAGEA3 is upregulated in GC and linked to poor OS and lymph node metastasis. MAGEA3 was also correlated with immune checkpoints, TMB, and affected the tumor immune microenvironment and the prognosis of GC through CIBERSORT, TIMER, and Kaplan-Meier plotter database analysis. In addition, GSEA-identified MAGEA3 is involved in the immune regulation of GC. Moreover, the protein-protein interaction (PPI) networks of MAGEA3 were constructed through STRING database and MAGEA3-correlated miRNAs were screened based on the joint analysis of multiple databases. In terms of experimental verification, we constructed pET21a (+)/MAGEA3 restructuring plasmids and transformed to Escherichia coli Rosetta. MAGEA3 protein was used as an antigen after being expressed and purified and can effectively detect the specific IgG in 93 GC patients' serum specimens with 44.08% sensitivity and 92.54% specificity. Through further analysis, the positive rate of MAGEA3 was related to the stage and transfer number of lymph nodes. These results indicated that MAGEA3 is a novel biomarker and correlated with lymph node metastasis and immune infiltrates in GC, which could be a new target for immunotherapy.

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Metabolic syndrome-related sarcopenia is associated with worse prognosis in patients with gastric cancer: A prospective study.

OBJECTIVES: Sarcopenia and metabolic syndrome (MetS) are associated with the prognosis from malignant tumors. However, evidence of the relationship between sarcopenia and MetS among gastric cancer (GC) patients following radical gastrectomy is lacking. This study assessed the association between preoperative sarcopenia and MetS among GC patients and analyzed the prognosis of patients with different malnutrition statuses. METHODS: We prospectively assessed the preoperative statuses of sarcopenia and MetS among patients who underwent radical gastrectomy from July 2014 to December 2017. We combined sarcopenia and MetS to generate four groups: MetS-related sarcopenia group (MSS), sarcopenia group (S), MetS group (MS), and normal group (N). RESULTS: A total of 749 patients with resectable GC were included in this study. Preoperative MetS was associated with sarcopenia (p < 0.001). Multivariate logistic regression presented that MetS-related sarcopenia (OR = 2.445; p = 0.010) and sarcopenia alone (OR = 2.117; p = 0.001) were independent predictors of grade Ⅱ and above complications, while MetS alone was not (p = 0.342). Cox regression analysis revealed that MetS-related sarcopenia led to the worst prognosis in the four groups (MSS vs MS: HR = 3.555, p < 0.001; MSS vs N: HR = 2.020, p = 0.003; MSS vs S: HR = 1.763, p = 0.021). However, the MetS group had better prognosis than the normal group (MS vs N: HR = 0.568, p = 0.048). CONCLUSION: Preoperative MetS was associated with sarcopenia among GC patients. MetS-related sarcopenia resulted in a significantly worse prognosis. The long-term prognoses of patients with sarcopenia were impaired by preoperative MetS, while patients without sarcopenia benefited. Thus, patients with both sarcopenia and MetS require more medical interventions.

Diffuse Reduction of Spleen Density Is an Independent Predictor of Post-Operative Outcomes After Curative Gastrectomy in Gastric Cancer: A Multi-Center Study.

Objectives: The present study aimed to explore the association between spleen density and post-operative outcomes of patients after curative gastrectomy. Methods: From June 2014 to December 2015, we conducted a retrospective study to analyze pertinent clinical data from gastric cancer patients who underwent gastrectomy at the First and the Second Affiliated Hospital of Wenzhou Medical University. Spleen density was determined via computed tomography scans. Univariate and multivariate analyses were performed to determine the risk factors associated with post-operative outcomes after gastric cancer surgery. Results: Three hundred and ninety five patients were included, of whom 98 (24.8%) were defined as having a diffuse reduction of spleen density based on diagnostic cutoff values (spleen density ≤43.89 HU). Multivariate analysis revealed diffuse reduction of spleen density as an independent risk factor for post-operative complications and long-term overall survival. Conclusions: Spleen density can predict severe postoperative complications and long-term overall survival in gastric cancer patients. As an imaging evaluation method, spleen density is a novel tool can be used in clinical as a prognostic predictor for patients with gastric cancer.

Preoperative Cachexia predicts poor outcomes in young rather than elderly gastric cancer patients: a prospective study.

BACKGROUND: Cachexia affects nearly 50-80% of cancer patients, and most studies have only focused on elderly patients. We investigated preoperative cachexia in gastric cancer (GC) patients by age group and comprehensively analyzed the impact of preoperative cachexia on the prognosis of GC patients in all age groups. METHODS: In total, 575 patients were prospectively analyzed. The effect of preoperative cachexia on overall survival (OS) in all the patients and in patients with different age groups were investigated using log-rank test and Cox proportional hazards regression, respectively. RESULTS: In total, 35.8% (206 of 575) individuals were diagnosed with cachexia. The median survival of cachexia patients (29.2 months) was shorter than that of non-cachexia patients (35.7 months). Cachexia (HR =1.976, P<0.001), age (HR =1.811, P<0.001), readmission (HR =2.559, P<0.001), tumor size (HR =1.639, P=0.003), TNM stage (stage II: HR =2.215, P=0.017; stage III: HR =5.758, P<0.001), whole stomach cancer (HR =2.639, P<0.001), and combined operation (HR =1.598, P=0.032) were independently associated with worse OS. After grouping by age, cachexia was associated with OS in patients younger than 50 years old (HR =4.947, P=0.029), patients 51-60 years old (HR =2.232, P=0.026), and patients 61-70 years old (HR =1.806, P=0.032), but not in patients older than 71 years (HR =1.411, P=0.119). Further, cachexia only significantly affected the postoperative length of stay (P=0.015) and hospitalization costs (P=0.032) in patients younger than 50 years old. CONCLUSIONS: Preoperative cachexia predicts poor outcome in younger GC patients, and greater attention should be paid to these patients.

A quantified risk-scoring system including the visceral fat area for peritoneal metastasis of gastric cancer.

Background: Peritoneal metastases of gastric cancer are usually detected using imaging, However, the results of imaging modalities are not always reliable; therefore, the prediction of prognosis based on these findings is therefore inaccurate. As visceral obesity has been identified as a potential risk factor for cancer, the present study aimed to evaluate the predictive value of visceral fat area (VFA), a representative marker of visceral obesity, for peritoneal metastasis in patients with gastric cancer and to construct a reliable preoperative prediction system for peritoneal metastasis. Patients and methods: We enrolled 859 patients with gastric cancer. The VFA and other objective clinical tumor characteristics were evaluated using receiver operating characteristic (ROC) curves. Independent predictors of peritoneal metastasis were determined using logistic regression analysis; a prediction system was also evaluated using ROC curves. Results: The ROC curves indicated a VFA cutoff value of 91.00 cm2 as predictive of peritoneal metastasis. On logistic regression, visceral obesity (VFA ≥91.00 cm2) was identified as an independent predictor of peritoneal metastasis, with an area under the ROC curve of 0.659; the platelet-to-lymphocyte ratio (PLR), invasion depth, and vascular invasion were also identified as independent predictors. On integrating these predictors into a single prediction system, peritoneal metastases were more reliably predicted (area under the ROC curve=0.779). Conclusions: Visceral obesity, as defined by the VFA, effectively predicted peritoneal metastases in our cohort. Our scoring system may be a reliable instrument for identifying patients with peritoneal metastasis.

Muscle Mass, Density, and Strength Are Necessary to Diagnose Sarcopenia in Patients With Gastric Cancer.

BACKGROUND: Accurate evaluation of muscle strength and function is difficult. Commonly known as sarcopenia, skeletal muscle loss is closely correlated with the prognosis of patients diagnosed with gastric cancer (GC). We wondered the correlation between skeletal muscle measures combined with computed tomography and grip strength (GS) and short-term outcomes after radical gastrectomy (RG) in patients with GC. MATERIALS AND METHODS: We analyzed 594 patients with GC who underwent RG. The skeletal muscle index (SMI), skeletal muscle density (Hounsfield unit average calculation [HUAC]), and GS were measured. The skeletal muscle gauge (SMG) was created by multiplying SMI and HUAC. Logistic regression modeling and multivariate analysis were used. RESULTS: Univariate analysis showed that low SMI, low HUAC, low GS, and low SMG were predictors of short-term complications after surgery. Compared with other muscle-related factors (AUCHUAC = 0.559, AUCSMI = 0.575, AUCGS = 0.580, AUCSMG = 0.598, AUCSMI+GS = 0.559), low GS plus SMG (AUCGS plus SMG = 0.614, P < 0.01) was a more accurate independent risk factor for postoperative complications. Moreover, the risk model with SMG plus GS for the diagnosis of skeletal muscle loss was superior to the other models (c-index = 0.729). CONCLUSIONS: Skeletal muscle measures using computed tomography and GS are closely correlated with short-term outcomes of patients diagnosed with GC after RG. The model contained SMG plus GS could effectively predict for patients with GC after RG at high risk of short-term outcomes. SMG plus GS has the highest accuracy for the several evaluation methods of sarcopenia.

Overexpression of SIRT4 inhibits the proliferation of gastric cancer cells through cell cycle arrest.

The sirtuins (SIRTs) are a family of nicotinamide-adenine dinucleotide (NAD)+-dependent protein deacetylases. SIRT4 is a mitochondrial NAD+-dependent adenosine diphsophate-ribosyltransferase. Recent studies demonstrated that SIRT4 can regulate glutamine metabolism and thus act as a tumor suppressor. However, the association of SIRT4 with gastric cancer remains unknown. The present study investigated the potential role of SIRT4 in the proliferation of human gastric cancer cells. Gastric cancer cell lines (SGC-7901 and MNK45) overexpressing SIRT4 were established by lentiviral infection. The effect of overexpression of SIRT4 in gastric cancer was evaluated by determining the cell viability, proliferation activity and colony-forming ability of gastric cancer cells in vitro. Furthermore, the cell cycle profiles of SGC-7901 and MNK45 cells overexpressing SIRT4 were evaluated to provide insights into potential underlying molecular mechanisms. Overexpression of SIRT4 significantly inhibited the proliferation and colony-forming ability of the gastric cancer cells in vitro. Furthermore, overexpression of SIRT4 induced G1 cell cycle arrest via suppression of phosphorylated extracellular signal-regulated kinase, cyclin D and cyclin E. In conclusion, the results of the present study indicated that SIRT4 may function as a tumor suppressor in gastric cancer by regulating cell proliferation, therefore SIRT4 may be a potential therapeutic target against this disease.

Novel ELISA for serodiagnosis of nasopharyngeal carcinoma based on a B cell epitope of Epstein-Barr virus latent membrane protein 2.

Epstein-Barr virus (EBV) is widespread and is associated with nasopharyngeal carcinoma (NPC). Serological detection of EBV is commonly used for screening, diagnosis and epidemiological surveys of NPC. In the present study, a novel B cell multi-epitope peptide fusion protein (EBV-LMP2-3B), which is composed of three B cell linear epitopes (RIEDPPFNSLL, TLNLT and KSLSSTEFIPN) of EBV latent membrane protein 2 (LMP2), was expressed in a prokaryotic expression system and purified using Ni2+-nitrilotriacetate-Sepharose. The immunogenicity and binding specificity of EBV-LMP2-3B were evaluated on the basis of antibody responses in immunized BALB/c mice, western blotting and indirect immunofluorescence assay. Evaluation of EBV-LMP2-3B as a serological diagnostic reagent was performed using an indirect ELISA in 198 patients with NPC and 102 healthy adults. These results revealed that EBV-LMP2-3B was able to eliminate the high-titer serum antibody response in BALB/c mice. Western blot analysis and indirect immunofluorescence assay confirmed that the mouse immune sera recognized the native LMP2. Compared with healthy adults, patients with NPC demonstrated significantly greater reactivity to EBV-LMP2-3B (P<0.05). Furthermore, it was possible to effectively detect specific IgG in sera from patients with NPC, with a sensitivity of 91.91% and specificity of 93.14%, representing an improvement over the traditional viral capsid antigen-IgA-based detection method with 59.59% sensitivity and 75.49% specificity. In conclusion, the EBV-LMP2-3B protein may be used as a serological diagnostic reagent to screen for and diagnose NPC.

Sirtuin-4 (SIRT4), a therapeutic target with oncogenic and tumor-suppressive activity in cancer.

Several members of the sirtuin (SIRT) family, a highly conserved family of NAD+-dependent enzymes, have been shown to play a critical role in both promoting and/or suppressing tumorigenesis. In this study, recent progress in the field concerning SIRT4 and cancer was reviewed, and the relationship between SIRT4 and tumors was investigated. Subsequently, we evaluated the role of SIRT4 with oncogenic or tumor-suppressive activity in cancer, which may provide insight in identifying the underlying mechanism of action of SIRT4 in cancer. Finally, we explored the potential of SIRT4 as a therapeutic target in cancer therapy.