Deep Learning Radiomics Nomogram Based on Enhanced CT to Predict the Response of Metastatic Lymph Nodes to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Effect of preoperative immunonutrition on postoperative short-term clinical outcomes in patients with gastric cancer cachexia: a prospective randomized controlled trial.

BACKGROUND: Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of the recommendation is weak, and the level of evidence is low. The benefits of preoperative immunonutrition still remain controversial. PATIENTS AND METHODS: 112 patients with gastric cancer cachexia were enrolled in the study and randomly assigned in a 1:1 ratio to receive either preoperative enteral immunonutrition support (IN, n = 56) or standard enteral nutrition support (SEN, n = 56). The primary endpoint was the incidence of infectious complications, and the secondary endpoints included the nutritional indicators, inflammatory markers, immune parameters, postoperative recovery and complications and gastrointestinal intolerance reactions. RESULTS: The incidence of postoperative infectious complications(P = 0.040) and overall complications (P = 0.049)was significantly lower in the IN group compared to the SEN group. In terms of laboratory inflammatory indexes, patients in the IN group demonstrated significantly lower levels of white blood cells (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6), as well as higher levels of lymphocytes (LYMPH) and immunoglobulin A (IgA), compared to patients in the SEN group, with statistically significant differences. In terms of clinical outcomes, the IN group had a shorter duration of antibiotic use (P = 0.048), shorter hospital stay (P = 0.018), and lower total hospital costs (P = 0.034) compared to the SEN group. The IN group also experienced significantly less weight loss after surgery (P = 0.043). CONCLUSION: Preoperative administration of immunonutrition formula has a positive impact on the incidence of infectious complications in patients with gastric cancer cachexia after surgery. It improves patients' inflammatory and immune status, shortens hospital stays, and reduces healthcare costs. Preoperative use of immunonutrition may contribute to the improvement of prognosis in this high-risk population.

Development and validation of nomograms for predicting overall survival and cancer-specific survival in elderly patients with locally advanced gastric cancer: a population-based study.

OBJECTIVE: To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. METHODS: The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell's concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. RESULTS: In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C-index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. CONCLUSION: The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.

Comparison of short- and long-term outcomes between laparoscopic and open gastrectomy for locally advanced gastric cancer following neoadjuvant chemotherapy: a propensity score matching analysis.

BACKGROUND: This study was performed to evaluate the safety and efficacy of laparoscopic gastrectomy (LG) in patients with locally advanced gastric cancer (LAGC) who received neoadjuvant chemotherapy (NACT). METHODS: We retrospectively analyzed patients who underwent gastrectomy for LAGC (cT2-4aN+M0) after NACT from January 2015 to December 2019. The patients were divided into a LG group and an open gastrectomy (OG) group. The short- and long-term outcomes in both groups were examined following propensity score matching. RESULTS: We retrospectively reviewed 288 patients with LAGC who underwent gastrectomy following NACT. Of these 288 patients, 218 were enrolled; after 1:1 propensity score matching, each group comprised 81 patients. The LG group had significantly lower estimated blood loss than the OG group [80 (50-110) vs. 280 (210-320) mL, P < 0.001) but a longer operation time [205 (186.5-222.5) vs. 182 (170-190) min, P < 0.001], a lower postoperative complication rate (24.7% vs. 42.0%, P = 0.002), and a shorter postoperative hospitalization period [8 (7-10) vs. 10 (8-11.5) days, P = 0.001]. Subgroup analysis revealed that patients who underwent laparoscopic distal gastrectomy had a lower rate of postoperative complications than patients in the OG group (18.8% vs. 38.6%, P = 0.034); however, such a pattern was not seen in patients who underwent total gastrectomy (32.3% vs. 45.9%, P = 0.251). The 3-year matched cohort analysis showed no significant difference in overall survival or recurrence-free survival (log-rank P = 0.816 and P = 0.726, respectively) (71.3% and 65.0% in OG vs. 69.1% and 61.7% in LG, respectively). CONCLUSION: In the short term, LG following NACT is safer and more effective than OG. However, the long-term results are comparable.

Short- and long-term outcomes of laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making: a high-volume center retrospective study with propensity score matching.

BACKGROUND: Some studies have demonstrated the short-term recovery course for patients who underwent laparoscopic gastrectomy according to preoperative computed tomography angiography (CTA) assessment. However, reports of the long-term oncological outcomes are still limited. METHODS: The data of 988 consecutive patients who underwent laparoscopic or robotic radical gastrectomy between January 2014 and September 2018 were analyzed retrospectively at our center, and propensity score matching was used to eliminate bias. Study cohorts were divided into the CTA group (n = 498) and the non-CTA group (n = 490) depending on whether preoperative CTA was available. The primary and secondary endpoints were the 3-year overall survival (OS) and disease-free survival (DFS) rates and the intraoperative course and short-term outcomes, respectively. RESULTS: 431 patients were included in each group after PSM. Compared with the non-CTA group, the CTA group had more harvested lymph nodes and less operative time, blood loss, intraoperative vascular injury and total cost, especially in the subgroup analysis with BMI ≥ 25 kg/m2 patients. There was no difference in the 3 year OS and DFS between the CTA group and the non-CTA group. When further stratified by BMI < 25 or ≥ 25 kg/m2, the 3-year OS and DFS were significantly higher in the CTA group than in the non-CTA group in terms of BMI ≥ 25 kg/m2. CONCLUSIONS: Laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making has the possibility of improving short-term outcomes. However, there is no difference in the long-term prognosis, except for a subgroup of patients with BMI ≥ 25 kg/m2.

FXR Maintains the Intestinal Barrier and Stemness by Regulating CYP11A1-Mediated Corticosterone Synthesis in Biliary Obstruction Diseases.

Biliary obstruction diseases are often complicated by an impaired intestinal barrier, which aggravates liver injury. Treatment of the intestinal barrier is often neglected. To investigate the mechanism by which intestinal bile acid deficiency mediates intestinal barrier dysfunction after biliary obstruction and identify a potential therapeutic modality, we mainly used a bile duct ligation (BDL) mouse model to simulate biliary obstruction and determine the important role of the bile acid receptor FXR in maintaining intestinal barrier function and stemness. Through RNA-seq analysis of BDL and sham mouse crypts and qRT-PCR performed on intestinal epithelial-specific Fxr knockout (FxrΔIEC) and wild-type mouse crypts, we found that FXR might maintain intestinal stemness by regulating CYP11A1 expression. Given the key role of CYP11A1 during glucocorticoid production, we also found that FXR activation could promote intestinal corticosterone (CORT) synthesis by ELISA. Intestinal organoid culture showed that an FXR agonist or corticosterone increased crypt formation and organoid growth. Further animal experiments showed that corticosterone gavage treatment could maintain intestinal barrier function and stemness, decrease LPS translocation, and attenuate liver injury in BDL mice. Our study hopefully provides a new theoretical basis for the prevention of intestinal complications and alleviation of liver injury after biliary obstruction.

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.

Short- and long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer by the same surgical team: a propensity score matching analysis.

BACKGROUND: Research on short-term outcomes and oncology results after robotic gastrectomy (RG) is still limited, especially from a single surgical team. The purpose of this study was to compare the short-term and long-term outcomes of robotic and laparoscopic gastrectomy (LG). METHODS: Between October 2014 and September 2019, 1686 consecutive patients who underwent MIS gastrectomy were enrolled. The patients were divided into RG and LG groups according to surgical type. Groups were matched at a 1:1 ratio using propensity scores based on the following variables: age, sex, ASA score, primary tumor location, histologic type, pathological stage, and neoadjuvant chemotherapy. The primary outcomes were 3-year overall survival (OS) and relapse-free survival (RFS). The secondary outcomes were postoperative short-term outcomes. RESULTS: Demographic and baseline characteristics were similar between the two groups after matching. Compared to the LG group, the RG group had a significantly higher retrieved lymph node (LN) number (32.15 vs 30.82, P = 0.040), more retrieved supra-pancreatic LNs (12.45 vs 11.61, P = 0.028), lower estimated blood loss (73.67 vs 98.08 ml, P < 0.001), but longer operation time (205.18 vs 185.27 min, P < 0.001) and higher hospitalization costs ($13,607 vs $10,928, P < 0.001) in the matched cohort. In the subgroup analysis, we observed that compared with LG, patients with advanced gastric cancer benefitted more from RG surgery. The matched cohort analysis demonstrated no statistically significant differences for 3-year OS or RFS (log-rank, P = 0.648 and P = 0.951, respectively): 80.3% and 77.0% in LG vs. 81.2% and 76.6% in RG, respectively. CONCLUSION: RG has certain technical advantages over LG, especially in patients with advanced gastric cancer. However, RG does not improve long-term oncology outcomes.

A novel prognostic factor TIPE2 inhibits cell proliferation and promotes apoptosis in pancreatic ductal adenocarcinoma (PDAC).

Background: Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly discovered negative immune regulator. Studies have shown that TIPE2 causes significant malignant biological effects and is differentially expressed in various malignant tumors. However, the expression and roles of TIPE2 in pancreatic ductal adenocarcinoma (PDAC) are largely unknown. Materials and Methods: The expression of TIPE2 in PDAC tissues was assessed by immunohistochemistry, qPCR and western blot analysis and related clinicopathological parameters including survival time were analyzed. After overexpression of TIPE2, cell proliferation and apoptosis analysis were conducted, and the associated underlying molecular mechanism was also explored. Results: In the present study, TIPE2 was upregulated in early PDAC tissues, and TIPE2 expression decreased as the tumor progressed (P<0.001). TIPE2 expression was negatively associated with tumor size, TNM stage and metastasis of lymph nodes. Furthermore, as an independent risk factor, TIPE2 could be used to predict the survival of patients with PDAC (P=0.035). TIPE2 overexpression significantly suppressed the viability, proliferation and induced apoptosis of PDAC cells by inhibiting survivin and increasing the activity of caspase3/7. Conclusions: For the first time, this study demonstrated that TIPE2 is an independent prognostic factor in PDAC. TIPE2 inhibited the proliferation and induced apoptosis via regulating survivin/caspase3/7 signaling pathway. These results indicated that TIPE2 is a potential biomarker for predicting the prognosis of PDAC patients and plays a pivotal role in the progression of PDAC.

A novel role for farnesoid X receptor in the bile acid-mediated intestinal glucose homeostasis.

The farnesoid X receptor (FXR), as a bile acid (BA) sensor, plays an important role in the regulation of lipid metabolism. However, the effects and underlying molecular mechanisms of FXR on intestinal glucose homeostasis remain elusive. Herein, we demonstrated that FXR and glucose transporter 2 (GLUT2) are essential for BA-mediated glucose homeostasis in the intestine. BA-activated FXR enhanced glucose uptake in intestinal epithelial cells by increasing the expression of GLUT2, which depended on ERK1/2 phosphorylation via S1PR2. However, it also reduced the cell energy generation via inhibition of oxidative phosphorylation, which is crucial for intestinal glucose transport. Moreover, BA-activated FXR signalling potently inhibited specific glucose flux through the intestinal epithelium to the circulation, which reduced the increase in blood glucose levels in mice following oral glucose administration. This trend was supported by the changed ratio of GLUT2 to SGLT1 in the brush border membrane (BBM), including especially decreased GLUT2 abundance in the BBM. Furthermore, impaired intestinal FXR signalling was observed in the patients with intestinal bile acid deficiency (IBAD). These findings uncover a novel function by which FXR sustains the intestinal glucose homeostasis and provide a rationale for FXR agonists in the treatment of IBAD-related hyperglycaemia.

Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis.

Long noncoding RNAs (lncRNAs) display essential roles in cancer progression. FLVCR1-AS1 is a rarely investigated lncRNAs involved in various human cancers, such as hepatocellular carcinoma and lung cancer. However, its function in glioma has not been clarified. In our study, we found that FLVCR1-AS1 was highly expressed in glioma tissues and cell lines. And upregulation of FLVCR1-AS1 predicted poor prognosis in patients with glioma. Moreover, FLVCR1-AS1 knockdown inhibited proliferation, migration and invasion of glioma cells. Through bioinformatics analysis, we identified that FLVCR1-AS1 was a sponge for miR-4731-5p to upregulate E2F2 expression. Moreover, rescue assays indicated that FLVCR1-AS1 modulated E2F2 expression to participate in glioma progression. Altogether, our research demonstrates that the FLVCR1-AS1/miR-4731-5p/E2F2 axis is a novel signaling in glioma and may be a potential target for tumor therapy.

Prognostic Factors for Primary Localized Gastrointestinal Stromal Tumors After Radical Resection: Shandong Gastrointestinal Surgery Study Group, Study 1201.

BACKGROUND: Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. METHODS: Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. RESULTS: Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8-95.4), 85.9% (95% CI 84.7-87.1), and 78.8% (95% CI 77.0-80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed: PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.350 (if non-gastric GIST) + 0.000 (if no tumor rupture) + 1.259 (if tumor rupture) + 0.000 (tumor mitotic count < 6 per 50 high-power fields [HPFs]) + 1.442 (tumor mitotic count between 6 and 10 per 50 HPFs) + 2.026 (tumor mitotic count > 10 per 50 HPFs) + 0.096 × tumor size (cm). Model-predicted 1-, 3-, and 5-year RFS was S(12, X) = 0.9926exp(PI), S(36, X) = 0.9739exp(PI) and S(60, X) = 0.9471exp(PI), respectively. CONCLUSIONS: Sex, tumor location, size, mitotic count, and rupture were independently prognostic for GIST recurrence. Our RFS prediction model is effective for Chinese GIST patients.

A Nomogram for Prediction of Survival in Patients After Gastrectomy Within Enhanced Recovery After Surgery (ERAS): A Single-Center Retrospective Study.

BACKGROUND Enhanced Recovery After Surgery (ERAS) programs can optimize clinical outcomes and have been widely used across multiple specialties, but a personalized prediction model involving ERAS for the prognosis of gastric cancer is lacking. MATERIAL AND METHODS We retrospectively collected clinical data on 725 gastric cancer patients within ERAS who underwent curative gastric resection in the Affiliated Hospital of Qingdao University from 2007 to 2014. Kaplan-Meier method, log-rank test, and Cox proportional risk model were used to determine the independent prognostic factors of patients. The accuracy of model was evaluated by C-index, calibration curve, and Decision Curve Analysis (DCA), and the receiver operator characteristic (ROC) curve was used to compare the nomogram model with the predictive value of TNM staging system. RESULTS The 5-year overall survival (OS) of 725 patients within ERAS was 72.5%. Age at diagnosis, T stage, N stage, and postoperative complications were determined to be independent factors affecting the prognosis of patients within ERAS, and nomogram model was constructed. The C-index of the training group was 0.809 and that of the verification group was 0.804; the calibration curves and DCA of the 2 groups showed good accuracy. Through verification, we found that, compared with the TNM staging assessment method, the nomogram model was more accurate in predicting the prognosis of gastric cancer. CONCLUSIONS This study identified factors affecting the prognosis of patients with gastric cancer, and we constructed the first prognostic nomogram model in ERAS mode to facilitate postoperative personalized prognostic evaluation.

Concordance Between Watson for Oncology and a Multidisciplinary Clinical Decision-Making Team for Gastric Cancer and the Prognostic Implications: Retrospective Study.

BACKGROUND: With the increasing number of cancer treatments, the emergence of multidisciplinary teams (MDTs) provides patients with personalized treatment options. In recent years, artificial intelligence (AI) has developed rapidly in the medical field. There has been a gradual tendency to replace traditional diagnosis and treatment with AI. IBM Watson for Oncology (WFO) has been proven to be useful for decision-making in breast cancer and lung cancer, but to date, research on gastric cancer is limited. OBJECTIVE: This study compared the concordance of WFO with MDT and investigated the impact on patient prognosis. METHODS: This study retrospectively analyzed eligible patients (N=235) with gastric cancer who were evaluated by an MDT, received corresponding recommended treatment, and underwent follow-up. Thereafter, physicians inputted the information of all patients into WFO manually, and the results were compared with the treatment programs recommended by the MDT. If the MDT treatment program was classified as "recommended" or "considered" by WFO, we considered the results concordant. All patients were divided into a concordant group and a nonconcordant group according to whether the WFO and MDT treatment programs were concordant. The prognoses of the two groups were analyzed. RESULTS: The overall concordance of WFO and the MDT was 54.5% (128/235) in this study. The subgroup analysis found that concordance was less likely in patients with human epidermal growth factor receptor 2 (HER2)-positive tumors than in patients with HER2-negative tumors (P=.02). Age, Eastern Cooperative Oncology Group performance status, differentiation type, and clinical stage were not found to affect concordance. Among all patients, the survival time was significantly better in concordant patients than in nonconcordant patients (P<.001). Multivariate analysis revealed that concordance was an independent prognostic factor of overall survival in patients with gastric cancer (hazard ratio 0.312 [95% CI 0.187-0.521]). CONCLUSIONS: The treatment recommendations made by WFO and the MDT were mostly concordant in gastric cancer patients. If the WFO options are updated to include local treatment programs, the concordance will greatly improve. The HER2 status of patients with gastric cancer had a strong effect on the likelihood of concordance. Generally, survival was better in concordant patients than in nonconcordant patients.

Expression of Interleukin-6 and Integrin ανß6 in Colon Cancer: Association with Clinical Outcomes and Prognostic Implications.

As important factors in the tumor microenvironment, interleukin-6 (IL-6) and integrin ανß6 play significant roles in accumulating mutations that drive the progression and metastatic capacities of cancer. The aim of this study was to investigate the expression of IL-6 and integrin ανß6, their clinical significance, as well as their correlation in the colon cancer tissues of 145 cases using immunohistochemistry. Our results showed that IL-6 and integrin ανß6 are indicators of cancer progression and poor prognosis in patients with colon cancer. Moreover, their relationship may provide clues for further studies on how the tumor microenvironment mediates the development of colon cancer, as well as strategies for the identification of novel therapeutic targets in the prevention and treatment of colon cancer.

The effect of a multi-strain probiotic on growth performance, non-specific immune response, and intestinal health of juvenile turbot, Scophthalmus maximus L.

Probiotic is well known because of its health benefit on the host, including improve growth, treat disease, and enhance immunity. Currently, probiotic has been widely used in aquaculture. However, there is little information about the effect of probiotic on turbot. Therefore, an effort was made to explore the effect of a multi-strain probiotic on growth performance, non-specific immune response, and intestinal health of juvenile turbot, Scophthalmus maximus L. One hundred eighty juvenile turbot (20.04 ± 0.23 g) were randomly divided into three groups (T0, T1, T2), and fed diet were formulated to contain 0%, 1%, and 5% multi-strain probiotic, respectively. Sixty days after the feeding experiment, the growth performance, body composition, enzyme activities, and intestinal microorganism of turbot were analyzed. T2 and T1 showed better growth performance and significant higher (P < 0.05) enzyme activities than T0 (except lysozyme). Moreover, the IV (intestinal villus), IW (intestinal wall), and GC (goblet cell) were well modulated in probiotic treatments. Furthermore, Lactobacillus was found colonized in the intestine of the group fed with 5% multi-strain probiotic. These results suggested adding dietary multi-strain probiotic could positively affect for turbot aquaculture.

Suppression of NLRP3 inflammasome attenuates stress-induced depression-like behavior in NLGN3-deficient mice.

Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm. CUMS up-regulated corticosterone (CORT) in serum, and down-regulated serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in hippocampus of mice, which were significantly reversed by NLGN3 deficiency. The results further demonstrated that NLGN3-knockout improved the degenerative neurons in cortex and hippocampus of CUMS-treated mice, accompanied with a significant decrease of ionized calciumbinding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expressions. Additionally, NLGN3-KO mice challenged with CUMS showed a significant reduction of pro-inflammatory cytokines and chemokine, including tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18), interleukin-1 beta (IL-1ß), interleukin-4 (IL-4), CC-chemokine ligand-1 (CCL-1) and CXC-chemokine ligand-1 (CXCL-1), in cortex, hippocampus and amygdala tissue samples. Western blot analysis suggested that NLGN3-knockout inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor of apoptosis-associated speck like protein (ASC), and reduced the expression of Caspase-1, along with the inactivation of nuclear factor-κB (NF-κB) in CUMS-challenged mice. The role of NLGN3 in regulating depression in mice was confirmed in vitro using astrocytes stimulated by LPS that NLGN3 knockdown reduced LPS-induced inflammation. Importantly, the suppressive effects of NLGN3-knockdown on inflammatory response were reversed by NLRP3 or ASC over-expression in AST exposed to LPS. In sum, our findings indicated that suppressing NLGN3 played a potential antidepressant role in CUMS animal model by inactivating NLRP3 inflammasome, providing a new therapeutic avenue for depression.

Inhibition of KLHL21 prevents cholangiocarcinoma progression through regulating cell proliferation and motility, arresting cell cycle and reducing Erk activation.

Kelch-like family member 21 (KLHL21) is involved in cell mitosis and motility. Nevertheless, the clinical significance and biological function of KLHL21 in cholangiocarcinoma (CCA) are elusive. This is the first study to describe a pivotal role for KLHL21 in the progression of CCA. The expression of KLHL21 was elevated in CCA tissues compared with paired normal bile duct tissues. In addition, immunohistochemical and statistical analyses demonstrated that the expression of KLHL21 correlated inversely with tumor histological grade (p < 0.05) and the overall survival of patients (p < 0.01). In CCA cells, we found that the inhibition of KLHL21 significantly reduced proliferation, migration and invasion. Further results indicated that inhibition of KLHL21 triggered G0/G1 cell cycle arrest, leading to the increased expression of P21 and P27 and decreased expression of Cyclin E1, which eventually resulted in proliferation suppression in CCA cells. Furthermore, KLHL21 knockdown alleviated the activation of the Erk signaling pathway via decreasing the expression of phospho-Erk1/2. Our data demonstrated that KLHL21 plays an essential role in the tumorigenesis and progression of CCA, implying that it might serve as a potential therapeutic target for CCA treatment.