Comparison of Short-Term Outcomes After Robotic Versus Laparoscopic Radical Gastrectomy for Advanced Gastric Cancer in Elderly Individuals: A Propensity Score-Matching Study.

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

Trajectories of neutrophil-to-lymphocyte ratios during neoadjuvant chemotherapy correlate with short- and long-term outcomes in gastric cancer: a group-based trajectory analysis.

BACKGROUND: Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported. METHODS: This study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups. RESULTS: Ultimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005). CONCLUSION: There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

Activation of lipophagy ameliorates cadmium-induced neural tube defects via reducing low density lipoprotein cholesterol levels in mouse placentas.

Neural tube defects (NTDs) represent a prevalent and severe category of congenital anomalies in humans. Cadmium (Cd) is an environmental teratogen known to cause fetal NTDs. However, its underlying mechanisms remain elusive. This study aims to investigate the therapeutic potential of lipophagy in the treatment of NTDs, providing valuable insights for future strategies targeting lipophagy activation as a means to mitigate NTDs.We successfully modeled NTDs by Cd exposure during pregnancy. RNA sequencing was employed to investigate the transcriptomic alterations and functional enrichment of differentially expressed genes in NTD placental tissues. Subsequently, pharmacological/genetic (Atg5-/- placentas) experiments confirmed that inducing placental lipophagy can alleviate Cd induced-NTDs. We found that Cd exposure caused NTDs. Further analyzed transcriptomic data from the placentas with NTDs which revealed significant downregulation of low-density lipoprotein receptor associated protein 1(Lrp1) gene expression responsible for positive regulation of low-density lipoprotein cholesterol (LDL-C) transport. Correspondingly, there was an increase in maternal serum/placenta/amniotic fluid LDL-C content. Subsequently, we have discovered that Cd exposure activated placental lipophagy. Pharmacological/genetic (Atg5-/- placentas) experiments confirmed that inducing placental lipophagy can alleviate Cd induced-NTDs. Furthermore, our findings demonstrate that activation of placental lipophagy effectively counteracts the Cd-induced elevation in LDL-C levels. Lipophagy serves to mitigate Cd-induced NTDs by reducing LDL-C levels within mouse placentas.

Design, synthesis, and evaluation of formylpiperazine analogs of Ferrostatin-1 as novel improved ferroptosis inhibitors.

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Construction and validation of risk model of EMT-related prognostic genes for kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a prevalent type of urological malignancy. The present study aimed to predict biomarkers for KIRC. METHODS: We collected transcriptomic and clinical information for KIRC from The Cancer Genome Atlas and GSE22541 cohorts. RESULTS: Unsupervised clustering of 35 epithelial-mesenchymal transformation (EMT)-related differentially expressed gene profiles divided samples into two clusters with distinct immune characteristics. Six genes (IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN) were found to construct a prognostic risk model using multivariate Cox regression analysis. Kaplan-Meier analysis suggested the better prognosis of the KIRC patients in the low-risk group than that in the high-risk group. Immune infiltration analyses was conducted using xCell and single-sample gene set enrichment analysis, indicating that the risk score was associated with the immune microenvironment of the KIRC. Prognostic marker gene-targeted medications with high drug sensitivity were predicted in KIRC patients. CONCLUSIONS: In summary, the present study identified IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN as prognostic biomarkers, providing insight into immunotherapy and gene-targeted drugs of KIRC.

Value of the Preoperative D-Dimer to Albumin Ratio for Survival and Recurrence Patterns in Gastric Cancer.

BACKGROUND: D-dimer (DDI) and albumin are prognostic markers for numerous cancers; however, the predictive value of the preoperative DDI-to-albumin ratio (DAR) on the survival and recurrence patterns of gastric cancer (GC) remains unclear. OBJECTIVE: The aim of this study was to explore the prognostic value of the DAR in GC. METHODS: Our study included 1766 patients with GC, divided into training and testing cohorts at a ratio of 7:3. Patients were classified into either a high-DAR group (> 0.0145) or low-DAR group (≤ 0.0145) according to the cut-off value of receiver operating characteristic (ROC) curve analysis. The relationship between the DAR and recurrence pattern was analyzed in stage II/III patients. RESULTS: Eight preoperative hematological factors were included and 17 composite inflammatory markers were constructed. ROC and random forest analyses indicated that among 17 markers, DAR was the best predictor for overall survival (OS) in GC (p < 0.01). High DAR was significantly associated with poor OS (hazard ratio [HR] 1.89, p < 0.001) and recurrence-free survival (RFS; HR 1.85, p < 0.001). Subgroup analysis showed no differences in OS and RFS between the high- and low-DAR groups in stage I or pT1/2 or pN0/1 patients; however, in stage II/III or pT3/4 or pN2/3 patients, the high-DAR group had shorter OS and RFS rates than the low-DAR group (p < 0.001). Similar results were found in the testing cohort. According to the multivariate analysis based on the training cohort, five indices, including DAR, cT stage, cN stage, age and body mass index (BMI), were incorporated to establish a nomogram model to predict the long-term prognosis of GC. The model showed comparable forecast performance in predicting OS (C-index: 0.773 vs. 0.786) and RFS (C-index: 0.788 vs. 0.795) compared with pTNM. Recurrence pattern analysis in stage II/III patients showed that the high-DAR group had a higher incidence of peritoneal implantation and early recurrence (ER) than the low-DAR group, and the post-recurrence survival in the high-DAR group was significantly shorter than that in the low-DAR group (p = 0.016). CONCLUSION: The preoperative DAR is a new biomarker for the long-term survival prediction of GC. In advanced GC, a preoperative DAR > 0.0145 aids the timely detection of ER and peritoneal recurrence after surgery, thus guiding individual follow-up strategies.

CDK5 promotes apoptosis and attenuates chemoresistance in gastric cancer via E2F1 signaling.

BACKGROUND: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. METHODS: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. RESULTS: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. CONCLUSION: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer.

Evaluation of dynamic recurrence risk for locally advanced gastric cancer in the clinical setting of adjuvant chemotherapy: a real-world study with IPTW-based conditional recurrence analysis.

BACKGROUND: The long-term dynamic recurrence hazard of locally advanced gastric cancer (LAGC) in the clinical setting of adjuvant chemotherapy (ACT) remains unclear. PURPOSE: This study aimed to investigate the dynamic recurrence risk of LAGC in patients who received ACT or not. METHODS: The study assessed data from patients with LAGC who underwent radical gastrectomy between January, 2010 and October, 2015. Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias between the ACT and observational (OBS) groups. Conditional recurrence-free survival (cRFS) and restricted mean survival time (RMST) were used to assess the survival differences. RESULTS: In total, 1,661 LAGC patients were included (ACT group, n = 1,236 and OBS group, n = 425). The recurrence hazard gradually declined; in contrast, cRFS increased with RFS already accrued. Following IPTW adjustment, the cRFS rates were higher in the ACT group than those in the OBS group for patients at baseline or with accrued RFS of 1 and 2 years (p˂0.05). However, the cRFS rates of the ACT group were comparable with those of the OBS group for patients with accrued RFS of 3 or more years (p > 0.05). Likewise, the 5-year △RMST between the ACT and OBS groups demonstrated a similar trend. Moreover, the hematological metastasis rate of the ACT group was significantly lower than that of the OBS group for patients at baseline or with accrued RFS of 1 and 2 years, respectively (p˂0.05). CONCLUSIONS: Although ACT could provide substantial benefits for patients with LAGC, the differences in recurrence hazard between the ACT and OBS groups may attenuate over time, which could help guide surveillance and alleviate patients' anxiety. Further prospective large-scale studies are warranted.

Discovery of marine phidianidine-based Nrf2 activators and their potential against oxLDL- and HG-induced injury in HUVECs.

One effective strategy for treating atherosclerosis is to inhibit the injury of vascular endothelial cells (VECs) induced by oxidized low-density lipoprotein (oxLDL) and high glucose (HG). This study synthesized and evaluated a series of novel Nrf2 activators derived from the marine natural product phidianidine for their ability to protect human umbilical VECs against oxLDL- and HG-induced injury. The results of in vitro bioassays demonstrated that compound D-36 was the most promising Nrf2 activator, effectively inhibiting the apoptosis of HUVECs induced by oxLDL and HG. Furthermore, Nrf2 knockdown experiments confirmed that compound D-36 protected against oxLDL- and HG-induced apoptosis in HUVECs by activating the Nrf2 pathway. These findings provide important insights into a new chemotype of marine-derived Nrf2 activators that could potentially be optimized to develop effective anti-atherosclerosis agents.

Oncological outcomes of laparoscopic versus open radical total gastrectomy for upper-middle gastric cancer after neoadjuvant chemotherapy: a study of real-world data.

BACKGROUND: Laparoscopic technique has been increasingly used in gastrectomy, but the safety and feasibility of the laparoscopic total gastrectomy (LTG) for advanced proximal gastric cancer (PGC) after neoadjuvant chemotherapy (NAC) is unclear. METHODS: A retrospective analysis of 146 patients who received NAC followed by radical total gastrectomy at Fujian Medical University Union Hospital from January 2008 to December 2018 was performed. The primary endpoints were long-term outcomes. RESULTS: The patients were divided into two groups: 89 were in the LTG group and 57 were in the open total gastrectomy (OTG) group. The LTG group had a significantly shorter operative time (median 173 min vs. 215 min, p < 0.001), less intraoperative bleeding (62 ml vs. 135 ml, p < 0.001), higher total lymph node (LN) dissections (36 vs 31, p = 0.043), and higher total chemotherapy cycle completion rate (≥ 8 cycles) (37.1% vs. 19.7%, p = 0.027) than OTG. The 3-year overall survival (OS) of the LTG group was significantly higher than that of the OTG group (60.7% vs. 35%, p = 0.0013). Survival with inverse probability weighting(IPW) correction for Lauren type, ypTNM stage, NAC schemes and the times at which the surgery was performed showed that there was no significant difference in OS between the two groups (p = 0.463). Postoperative complications (25.8% vs. 33.3%, p = 0.215) and recurrence-free survival (RFS) (p = 0.561) between the LTG and OTG groups were also comparable. CONCLUSION: In experienced gastric cancer surgery centers, LTG is recommended as the preferred option for such patients who performed NAC, owing to its long-term survival is not inferior to OTG, and it offers less intraoperative bleeding, better chemotherapy tolerance than conventional open surgery.

Comparison of robotic versus laparoscopic versus open distal gastrectomy for locally advanced gastric cancer: a prospective trial-based economic evaluation.

IMPORTANCE: It is largely unclear whether robotic distal gastrectomy (RDG) is cost-effective for locally advanced gastric cancer (LAGC). OBJECTIVE: To evaluate the cost-effectiveness of RDG, laparoscopic distal gastrectomy (LDG), and open distal gastrectomy (ODG) for patients with LAGC. DESIGN, SETTING, AND PARTICIPANTS: Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. A decision-analytic model was constructed to evaluate the cost-effectiveness of RDG, LDG, and ODG. EXPOSURES: RDG, LDG, and ODG. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio (ICER) and quality-adjusted life year (QALY). RESULTS: This pooled analysis of two randomized controlled trials included 449 patients: 117, 254, and 78 patients in the RDG, LDG, and ODG groups, respectively. After IPTW, RDG demonstrated its priority in terms of less blood loss, postoperative length, and complication rate (all P < 0.05). RDG also showed higher QOL with more cost, representing an ICER of $85,739.73 per QALY and $42,189.53 per QALY compared to LDG and ODG, respectively. In probabilistic sensitivity analysis, RDG achieved the best cost-effectiveness for patients with LAGC only when the willingness-to-pay threshold was > $85,739.73 per QALY, which significantly exceeded 3 times Chinese per capita GDP. Furthermore, one of the most important factors was the indirect costs of robotic surgery in terms of the cost-effectiveness of RDG compared to that of LDG or ODG. CONCLUSIONS AND RELEVANCE: Although improved short-term outcomes and QOL were seen in patients underwent RDG, the economic burden should be considered in the clinical decision-making regarding robotic surgery use for patients with LAGC. Our findings may vary in different health care settings and affordability. Trial registration CLASS-01 trial (ClinicalTrials.gov, CT01609309) and FUGES-011 trial (ClinicalTrials.gov, NCT03313700).

A Novel ypTLM Staging System Based on LODDS for Gastric Cancer After Neoadjuvant Therapy: Multicenter and Large-Sample Retrospective Study.

BACKGROUND: The accuracy of the eighth AJCC ypTNM staging system on the prognosis of gastric cancer (GC) patients after neoadjuvant therapy (NAT) is controversial. This study aimed to develop and validate a novel staging system using the log odds of positive lymph nodes scheme (LODDS). METHODS: A retrospective analysis of 606 GC patients who underwent radical gastrectomy after neoadjuvant therapy was conducted as the development cohort. (Fujian Medical University Affiliated Union Hospital (n = 183), Qinghai University Affiliated Hospital (n = 169), Mayo Clinic (n = 236), Lanzhou University First Hospital (n = 18)). The validation cohort came from the SEER database (n = 1701). A novel ypTLoddsS (ypTLM) staging system was established using the 3-year overall survival. The predictive performance of two systems was compared. RESULTS: Two-step multivariate Cox regression analysis in both cohorts showed that ypTLM was an independent predictor of overall survival of GC patients after neoadjuvant therapy (HR: 1.57, 95% CI: 1.30-1.88, p < 0.001). In the development cohort, ypTLM had better discrimination ability than ypTNM (C-index: 0.663 vs 0.633, p < 0.001), better prediction homogeneity (LR: 97.7 vs. 70.9), and better prediction accuracy (BIC: 3067.01 vs 3093.82; NRI: 0.36). In the validation cohort, ypTLM had a better prognostic predictive ability (C-index: 0.614 vs 0.588, p < 0.001; LR: 11,909.05 vs. 11,975.75; BIC: 13,263.71 vs 13,328.24; NRI: 0.22). The time-dependent ROC curve shows that the predictive performance of ypTLM is better than ypTNM, and the analysis of the decision curve shows that ypTLM achieved better net benefits. CONCLUSION: A LODDS-based ypTLM staging system based on multicenter data was established and validated. The predictive performance was superior to the eighth AJCC ypTNM staging system.

First record of Fusarium concentricum (Hypocreales: Hypocreaceae) isolated from the moth Polychrosis cunninhamiacola (Lepidoptera: Tortricidae) as an entomopathogenic fungus.

Fusarium concentricum Nirenberg & O' Donnell (Ascomycota: Hypocreales) is a fungal species known to infect plants, but never reported as entomopathogenic. Polychrosis cunninhamiacola Liu et Pei (Lepidoptera: Tortricidae: Olethreutinae) is a major and widespread insect pest causing economic losses to cultivated Chinese fir Cunninghamia lanceolata (Lamb.) Hook. It is routinely controlled by extensive use of chemical insecticides, which is perceived as environmentally unsustainable. During March and April of 2019-2020, muscardine cadavers of larvae and pupae of P. cunninhamiacola infected with growing fungus were collected in a fir forest in northern Guangdong Province, China. Conidia were isolated and cultured on PDA medium, from which the fungal strain was identified as F. concentricum FCPC-L01 by morphology and by sequence alignment match with Tef-1α gene. Pathogenicity bioassays at the conidial concentration 1 × 107 revealed P. cunninhamiacola adults and Danaus chrysippus (L.) (Lepidoptera: Nymphalidae) larvae are sensitive to the fungal infection, but not the fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae). We believe results indicate this fungal strain might be applicable against specific target insect pests. As this is the first record of a natural infection caused by F. concentricum in insects, we propose host specificity tests should be done to evaluate its potential as a biocontrol agent.

Delta computed tomography radiomics features-based nomogram predicts long-term efficacy after neoadjuvant chemotherapy in advanced gastric cancer.

BACKGROUND AND OBJECTIVE: No effective preoperative tool is available for predicting the prognosis of advanced gastric cancer (AGC) treated by neoadjuvant chemotherapy (NAC). We aimed to explore the association between change values ("delta") in the radiomic signatures of computed tomography (CT) (delCT-RS) before and after NAC for AGC and overall survival(OS). METHODS AND DESIGN: A total of 132 AGC patients with AGC were studied as a training cohort in our center, and 45 patients from another center were used as an external validation set. A radiomic signatures-clinical-nomogram(RS-CN) was established using delCT-RS and preoperative clinical variables. The prediction performance of RS-CN was evaluated using the area under the receiver operating characteristic (ROC)curve (AUC values), time-dependent ROC, decision curve analysis(DCA) and C-index. RESULTS: Multivariable Cox regression analyses showed that delCT-RS, cT-stage, cN-stage, Lauren-type and the value of variation of carcinoma embryonic antigen (CEA) between NAC were independent risk factors for 3-year OS of AGC. In the training cohort, RS-CN had a good prediction performance for OS (C-Index 0.73) and AUC values were significantly better than those of delCT-RS, ypTNM-stage and tumor regression grade(TRG) (0.827 vs 0.704 vs 0.749 vs 0.571, p < 0.001). DCA and time-dependent ROC of RS-CN were better than those of ypTNM stage, TRG grade and delCT-RS. The prediction performance of the validation set was equivalent to that of the training set. The cut-off (177.2) of RS-CN score was obtained from X-Tile software, a score of > 177.2 was defined as high-risk group(HRG), and scores of ≤ 177.2 were defined as the low-risk group(LRG). The 3-year OS and disease free survival(DFS) of patients in the LRG were significantly better than those in the HRG. Adjuvant chemotherapy(AC) can only significantly improve the 3-year OS and DFS of the LRG. (p < 0.05). CONCLUSIONS: Our nomogram based on delCT-RS has good prediction of prognosis before surgery and helps identify patients that are most likely to benefit from AC. It works well in precise and individualised NAC in AGC.

Real-Time Transformation of Flux-Closure Domains with Superhigh Thermal Stability.

Polar topologies have received extensive attention due to their exotic configurations and functionalities. Understanding their responsive behaviors to external stimuli, especially thermal excitation, is highly desirable to extend their applications to high temperature, which is still unclear. Here, combining in situ transmission electron microscopy and phase-field simulations, the thermal dynamics of the flux-closure domains were illuminated in PbTiO3/SrTiO3 multilayers. In-depth analyses suggested that the topological transition processes from a/c domains to flux-closure quadrants were influenced by the boundary conditions of PbTiO3 layers. The symmetrical boundary condition stabilized the flux-closure domains at higher temperature than in the asymmetrical case. Furthermore, the reversible thermal responsive behaviors of the flux-closure domains displayed superior thermal stability, which maintained robust up to 450 °C (near the Curie temperature). This work provides new insights into the dynamics of polar topologies under thermal excitation and facilitates their applications as nanoelectronics under extreme conditions.

Surgical Outcomes, Technical Performance, and Surgery Burden of Robotic Total Gastrectomy for Locally Advanced Gastric Cancer: A Prospective Study.

OBJECTIVE: To compare the short-term outcomes, surgery burden, and technical performance of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for gastric cancer (GC). SUMMARY OF BACKGROUND DATA: The impact of robotic systems on total gastrectomy remains obscure. METHODS: This prospective study included 50 patients with advanced proximal GC underwent RTG combined with spleen-preserving splenic hilar lymphadenectomy between March 2018 and February 2020. Patients who underwent LTG in the FUGES-002, http://links.lww.com/SLA/C929 study were enrolled to compare the outcomes between RTG and LTG. RESULTS: After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The RTG group had a lower volume of intraoperative blood loss than the LTG group (38.7 vs 66.4 mL, P = 0.042). Significantly more extraperigastric lymph nodes were retrieved in the RTG group than in the LTG group (20.2 vs 17.5, P = 0.039). The average number of errors was lower in the RTG group than in the LTG group (43.2 vs 53.8 times/case, P < 0.001). The RTG group had a higher technical skill score (30.2 vs 28.4, P < 0.001) and a lower surgery task load index (33.2 vs 39.8, P < 0.001) than the LTG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.6% vs 16.7%, P = 0.748). CONCLUSIONS: In complex total gastrectomy for GC, compared with traditional laparoscopic surgery, robotic surgery provides a technically superior operative environment and reduces surgeon workload at high-volume specialized institutions.

Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study.

BACKGROUND: Language deficits frequently occur during the prodromal stages of Alzheimer's disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD. METHODS: The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance. RESULTS: In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks. CONCLUSIONS: PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.

Preoperative Muscle-Adipose Index: A New Prognostic Factor for Gastric Cancer.

BACKGROUND: Studies have shown that traditional nutrition indicators and body composition indicators are closely related to prognosis after radical gastric cancer (GC) surgery. However, the effect of the combined muscle and adipose composite on the prognosis of GC has not been reported. METHODS: The clinicopathological data of 514 patients with GC were retrospectively analyzed. The skeletal muscle adipose tissue were measured by preoperative CT images to obtain the muscle index and adipose index. X-tile software was used to determine the diagnostic threshold of muscle-adipose imbalance. RESULTS: The 5-year OS and RFS of the muscle-adipose imbalanced group were significantly worse than those of the balanced group. Multivariate analysis showed that muscle-adipose imbalance and the CONUT score were independent prognostic factors of OS and RFS (p < 0.05). The nuclear density curve showed that the recurrence risk of the muscle-adipose imbalanced group was higher than that of the balanced group, whereas the nuclear density curve of the CONUT score was confounded. Incorporating the muscle-adipose index into cTNM has the same prognostic performance as the pTNM staging system. Chemotherapy-benefit analysis showed that stage II/III patients in the muscle-adipose balanced group could benefit from adjuvant chemotherapy. CONCLUSIONS: The preoperative muscle-adipose index discovered for the first time is a new independent prognostic factor that affects the prognosis with GC. In addition, the preoperative muscle-adipose index is better than traditional nutrition and body composition indicators in terms of the prognostic evaluation of GC patients and the predictive value of recurrence risk.

A matched cohort study of the failure pattern after laparoscopic and open gastrectomy for locally advanced gastric cancer: does the operative approach matter?

BACKGROUND: Due to lacking evidence for confirming the efficacy of performing laparoscopic surgery for locally advanced gastric cancer (LAGC). Therefore, this study aimed to compare the static and dynamic failure patterns after laparoscopic gastrectomy (LG) and open gastrectomy (OG) in LAGC. METHODS: A total of 1792 LAGC patients who underwent radical resection between January 2010 and January 2017 were divided into the LG group (n = 1557) and the OG group (n = 235). Propensity score matching was performed to balance the two groups. Dynamic hazard rates of failure were calculated using the hazard function. Early and late failure were defined as failure occurring before and after 2 years since surgery, respectively. RESULTS: A total of 1175 patients with LAGC were included after matching (LG group, n = 940; OG, n = 235). The failure rate of the whole cohort was 43.2% (508/1175), accounting for 41.4% (389/940) and 50.6% (119/235) in the LG and OG groups, respectively. Although the two groups showed no significant differences in failure rate for any failure type, landmark analysis showed a lower early distant recurrence rate in the stage IIa-IIIb subgroup of the LG group (OG versus LG: 30.3% versus 21.1%, P = 0.004). The dynamic hazard rate peaked at 9.4 months (peak rate = 0.0186) before gradually declining. In stage IIa-IIIb patients, the hazard rate of the OG group remained significantly higher than that of the LG group within the first 2 years in terms of distant recurrence (peak rate: OG versus LG, 0.0091 versus 0.0055). CONCLUSION: Given the differences in early failure between LG and OG, more intensive surveillance for distant recurrence within the first 2 years should be considered for patients with stage IIa-IIIb after OG.