Constructing Dynamic Cross-Linking Networks as Durable Bifunctional Coating for Highly Stable Zinc Anodes.

The serious dendrite growth and H2O-induced side reactions on the Zn electrode lead to a significant fading in the cycling performance, hindering the development of commercial applications of aqueous Zn-ion batteries (AZIBs). Herein, a novel bifunctional network coating of dynamically cross-linking sodium alginate with trehalose has been rationally constructed on the Zn anode (Zn@AT). Firstly, the AT coating possesses abundant zinophilic oxygen-containing functional groups, which are able to induce uniform Zn2+ ion flux. Secondly, the AT coating as a solid barrier can effectively inhibit H2O-induced side reactions by lowering the activity of H2O molecules. More specially, based on the dynamic cross-linking, AT network coating is endowed with self-healing capacity during cycling for durable battery operation. Consequentially, Zn@AT anodes in symmetric cells can cycle stably for 2787 h at 2 mA cm-2/2 mAh cm-2, and even achieve a significantly long cycle performance of 1087 h at large charge/discharge depths of 10 mA cm-2/10 mAh cm-2. Moreover, the Zn@AT//MnO2 full cell shows excellent specific capacity of 175 mAh g-1 after 400 cycles. This study lights an effective strategy to enhance the durability of Zn electrodes in AZIBs.

Massively Reconstructing Hydrogen Bonding Network and Coordination Structure Enabled by a Natural Multifunctional Co-Solvent for Practical Aqueous Zn-Ion Batteries.

The practical application of aqueous Zn-ion batteries (AZIBs) is hindered by the crazy Zn dendrites growth and the H2O-induced side reactions, which rapidly consume the Zn anode and H2O molecules, especially under the lean electrolyte and Zn anode. Herein, a natural disaccharide, d-trehalose (DT), is exploited as a novel multifunctional co-solvent to address the above issues. Molecular dynamics simulations and spectral characterizations demonstrate that DT with abundant polar -OH groups can form strong interactions with Zn2+ ions and H2O molecules, and thus massively reconstruct the coordination structure of Zn2+ ions and the hydrogen bonding network of the electrolyte. Especially, the strong H-bonds between DT and H2O molecules can not only effectively suppress the H2O activity but also prevent the rearrangement of H2O molecules at low temperature. Consequently, the AZIBs using DT30 electrolyte can show high cycling stability even under lean electrolyte (E/C ratio = 2.95 µL mAh-1), low N/P ratio (3.4), and low temperature (-12 °C). As a proof-of-concept, a Zn||LiFePO4 pack with LiFePO4 loading as high as 506.49 mg can be achieved. Therefore, DT as an eco-friendly multifunctional co-solvent provides a sustainable and effective strategy for the practical application of AZIBs.

The Gastric Cancer Immune Prognostic Score (GCIPS) Shows Potential in Predicting an Unfavorable Prognosis for Gastric Cancer Patients Undergoing Immune Checkpoint Inhibitor Treatment.

(1) Background: This study aims to explore the predictive capability of the Gastric Cancer Immune Prognostic Score (GCIPS) for an unfavorable prognosis in gastric cancer patients undergoing immune checkpoint inhibitor (ICI) treatment. (2) Methods: This study included 302 gastric cancer patients who underwent treatment with ICIs at our institution from January 2017 to December 2022. The patients were randomly divided into a test set (201 cases) and a validation set (101 cases) using a random number table. Kaplan-Meier survival analysis and the log-rank test were used to investigate survival differences. Cox regression analysis and Lasso regression analysis were employed to establish the GCIPS and identify independent prognostic indicators. ROC curves, time-ROC curves, and nomograms were utilized to further explore the predictive performance of GCIPS. (3) Results: The test set and validation set showed no statistical differences in clinical and pathological features, as well as blood parameters (all p > 0.05). Cox regression analysis revealed that white blood cells (WBC), lymphocytes (LYM), and the international normalized ratio (INR) emerged as independent prognostic blood indicators after eliminating collinearity through Lasso analysis. The GCIPS was established using ß coefficients with the following formula: GCIPS = WBC (109/L) × 0.071 - LYM (109/L) × 0.375 + INR × 2.986. ROC curves based on death and time-ROC curves demonstrated that the GCIPS had higher AUCs than other classical markers at most time points. Survival analyses of all subgroups also revealed a significant correlation between the GCIPS and patients' progression-free survival (PFS) and overall survival (OS) (all p < 0.05). Furthermore, the GCIPS was identified as an independent prognostic factor for both PFS and OS. Analyses in the validation set further confirmed the reliability and stability of the GCIPS in predicting patient prognosis. Finally, nomograms incorporating the GCIPS exhibited high accuracy in both the test and validation sets. Additionally, the nomograms revealed that the GCIPS had a higher prognostic value than any other factor, including the TNM stage. (4) Conclusions: The GCIPS demonstrated its ability to predict adverse outcomes in gastric cancer patients undergoing ICIs treatment and had a high prognostic value. As a readily accessible and simple novel biomarker, it effectively identified high-risk patients.

Body composition change indices combined with Prognostic Nutritional Index predicts the clinical outcomes of patients with gastric cancer treated with immune checkpoint inhibitor.

OBJECTIVE: This study aimed to investigate the prognostic significance of the Prognostic Nutritional Index (PNI) in conjunction with body composition change indices, namely subcutaneous fat area (SFA) and skeletal muscle index (SMI), with regard to clinical outcomes in patients with gastric cancer (GC) undergoing immune checkpoint inhibitors (ICIs) treatment. METHODS: This retrospective investigation encompassed patients with comprehensive clinical and pathological data, inclusive of portal phase enhanced CT images. Continuous variables underwent analysis utilizing the Student t-test or Mann-Whitney U-test, while categorical variables were assessed employing the Pearson chi-squared test or Fisher test. Survival outcomes were evaluated using Kaplan-Meier survival curves and the Log-rank test. Independent prognostic indicators were determined through Cox regression analysis, and a nomogram predicting survival probability for progression-free survival (PFS) and overall survival (OS) was constructed. RESULTS: Within the PNI-SFA groups, patients in Group 1 exhibited inferior PFS and OS compared to the other two groups. Similarly, among the PNI-SMI groups, Group 1 patients demonstrated poorer PFS and OS. PNI-SMI and Eosi were identified as independent prognostic factors through Cox regression analysis. Furthermore, positive associations with patient prognosis were observed for BMI, SAF, SMI, and PNI. CONCLUSION: The comprehensive consideration of PNI-SFA and PNI-SMI proved to be a superior prognostic predictor for GC patients undergoing ICI treatment.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

The occupational burnout among medical staff with high workloads after the COVID-19 and its association with anxiety and depression.

Objective: After the end of COVID-19, medical staff were immediately faced with a high workload, leading to widespread occupational burnout. This study aims to explore the level and influencing factors of burnout among medical staff during this period, as well as its relationship with anxiety and depression. Methods: The participants' levels of burnout were assessed using Maslach Burnout Inventory-Human Services Survey (MBI-HSS), and the reliability and validity of the questionnaire were evaluated through Cronbach's α and Confirmatory Factor Analysis (CFA). Independent sample t-test, chi-square test, and Pearson analysis were employed to determine the correlation between two sets of variables. Univariate and multivariate logistic regression analyses were conducted to identify significant factors influencing burnout. Finally, nomograms were used to predict the probability of burnout occurrence. Results: This study collected a total of 1,550 questionnaires, and after excluding 45 questionnaires that were duplicates or incomplete, a sample of 1,505 (97.1%) participants were included in the final statistical analysis. Both Cronbach's α and the fit indices of CFA demonstrated excellent adaptability of the Chinese version of MBI-HSS in this study. The overall prevalence rates for emotional exhaustion (EE), depersonalization (DP), and diminished personal accomplishment (PA) were 52.4, 55.3, and 30.6%, respectively. Obtaining psychological support, health condition, relationship with family members, and insufficient sleep were identified as common contributing factors to burnout among medical staff. Additionally, age and promotion pressure were also associated with burnout among doctors, and exceeding legal working hours was an important factor for nurse burnout. The C-index for the nomograms predicting burnout among doctors and nurses was 0.832 and 0.843, respectively. Furthermore, burnout exhibited a significant linear correlation with anxiety and depression. Conclusion: After the end of COVID-19, medical staff in high workload environments were facing severe burnout, which might lead to anxiety and depression. The occupational burnout of medical staff needed to be taken seriously and actively intervened.

An oxidative stress biomarkers predict prognosis in gastric cancer patients receiving immune checkpoint inhibitor.

Objective: The development and advance of gastric cancer are inextricably linked to oxidative and antioxidant imbalance. Although immunotherapy has been shown to be clinically effective, the link between oxidative stress and gastric cancer patients treated with immune checkpoint inhibitor (ICIs) remains unknown. This study aims at looking into the prognostic value of oxidative stress scores in gastric cancer patients treated with ICIs. Methods: By taking the propagation to receiver operating characteristic (ROC) we got the best cut-off values, and divided 265 patients receiving ICIs and chemotherapy into high and low GC-Integrated Oxidative Stress Score (GIOSS) groups. We also used Kaplan-Meier and COX regression models to investigate the relationship between oxidative stress biomarkers and prognosis. Results: Through both univariate and multivariate analyses, it's shown that GIOSS severs as an independent prognostic factor for progression-free survival (PFS) and Overall survival (OS). Based on GIOSS cutoff values, patients with high GIOSS levels, compared to those with low levels exhibited shorter PFS and OS, both in the high GIOSS group, which performed poorly in the ICIs subgroup and other subgroup analyses. Conclusion: GIOSS is a biomarker that responds to systemic oxidative stress in the body and can predict prognosis in patients with gastric cancer who are taking ICIs. Additionally, it might come to medical professionals' aid in making more effective or more suitable treatment plans for gastric cancer.

Combined with prognostic nutritional index and IgM for predicting the clinical outcomes of gastric cancer patients who received surgery.

Objective: Although the survival rate of patients who undergo surgery for gastric cancer has greatly improved, still many patients have a poor prognosis. This retrospective study aimed to investigate the predictive ability of the PNI-IgM score, a combined prognostic nutritional index (PNI), and immunoglobulin M (IgM), on the prognosis of patients undergoing surgery for gastric cancer. Methods: 340 patients with gastric cancer who underwent surgery from January 2016 to December 2017 were selected. The PNI-IgM score ranged from 1 to 3: score of 1, low PNI (< 48.45) and low IgM (< 0.87); score of 2, low PNI and high IgM, or high PNI and low IgM; score of 3, high PNI and high IgM. We compared the differences in disease-free survival (DFS) and overall survival (OS) among the three groups, while univariate and multivariate analyses calculated prognostic factors for DFS and OS. In addition, the nomograms were constructed based on the results of multivariate analysis to estimate the 1-, 3- and 5-year survival probability. Results: There were 67 cases in the PNI-IgM score 1 group, 160 cases in the PNI-IgM score 2 group, and 113 cases in the PNI-IgM score 3 group. The median survival times of DFS in the PNI-IgM score group 1, the PNI-IgM score group 2, and the PNI-IgM score group 3 were 62.20 months, not reached, and not reached, and 67.57 months vs. not reached vs. not reached in three groups for OS. Patients in the PNI-IgM score group 1 had a lower DFS than the PNI-IgM score group 2 (HR = 0.648, 95% CI: 0.418-1.006, P = 0.053) and the PNI-IgM score group 3 (HR = 0.337, 95% CI: 0.194-0.585, P < 0.001). In stratified analysis, PNI-IgM score 1 had a worse prognosis in the age < 60 years group and CA724 < 2.11 U/m group. Conclusion: PNI-IgM score is a novel combination of nutritional and immunological markers that can be used as a sensitive biological marker for patients with gastric cancer who undergo surgery. The lower the PNI-IgM score, the worse the prognosis.

CD19 (+) B Cell Combined with Prognostic Nutritional Index Predicts the Clinical Outcomes of Patients with Gastric Cancer Who Underwent Surgery.

(1) Background: The aim of this study was to explore the predictive ability of lymphocyte subsets for the prognosis of gastric cancer patients who underwent surgery and the prognostic value of CD19 (+) B cell combined with the Prognostic Nutritional Index (PNI). (2) Methods: This study involved 291 patients with gastric cancer who underwent surgery at our institution between January 2016 and December 2017. All patients had complete clinical data and peripheral lymphocyte subsets. Differences in clinical and pathological characteristics were examined using the Chi-square test or independent sample t-tests. The difference in survival was evaluated using Kaplan-Meier survival curves and the Log-rank test. Cox's regression analysis was performed to identify independent prognostic indicators, and nomograms were used to predict survival probabilities. (3) Results: Patients were categorized into three groups based on their CD19 (+) B cell and PNI levels, with 56 cases in group one, 190 cases in group two, and 45 cases in group three. Patients in group one had a shorter progression-free survival (PFS) (HR = 0.444, p < 0.001) and overall survival (OS) (HR = 0.435, p < 0.001). CD19 (+) B cell-PNI had the highest area under the curve (AUC) compared with other indicators, and it was also identified as an independent prognostic factor. Moreover, CD3 (+) T cell, CD3 (+) CD8 (+) T cell, and CD3 (+) CD16 (+) CD56 (+) NK T cell were all negatively correlated with the prognosis, while CD19 (+) B cell was positively associated with the prognosis. The C-index and 95% confidence interval (CI) of nomograms for PFS and OS were 0.772 (0.752-0.833) and 0.773 (0.752-0.835), respectively. (4) Conclusions: Lymphocyte subsets including CD3 (+) T cell, CD3 (+) CD8 (+) T cell, CD3 (+) CD16 (+) CD56 (+) NK T cell, and CD19 (+) B cell were related to the clinical outcomes of patients with gastric cancer who underwent surgery. Additionally, PNI combined with CD19 (+) B cell had higher prognostic value and could be used to identify patients with a high risk of metastasis and recurrence after surgery.

Corrigendum: Controlling nutritional status (CONUT) predicts survival in gastric cancer patients with immune checkpoint inhibitor (PD-1/PD-L1) outcomes.

[This corrects the article DOI: 10.3389/fphar.2022.836958.].

Prognostic nutritional index for predicting the clinical outcomes of patients with gastric cancer who received immune checkpoint inhibitors.

Objective: Although the application of immunotherapy in gastric cancer has achieved satisfactory clinical effects, many patients have no response. The aim of this retrospective study is to investigate the predictive ability of the prognostic nutrition index (PNI) to the prognosis of patients with gastric cancer who received immune checkpoint inhibitors (ICIs). Materials and methods: Participants were 146 gastric cancer patients with ICIs (PD-1/PD-L1 inhibitors) or chemotherapy. All patients were divided into a low PNI group and a high PNI group based on the cut-off evaluated by the receiver operating characteristic (ROC) curve. We contrasted the difference in progression-free survival (PFS) and overall survival (OS) in two groups while calculating the prognosis factors for PFS and OS by univariate and multivariate analyses. Moreover, the nomogram based on the results of the multivariate analysis was constructed to estimate the 1- and 3-year survival probabilities. Results: There were 41 (28.1%) cases in the low PNI group and 105 (71.9%) cases in the high PNI group. The median survival time for PFS in the low PNI group and high PNI group was 12.30 months vs. 33.07 months, and 18.57 months vs. not reached in the two groups for OS. Patients in low PNI group were associated with shorter PFS and OS in all patients [Hazard ratio (HR) = 1.913, p = 0.013 and HR = 2.332, p = 0.001]. Additionally, in subgroup analysis, low PNI group cases also had poorer PFS and OS, especially in patients with ICIs. In addition, the multivariate analysis found that carbohydrate antigen 724 (CA724) and TNM stage were independent prognostic factors for PFS. At the same time, indirect bilirubin (IDBIL), CA724, PNI, and TNM stage were independent prognostic factors for OS. Conclusion: Prognostic nutrition index was an accurate inflammatory and nutritional marker, which could predict the prognosis of patients with gastric cancer who received ICIs. PNI could be used as a biomarker for ICIs to identify patients with gastric cancer who might be sensitive to ICIs.

The Prognostic Value of Gastric Immune Prognostic Index in Gastric Cancer Patients Treated With PD-1/PD-L1 Inhibitors.

Objective: This study aimed to investigate the prognostic value of the gastric immune prognostic index (GIPI) in gastric cancer patients treated with programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Methods: This study was conducted to elucidate the role of GIPI using the data from 146 gastric cancer patients treated with PD-1/PD-L1 inhibitors between August 2016 and December 2020 in Harbin Medical University Cancer Hospital. The GIPI calculation was based on dNLR and LDH. Patients were categorized into three groups: 1) GIPI good (LDH ≤250 U/L and dNLR ≤3); 2) GIPI intermediate (LDH >250 U/L and NLR >3); 3) GIPI poor (LDH >250 U/L and dNLR >3). The correlations between GIPI and clinicopathologic characteristics were determined by the Chi-square test or the Fisher's exact test. The Kaplan-Meier analysis and log-rank test were used to calculate and compare progression-free survival (PFS) and overall survival (OS). The univariate and multivariate Cox proportional hazards regression model was used to detect prognostic and predictive factors of PFS and OS. Results: 146 patients treated with PD-1/PD-L1 inhibitors were included in this study, of which, 72.6% were GIPI good, 23.3% were GIPI intermediate, and 4.1% were GIPI poor. The GIPI was associated with the common blood parameters, including neutrophils and lymphocytes. The multivariate analysis showed that platelet, TNM stage, and treatment were the independent prognostic factors for PFS and OS. Patients with GIPI intermediate/poor were associated with shorter PFS (median: 24.63 vs. 32.50 months; p = 0.078) and OS (median: 28.37 months vs. not reached; p = 0.033) than those with GIPI good. GIPI intermediate/poor was correlated with shorter PFS and OS than GIPI good, especially in subgroups of patients with ICI treatment and patients with PD-1/PD-L1 positive status. Conclusions: The GIPI correlated with poor outcomes for PD-1/PD-L1 expression status and may be useful for identifying gastric cancer patients who are unlikely to benefit from treatment.

Controlling Nutritional Status (CONUT) Predicts Survival in Gastric Cancer Patients With Immune Checkpoint Inhibitor (PD-1/PD-L1) Outcomes.

Objective: The controlling nutritional status (CONUT), based on total lymphocyte count (TL), total cholesterol level (T-CHOL), and serum albumin (ALB), can provide a useful immunological prognostic biomarker for cancer patients. The present study aims to investigate the correlation between CONUT and prognosis in gastric cancer patients receiving immune checkpoint inhibitor (ICI) treatment. Methods: We retrospectively enrolled 146 patients with gastric cancer treated with ICIs (PD-1/PD-L1 inhibitors) from August 2016 to December 2020. The clinicopathologic characteristics were analyzed by Chi-square test or Fisher's exact test. The Kaplan-Meier and log-rank test were used to calculate and compare progression-free survival (PFS) and overall survival (OS). The prognostic and predictive factors of PFS and OS were identified by univariate and multivariate analyses. A nomogram was developed to estimate 1-, 3-, and 5-year PFS and OS probability. Results: Through the CONUT score, there were 75 (51.37%) patients in the low CONUT group and 71 (48.63%) patients in the high CONUT group. There was a correlation between the CONUT score and age (p = 0.005), pathology (p = 0.043), ALB (p = 0.020), PALB (p = 0.032), and Hb (p = 0.001). The CA724, TNM stage, and treatment (ICIs vs. chemotherapy) were the independent prognostic factors for PFS and OS by multivariate analyses. Patients with high CONUT score had poorer PFS and OS (χ2 = 3.238, p = 0.072, and χ2 = 4.298, p = 0.038). In the subgroup analysis, the patients with high CONUT score were associated with shorter PFS and OS with ICIs or chemotherapy. With the PD-1/PD-L1 positive expression, the patients with high CONUT score had shorter PFS and OS than those with low CONUT score. Furthermore, the patients with high CA724 value were associated with shorter PFS and OS. The toxicity assessment in ICIs or chemotherapy was significantly associated with anemia. The nomograms were constructed to predict the probability of 1-, 3-, and 5-year PFS, and 1-, 3-, and 5-year OS with C-indices of 0.749 and 0.769, respectively. Conclusion: The CONUT, as a novel immuno-nutritional biomarker, may be useful in identifying gastric cancer patients who are unlikely to benefit from ICI treatment.

In Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy Systemic Inflammation Response Index is a Useful Prognostic Indicator.

Background: The preoperative systemic inflammation response index (SIRI), based on peripheral neutrophil (N), monocyte (M), and lymphocyte (L) counts, has shown mounting evidence as an effective prognostic indicator in some malignant tumors. The aim of the present study was to evaluate the prognostic significance of pre-treatment SIRI in gastric cancer patients who received neoadjuvant chemotherapy (NACT). Methods: This retrospective study comprised 107 patients with advanced gastric cancer treated with NACT between July 2007 and September 2015 in our hospital. SIRI was calculated from peripheral venous blood samples obtained prior to treatment. The best cutoff value for SIRI by receiver operating characteristic (ROC) curve was 1.2 (low SIRI <1.21, high SIRI ≥1.21). The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model. Results: The results demonstrated that the low SIRI group was statistically associated with gender, primary tumor site, white blood cell, neutrophil, and monocyte counts, NLR (neutrophil to lymphocyte ratio), MLR (monocyte to lymphocyte ratio), and PLR (platelet to lymphocyte ratio). The SIRI was predictive for DFS and OS by univariate and multivariate analysis; the low SIRI group had better median DFS and OS than the high SIRI group (median DFS 27.03 vs. 22.33 months, median OS 29.73 vs. 24.43 months). The DFS and OS in the low SIRI group were longer than the high SIRI group. Conclusions: SIRI may qualify as a useful, reliable, and convenient prognostic indicator in patients with advanced gastric cancer to help physicians to provide personalized prognostication for gastric cancer patients treated with NACT.

Precise Targeting Therapy of Orthotopic Gastric Carcinoma by siRNA and Chemotherapeutic Drug Codelivered in pH-Sensitive Nano Platform.

Gastric cancer is one of the most common malignant tumors, which remains as an obstacle to human health. Nowadays, targeted nanoparticles to gastric tumor tissues, provide new strategy for improved therapy but still remain challenging. The major hurdle of targeted therapeutic nanoparticles comes from the limited enrichment and poor selectivity of therapeutic agents in in situ tumor. Herein, a pH-sensitive targeted nano platform coloaded As2 O3 and human epidermal growth factor receptor-2 (HER2)-siRNA (AH RNPs) is developed to achieve targeting therapy in orthotopic gastric carcinoma. AH RNPs can effectively prevent the degradation of siRNA and overcome the poor solubility of As2 O3 . In vitro studies show that AH RNPs could achieve synergistic inhibition of growth and metastasis on SGC7901 cells. Surprisingly, AH RNPs not only target gastric subcutaneous tumor, but also target in situ tumor, and express loaded genes in in situ tumor. Moreover, AH RNPs show excellent antitumor effect in orthotopic gastric tumor model and the anticancer mechanism is related about inhibiting the activation of ERK signal and downregulating the expression of cxc chemokine receptor 4 (CXCR4), HER2, MMP2, and MMP9 protein. This study provides a multi-functional vector for precise targeting therapy of gastric cancer, which may serve as a potential clinical application for future gastric cancer.

Therapy With Carboplatin and Anti-PD-1 Antibodies Before Surgery Demonstrates Sustainable Anti-Tumor Effects for Secondary Cancers in Mice With Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) suffer an unfavorable prognosis. Carboplatin (CBDCA) as a cytotoxic reagent has been widely administered to patients with cancer including TNBC. Programmed cell death protein 1 (PD-1) is an immune checkpoint, blockade of which unleashes T cell functions that kill cancer cells. However, the efficacy of CBDCA combined with anti-PD-1 antibodies in TNBC has not been determined. Patient-derived xenografts (PDX) were implanted to immune-deficient mice. Three mouse TNBC cell lines (4T1, EMT6, and E0771) were seeded to immune-competent mice. Tumor volumes and survival rates were monitored. CBDCA and anti-PD-1 antibodies were administered by intra-peritoneal injection at designated time points. Total CD8+ T cells, memory CD8+ T cells, and CD103+ dendritic cells (DC) in the tumor were measured by flow cytometry. Tumor-specific CD8+ T cells were quantified by the ELISpot assay. Administration of CBDCA to PDX-bearing mice induced increased levels of tumor cell necrosis and reduced tumor size. Treatment with CBDCA and anti-PD-1 antibodies reduced TNBC tumor volumes and slightly improved survival rates. More importantly, therapy with CBDCA and anti-PD-1 antibodies before surgery showed a remarkably improved, sustainable protection against a secondary tumor after surgery by a CD8+- T-cell-dependent manner, which required CCL4 expressed in the tumor and subsequently CD103+ DC recruited to the tumor microenvironment. Immunochemotherapy with CBDCA and anti-PD-1 antibodies before surgery improves the outcome of a secondary tumor after surgery via increasing the number of tumor-specific CD8+ T cells in the tumor microenvironment of murine TNBC. These results highlight the possibility to utilize this regimen in clinical practice.

Roxatidine inhibits fibrosis by inhibiting NF­κB and MAPK signaling in macrophages sensing breast implant surface materials.

Capsular contracture is an important complication after silicone mammary implant surgery. Fibroblasts and macrophages play critical roles in the pathogenesis of capsular contracture, making these two cell types therapeutic targets. It has been reported that inhibiting histamine receptors results attenuates fibrosis, but the role of roxatidine (a histamine receptor 2 inhibitor) in preventing fibrosis caused by breast implant materials remains unknown. The aim of the present study was to assess the hypothesis that roxatidine might have a prophylactic effect in capsular contracture induced by implant material. Inflammation induced by breast implant materials was mimicked by co­culturing macrophages or fibroblasts with these materials in vitro. Capsular contracture was modeled in mice by planting breast implant materials in a subcutaneous pocket. Roxatidine was added in the culture medium or administered to mice bearing breast implant materials. By co­culturing macrophages or fibroblasts with common breast implant materials (micro­textured or smooth breast implants), the present study demonstrated that macrophages respond to these materials by producing pro­inflammatory cytokines, a process that was abolished by addition of roxatidine to the culture medium. Although fibroblasts did not respond to implant surface materials in the same way as macrophages, the conditioned media of macrophages induced proliferation of fibroblasts. Mechanistically, administration of roxatidine inhibited activation of NF­κB and p38/mitogen­activated protein kinase (MAPK) signaling in macrophages. Furthermore, treatment with roxatidine in implant­bearing mice reduced serum concentrations of transforming growth factor­ß and the abundance of fibroblasts around the implant. The present study concluded that roxatidine plays an important role in preventing fibrosis by inhibiting activation of NF­κB and p38/MAPK signaling in macrophages.

Prognostic significance of preoperative albumin-to-globulin ratio and prognostic nutritional index combined score in Siewert type 3 adenocarcinoma of esophagogastric junction.

PURPOSE: Preoperative nutrition-inflammation-based indicators have been reported to predict the prognosis of malignancies. We evaluated the prognostic significance of a combined score of the albumin-to-globulin ratio (AGR) and prognostic nutritional index (PNI) for overall survival (OS) outcomes in patients with Siewert type 3 adenocarcinoma of esophagogastric junction (S3-AEG). PATIENTS AND METHODS: The prognostic significance of variables associated with 215 S3-AEG patients' OS were assessed through univariate and multivariate analyses. The cutoff value of the preoperative AGR and PNI were calculated by the receiver operating characteristic curve (ROC). Patients with either an elevated AGR (≥1.72, cutoff value) or PNI (≥45.55, cutoff value) were given a score of 1; otherwise, they were given a score of 0. The AGR-PNI score ranged from 0 to 2. RESULTS: OS was independently associated with the N stage (HR: 0.336, 95% CI: 0.141-0.805, P=0.014) and AGR-PNI score (HR: 0.623, 95% CI: 0.487-0.797, P<0.001). Patients with AGR-PNI scores of 0, 1 and 2 had significant differences in OS (P=0.001). The prognostic role of AGR-PNI was significant in patients with stage I + II (P=0.043) and stage III S3-AEGs (P=0.003). ROC analysis indicated that the predictive ability of the AGR-PNI score was better than that of the other parameters. CONCLUSION: The preoperative AGR-PNI score was a significant prognosticator of postoperative survival in patients with S3-AEG and could identify high-risk populations for reasonable therapy and effective follow-up.

Macrophages on the Peritoneum are involved in Gastric Cancer Peritoneal Metastasis.

Tumor-associated macrophages (TAM) have been shown to support tumor growth and progression by various mechanisms. However, the roles of TAM in gastric cancer (GC) peritoneal metastasis remain elusive. To explore the roles of macrophages in the process of GC peritoneal metastasis, we performed the present study. Samples from the primary GC tumor beds, surgical margins, peritoneal metastatic lesions and surrounding tissue, and the Pouch of Douglas, were collected, fixed by formalin, and embedded with paraffin. Immunohistochemistry staining for macrophages markers was performed. The peritoneal lavage was obtained from a fraction of patients to analyze the ratios of epidermal growth factor (EGF)- and vascular endothelial growth factor (VEGF)-secreting macrophages in the peritoneal cavity. GC patients with peritoneal metastasis had increased levels of macrophages and alternatively activated macrophages in the peritoneum compared to those without dissemination. Patients bearing more macrophages in the peritoneum had a poorer prognosis. GC patients bearing peritoneal metastasis harbored an increased level of angiogenesis. Macrophages in the peritoneal cavity were a source of EGF and VEGF. Macrophages in the peritoneum of GC patients play a supportive role for peritoneal metastasis by producing EGF and VEGF. Macrophages in the peritoneum might be a therapeutic target in the future.

Peripheral Venous Blood Platelet-to-Lymphocyte Ratio (PLR) for Predicting the Survival of Patients With Gastric Cancer Treated With SOX or XELOX Regimen Neoadjuvant Chemotherapy.

BACKGROUND: Inflammation plays an important role in tumor progression. Predicting survival is remarkably difficult in patients with gastric cancer receiving neoadjuvant chemotherapy. The aim of the present study is to investigate the potential prognostic significance of the platelet-to-lymphocyte ratio in patients with gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen. METHODS: Ninety-one patients with gastric cancer treated with neoadjuvant chemotherapy were enrolled in this study and then underwent operation. The optimal cutoff value was calculated using receiver-operating characteristic curve analyses. The optimal cutoff value of platelet-to-lymphocyte ratio was divided into low platelet-to-lymphocyte ratio <162 group and high platelet-to-lymphocyte ratio ≥162 group. Kaplan-Meier method and log-rank test were used to analyze the survival curves. The independent prognostic factors and prognostic value of the platelet-to-lymphocyte ratio were assessed by univariate and multivariate Cox proportional hazards regression model. The toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria. RESULTS: Kaplan-Meier analyses revealed that patients with low platelet-to-lymphocyte ratio correlated remarkably with better mean disease-free survival and mean overall survival than those with high platelet-to-lymphocyte ratio (mean disease-free survival 47.33 and 33.62 months, respectively; mean overall survival 51.21 and 36.80 months, respectively). The results demonstrated that platelet-to-lymphocyte ratio had prognostic significance using the cutoff value of 162 on disease-free survival and overall survival, and the mean disease-free survival and overall survival time for patients with low platelet-to-lymphocyte ratio were longer than those with high platelet-to-lymphocyte ratio. Meanwhile, patients with gastric cancer who had lower platelet-to-lymphocyte ratio had longer 1-, 3-, and 5-year rates of disease-free survival and overall survival. Moreover, patients with low platelet-to-lymphocyte ratio had longer mean disease-free survival and overall survival than those with high platelet-to-lymphocyte ratio in receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen. CONCLUSIONS: The preoperative platelet-to-lymphocyte ratio may be a promising and convenient prognostic biomarker for patients gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen neoadjuvant chemotherapy. It may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.