Source identification and driving factor apportionment for soil potentially toxic elements via combining APCS-MLR, UNMIX, PMF and GDM.

The contamination and quantification of soil potentially toxic elements (PTEs) contamination sources and the determination of driving factors are the premise of soil contamination control. In our study, 788 soil samples from the National Agricultural Park in Chengdu, Sichuan Province were used to evaluate the contamination degree of soil PTEs by pollution factors and pollution load index. The source identification of soil PTEs was performed using positive matrix decomposition (PMF), edge analysis (UNMIX) and absolute principal component score-multiple line regression (APCS-MLR). The geo-detector method (GDM) was used to analysis drivers of soil PTEs pollution sources to help interpret pollution sources derived from receptor models. Result shows that soil Cu, Pb, Zn, Cr, Ni, Cd, As and Hg average content were 35.2, 32.3, 108.9, 91.9, 37.1, 0.22, 9.76 and 0.15 mg/kg in this study area. Except for As, all are higher than the corresponding soil background values in Sichuan Province. The best performance of APCS-MLR was determined by comparison, and APCS-MLR was considered as the preferred receptor model for soil PTEs source distribution in the study area. ACPS-MLR results showed that 82.70% of Cu, 61.6% of Pb, 75.3% of Zn, 91.9% of Cr and 89.4% of Ni came from traffic-industrial emission sources, 60.9% of Hg came from domestic-transportation emission sources, 57.7% of Cd came from agricultural sources, and 89.5% of As came from natural sources. The GDM results showed that distance from first grade highway, population, land utilization and total potassium (TK) content were the main driving factors affecting these four sources, with q values of 0.064, 0.048, 0.069 and 0.058, respectively. The results can provide reference for reducing PTEs contamination in farmland soil.

CD177 drives the transendothelial migration of Treg cells enriched in human colorectal cancer.

Objectives: Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor-infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor-infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods: Single-cell RNA sequencing (scRNA-seq) data and survival data were obtained from public databases. Twenty-one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results: ScRNA-seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177- Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177-overexpressing induced Treg (iTreg) cells had lower levels of PD-1 than their CD177- counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions: These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR-T) cell therapy.

Task-Wise Sampling Convolutions for Arbitrary-Oriented Object Detection in Aerial Images.

Arbitrary-oriented object detection (AOOD) has been widely applied to locate and classify objects with diverse orientations in remote sensing images. However, the inconsistent features for the localization and classification tasks in AOOD models may lead to ambiguity and low-quality object predictions, which constrains the detection performance. In this article, an AOOD method called task-wise sampling convolutions (TS-Conv) is proposed. TS-Conv adaptively samples task-wise features from respective sensitive regions and maps these features together in alignment to guide a dynamic label assignment for better predictions. Specifically, sampling positions of the localization convolution in TS-Conv are supervised by the oriented bounding box (OBB) prediction associated with spatial coordinates, while sampling positions and convolutional kernel of the classification convolution are designed to be adaptively adjusted according to different orientations for improving the orientation robustness of features. Furthermore, a dynamic task-consistent-aware label assignment (DTLA) strategy is developed to select optimal candidate positions and assign labels dynamically according to ranked task-aware scores obtained from TS-Conv. Extensive experiments on several public datasets covering multiple scenes, multimodal images, and multiple categories of objects demonstrate the effectiveness, scalability, and superior performance of the proposed TS-Conv.

Clinicopathological characteristics of gastric cancer patients with dermatomyositis and analysis of perioperative management: a case series study.

Background: This study aimed to investigate the clinical characteristics of gastric cancer (GC) patients with dermatomyositis (DM) and summarize the perioperative outcomes. Methods: The clinical and pathological data of five patients diagnosed with co-occurring DM and GC (DM-GC group) were retrospectively analyzed, who were admitted to the Department of Gastrointestinal Surgery at Ren ji Hospital, Shanghai Jiao Tong University, between January 2012 and April 2023. Their data were compared with 618 GC patients (GC-1 group) from September 2016 to August 2017 and 35 GC patients who were meticulously screened from 14,580 GC cases from January 2012 and April 2023. The matching criteria included identical gender, age, tumor location, TNM stage, and surgical procedure (7 GC patients were matched for each DM-GC patient). Results: Analysis indicated that the DM-GC group comprised four female and one male patient. The female proportion was significantly higher (P = 0.032) than that of GC-1 group. In DM-GC group, four DM patients were diagnosed as GC within 12 months. One DM patients was diagnosed as GC within 15 months. Among them, four patients presented with varying degrees of skin rashes, muscle weakness while one patient had elevated CK levels as the typical symptom. Similarly, the preoperative tumor markers (CA-199 and CA-125) in the DM-GC group were significantly higher than normal levels (CA-199: 100 vs. 28.6%, P = 0.002; CA-125: 40 vs. 2.9%, P = 0.003) compared to GC-2 group. Moreover, postoperative complication incidence and the length of hospital stay were significantly higher in the DM-GC than GC-2 group [complication rate: 40 vs. 8.6%, P = 0.047; hospital stay: 15 days (range: 9-28) vs. 9 days (range: 8-10), P = 0.021]. Conclusion: GC Patients with dermatomyositis are more prone to experience postoperative complications and longer hospital stay.

Geochemical characteristics and ecological risks of rare earth elements in river sediments of coal-grain composite area in eastern China.

Coal and grain complex areas influence the geochemical characterization of REEs through coal mining activities and agricultural production. However, there is a lack of relevant studies. In this study, we investigated the geochemical characterization and risk assessment of REEs in river sediments of the northern Anhui plain, a typical coal-grain composite area. The results showed that the average concentrations of ∑REE in the sediments ranged from 134.7 to 220.3 µg/g, and LREE was significantly enriched. Among the 14 REEs, Gd and Eu were the most enriched, with enrichment factors of 1.792 and 1.764, respectively. In addition, the differences in REEs content and enrichment between different rivers were related to the location of coal mines and the degree of population concentration. The average values of δCe and δEu in the sediments were 0.990 and 1.080, respectively, and most of the sampling sites showed a weak positive Ce, Eu anomaly. The results of Pearson's correlation and RDA redundancy analyses showed that Fe, Al, Mn and sand contributed more to the enrichment of REEs. The river sediments in the whole area had a slight potential ecological risk, with Eu (Er=13.05) and Lu (Er=14.07) having the highest potential risk. The ADD results also showed that the average daily dose of REEs by children was around 2.000 (µg/(kg·day)), which was significantly higher than that of adults. The results of this study can be used as a basis for the prevention and control of REEs in rivers in northern Anhui Province.

Synchronous primary colorectal mucinous adenocarcinoma and pancreatic ductal adenocarcinoma: A case report.

The present study reports a rare case of synchronous colorectal mucinous adenocarcinoma (CMAC) and pancreatic ductal adenocarcinoma (PDAC). A 61-year-old man complained of hematochezia for half a month. Colonoscopy and biopsy in a local hospital revealed mucinous adenocarcinoma in the sigmoid colon, and a subsequent abdominal computed tomography examination in Ren Ji Hospital (Shanghai, China) identified an unexpectedly hypovascular lesion in the body and tail of the pancreas, in addition to a mass in the colon. The patient then underwent combined surgery consisting of a distal pancreaticosplenectomy and a sigmoidectomy, and the postoperative pathological tests confirmed the co-occurrence of CMAC and PDAC. Next-generation sequencing demonstrated no deleterious germline mutations, but did find some critical somatic mutations concerning both tumors. The patient received 12 cycles of a combination of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (modified FOLFIRINOX regimen) as adjuvant chemotherapy thereafter. Complete remission was achieved at 1 year after the surgery. To the best of our knowledge, this is the first documented case of such synchronous malignances (CMAC and PDAC) in the literature, and its publication therefore improves our overall understanding in this field.

Liposomal Enzyme Nanoreactors Based on Nanoconfinement for Efficient Antitumor Therapy.

Enzymatic reactions can consume endogenous nutrients of tumors and produce cytotoxic species and are therefore promising tools for treating malignant tumors. Inspired by nature where enzymes are compartmentalized in membranes to achieve high reaction efficiency and separate biological processes with the environment, we develop liposomal nanoreactors that can perform enzymatic cascade reactions in the aqueous nanoconfinement of liposomes. The nanoreactors effectively inhibited tumor growth in vivo by consuming tumor nutrients (glucose and oxygen) and producing highly cytotoxic hydroxyl radicals (⋅OH). Co-compartmentalization of glucose oxidase (GOx) and horseradish peroxidase (HRP) in liposomes could increase local concentration of the intermediate product hydrogen peroxide (H2 O2 ) as well as the acidity due to the generation of gluconic acid by GOx. Both H2 O2 and acidity accelerate the second-step reaction by HRP, hence improving the overall efficiency of the cascade reaction. The biomimetic compartmentalization of enzymatic tandem reactions in biocompatible liposomes provides a promising direction for developing catalytic nanomedicines in antitumor therapy.

The expression profile of Gasdermin C-related genes predicts the prognosis and immunotherapy response of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) has a poor prognosis and is relatively unresponsive to immunotherapy. Gasdermin C (GSDMC) induces pyroptosis in cancer cells and inflammation in the tumor microenvironment. However, whether GSDMC expression in PAAD is associated with survival or response to immunotherapy remains unknown. GSDMC expression and the relationship between GSDMC and patient survival or immune infiltration in PAAD were examined using data in the The Cancer Genome Atlas (TCGA), Gene Expression Ominbus (GEO), Genotype-Tissue Expression (GTEx) and Cancer Cell Line Encyclopedia (CCLE) databases. The TCGA PAAD cohort could be divided into two distinct risk groups based on the expression of GSDMC-related genes (GRGs). The TIDE algorithm predicted that the low-risk group was more responsive to immune checkpoint blockade therapy than the high-risk group. A novel 15-gene signature was constructed and could predict the prognosis of PAAD. In addition, the 15-gene signature model predicted the infiltration of immune cells and Immune checkpoint blockade (ICB) treatment response. Immunohistochemical staining assessment of patient-derived human tissue microarray (TMA) from 139 cases of local PAAD patients revealed a positive correlation between GSDMC expression and PD-L1 expression but a negative correlation between GSDMC expression and infiltration of low CD8+ T cells. Moreover, the overexpression of GSDMC was related to poor overall survival (OS). This study suggests that GSDMC is a valuable biomarker for predicting PAAD prognosis and predicts the immunotherapy response of PAAD.

CuO nanorod arrays by gas-phase cation exchange for efficient photoelectrochemical water splitting.

CuO has been considered a promising candidate for photoelectrochemical water splitting electrodes owing to its suitable bandgap, favorable band alignments, and earth-abundant nature. In this paper, a novel gas-phase cation exchange method was developed to synthesize CuO nanorod arrays by using ZnO nanorod arrays as the template. ZnO nanorods were fully converted to CuO nanorods with aspect ratios of 10-20 at the temperature range from 350 to 600 °C. The as-synthesized CuO nanorods exhibit a photocurrent as high as 2.42 mA cm-2 at 0 V vs. RHE (reversible hydrogen electrode) under 1.5 AM solar irradiation, demonstrating the potential as the photoelectrode for efficient photoelectrochemical water splitting. Our method provides a new approach for the rational fabrication of high-performance CuO-based nanodevices.

Tumor-associated macrophage-derived GDNF promotes gastric cancer liver metastasis via a GFRA1-modulated autophagy flux.

PURPOSE: Liver metastasis, a lethal malignancy of gastric cancer (GC) patients, execrably impairs their prognosis. As yet, however, few studies have been designed to identify the driving molecules during its formation, except screening evidence pausing before their functions or mechanisms. Here, we aimed to survey a key driving event within the invasive margin of liver metastases. METHODS: A metastatic GC tissue microarray was used for exploring malignant events during liver-metastasis formation, followed by assessing the expression patterns of glial cell-derived neurotrophic factor (GDNF) and GDNF family receptor alpha 1 (GFRA1). Their oncogenic functions were determined by both loss- and gain-of-function studies in vitro and in vivo, and validated by rescue experiments. Multiple cell biological studies were performed to identify the underlying mechanisms. RESULTS: In the invasive margin, GFRA1 was identified as a pivotal molecule involved in cellular survival during liver metastasis formation, and we found that its oncogenic role depends on tumor associated macrophage (TAM)-derived GDNF. In addition, we found that the GDNF-GFRA1 axis protects tumor cells from apoptosis under metabolic stress via regulating lysosomal functions and autophagy flux, and participates in the regulation of cytosolic calcium ion signalling in a RET-independent and non-canonical way. CONCLUSION: From our data we conclude that TAMs, homing around metastatic nests, induce the autophagy flux of GC cells and promote the development of liver metastasis via GDNF-GFRA1 signalling. This is expected to improve the comprehension of metastatic pathogenesis and to provide a novel direction of research and translational strategies for the treatment of metastatic GC patients.

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light.

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (1 O2 ) for PDT with 808 nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808 nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.

Potassium-Derived Charge Channels in Boron-Doped g-C3N4 Nanosheets for Photocatalytic NO Oxidation and Hydrogen Evolution.

The application of graphitic carbon nitride (g-C3N4) in photocatalytic NO oxidation was limited due to severe recombination of photogenerated carriers and low concentration of oxidizing species. In this work, K and B were introduced into the interlayer and in-plane framework of g-C3N4 to address this challenge through the thermal polymerization process. The synthesized K-doped B-g-C3N4 nanosheets exhibited expanded light absorption and low charge recombination efficiency. In addition, the doping of K and B reduced the band gap of g-C3N4, which corresponded to enhanced light absorption. B was introduced into the in-plane structure by replacing C atoms, which adjusted the in-plane electron distribution. K was inserted into the interlayer by binding to the N and C atoms of adjacent layers. K-derived electron transfer channels were constructed, which increased electron delocalization and expanded the π-conjugate system. More electrons were transferred through the interlayer channels and were involved in the reaction process. The severe carrier recombination and weak transfer were improved due to the synergistic effect of K and B doping. K-doped B-g-C3N4 nanosheets exhibited enhanced generation of superoxide radicals and hydroxyl radicals, which played a key role during NO oxidation. The photocatalytic NO oxidation efficiency of codoped g-C3N4 nanosheets reached 61%, which was 2.1 and 1.2 times of that of pristine g-C3N4 and B-doped g-C3N4, respectively. The codoped g-C3N4 sample still exhibited stable photocatalytic NO oxidation efficiency after five cycles. This result provided a potential idea for improving the charge distribution and transfer of layered materials by codoping metallic and nonmetallic elements and for photocatalytic NO oxidation.

Central Attention Network for Hyperspectral Imagery Classification.

In this article, the intrinsic properties of hyperspectral imagery (HSI) are analyzed, and two principles for spectral-spatial feature extraction of HSI are built, including the foundation of pixel-level HSI classification and the definition of spatial information. Based on the two principles, scaled dot-product central attention (SDPCA) tailored for HSI is designed to extract spectral-spatial information from a central pixel (i.e., a query pixel to be classified) and pixels that are similar to the central pixel on an HSI patch. Then, employed with the HSI-tailored SDPCA module, a central attention network (CAN) is proposed by combining HSI-tailored dense connections of the features of the hidden layers and the spectral information of the query pixel. MiniCAN as a simplified version of CAN is also investigated. Superior classification performance of CAN and miniCAN on three datasets of different scenarios demonstrates their effectiveness and benefits compared with state-of-the-art methods.

High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer.

Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of human gastric cancer (GC) and used flow to explore the GITR expression across T cell subsets and tissue types in GC patients. We revealed that GITR+ CD4 T cells, including regulatory CD4 T (Treg) cells and conventional CD4 T (Tconv) cells, might contribute to the immunosuppressive microenvironment in GC. The enrichment of these cells was associated with a worse prognosis. Moreover, we found the cellular distribution of GITR protein in Treg cells was microenvironment dependent. In conclusion, GITR is still an important immune checkpoint need to be studied.

Spatial distribution characteristics of heavy metal(loid)s health risk in soil at scale on town level.

In order to reveal the Spatial distribution characteristics of heavy metal(loid)s health risk in soil on the town-scale, 788 topsoil samples were collected from a town in the hinterland of Chengdu Plain, with 5 subordinate communities and 17 administrative villages as the research sub regions. The USEPA health risk assessment model was used to assess the health risks of heavy metal(loid)s Cd, Hg, As, Cu, Pb, Cr, Zn and Ni in the soil, the health risk analysis method system based on the geographic detector and the optimized rank-size theory model are used to clarify the spatial differentiation and risk level difference of health risk in the study area. The results showed that the average values of Cd, Hg, As, Pb, Cr, Cu, Ni and Zn in the soil of the study area were 0.221, 0.155, 9.76, 32.2, 91.9, 35.2, 37.1 and 108.8 mg/kg, respectively. The health risks of heavy metal(loid)s in soil to adults and children are generally within the acceptable range, but the maximum hazard index of children and the maximum non-carcinogenic risk value of Cr to children are 2.653303 and 1.213098 respectively, which were exceeding the acceptable range. The carcinogenic risk of Cr and As to adults and children and the carcinogenic risk of Cd to children are at 1 × 10-4 to 1 × 10-6, exceeding the 10-6 health threshold. The q-value range of heavy metal(loid)s health risk spatial differentiation of soil in the study area is 0.016-0.425. The spatial differentiation of non-carcinogenic risk of Hg, As, Ni, Pb, Cd and Cr and the spatial differentiation of carcinogenic risk of Cr and As are larger, which needs further attention. The strictly controlled area of heavy metal(loid)s health risk in the soil of the study area (R ≥ 1.1) is mainly concentrated in the central, western and northeast sub regions, and most sub regions belong to the safe utilization area (0.9 < R < 1.1). The health risk assessment of heavy metal(loid)s in soil on a town scale is of positive significance for enriching health risk research methods, measuring health risk levels at different scales, and formulating refined risk management and control strategies.

Clinical outcomes and potential therapies prediction of subgroups based on a ferroptosis-related long non-coding RNA signature for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignant tumors worldwide. Ferroptosis is a kind of iron-dependent cell death, which is proved to be closely related to tumor progression. In this study, we aim at constructing a ferroptosis-related lncRNAs signature to predict the prognosis of GC and explore potential therapies. METHODS: Ferroptosis-Related LncRNAs Signature for GC patients (FRLSG) was constructed through univariate Cox regression, the LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, receiver operating characteristic curves, and risk score plot were applied to verify the predictive power of FRLSG. Gene Set Enrichment Analysis (GSEA) and immune infiltration analyses were conducted to explore the potential clinical value of the FRLSG. In addition, drug sensitivity prediction was applied to identify chemotherapeutic drugs with potential therapeutic effect. RESULTS: Five ferroptosis-related lncRNAs (AC004816.1, AC005532.1, LINC01357, AL355574.1 and AL049840.4) were identified to construct FRLSG, whose expression level in GC were confirmed by experimental validation. Kaplan-Meier curve and ROC curve proved the reliability and effectiveness of the FRLSG in predicting the prognosis for GC patients. Several immune-related pathways were enriched in the high-FRLSG group, and further immune infiltration analyses demonstrated the high immune infiltration status of the high-FRLSG group. In addition, 19 and 24 candidate drugs with potential therapeutic effect were identified for the high- and low-FRLSG groups, respectively. CONCLUSIONS: FRLSG was an effective tool in predicting the prognosis of GC, which might help to prioritize potential therapeutics for GC patients.

Nanoarchitectonics of g-C3N4 Nanosheets with a AuCu Enhancement Effect for Superior Photo- and Electrochemical Activity.

AuCu alloy nanoparticles (NPs) were embedded in superior thin g-C3N4 nanosheets by a mechanochemical pre-reaction and subsequent thermal polymerization at high temperature. The introduction of AuCu NPs increased conductivity, decreased the band gap, expended light absorption, and improved the separation and transfer efficiencies of photogenerated electrons and holes. Moreover, the uniform distribution of AuCu NPs in g-C3N4 nanosheets is ascribed to the pre-reaction of bulk g-C3N4 and metal salts to create activity cites. The adsorption ability in the visible light region was improved due to the plasma effect of Au. AuCu/g-C3N4 composites (AuCu/CN-1%) with optimized component ratios revealed the highest transient photocurrent responses, the lowest electrochemical impedance arc radius, and the best photocatalytic H2 evolution rate of 930.2 µmol g-1 h-1. These findings exhibited that loading AuCu bimetallic NPs could efficiently offset some disadvantages of g-C3N4 and improve its photocatalytic performances.

Molecular response of Anoxybacillus sp. PDR2 under azo dye stress: An integrated analysis of proteomics and metabolomics.

Treating azo dye wastewater using thermophilic bacteria is considered a more efficient bioremediation strategy. In this study, a thermophilic bacterial strain, Anoxybacillus sp. PDR2, was regarded as the research target. This strain was characterized at different stages of azo dye degradation by using TMT quantitative proteomic and non-targeted metabolome technology. A total of 165 differentially expressed proteins (DEPs) and 439 differentially metabolites (DMs) were detected in comparisons between bacteria with and without azo dye. It was found that Anoxybacillus sp. PDR2 can degrade azo dye Direct Black G (DBG) through extracellular electron transfer with glucose serving as electron donors. Most proteins related to carbohydrate metabolism, including acetoacetate synthase, and malate synthase G, were overexpressed to provide energy. The bacterium can also self-synthesize riboflavin as a redox mediator of in vitro electron transport. These results lay a theoretical basis for industrial bioremediation of azo dye wastewater.

Efficacy and Safety of Camrelizumab in Combination with Docetaxel + S-1 Sequenced by Camrelizumab + S-1 for Stage III (PD-1+/MSI-H/EBV+/dMMR) Gastric Cancer: Study Protocol for a Single-Center, Prospective, Open-Label, Single-Arm Trial.

Background: Gastric cancer occupies the fourth highest morbidity rate of cancers worldwide. A higher incidence of gastric cancer had been found in East Asia compared to the other regions. Gastrectomy with radical lymph node dissection is the cornerstone of curative treatment for Stage III gastric cancer, and postoperative systemic chemotherapy with docetaxel, S-1 improved patients' disease-free survival rates. However, advances in immunotherapy bring innovations in the management of patients with gastric cancer. The objective of this study was to explore the efficacy and safety of camrelizumab in combination with docetaxel + S-1, sequenced by camrelizumab + S-1 in stage III gastric cancer patients who are EBV positive, with defective mismatch repair and CPS ≥5. Methods and analysis: This prospective, open-label, single-arm trial was performed at Renji Hospital. In this study, a total of 70 adult patients aged 18-80 years with Stage III (PD-1+/MSI-H/EBV+/dMMR) gastric cancer confirmed by post-operative pathology will be enrolled after screening. Participants will receive the specific chemotherapy regimen until 1 year after the operation or until tumor recurrence or metastasis. The primary outcome is the 3-year disease-free survival rate measured by the Clopper-Pearson method and 95% confidence intervals. The secondary outcomes include overall survival, incidence and severity of adverse effects, and laboratory abnormalities. The data will be analyzed by the Kaplan-Meier method and log-rank test. The patients will be followed up every 3 months with imaging investigation until clinical remission. Ethics and dissemination: All participants will provide informed consent. The protocol has been approved by the Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (KY2019-191). The results will be disseminated through peer-reviewed manuscripts, reports and presentations. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR1900027123. Registration date November 2019; first enrolment December 2019; expected end date December 2021; trial status: Ongoing. Brief Abstract: A clinical trial for Stage III (PD-1+/MSI-H/EBV+/dMMR) gastric cancer patients who accepted anti-PD-1 therapy combined with docetaxel + S-1 as the first-line treatment and explored improvements in three-year disease-free survival rate.

Development and validation of two nomograms for predicting overall survival and cancer-specific survival in gastric cancer patients with liver metastases: A retrospective cohort study from SEER database.

BACKGROUND: Gastric cancer is heterogeneous and aggressive, especially with liver metastasis. This study aims to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer with liver metastasis (GCLM) patients. METHODS: From January 2000 to December 2018, a total of 1936 GCLM patients were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. They were further divided into a training cohort and a validation cohort, with the OS and CSS serving as the study's endpoints. The correlation analyses were used to determine the relationship between the variables. The univariate and multivariate Cox analyses were used to confirm the independent prognostic factors. To discriminate and calibrate the nomogram, calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used. DCA curves were used to examine the accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI) (IDI). Finally, the nomogram and the AJCC Stage System risk stratifications were compared. RESULTS: There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that six variables (bone metastasis, lung metastasis, surgery, chemotherapy, grade, age) and five variables (lung metastasis, surgery, chemotherapy, grade, N stage) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. CONCLUSION: Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of GCLM patients.