Search

We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers—GPX4, RBM4, TPM3, PFKFB2, and PGAM5—and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver (https://pumc.shinyapps.io/GastricCancer/) for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.

Abstract Background Gastric cancer (GC) stands out as one of the most prevalent malignancies affecting the digestive system, characterized by a substantial incidence rate and mortality. Maternal embryonic leucine zipper kinase (MELK) has been implicated in the advancement of various cancer types and the modulation of the tumor microenvironment. This study aims to delve into the involvement of MELK in chemoresistance and the tumor microenvironment of GC. Methods The MELK expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry. Lentiviral transfection was employed to establish stable cell lines with either overexpressed or silenced MELK. The impact of MELK on the chemoresistance of GC cells and the polarization of macrophages was investigated through in vitro and in vivo functional assays. Additionally, the correlation between MELK and the cytokines colony-stimulating factor 1 (CSF-1), as well as stromal macrophages, was analysed. The prognostic significance of MELK, CSF-1, and CD206 expression levels in clinical samples was further investigated. Results MELK was found to be highly expressed in chemoresistant GC cells and tissues. Furthermore, both in vitro and in vivo assays indicated that MELK overexpression conferred chemoresistance in GC cells. Additionally, MELK overexpression was observed to induce M2 macrophage polarization via the CSF-1/JAK2/STAT3 pathway, thereby contributing to chemoresistance within the tumor microenvironment. The expression of MELK in GC tissues from neoadjuvant chemotherapy patients correlated positively with CSF-1 and CD206. Moreover, patients with higher expression levels of MELK, CSF-1, or CD206 exhibited significantly shorter OS and DFS rates. Conclusions Our investigation underscores the critical role of MELK in promoting chemoresistance and inducing M2 macrophage polarization in GC. It proposes novel targets and methods for the treatment of GC, as well as prognostic factors for neoadjuvant chemotherapy.

Drainage is a crucial soil hydrological process that governs the partitioning of rainfall into runoff, groundwater recharge, soil water storage and evapotranspiration. Despite its significance, the drainage process is poorly understood due to the difficulty in direct measurements and insufficient understanding of its underlying physical mechanisms. To address these challenges, we present an innovative, physically-based, data-driven approach, SM2D (Soil Moisture to Drainage), to estimate drainage. SM2D was applied and examined using soil moisture data from a large-scale observation network over mountainous areas during 2014–2020. The soil moisture threshold governing drainage initiation proves to be significantly lower than the commonly employed field capacity metric in hydrological models. This threshold is influenced by factors such as mean soil moisture, bulk density, residual soil moisture, soil organic carbon, and parameters n and α of soil retention curve. Notably, field capacity has minimal impact on this threshold. Additionally, our analysis reveals that the drainage process is more influenced by the Soil Water Storage Increment (SWSI) than by mean soil moisture (MSM) that has traditionally been recognized as a key factor in drainage control. In comparison to commonly used exponential equations and those in models such as the Soil & Water Assessment Tool (SWAT), SM2D demonstrates superior performance in estimating drainage. The exponential equation derived from the SWSI outperforms those derived from other soil moisture metrics, including the commonly utilized MSM, challenging prevailing norms in drainage equations. SM2D holds the potential to generate extensive drainage datasets from satellite or large-scale soil moisture observations, advancing large-scale hydrological studies.

Abstract Background Gastric cancer (GC) remains a malignant tumor with high morbidity and mortality, accounting for approximately 1,080,000 diagnosed cases and 770,000 deaths worldwide annually. Disulfidptosis, characterized by the stress-induced abnormal accumulation of disulfide, is a recently identified form of programmed cell death. Substantial studies have demonstrated the significant influence of immune clearance on tumor progression. Therefore, we aimed to explore the intrinsic correlations between disulfidptosis and immune-related genes (IRGs) in GC, as well as the potential value of disulfidptosis-related immune genes (DRIGs) as biomarkers. Methods This study incorporated the single-cell RNA sequencing (scRNA-seq) dataset GSE183904 and transcriptome RNA sequencing of GC from the TCGA database. Disulfidptosis-related genes (DRGs) and IRGs were derived from the representative literature on both cell disulfidptosis and immunity. The expression and distribution of DRGs were investigated at the single-cell level in different GC cell types. Pearson correlation analysis was used to identify the IRGs closely related to disulfidptosis. The prognostic signature of DRIGs was established using Cox and LASSO analyses. We then analyzed and evaluated the differences in long-term prognosis, Gene Set Enrichment Analysis (GSEA), immune infiltration, mutation profile, CD274 expression, and response to chemotherapeutic drugs between the two groups. A tissue array containing 63 paired GC specimens was used to verify the expression of 4 DRIGs and disulfidptosis regulator SLC7A11 through immunohistochemistry staining. Results The scRNA-seq analysis found that SLC7A11, SLC3A2, RPN1 and NCKAP1 were enriched in specific cell types and closely related to immune infiltration. Four DIRGs (GLA, HIF-1α, VPS35 and CDC37) were successfully identified to establish a signature to potently predict the survival time of GC patients. Patients with high risk scores generally experienced worse prognoses and exhibited greater resistant to classical chemotherapy drugs. Furthermore, the expression of GLA, HIF-1α, VPS35, CDC37 and SLC7A11 were elevated in GC tissues. A high expression of GLA, HIF-1α, VPS35 or CDC37 was associated with more advanced clinical stage of GC and increased SLC7A11 expression. Conclusion Current study first highlights the potential value of DRIGs as biomarkers in GC. We successfully constructed a robust model incorporating four DRIGs to accurately predict the survival time and clinicopathological characteristics of GC patients.

ABSTRACTStreptococcus suis is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different S. suis serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of S. suis serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.

ABSTRACTStreptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.

Considering the anisotropic characteristics of carbon fiber reinforced composites, the couple stress theory was modified, and the loading model of microscale Mindlin laminates in a hygrothermal environment was established. The material scale parameters affected by the environment were introduced, and the governing equations and boundary conditions were solved by using the principle of virtual work. Taking the four-sided simply supported square laminate by the orthogonal layer as an example, the displacement function of the Navier solution method was set to calculate the critical loads of the Mindlin laminates in a hygrothermal environment. The results show that the critical loads of Mindlin micro-laminate are greater than those of classical macro-theory under unidirectional axial compressive loads. The scale effect strengthens with the increase of material scale parameters, and the scale effect becomes more obvious with an increase in temperature change and hygroscopic concentration. The scale effect gradually disappears with the increase of the geometric parameters of the laminate, and the model degenerates into a macroscopic model.

Abstract Background and purpose Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis. Methods GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan–Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients. Results Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan–Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression. Conclusions Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential. Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear.MethodsIn this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models.ResultsMR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC.ConclusionUsing MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Abstract Background Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. Methods Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan–Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. Results A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P

The complexity of the spatial distribution and temporal occurrence of preferential flow (PF) makes it challenging to understand the mechanisms of PF. This study aims to identify the spatial and temporal patterns of PF occurrence using machine learning (Classification and Regression Trees and Random Forests) in the Qilian Mountains, Northwest China. Our results show that detected PF events transport much more rainfall down to the subsoil than non-PF events. Different vegetation types exhibit variations in the main soil layers where PF occurs, which is closely related to the distribution of roots. The PF proportion varies significantly both vertically and horizontally. Based on the Random Forests, we found that the spatial distribution of the PF proportion is mainly controlled by the saturated hydraulic conductivity and residual soil moisture, which cannot be identified by conventional correlation analysis methods. With these soil properties, the spatial distribution of the PF proportion can be estimated with reasonable performance. Using the Classification and Regression Trees method, we identified the temporal occurrence pattern of the PF for different vegetation types and all observation stations. Results indicate that the dominant factors controlling the temporal occurrence of the PF varied for different vegetation types. The thresholds at which these factors initiate the PF also varied. Finally, we found that the PF occurs particularly under wet conditions (except for hydrophobic soils), under denser vegetation, and under conditions of high rainfall amount and intensity, regardless of vegetation type. Our study confirms that both site factors (e.g., soil properties and vegetation) and temporal factors (e.g., initial soil moisture and rainfall characteristics) control the occurrence of the PF in mountainous regions such as the Qilian Mountains and that the Classification and Regression Trees has great potential to study the temporal occurrence of the PF.

Abstract Background Perioperative chemotherapy combined with curative gastrectomy has been increasingly represented the standard therapeutic strategy for resectable gastric cancer (GC). However, it is still unclear whether postoperative chemotherapy has a survival benefit for ypT1-2N0 gastric cancer patients who have undergone preoperative chemotherapy followed curative gastrectomy. Methods The data of patients who undergone neoadjuvant chemotherapy followed by gastrectomy and had pathological classification of ypT1–2N0 between March 2016 and December 2020 at Peking Union Medical College Hospital were retrospectively reviewed. Chi-square test was adopted to compare the difference between the patients with postoperative chemotherapy (pCHT) and without postoperative chemotherapy (no pCHT). Survival curves for overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. Results A total of 134 patients met the inclusion criteria and 56 (41.8%) of them have undergone postoperative chemotherapy. There were no statistically significant differences in demographic and clinicopathologic characteristics between pCHT group and no pCHT group (all p > 0.05). Postoperative chemotherapy was not associated with a significant improvement in overall survival (OS) (Hazard ratio [HR] 0.815, 95% confidence interval [CI] 0.403–1.650; p = 0.474). Subgroup analyses demonstrated survival was equivalent between pCHT and no CHT group in ypT1N0 patients (HR 0.832, CI 0.222–3.121; p = 0.786) and ypT2N0 patients (HR 1.284, CI 0.564–2.924; p = 0.551). Multivariable analysis identified that clinical T stage independently influenced prognosis (cT3 vs. cT2: HR 2.875, 95% CI 0.998–8.281, p = 0.050; cT4 vs. cT2: HR 7.382, 95% CI 2.569–21.211, p < 0.001). In clinical T3–4 patients, there was an overall survival benefit for postoperative chemotherapy (HR 0.270, 95% CI 0.114–0.634; p = 0.006). No survival benefit of postoperative chemotherapy was identified in clinical T2 patients (HR 0.689, 95% CI 0.200–2.372; p = 0.579). Furthermore, postoperative chemotherapy was proved to be an independently positive prognostic factor for clinical T3–4 patients (HR 0.132, 95% CI 0.051–0.345; p < 0.001). Conclusion Postoperative chemotherapy might offer survival benefit to patients with ypT1-2N0 gastric cancer whose clinical T stage was T3–4 before preoperative chemotherapy.

Abstract Background 5-fluorouracil (5-FU)-based chemotherapy regimen has been widely used for the treatment of gastric cancer, but meanwhile the development of chemotherapeutic resistance remains a major clinical challenge. Tumor microenvironment (TME) frequently correlates with the development of chemoresistance in human cancer. As a major component of TME, the role of tumor-associated macrophages (TAMs) in the chemoresistance of gastric cancer has not been fully elucidated. Methods Immunohistochemistry (IHC) was applied to detect the density of TAMs in clinical samples of 103 patients with gastric cancer who had undergone 5-FU-based neoadjuvant chemotherapy. 5-FU-resistant gastric cell lines MKN45-R and HGC27-R were established, macrophages were then separately co-cultured with MKN45-R, HGC27-R cells and their parental cells. The effect of gastric cancer cells on the polarization of macrophages, the biological function of M2-polaried macrophages and the mechanism for promoting 5-FU-resistance were investigated. Then the correlation between the expression of CXC motif chemokine ligand 5 (CXCL5) and the infiltration of hemoglobin scavenger receptor (CD163) positive and mannose receptor (CD206) positive macrophages was analyzed, the prognostic value of CXCL5 expression in clinical samples was further explored. Results The high infiltration of macrophages marked by CD68 in gastric cancer samples was significantly associated with the resistance of gastric cancer to chemotherapy. Gastric cancer cells could modulate macrophages to M2-like polarization through indirect co-culture, and chemoresistant cells were more efficient in inducing macrophages polarization to M2 phenotype. Co-culturing M2-polarized macrophages in turn enhanced 5-FU-resistance of gastric cancer cells, and it was further verified that CXCL5 derived from M2-polarized macrophages promoted chemoresistance through activing the PI3K/AKT/mTOR pathway. Besides, high level of CXCL5 could recruit monocytes to form more M2-polarized macrophages. Clinically, high expression of CXCL5 in gastric cancer samples was associated with the high infiltration of CD163 positive macrophages and CD206 positive macrophages, and patients with high expression of CXCL5 presented lower overall survival (OS) rates than those with low expression of CXCL5. Conclusion Interaction between TAMs and gastric cancer cells promoted chemoresistance in gastric cancer via CXCL5/PI3K/AKT/mTOR pathway. Thus, targeting TAMs and blocking the cell–cell crosstalk between TAMs and gastric cancer cells may represent prospective therapeutic strategies for patients with gastric cancer.

Abstract Background Gastric cancer (GC) is a malignant tumour, with high morbidity and mortality rates worldwide. The occurrence and development of GC is a complex process involving genetic changes in tumour cells and the influence of the surrounding tumour microenvironment (TME). Accumulative evidence shows that tumour‐associated macrophages (TAMs) play a vital role in GC, acting as plentiful and active infiltrating inflammatory cells in the TME. Main body In this review, the different functions and mechanisms of TAMs in GC progression, including the conversion of phenotypic subtypes; promotion of tumour proliferation, invasion and migration; induction of chemoresistance; promotion of angiogenesis; modulation of immunosuppression; reprogramming of metabolism; and interaction with the microbial community are summarised. Although the role of TAMs in GC remains controversial in clinical settings, clarifying their significance in the treatment selection and prognostic prediction of GC could support optimising TAM‐centred clinicaltherapy. Conclusion In summary, we reviewed the the phenotypic polarisation, function and molecular mechanism of TAMs and their potential applications in the treatment selection and prognostic prediction of GC.

Evapotranspiration (ET) is critical for ecosystem protection and water services, especially in the mountainous areas of arid and semi-arid watersheds. The lysimeter and Eddy Covariance (EC) methods are widely used for directly measuring ET, but are difficult to install and apply in mountainous areas with complex topography. The commonly used indirect methods for estimating ET, such as the Penman-Monteith (PM) method, present significant challenges in mountainous areas with scarce data. The simple soil water balance (SWB) method, which estimates ET from soil moisture dynamics, is another reliable and simple method for estimating ET. However, a drawback of the original SWB method is that it assumes soil moisture depletion only occurs through ET, ignoring the process of deep percolation. This restriction limits the applicability of the SWB method. In this study, we improve the SWB method (ISWB) by incorporating a deep percolation module into the soil water balance equation. Subsequently, we compare the estimated ET obtained from the ISWB, the Food and Agriculture Organization (FAO)-56 PM, and the Hargreaves-Samani (HS) methods with the observed ET. Results show that the ISWB method for estimating ET performs better when using the soil moisture of the 0–25 cm and below layers, compared to the 0–20 cm and above layers. Meanwhile, there is no significant difference in performance between using the soil moisture of the 0–25 cm layer and the soil layers below 25 cm. In addition, ignoring interception evaporation has an obvious influence on ET estimation using the ISWB. Furthermore, the comparison indicated that the performance of the ISWB method is superior to that of the FAO-56 PM and HS methods in the study areas. Our study shows that the ISWB method has significant potential for ET estimation in data-scarce and topographic-complex mountainous areas.

IntroductionGastric cancer (GC) is the fourth leading cause of cancer death worldwide. Due to the lack of effective chemotherapy methods for advanced gastric cancer and poor prognosis, the emergence of immunotherapy has brought new hope to gastric cancer. Further research is needed to improve the response rate to immunotherapy and identify the populations with potential benefits of immunotherapy. It is unclear whether m7G-related lncRNAs influence tumour immunity and the prognosis of immunotherapy.MethodsThis study evaluated 29 types of immune cells and immune functions in gastric cancer patients, and m7G-related lncRNAs and their molecular subtypes were identified. In addition, we also studied the biological function characteristics of m7G-related lncRNA molecular subtypes. Finally, the patient's risk score was calculated based on m7G-related lncRNAs, and a nomogram of staging and risk groups was established to predict the prognosis. For experimental verification, RT–qPCR were preformed from the native cohort.ResultsAfter identifying m7G-related lncRNAs and their molecular subtypes, we found three molecular subtypes, the B subtype had the highest level of infiltration, and the B subtype may benefit more from immunotherapy. We divided GC patients into two regulator subtypes based on biological function. The two subtypes have significant immunological differences and can be used to judge ICI treatment. We established a risk score formula based on five lncRNAs, including LINC00924, LINC00944, LINC00865, LINC00702, and ZFAS1. Patients with poor prognoses were closely related to patients in the high-risk group. After comprehensive analysis of different risk groups, the efficacy of the high-risk group on bleomycin, cisplatin, docetaxel, doxorubicin and etoposide was better than that of the low-risk group, suggesting that risk subgroups based on risk scores play a guiding role in chemotherapy and that the high-risk group may benefit more from immunotherapy. RT–qPCR results showed that LINC00924, LINC00944, and LINC00865 were highly expressed in tumour tissues, while LINC00702 and ZFAS1 were expressed at low levels in tumour tissues.DiscussionIn conclusion, we were the first to discover that m7G-related lncRNAs play a vital role in the tumour immune microenvironment of gastric cancer, and a risk prediction model was established to identify patients with potential benefits from immunotherapy and predict the prognosis of GC patients.

Objective: The impact of perioperative immunonutrition on patients undergoing radical gastrectomy remains undetermined. This study aimed to assess the influence of enteral immunonutrition support on postoperative immune function and intestinal mucosal barrier function following radical gastrectomy, contrasting findings with a control group to furnish evidence for perioperative enteral nutrition support. Methods: In this prospective randomized trial, 65 patients who underwent radical gastrectomy between June 2022 and June 2023 were included. Participants were allocated to either the study group (receiving enteral immunonutrition) or the control group (not receiving enteral immunonutrition). We compared postoperative rehabilitation and complications between the groups, analyzed the intestinal mucosal barrier function markers on the 3rd and 7th postoperative days, and delved deeper into peripheral blood cell immunity, inflammation, and nutritional indicators. Results: The cohort consisted of 30 patients in the study group and 35 in the control group, with no significant differences in demographic attributes between the two groups. On the 3rd postoperative day, the diamine oxidase, D-lactic acid, and endotoxin levels in the study group were significantly lower than those in the control group (p = 0.029, p = 0.044, and p = 0.010, respectively). By the 7th postoperative day, these levels continued to be significantly diminished in the study group (p = 0.013, p = 0.033, and p = 0.004, respectively). The times to first flatus (p = 0.012) and first bowel movement (p = 0.012) were significantly shorter in the study group. Moreover, postoperative complications in the study group were fewer than in the control group (p = 0.039). On the 7th postoperative day, the study group had lower peripheral white blood cell (WBC) levels (p = 0.020) and neutrophil–lymphocyte ratios (NLR) (p = 0.031), but displayed elevated albumin levels (p = 0.006). One month post-surgery, the CD4+T and CD8+T counts were significantly greater in the study group (p = 0.003 and p = 0.012, respectively). Correlation analyses indicated that NLR and complications were associated with endotoxin levels. Conclusion: Administering perioperative enteral immunonutrition enhances postoperative immune and intestinal mucosal barrier functions in patients undergoing radical gastrectomy. This effect leads to diminished inflammatory responses, a decreased rate of postoperative complications, and accelerated patient recovery.

Abstract OTUB2 is a deubiquitinating enzyme that contributes to tumor progression. However, the expression of OTUB2 and its prognostic importance in gastric cancer remain unclear. The expression of OTUB2 and KRT80 in GC tissues was investigated using western blotting, qRT-PCR, multiple immunofluorescence staining, and immunohistochemistry. For survival studies, Kaplan–Meier analysis with the log-rank test was used. The role of OTUB2 during GC proliferation was investigated using in vivo and in vitro assays. OTUB2 was found to be overexpressed in GC tissues and to act as an oncogene, which was linked to patients’ poor prognosis. Knockdown of OTUB2 inhibited the proliferative capacity of GC cells in vitro and in vivo, although the proliferative capacity was restored upon re-supplementation with KRT80. OTUB2 mechanically stabilized KRT80 by deubiquitinating and shielding it from proteasome-mediated degradation through Lys-48 and Lys-63. Furthermore, by activating the Akt signaling pathway, OTUB2 and KRT80 facilitated GC proliferation. In summary, OTUB2 regulates KRT80 stability via deubiquitination promoting proliferation in GC via activation of the Akt signaling pathway, implying that OTUB2 could be a novel prognostic marker.

BackgroundThe spleen is the largest peripheral lymphoid organ in the body. Studies have implicated the spleen in the development of cancer. However, it is unknown whether splenic volume (SV) is associated with the clinical outcome of gastric cancer.MethodsData of gastric cancer patients treated with surgical resection were retrospectively analyzed. Patients were divided into three groups: underweight, normal-weight and overweight. Overall survival was compared in patients with high and low splenic volume. The correlation between splenic volume and peripheral immune cells were analyzed.ResultsOf 541 patients, 71.2% were male and the median age was 60. Underweight, normal-weight and overweight patients accounted for 5.4%, 62.3% and 32.3%, respectively. High splenic volume was associated with unfavorable prognosis across the three groups. In addition, the increase of splenic volume during neoadjuvant chemotherapy was not associated with prognosis. The baseline splenic volume was negatively correlated with lymphocytes (r=-0.21, p

Streptococcus suis, an emerging zoonotic pathogen, is important reservoirs of antibiotic resistance genes that play critical roles in the horizontal transfer of corresponding resistances. In the present study, 656 antibiotic resistance (AR) genes were detected in 154 of 155 genomes of S. suis strains isolated from the nasopharynx of slaughtered pigs and the lungs of diseased pigs in China. The AR genes were clustered into 11 categories, consisting of tetracycline, macrolides, lincosamide, streptogramin, aminoglycoside, trimethoprim, amphenicols, nucleoside, quinupristin/dalfopristin, glycopeptide, and oxazolidinones resistance genes. In order to investigate the transmission patterns of the AR genes, AR genes-associated the mobile genetic elements (MGEs) were extracted and investigated. Twenty ICEs, one defective ICE, one tandem ICE, and ten prophages were found, which mainly carried tetracycline, macrolides/lincosamides/streptogramin (MLS), and aminoglycosides resistance genes. Three types of DNA cargo with AR genes were integrated into specific sites of ICEs: integrative mobilizable elements (IMEs), cis-IMEs (CIMEs), and transposon Tn916. Obvious differences in AR gene categories were found among the three cargo types. IMEs mainly harbored tetracycline and MLS resistance genes. CIMEs mainly carried aminoglycoside resistance genes, while transposon Tn916 carried only the tet (M) gene. Nearly all AR genes in ICEs were carried by IMEs and CIMEs. IMEs were prevalent and were also detected in additional 29 S. suis genomes. The horizontal transfer of IMEs and CIMEs may play critical role in ICE evolution and AR gene transmission in the S. suis population. Our findings provide novel insights into the transmission patterns of AR genes and the evolutionary mechanisms of ICEs in S. suis.

Abstract Background An abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients. Methods Three hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM). Results There were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(−) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31–0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21–0.87). Conclusions Low iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

Background: Significant survival benefit of adjuvant imatinib therapy has been observed in gastrointestinal stromal tumor (GIST). However, the impact of neoadjuvant imatinib on prognosis of GIST remains unclear. This meta-analysis aimed to compare the prognostic impact between upfront surgery and neoadjuvant imatinib plus surgery on GIST.Methods: A comprehensive literature search was performed to identify eligible studies up to 30 Sep 2021, through PubMed, Embase, Web of Science, and Cochrane Library. Studies compared the impact of upfront surgery and neoadjuvant imatinib plus surgery on disease-free (DFS) or overall survival (OS) in patients with GIST were selected.Results: Seven eligible studies with 17,171 patients were included. The reduction rates of tumor size in rectal and mixed site GIST were 33% and 29.8%, respectively. Neoadjuvant imatinib was not significantly associated with DFS compared with no-neoadjuvant therapy in rectal GIST (HR: 0.71, 95% CI: 0.35–1.41). The OS of rectal GIST was significantly improved by neoadjuvant imatinib compared with no-neoadjuvant therapy (HR: 0.36, 95% CI: 0.17–0.75).Conclusion: Neoadjuvant imatinib therapy contributed to tumor shrinkage and R0 resection of rectal GIST. Neoadjuvant imatinib plus surgery significantly improved overall survival of rectal GIST in comparison with upfront surgery.

Abstract Background Neoadjuvant chemotherapy is an important part of the comprehensive treatment of advanced gastric cancer (GC). The effect of neoadjuvant chemotherapy plays a key role in the prognosis of GC patients. Pathological response can represent the effect of neoadjuvant chemotherapy. However, evidence focused on pathological response and associated clinicopathological factors in GC patients is quite little. In this retrospective study, the clinicopathological factors affecting the effect of neoadjuvant chemotherapy in GC patients were investigated, and suggestions were proposed to improve the effect of neoadjuvant chemotherapy on GC. Methods Retrospective analysis was performed on GC patients who received radical surgery after neoadjuvant chemotherapy from February 2016 to December 2019 at Peking Union Medical College Hospital. Relevant clinicopathological data was collected to analyze the factors influencing the effect of neoadjuvant chemotherapy. Chi-square test was used for univariate analysis. Logistic regression was used for multivariate analysis. Receiver operating characteristic curve (ROC) was used to determine the cutoff value of variables which significantly influenced the effect of neoadjuvant chemotherapy. Results A total of 203 GC patients were included in the study. Analyses showed that patients < 60 years old (OR = 1.840 [1.016–3.332], P = 0.044), histological type of poor differentiation or signet-ring cell carcinoma (OR = 2.606 [1.321–5.140], P = 0.006), and weight loss during neoadjuvant chemotherapy (OR = 2.110 [1.161–3.834], P = 0.014) were independent risk factors for neoadjuvant chemotherapy effect. In ROC analysis of weight change and neoadjuvant chemotherapy effect, area under the curve (AUC) was 0.593 (P = 0.024) and cutoff value of weight change was − 2.95%. Chi-square test showed that patients without weight loss during neoadjuvant chemotherapy had a higher rate of oral nutritional supplement (ONS) than patients with weight loss (P = 0.039). Conclusions Patients 2.95% during neoadjuvant may have a worse chemotherapy effect. Timely nutritional support such as ONS to maintain patients’ body weight is crucial for improving the effect of neoadjuvant chemotherapy.

BackgroundTo evaluate the detailed relationship between total percent fat (TPF) and cardiovascular disease (CVD)-related lipid biomarkers among adults and find a non-invasive indicator for screening and monitoring of the high CVD risk population.MethodsData of 13,160 adults were obtained from the National Health and Examination Survey (NHANES) from 1999 to 2018. TPF was assessed by dual-energy x-ray absorptiometry (DXA), and CVD-related lipid biomarkers included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Multivariable linear regression models were used to examine associations between TPF with four kinds of lipid biomarkers, and smooth curve fittings and generalized additive models were used to address the non-linear relationship between them. The inflection points were calculated by the recursive algorithm when non-linearities were detected and then weighted two-piecewise linear regression models were constructed.ResultsIn multivariable regression, increasing TPF was positively associated with TC, TG, and LDL-C and negatively with HDL-C (all p < 0.001). In addition, the non-linear relationships between them were also identified by generalized additive models and smooth curve fittings. When further stratified TPF by sex, the fitted smooth curves were nearly inverted U-shaped and U-shaped curves, the inflection points were calculated, and the weighted two-piecewise linear regression models were constructed, respectively. The same results existed between android percent fat and these four lipid biomarkers.ConclusionsTotal percent fat was significantly associated with CVD-related lipid biomarkers in adults, positively with TC, TG, and LDL-C and negatively with HDL-C. It could be used as a non-invasive screener and monitor of high CVD risk population when their TPF values were less than the inflection points.

BackgroundSerum uric acid (SUA) has been proven to be closely associated with metabolic abnormalities, including obesity. This study aimed to investigate the detailed relationship between total percent fat (TPF) and SUA among adults.MethodsBriefly, 23,715 adults aged 18–59 years in the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were included in this study. Multivariable linear regression models were used to examine the association between TPF and SUA. Subgroup analyses stratified by sex and obesity status were also performed by multivariable linear regression. Then, fitted smoothing curves and generalized additive models were also applied to address the non-linear relationship between TPF and SUA. Finally, a recursive algorithm was used to calculate the inflection point in the non-linear relationship and a two-segment piecewise linear regression model was used to analyze the relationship between TPF and SUA on both sides of the inflection point.ResultsThere were 15,808 (66.7%) obese individuals in all 23,715 participants. In the fully adjusted model, there was a positive association between TPF and SUA (β = 0.99, 95% CI: 0.73–1.26). Besides, this positive association remained statistically significant in subgroup analyses stratified by sex and obesity status. Interestingly, in males, the association of TPF and SUA was an inverted U-shaped curve (inflection point: 34.3%).ConclusionOur study revealed a significant positive relationship between TPF and SUA among adults and this association remained statistically significant when stratified by sex and obesity status, but the shape of the smoothing curve in males differed from that in females.

microRNAs (miRNAs) are a type of small endogenous non-coding RNAs composed of 20-22 nucleotides, which can regulate the expression of a gene by targeting 3’ untranslated region (3’-UTR) of mRNA. Many studies have reported that miRNAs are involved in the occurrence and progression of human diseases, including malignant tumors. miR-1224 plays significant roles in different tumors, including tumor proliferation, metastasis, invasion, angiogenesis, biological metabolism, and drug resistance. Mostly, it serves as a tumor suppressor. With accumulating proofs of miR-1224, it can act as a potential bio-indicator in the diagnosis and prognosis of patients with cancer. In this article, we review the characteristics and research progress of miR-1224 and emphasize the regulation and function of miR-1224 in different cancer. Furthermore, we conclude the clinical implications of miR-1224. This review may provide new horizons for deeply understanding the role of miR-1224 as biomarkers and therapeutic targets in human cancer.

Radiotherapy (RT), or radiation therapy, has been widely used in clinical practice for the treatment of local advanced gastrointestinal carcinoma. RT causes DNA double-strand breaks leading to cell cytotoxicity and indirectly damages tumor cells by activating downstream genes. Non-coding RNA (including microRNAs, long non-coding RNAs (ncRNAs), and circular RNAs) is a type of RNA that does not encode a protein. As the field of ncRNAs increasingly expands, new complex roles have gradually emerged for ncRNAs in RT. It has been shown that ncRNAs can act as radiosensitivity regulators in gastrointestinal carcinoma by affecting DNA damage repair, cell cycle arrest, irradiation-induced apoptosis, cell autophagy, stemness, EMT, and cell pyroptosis. Here, we review the complex roles of ncRNAs in RT and gastrointestinal carcinoma. We also discuss the potential clinical significance and predictive value of ncRNAs in response to RT for guiding the individualized treatment of patients. This review can serve as a guide for the application of ncRNAs as radiosensitivity enhancers, radioresistance inducers, and predictors of response in RT of gastrointestinal carcinoma.

BackgroundThis meta-analysis aimed to determine the prognostic impact of microscopically positive margins (R1) on primary gastrointestinal stromal tumors.MethodsA literature search was performed using PubMed, Embase, Web of Science, and Cochrane Library for studies up to 23 November 2020. The pooled disease-free survival (DFS) and overall survival (OS) between R1 and negative margins (R0) were estimated using a random-effects model.ResultsTwenty studies with 6,465 patients were included. Compared with R0 resection, R1 was associated with poor DFS in patients who did not receive adjuvant Imatinib (HR: 1.62, 95% CI: 1.26–2.09; P = 0.48, I2 = 0%; reference: R0). This negative impact of R1 disappeared with the use of adjuvant Imatinib (HR: 1.23, 95% CI: 0.95–1.60; P = 0.38, I2 = 6%; reference: R0). R1 was related to poor DFS in gastric GISTs (HR: 2.15, 95% CI: 1.15–5.02, I2 = 0%; reference: R0), which was attenuated in the subgroup of adjuvant Imatinib (HR: 2.24, 95% CI: 0.32–15.60; P = 0.84, I2 = 0%; reference: R0). Rectal GIST with R1 margin who even received adjuvant Imatinib still had poor DFS (HR: 3.79, 95% CI: 1.27–11.31; P = 0.54, I2 = 0%; reference: R0). Patients who underwent R1 resection had similar OS compared with those underwent R0 resection regardless of the use of adjuvant Imatinib.ConclusionR1 was associated with poor DFS for primary GISTs, which was attenuated by adjuvant therapy with Imatinib. Similar result was observed in the gastric GISTs subgroup. Rectal GIST patients with R1 resection had poor DFS even when they received adjuvant Imatinib. The R1 margin did not influence the OS of GISTs.

Although therapeutic methods have been developed, gastric cancer (GC) still leads to high rates of mortality and morbidity and is the fourth leading cause of cancer-associated death and the fifth most common cancer worldwide. To understand the factors associated with the prognostic prediction of GC and to discover efficient therapeutic targets, previous studies on tumour pathogenesis have mainly focused on the cancer cells themselves; in recent years, a large number of studies have shown that cancer invasion and metastasis are the results of coevolution between cancer cells and the microenvironment. It seems that studies on the tumour microenvironment could help in prognostic prediction and identify potential targets for treating GC. In this review, we mainly introduce the research progress for prognostic prediction and the immune microenvironment in GC in recent years, focusing on cancer-associated fibroblasts (CAFs), tumour-associated macrophages (TAMs), and tumour-infiltrating lymphocytes (TILs) in GC, and discuss the possibility of new therapeutic targets for GC.

Background: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and chemoresistance is a major cause for its poor prognosis. Long non-coding RNAs (lncRNAs) are associated with cancer chemoresistance. The current study sought to explore the mechanism of lncRNA HNF1A antisense RNA 1 (HNF1A-AS1) in mediating 5-fluorouracil (5-FU) resistance of GC. Methods: qRT-PCR was performed to detect the expression level of HNF1A-AS1 in GC tissues and cells. Abnormal expression of HNF1A-AS1 in GC cells was induced by lentivirus infection. Protein levels of EIF5A2, E-Cadherin, Vimentin and N-Cadherin were detected using western blot. Competitive endogenous RNA (ceRNA) mechanisms were explored through luciferase assays and RNA immunoprecipitation (RIP) assays. Functional experiments of chemoresistance were performed by CCK-8 assays, colony formation assays and flow cytometry with the treatment of 5-FU. Mouse tumor xenograft assays were performed to verify the findings in vivo. Results: The findings showed HNF1A-AS1 was significantly upregulated in GC tissues especially in chemoresistance group. Findings from in vitro and in vivo experiments showed HNF1A-AS1 increased cell viability and proliferation, repressed apoptosis and promoted xenograft tumors growth in the presence of 5-FU. Mechanistic studies revealed HNF1A-AS1 promoted chemoresistance by facilitating epithelial mesenchymal transition (EMT) process through upregulating EIF5A2 expression and HNF1A-AS1 acted as a sponge of miR-30b-5p. Conclusions: The findings from the current study showed HNF1A-AS1 promoted 5-FU resistance by acting as a ceRNA of miR-30b-5p and promoting EIF5A2-induced EMT process in GC. This indicates that HNF1A-AS1 is a potential therapeutic target for alleviating GC chemoresistance.

BackgroundFat metabolism is associated with prediabetes and type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the detailed correlation of diabetes status with adiposity among adults.MethodsBriefly, 28,429 adults aged ≥18 years from both sexes in the National Health and Nutrition Examination Survey (NHANES) 1999–2018 were included in this study. Multivariable linear regression models were used to examine associations of prediabetes and diabetes status, disease duration of T2DM, serum glucose, glycohemoglobin (HbA1c) with total percent fat (TPF), and fat mass distribution.ResultsAfter adjusting for sociodemographic covariates, health behaviors, hypertension, hypercholesterolemia, there were direct associations of prediabetes and T2DM status with TPF, trunk fat mass, android fat mass, gynoid fat mass and android to gynoid ratio compared with non-diabetes. But the fat mass decreased with the increase of the disease duration in patients with T2DM. Besides, when stratifying by diabetes status, we found direct associations of serum glucose and HbA1c with TPF, trunk fat mass, android fat mass, gynoid fat mass, and android to gynoid ratio in non-diabetic and prediabetic participants. But in patients with T2DM, inverse associations of serum glucose and HbA1c with fat mass were observed.ConclusionsThis study indicated that adults with prediabetes and T2DM had significantly higher TPF, trunk fat mass, android fat mass, gynoid fat mass, and android to gynoid ratio compared with those without diabetes. Moreover, fat mass decreased as the disease duration increased in patients with T2DM. The associations of serum glucose and HbA1c with TPF and fat mass distribution in patients with T2DM were opposite to the relationships observed in non-diabetic and prediabetic participants.

BackgroundEndoscopic resection (ESR) is a novel minimally invasive procedure for superficial tumors. Its safety, efficiency, and outcome for gastric gastrointestinal stromal tumors (gGISTs) less than 5 cm remains unclear compared to laparoscopic resection (LAR) and open resection (ONR). The current network meta-analysis aimed to review and analyze the available evidence of this question.MethodsPubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify eligible studies published up to July 6, 2020. The perioperative and long-term oncological outcomes among ESR, LAR, and ONR for gGIST (

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria has been recently published for diagnosing malnutrition in adults. However, the validity of the GLIM criteria has not been well-established in patients with gastric cancer (GC) treated with neoadjuvant treatment (NT) followed by radical gastrectomy. The present study aimed to explore the prognostic value of GLIM-defined malnutrition before NT and after NT in GC patients and to investigate whether additional visceral adipose tissue (VAT) assessment could improve the predictive power of the GLIM criteria for NT-related adverse events (AEs) and long-term survival. Methods: GC patients who underwent radical surgery after NT from June 2016 to June 2020 were enrolled in this study. The cross-sectional areas of total skeletal muscle (TSM) and VAT were measured using computed tomography (CT) before NT and after NT. GLIM-defined malnutrition was diagnosed using the two-step approach, including nutritional risk screening and diagnostic assessment. Low VAT was also added to the diagnosis of malnutrition in this study. The predictive value of these malnutrition diagnoses for NT-related AEs, and long-term survival was evaluated in GC patients. Results: A total of 182 GC patients were included in this study, of which 66 (36.3%) patients before NT and 55 (30.2%) patients after NT were diagnosed with GLIM-defined malnutrition, respectively. In addition to GLIM-defined malnutrition, 54 (29.7%) patients had additional low VAT before NT, and 39 (21.4%) patients had additional low VAT after NT. GLIM-defined malnutrition alone before NT was not associated with NT-related AEs in GC patients. The addition of low VAT to GLIM-defined malnutrition led to a significant predictive value for NT-related AEs. Furthermore, GLIM-defined malnutrition before NT and after NT were both identified as independent risk factors for overall survival (OS) and disease-free survival (DFS). The combination of low VAT and GLIM-defined malnutrition showed a higher hazard ratio for the prediction of OS and DFS both before NT and after NT. Conclusions: The addition of VAT assessment using CT improved the predictive value of GLIM-defined malnutrition for NT-related AEs and long-term survival in GC patients treated with NT followed by radical gastrectomy, which further supports the prognostic importance of assessing adipose tissue simultaneously during the routine nutritional assessment in patients with cancer.

The overall efficacy of neoadjuvant chemoradiotherapy (NACT) for locally advanced gastric cancer (LAGC) has been recognized. However, the response rate of NACT is limited due to tumor heterogeneity. For patients who are resistant to NACT, not only the operation timing will be postponed, patients will also suffer from the side effects of it. Thus, it is important to develop a comprehensive strategy and screen out patients who may be sensitive to NACT. This article summarizes the related research progress on the sensitivity prediction of NACT for GC in the following aspects: microRNAs, metabolic enzymes, exosomes, other biomarkers; inflammatory indicators, and imageological assessments. The results showed that there were many studies on biomarkers, but no unified conclusion has been drawn. The inflammatory indicators are related to the survival and prognosis of patients under NACT. For imageological assessments such as CT, MRI, and PET, with careful integration and optimization, they will have unique advantages in early screening for patients who are sensitive to NACT.

Gastric cancer (GC) is one of the most prevalent and deadly malignancies worldwide. We aimed to assess the functional role and clinical significance of pyruvate dehydrogenase kinase (PDK) in GC and explored the underlying mechanisms. The bioinformatics method was used to investigate the expression of PDKs in GC, the effect on clinical outcomes, enriched pathways, interactive network, and the correlation between PDK4 and immune infiltration. Next, PDK expression in the GC cells and tissues were verified by qRT-PCR and western blotting. A Cell Counting Kit-8 (CCK8), colony-formation, Flow cytometry, Transwell and wound healing assays were carried out to evaluate the influence of PDK4 on cell proliferation, invasion and migration. Among PDKs, PDK4 expression was aberrant in GC and identified as an independent prognostic factor. GO analysis, GSEA, and PPI showed that PDK4 expression may regulate cell adhesion, metal ion transport, synaptic activity, and cancer cell metabolism in GC. Analyses of immune infiltration showed that PDK4 correlated with the abundant expression of various immunocytes. Finally, we verified that upregulation of PDK4 expression enhanced the ability of GC cells to proliferate, migrate, and invade. In conclusion, PDK4 was identified as a potential candidate diagnostic biomarker and therapeutic target for GC patients.

Objective Angiolipoma is a benign tumor that rarely occurs in the gastrointestinal (GI) tract. This case series was performed to increase clinicians’ understanding of the diagnosis and management of GI angiolipoma. Methods We evaluated the clinical presentations, diagnoses, and treatments of 3 patients with angiolipoma in the upper GI tract in our hospital and 27 cases reported in the literature. Results Among all 30 cases of GI angiolipoma, 2 originated in the esophagus, 4 in the stomach, 2 in the duodenum, 1 in the jejunum, 7 in the ileum, 1 in the cecum, 9 in the colon, 2 in the rectum, and 2 in both the duodenum and colon. Conclusion Angiolipoma of the GI tract may be more likely to occur in middle-aged and elderly men and be located in the ileum and colon. The clinical manifestations generally involve upper GI hemorrhage and lower GI pain and obstruction. Computed tomography and endoscopy may be effective diagnostic techniques, but postoperative histopathologic examination is still the gold standard. The management of angiolipoma in the GI tract depends on the size and type of lesion. Most cases in the present series were managed by complete surgical resection, after which no recurrence was found.

Objective The incidence of digestive tract malignancies (DTMs) is increasing, early diagnosis is limited, and treatment effects are unsatisfactory. DTMs express ghrelin, which might be involved in tumor formation and development; whether serum ghrelin can provide useful guidance remains unknown. Methods Sera of healthy individuals were obtained from October 2017 through March 2018; serum samples from patients with gastric (GC), colon (CC), and rectal (RC) cancers were collected during the same period. Serum ghrelin was tested by ELISA and correlated with clinicopathology of patients with DTMs. Results Serum ghrelin was higher in patients (GC, 38 patients; CC, 24; RC, 26) than in 69 healthy individuals and decreased significantly after tumor resection. Nutrition Risk Screening 2002 score and neutrophil:lymphocyte ratio affected perioperative serum ghrelin levels. The epithelial cell marker AE1/AE3 (pan keratin) in patients with GC, tumor location in the colon in patients with CC, and age in patients with RC also affected perioperative serum ghrelin. Conclusions Serum ghrelin might provide early warning of occurrence and guide prognosis of DTMs. Ghrelin can be used when screening for nutritional risk and inflammation. The clinicopathological influence on serum ghrelin in patients with DTMs is related to tumor location in the digestive tract.

Objective: To investigate the protective effects of synbiotics on intestinal barrier function, and its priority to probiotics and prebiotics on intestinal barrier function in rat models. Methods: We randomly divided 32 rats into four groups: control group (n = 8), probiotics group (n = 8), prebiotics group (n = 8) or synbiotics group (n = 8). All rats received cecectomy and gastrostomy, and tube feeding amoxicillin 50 mg and metronidazole 20 mg on operation day and the first operative day (POD1). After the establishment of impaired intestinal barrier model, rats in the 4 groups received intact protein enteral nutrition, intact protein enteral nutrition+ bifid-triple viable, intact protein enteral nutrition with dietary fiber, intact protein enteral nutrition with dietary fiber+ bifid-triple viable respectively. Samples of blood, urine and tissues of colonic mucose were collected on POD6. Thereafter we measured lactulose/mannitol (L/M) ratio, concentration of certain gut microflora, bacterial translocation rate, endotoxin level of portal vein serum and thickness of colonic mucose. Results: Concentration of lactobacilli in probiotics group [(0.828 ± 0.366) × 107 CFU/g] and synbiotics group [(1.424 ± 0.928) × 107 CFU/g] were significantly higher than those in control group [(0.046 ± 0.037) × 107 CFU/g] and prebiotics group [(0.074 ± 0.046) × 107 CFU/g], P < 0.05. Concentration of bifidobacteria in probiotics group [(0.876 ± 0.701) × 107 CFU/g] and synbiotics group [(2.246 ± 1.112) × 107 CFU/g] were significantly higher than those in control group [(0.072 ± 0.051) × 107 CFU/g] and prebiotics group [(0.072 ± 0.051) × 107 CFU/g], P < 0.05, meanwhile concentration of bifidobacteria in synbiotics group was significantly higher than that in the probiotics group, P < 0.05. L/M ratio in synbiotics group (0.78 ± 0.43) was significantly lower than those in control group (1.45 ± 0.40), probiotics group (1.08 ± 0.22) and prebiotics group (1.35 ± 0.38), P < 0.05. Colonic mucosa thickness in synbiotics group (228.2 ± 13.9 μm) was significantly higher than those in control (198.5 ± 10.3 μm), probiotics (199.8 ± 11.8 μm) and prebiotics group (206.2 ± 11.7 μm), P

Prevalence of malnutrition is a common and serious issue responsible for the morbidity and mortality rate among hospitalized patients. We aimed to provide an actual and comprehensive situation of the nutritional characteristics, nutritional support and the risk factors for malnutrition among hospitalized patients in China.We analyzed the data from nutritionDay audit 2016 in China. The international daylong cross-sectional survey was performed on November 10th, 2016 via filling out several questionnaires regarding information on patients' illness, food intake history, weight change and nutritional care. Re-assessment of patients' outcome questionnaire was performed 30 days later.Total of 781 patients from 9 hospitals and 8 kinds of departments were enrolled in this report. Of these, malnutrition rate was 29.6%. Parenteral nutrition (251/344, 73.0%) was the primary nutrition support form in Chinese hospitals. However, 41.8% (136/325) of patients at nutritional risk or already diagnosed with malnutrition did not received any form of nutritional support, whereas 34.0% (155/456) well-nourished patients did. Patients with malnutrition had extended length of hospital stay and poor 30-day outcomes compared to well-nourished patients. Nutritional support could benefit nutritional risk or malnutrition patients, rather than well-nourished patients. Moreover, major lesion types, self-related health, food intake last week were independent risk factors of malnutrition (all p