The effect of intermittent versus continuous enteral feeding for critically ill patients: a meta-analysis of randomized controlled trials.

Objectives: The appropriate strategy for enteral feeding in critically ill patients still remains controversial. Therefore, we conducted this meta-analysis to compare the effect of intermittent versus continuous enteral feeding method for critically ill patients. Methods: Electronic databases including PubMed, Embase, Scopus, and Cochrane Library were searched up to April 10th, 2023 for randomized controlled trials evaluating the effect of intermittent versus continuous enteral feeding for critically ill patients. The primary outcomes were feeding intolerances, including diarrhea, vomiting, distension, constipation, gastric retention, and aspiration pneumonia. The secondary outcomes were mortality in intensive care unit (ICU), length of stay in ICU, and achievement of nutritional goal. Results: Thirteen studies with a total of 884 patients were analyzed in this meta-analysis. Overall, the use of intermittent enteral feeding was associated with higher incidence of diarrhea (OR 1.66, 95%CI 1.13 to 2.43, I2 = 16%) and distension (OR 2.29, 95%CI 1.16 to 4.51, I2 = 0%), lower incidence of constipation (OR 0.58, 95%CI 0.37 to 0.90, I2 = 0%), and longer length of ICU stay (MD 1.09, 95%CI 0.53 to 1.64, I2 = 0%). Moreover, no significant difference was identified for other outcome measures. Conclusion: In critically ill patients, the implementation of intermittent enteral feeding was associated with higher incidence of diarrhea and distension, longer length of ICU stay, but lower occurrence of constipation. Nevertheless, the absence of sufficient high-quality randomized controlled clinical trials precludes any definitive conclusions regarding the optimal approach to enteral feeding in this population. There is an imperative need for more studies to further assess the efficacy of the two enteral feeding strategies.

Identifying immune cells-related phenotype to predict immunotherapy and clinical outcome in gastric cancer.

Background: The tumor microenvironment is mainly composed of tumor-infiltrating immune cells (TIICs), fibroblast, extracellular matrix, and secreted factors. TIICs are often associated with sensitivity to immunotherapy and the prognosis of multiple cancers, yet the predictive role of individual cells on tumor prognosis is limited. Methods: Based on single-sample gene set enrichment analysis, we combined three Gene Expression Omnibus (GEO) cohorts to build a TIIC model for risk stratification and prognosis prediction. The performance of the TIIC model was validated using our clinical cohort and the TCGA cohort. To assess the predictive power of the TIIC model for immunotherapy, we plotted the receiver operating characteristic curve with the IMvigor210 and GSE135222 cohorts. Results: Chemokines, tumor-infiltrating immune cells, and immunomodulators differed between the two TIIC groups. The TIIC model was vital for predicting the outcome of immunotherapy. In our clinical samples, we verified that the expression levels of PD-1 and PD-L1 were higher in the low TIIC score group than in the high TIIC score group, both in the tumor and stroma. Conclusions: Collectively, the TIIC model could provide a novel idea for immune cell targeting strategies in gastric cancer and predict the survival outcome of patients.

Preparation and Biocompatibility Study of Contrast-Enhanced Hernia Mesh Material.

BACKGROUND: Meshes play a crucial role in hernia repair. However, the displacement of mesh inevitably leads to various associated complications. This process is difficult to be traced by conventional imaging means. The purpose of this study is to create a contrast-enhanced material with high-density property that can be detected by computed tomography (CT). METHODS: The contrast-enhanced monofilament was manufactured from barium sulfate nanoparticles and medical polypropylene (PP/Ba). To characterize the composite, stress tensile tests and scanning electron microscopy (SEM) was performed. Toxicity and biocompatibility of PP/Ba materials was verified by in vitro cellular assays. Meanwhile, the inflammatory response was tested by protein adsorption assay. In addition, an animal model was established to demonstrate the long-term radiographic effect of the composite material in vivo. Subsequent pathological tests confirmed its in vivo compatibility. RESULTS: The SEM revealed that the main component of the monofilament is carbon. In vitro cell experiments demonstrated that novel material does not affect cell activity and proliferation. Protein adsorption assays indicated that the contrast-enhanced material does not cause additional inflammatory responses. In addition, in vivo experiments illustrated that PP/Ba mesh can be detected by CT and has good in vivo compatibility. CONCLUSION: These results highlight the excellent biocompatibility of the contrast-enhanced material, which is suitable for human abdominal wall tissue engineering.

GARP Correlates With Tumor-Infiltrating T-Cells and Predicts the Outcome of Gastric Cancer.

Accepting the crucial role of the immune microenvironment (TME) in tumor progression enables us to identify immunotherapeutic targets and develop new therapies. Glycoprotein A repetitions predominant (GARP) plays a vital part in maintaining regulatory T cell (Treg)-mediated immune tolerance. The impact of GARP in TME of gastric cancer is still worth exploring. We investigated public genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus to analyze the possible role of GARP and its relationship with TME of gastric cancer. Fluorescence-based multiplex immunohistochemistry and immunohistochemistry for T-cell immune signatures in a series of tissue microarrays were used to validate the value of GARP in the TME. We initially found that GARP expression was upregulated in gastric carcinoma cells, and diverse levels o3f immune cell infiltration and immune checkpoint expression were detected. Gene expression profiling revealed that GARP expression was related to the TME of gastric cancer. GARP upregulation was usually accompanied by increased FOXP3+ Treg and CD4+ T cell infiltration. In addition, GARP expression had positive relationships with CTLA-4 and PD-L1 expression in gastric cancer. Cox regression analysis and a nomogram highlighted that the probability of poor overall survival was predicted well by GARP or GARP+CD4+ T cell. Taken together, this research underlines the potential effect of GARP in regulating survival and tumor-infiltrating T-cells. In addition, the function of CD4+ T cell immune signatures in the prognosis can be clinically meaningful, thereby providing a new idea for the immunotherapeutic approach.

Efficient Enantioselective Biocatalytic Production of a Chiral Intermediate of Sitagliptin by a Newly Filamentous Fungus Isolate.

(S)-3-Hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one ((S)-HTPP) is a crucial intermediate for the synthesis of Sitagliptin. A fungal strain ZJPH1308, capable of the biocatalysis of ketoamide 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-one (OTPP) to (S)-HTPP with excellent enantioselectivity, was isolated from a soil sample and identified as Rhizopus microsporus var. rhizopodiformis ZJPH1308 based on its morphological characteristics and internal transcribed spacer (ITS) sequence. Some key reaction parameters involved in the bioreduction catalyzed by isolate ZJPH1308 were then optimized. It demonstrated that the bioreduction of OTPP was effective conducted at relative high temperature (45 °C), along with distilled water as reaction medium and glycerol-coupling approach for cofactor regeneration. Under the optimal conditions, the preparative-scale bioreduction gave a 93.2 % yield (with >99.9 % of enantiomeric excess (ee)) at 15 mM of OTPP and 45 °C, reaction for 24 h. The results indicated that fungal isolate ZJPH1308 can afford a thermostable carbonyl reductase and is a promising biocatalyst for clean and efficient production of valuable chiral intermediate.