Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective To investigate the gene expression characteristics and functional prediction of decidual polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)in patients with unexplained recurrent abortion(URSA).Methods Decidual tissues were collected from 3 normal early pregnancy patients undergoing artificial abortion and 3 URSA patients at the First People's Hospital of Yunnan Province between July and December 2023.Magnetic-activated cell sorting(MACS)technology was used to separate decidual PMN-MDSCs,and gene expression differences were detected using gene chip technology.Differential genes were analyzed using DESeq2 or edgeR,controlling false positives with P-value and FDR.GO and KEGG analyses were performed to investigate the functional pathways of differential genes,and protein-protein interaction(PPI)network analysis and hub gene screening were conducted.Key genes were verified through immunofluorescence staining and quantitative analysis.Results Compared to the normal pregnancy group,a total of 163 genes in the decidual PMN-MDSCs of URSA patients showed significant changes(P<0.05),with 67 genes upregulated and 96 genes downregulated.GO and KEGG enrichment analyses revealed that these differential genes were involved in cellular components,biological processes,molecular functions,protein binding,complement system signaling pathways,leukocyte-mediated inflammatory response pathways,and proteoglycan and extracellular matrix receptor interactions.PPI network analysis and hub gene identification showed that among the top 10 hub genes,the upregulated genes were SPP1,CCL5,C3AR1,and TNF,while the downregulated genes included MXRA8,IGFBP5,SPARCL1,SAA1,DCN,and COL3A1.These hub genes were primarily associated with key biological processes such as immune regulation,inflammatory responses,and intercellular interactions.Immunofluorescence quantification results demonstrated that the expression level of SPP1 in decidual PMN-MDSCs of URSA patients was significantly higher than that in the normal pregnancy group,with a statistically significant difference(P<0.05).Conclusion PMN-MDSCs in URSA patients'decidual tissues exhibit functional abnormalities,characterized by weakened regulatory effects on extracellular matrix remodeling,reduced cell-cell interaction capabilities,decreased immunosuppressive capacity,and enhanced pro-inflammatory responses.This may be one of the important immunological mechanisms underlying pregnancy failure.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Sepsis-associated delirium(SAD)is a common and severe central nervous system(CNS)complication in patients with sepsis,whose occurrence mechanism is unclear and there is no effective treatment at present.Neuroendocrine immune regulation disorder is closely related to occurrence and development of SAD.Immune mediators can deliver peripheral immune information to CNS by humoral transport or through afferent nerves.Immune mediators invading center can not only directly damage neurons,but also activate innate immune cells of brain,further aggravate neuroinflammation,and cause neurotransmitter imbalance,neurotoxic effects,resulting in neuronal dysfunction,even apoptosis and subsequent behavioral and cognitive symptoms.This paper aims to review mechanisms of neuro-endocrine-immune regulation in occurrence and development of SAD,and to find effective targets for prevention and treatment of sepsis and SAD.

OBJECTIVE To investigate the effects of triptolide(TP)exposure during pregnancy and lactation on the reproductive system development and function in male offspring of rats,providing a reference for medication safety during pregnancy and lactation.METHODS Pregnant rats were randomly divided into control group(12 rats,normal saline)and T1-T4 groups[12,13,14,17 rats that received TP at 200,400,600,and 800 μg/(kg·d)respectively].They were given relevant medicine/normal saline intragastrically,once a day,until the offspring were born and naturally weaned,the intragastric administration volume of each rat was consistently 2 mL.After 60 days of feeding,reproductive organ weights and coefficients were measured in male offspring,testicular and epididymal histology and sperm morphology were observed.Sperm motility,sperm count,and serum levels of gonadotropin-releasing hormone(GnRH),follicle stimulating hormone(FSH),luteinizing hormone(LH),and testosterone(T)in the epididymides were analyzed.Protein expressions of glycogen synthase kinase 3α(GSK3α),phosphorylated GSK3α(p-GSK3α),and phosphatase 1γ2(PP1γ2)in sperm were also determined.RESULTS Compared with the control group,the testicular and epididymal weights,serum levels of GnRH and T,the relative protein expression of PP1γ2 were significantly decreased in T1-T4 groups.Additionally,in the T2 to T4 groups,there were significant reductions in the weight and coefficient of the seminal vesicle,total number of sperm,sperm concentration,sperm motility as well as relative protein expressions of GSKα,p-GSK3α in the offspring rats.Furthermore,the epididymal coefficient in the T3 and T4 groups,the testicular coefficient,mean sperm track velocity and sperm curvature velocity in the T4 group were significantly decreased(P＜0.05);the number of abnormal sperm,rate of sperm abnormality,and levels of FSH and LH in the offspring rats of the T1 to T4 groups were all significantly increased(P＜0.05);in the offspring rats of the T1 to T4 groups,there was a decrease in the number of epithelial cells in the seminiferous tubules of the testes.Within the epididymal tissue,degenerative and necrotic changes in the epithelial cells were visible,accompanied by mild infiltration of inflammatory cells in the stroma.CONCLUSIONS TP exposure during pregnancy and lactation disrupts reproductive organ development,impairs spermatogenesis and sperm motility,as well as suppresses androgen synthesis in male offspring,thereby having a negative impact on the development of the reproductive system.These effects may be mechanistically linked to regulation of GSK3α,p-GSK3α and PP1γ2 protein expressions.

Sepsis-associated delirium(SAD)is a common and severe central nervous system(CNS)complication in patients with sepsis,whose occurrence mechanism is unclear and there is no effective treatment at present.Neuroendocrine immune regulation disorder is closely related to occurrence and development of SAD.Immune mediators can deliver peripheral immune information to CNS by humoral transport or through afferent nerves.Immune mediators invading center can not only directly damage neurons,but also activate innate immune cells of brain,further aggravate neuroinflammation,and cause neurotransmitter imbalance,neurotoxic effects,resulting in neuronal dysfunction,even apoptosis and subsequent behavioral and cognitive symptoms.This paper aims to review mechanisms of neuro-endocrine-immune regulation in occurrence and development of SAD,and to find effective targets for prevention and treatment of sepsis and SAD.

Objective:To consolidate the current evidences regarding the efficacy of vitamin D supplementation in age-related sarcopenia.Methods:In this systemic review, a comprehensive literature search of scientific research including journal articles and academic dissertations was performed in prominent databases such as PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang Database platforms, spanning from January 31, 2014 to January 31, 2024. Two search protocols integrating keywords and citation tracking were adopted to ensure comprehensiveness of the literature. Using “vitamin D” “ergocalciferols” “cholecalciferol” “sarcopenia” “muscle mass” “muscle strength” “myopenia” “muscle loss” “muscle reduction” “gait speed” “grip strength” “handgrip” as the main key words, focusing on the systematic reviews, meta-analyses of randomized controlled trials (RCT), and individual RCT, the scientific evidence of individual vitamin D intervention on age-related sarcopenia was evaluated and summarized. Research concerning particular disease conditions, children and adolescents, menopausal women, athletes and other specific populations were excluded.Results:A initial search yielded 2 448 articles in Chinese or English. A total of 8 systemic reviews/meta-analysis and 22 individual RCT literatures were included in the final analysis. Although some earlier lower-quality studies reported subtle improvements in skeletal muscle strength with vitamin D supplementation, high-quality systematic reviews/meta-analysis over the past three years had not shown significant positive effects of vitamin D intervention on sarcopenia and its breakdown parameters, such as skeletal muscle mass, muscle strength, and muscle function. Furthermore, the efficiency was influenced to some extent by the participants′ baseline status, such as muscle health and vitamin D nutritional status.Conclusions:Present evidence does not robustly support the efficacy of sole vitamin D supplement on age-related sarcopenia. High-quality clinical trials are imperative to accumulate more robust evidence in the future.