As a leading cause of cancer-related mortality among gastrointestinal malignancies, gastric carcinoma (GC) necessitates enhanced molecular diagnostic paradigms for early intervention. The thymidine kinase enzymatic family, particularly thymidine kinase 1 (TK1, EC 2.7.1.21), serves as an enzymatic orchestrator of deoxyribonucleotide salvage pathways critical for genomic integrity maintenance, and its oncogenic overexpression acts in concert with Helicobacter pylori-mediated chronic inflammatory microenvironments, and potentiates the histopathological progression from premalignant metaplasia review delineates the utility of TK1 as a serological biomarker for early detection, tumor staging, therapeutic monitoring, and prognostic stratification in GC. We have hypothesized the molecular mechanisms underlying TK1-mediated oncogenesis and its interplay with H. pylori-induced pathogenesis. Additionally, we have explored emerging TK1-targeted therapeutic modalities, including gene-directed enzyme prodrug therapy (GDEPT), nanoscale drug delivery platforms, and adoptive cell therapy, while evaluating TK1’s translational potential in GC management. Although the precise regulatory networks of TK1 in gastric carcinogenesis remain incompletely characterized, ongoing research positions TK1 as a promising diagnostic and therapeutic target, potentially revolutionizing strategies to ameliorate clinical outcomes.

INTRODUCTION:sepsis is a life-threatening syndrome marked by systemic inflammation, nutritional imbalance, and high prevalence of vitamin D deficiency. However, the mechanistic interconnections between serum vitamin D levels, nutritional status, and inflammatory activity in sepsis remain poorly characterized. OBJECTIVES:to investigate the associations among these factors in septic patients and identify an optimal serum 25-hydroxyvitamin D cutoff value for clinical assessment of sepsis. METHODS:a cross-sectional study enrolled 97 septic patients in the Intensive Care Unit (ICU) (October 2023-October 2024) and 95 age/sex-matched healthy controls. Serum 25-hydroxyvitamin D [25-(OH)D] levels, nutritional indicators, inflammatory markers, and biochemical parameters were measured and compared between groups; correlation and reveiver operating characteristic (ROC) curve analyses were performed. RESULTS:septic patients had significantly lower 25(OH)D levels, poorer nutritional status, and higher inflammatory markers than controls. The optimal 25(OH)D cutoff for predicting sepsis was 22.55 ng/ml. Serum 25(OH)D concentrations correlated positively with nutritional parameters and negatively with inflammatory indices in septic patients. CONCLUSIONS:serum vitamin D is a valid indicator for sepsis progression. The interrelated associations between vitamin D levels, nutritional status, and inflammation highlight vitamin D's role in modulating sepsis severity and prognosis, supporting its integration into sepsis clinical management and risk stratification.

Chronic gastrointestinal diseases, including inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS), impose a growing global burden. Their relapsing-remitting nature and variable clinical course challenge the paradigm of long-term continuous therapy, which is associated with adverse effects, poor adherence, and high costs. While dynamic precision therapy (DPT) has emerged as an intuitive solution, its conventional definition—symptom-driven, intermittent drug use—is too narrow and fails to harness the full potential of precision medicine. As a narrative review and perspective article, this paper proposes a paradigm shift by introducing a novel, multidimensional framework for DPT that integrates four synergistic dimensions: symptom-guided relief for acute episodes, disease subtype-guided baseline therapy, pathophysiology-guided dynamic adjustments using biomarkers and smart technologies, and individual patient context-guided shared decision-making. Applying this framework to IBD, GERD, and IBS, we demonstrate how it transforms precision treatment from a simple dosing strategy into a comprehensive platform for precision management. We review cutting-edge tools enabling this vision, from 24-hour pH-impedance monitoring and therapeutic drug monitoring to smart drug delivery systems like MMP-responsive hydrogels. This framework provides a practical guide for transitioning from empirical methods to mechanism-based, patient-centered care, presenting a forward-looking model that could transform future treatment approaches in gastroenterology.

BACKGROUND:Primary sclerosing cholangitis (PSC) is a chronic liver disease strongly linked to inflammatory bowel disease (IBD), yet its causal genetic drivers and the mechanisms underlying this comorbidity remain poorly understood. This study aimed to identify causal genes for PSC and elucidate the role of the gut-liver axis in its pathogenesis. METHODS:We performed a multi-omics study integrating transcriptome-wide association studies (TWAS), summary Mendelian randomization (SMR), and colocalization using PSC GWAS data (2871 cases; 12 019 controls) and tissue-specific eQTL data. Bidirectional Mendelian randomization (MR) was employed to dissect causal relationships between identified genes, PSC, IBD, gut microbiota, and metabolites. RESULTS:Seven genes were prioritized as potential causal targets for PSC: MMEL1, FUT2, PRKD2, C4A, HLA-DMA, VARS2, and RPL23AP1, with evidence supported by colocalization and expression in relevant immune and intestinal tissues. Bidirectional MR confirmed a causal link from IBD to PSC and identified shared genetic pathways. Crucially, MR analysis provided causal evidence for the role of specific gut microbiota in PSC risk, including increased risk with higher abundance of Clostridium and Veillonella . Mediation analyses further implicated FUT2 and HLA-DMA in modulating PSC risk via the gut microbiota, particularly through taxa such as Clostridium, Butyrivibrio crossotus , and Rhodospirillaceae . CONCLUSION:This study delineates PSC's genetic architecture by identifying novel causal genes and confirms the gut-liver axis's central role in its pathogenesis. We propose an integrated "dual-hit" model where host genetic susceptibility constitutes the "first hit" and subsequent gut dysbiosis acts as a "second hit." These findings offer novel therapeutic targets and a mechanistic framework with potential implications for patient management in liver transplantation.

Prior research has examined the advantageous impacts of probiotics in preventing and treating sepsis; however, the protective actions of Bifidobacterium against sepsis are still not understood. In this review, we innovatively discussed the mechanisms by which Bifidobacterium can prevent and treat sepsis by regulating the intestinal mucosal barrier during homeostasis and when damaged. Surprisingly, we found that the mechanisms include blocking NF-κB and p38 MAPK signaling pathways, regulating AHR/NRF2/NLRP3 inflammasome pathways, inhibiting NLRP3/ASC/Caspase1 signaling pathways, regulating enteric glial cells (EGCs) network development, regulating immunity, and restoring intestinal symbiosis, etc. Through continued pathway researches into mechanisms of probiotics on sepsis, we try to get more evidence of Bifidobacterium on the prevention and treatment of sepsis.

Previous studies have suggested a comorbidity between psoriasis (PSO) and immune-mediated gastrointestinal (GI) diseases; however, the underlying genetic correlations and mechanisms remain unclear. This study aimed to elucidate the shared genetic architecture and biological mechanisms between PSO and immune-mediated GI diseases, providing insights for precision treatment strategies. We integrated publicly available GWAS summary statistics for PSO and multiple immune-mediated GI diseases, including Crohn’s disease (CD), ulcerative colitis (UC), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease (COELIAC), and chronic gastritis (CG). Linkage Disequilibrium Score Regression (LDSC) and High-Definition Likelihood (HDL) estimation were employed, while bidirectional Mendelian Randomization (MR) was used to investigate causal relationships. Cross-phenotype analyses were employed to identify shared loci and genes, integrating Pleiotropy Analysis Under the Composite Null Hypothesis (PLACO) and Functional Mapping and Annotation (FUMA), followed by Multi-marker Analysis of Genomic Annotation (MAGMA). The Summary-data-based Mendelian Randomization (SMR) method combined GWAS summary-level data with expression quantitative trait loci (eQTL) studies to pinpoint genes whose expression mediated the observed associations. Potential drug interventions targeting pleiotropic genes were predicted using the DSigDB database. Genetic enrichment analysis was performed to identify key cell types and tissues, and shared immune-related phenotypes were delineated through Hypothesis Prioritisation in multi-trait Colocalization (HyPrColoc). Significant genetic correlations between PSO and immune-mediated GI diseases were confirmed by genome-wide analyses using LDSC and HDL, while bidirectional MR indicated potential causal relationships. Cross-trait pleiotropic analysis using PLACO and FUMA identified 113 pleiotropic loci, including 35 shared across trait combinations (e.g., 5q33.3, 2p16.1, 5q31.1). Identification and enrichment analysis of shared pathogenic genes, performed using SMR and MAGMA, revealed 38 pleiotropic genes, notably PEX13, RGS14, and C5orf56, which were involved in peroxisome homeostasis, lymphocyte adhesion and migration, and Th1/Th2 immune balance, respectively. Pathway enrichment highlighted lymphocyte differentiation, immune activation, and intercellular adhesion. Shared genetic signals exhibited strong tissue and cell-type specificity, particularly in the spleen, whole blood, EBV-transformed lymphocytes, bone marrow B cells, and spleen T cells. Finally, potential therapeutic targets were predicted using DSigDB, providing valuable insight into targeted treatment strategies. This study systematically, for the first time, reveals the shared genetic structure between PSO and immune-mediated GI diseases, identifying novel pleiotropic loci and functional genes, laying the foundation for understanding comorbid disease mechanisms, and developing targeted therapeutic strategies.

Abstract Introduction Although observational studies have shown an association between testosterone (T) and inflammatory bowel disease (IBD), the correlation remains controversial. In this study, we aimed to explore the potential causal relationship between T and IBD among men. Methods We utilized two-sample Mendelian randomization (MR) to investigate the causal relationship between testosterone and IBD among men using SNPs as genetic instrumental variables for exposure and outcome. The two-sample Mendelian randomization methods we used included inverse variance weighted (IVW) and MR‒Egger regression. Odds ratios (ORs) were applied to evaluate the results. Results A total of 112 SNPs were included in the MR study. The causal relationship between exposure factors and outcomes was derived using the two-sample Mendelian randomization method. The results of MR analysis demonstrated that testosterone among men was associated with an increased risk of inflammatory bowel disease (β=0.146 [OR 1.157 95% CI 1.102, 2.568], p=0.022, IVW), and MR‒Egger tests also supported this conclusion. (0.196[1.218 0.968, 1.534]0.095) The Cochran Q tests indicated that there was heterogeneity but not horizontal pleiotropy of SNPs, so we believe that the results remain robust. Conclusion This MR analysis provided evidence that testosterone was causally responsible for IBD among men, indicating that heterogeneous therapeutic measurements should be taken between male and female.

Background Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations.Objective We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota.Methods Independent genetic instruments linked with iron status were selected using a genome-wide threshold of p = 5 x 10-6 from corresponding genome-wide association studies. Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia.Results Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer. Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases.Conclusion This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease.

Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 +/- 874 ng/ml) and controls (18,48 +/- 1,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.

Inflammatory bowel disease (IBD) is a complex condition resulting from environmental, microbial, immunologic, and genetic factors. With the advancement of Mendelian randomization research in IBD, we have gained new insights into the relationship between these factors and IBD. Many animal models of IBD have been developed using different methods, but few studies have attempted to model IBD by combining environmental factors and microbial factors. In this review, we examine how environmental factors and microbial factors affect the development and progression of IBD, and how they interact with each other and with the intestinal microbiota. We also summarize the current methods for creating animal models of IBD and compare their advantages and disadvantages. Based on the latest findings from Mendelian randomization studies on the role of environmental factors in IBD, we discuss which environmental and microbial factors could be used to construct a more realistic and reliable IBD experimental model. We propose that animal models of IBD should consider both environmental and microbial factors to better mimic human IBD pathogenesis and to reveal the underlying mechanisms of IBD at the immune and genetic levels. We highlight the importance of environmental and microbial factors in IBD pathogenesis and offer new perspectives and suggestions for improving experimental animal modeling. Our goal is to create a model that closely resembles the clinical picture of IBD.

Abstract Background Numerous observational studies have indicated correlations between gut microbiota and anemia, specific causal relationships remain unclear. We investigated these relationships using Mendelian randomization (MR) analysis. Methods We acquired gut microbiota data at the multiple phylogenetic levels (five phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) from the Dutch Microbiome Project. We also gathered data on regarding iron deficiency anemia (IDA) and aplastic anemia (AA) from the Integrative Epidemiology Unit project. We performed MR analysis by methods including inverse variance weighting and median weighting. Next, we performed sensitivity analyses to assess pleiotropy and heterogeneity, ensuring result reliability. Finally, we used data from the MiBioGen consortium as a corroborating control. Results For IDA, we identified one class, one order, and three genera associated with decreased risk; three genera associated with increased risk. These included the genus Desulfovibrio (odds ratio [OR]: 0.86, P = 1.45×10^-2), genus Ruminococcus (OR: 0.87, P = 1.81×10^-3), species Streptococcus thermophilus (OR: 0.92, P = 2.08×10^-2), and species Sutterella wadsworthensis (OR: 1.18, P = 3.48×10^-3). For AA, one genus was associated with decreased risk; one phylum, one class, three orders, four families, and five genera were associated with increased risk. These included the genus Parasutterella (OR: 0.83, P = 2.65×10^-2), species Eubacterium hallii (OR: 1.22, P = 4.17×10^-2), genus Dorea (OR: 0.90, P = 3.46×10^-2), genus Anaerotruncus (OR: 1.32, P = 2.00×10^-2), genus Intestinibacter (OR: 1.24, P = 2.05×10^-2), and species Bilophila wadsworthia (OR: 1.30, P = 3.31×10^-2). Both types of anemia had a strong association with the order Clostridiales. The Dutch Microbiome Project results demonstrated superior efficacy, corroborated by data from the MiBioGen consortium. Conslusions Our MR analysis offers genetic insights into the associations between gut microbiota and both IDA and AA, providing new avenues for disease prevention and intervention.

Abstract Background Unfolded protein response (UPR), an orchestrating adaptive mechanism activated by endoplasmic reticulum (ER) stress, plays an instrumental protumoral roles in several kinds of cancers, and high unfolded protein response is correlated to poorer prognosis and malignant hallmark. Considerable evidence indicates that UPR induced by oncogenic conditions is a distinguishing feature of cancer. Methods Bioinformatics mining was carried out by using the public pancer data of TCGA and other public databases to analyze the differential gene expression profiles of the patients and Cox regression analysis to find out the differentially expressed endoplasmic reticulum stress related genes with prognostic value. ER-stress Potential Index (EPI) was defined to computationally dissect the UPR trends via gene set enrichment analysis using R package ‘GSVA’. Combined with TCGA and GEO databases, the clinical characteristics of EPI were comprehensively analyzed in LIHC. Virtual screening was performed to find out potential compounds targeting STC2, which was a good diagnostic marker and pharmacological target towards endoplasmic reticulum stress in LIHC. Results Pan-cancer analysis results showed that unfolded protein response pathway was generally positive associated with poor prognosis of patients across different cancer types. It would be an important and ubiquitous mechanism in different tumors. High EPI was positive associated with tumor malignant phenotype, including higher death rate, recurrence rate, metastatic risk, larger tumor size and other undesirable aggressive clinical traits. In addition, EPI was also responsible for immune evasion via upregulating the expression of immunosuppressive gene and facilitating the production of pro-inflammatory and immunomodulatory cytokines. Besides, EPI played pivotal role in liver cancers’ resistance of chemotherapy and therapeutic targeting UPR would be enhance the anti-tumor effectiveness. STC2 would be a good diagnostic marker and pharmacological target in LIHC. Through virtual screening, we found that flavonoids compounds could be a good compound targeting STC2. Flavonoids could become a good pharmaceutical therapeutic candidate in unique or adjuvant therapeutic approaches toward LIHC. Conclusion EPI was associated with subtypes and clinical features and providing new insight into tumor biology and can guide efficient pharmalogical intervention of unfolded protein response to help patients.

Abstract Background: Type 1 diabetes mellitus (T1DM) and inflammatory bowel disease (IBD) are common autoimmune diseases. Previous studies reported an association between these two diseases. However, due to the limitations of observational research, it cannot provide sufficient evidence to support the existence of causality or reverse causality. Objective: This study aimed to evaluate the existence of the causal relationship between T1DM and IBD. Methods: A two-sample bidirectional Mendelian randomization (MR) was employed to investigate a possibility of the causal relationship between T1DM and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Independent genetic variants of T1DM and IBD were retrieved from the IEU OpenGWAS project，and the individuals were of European ancestry. After filtering the single nucleotide polymorphisms (SNPs), several MR methods, including MR–Egger regression, weighted median, inverse variance-weighted (IVW), and weighted mode with IVW as the primary analysis method, were used to test the causal association between the two diseases. Furthermore, a sensitivity analysis was conducted to detect the heterogeneity and pleiotropy of the instrumental variables. Results: Bidirectional MR analysis indicated a negative correlation between T1DM and IBD (IVW OR: 0.95, 95% Confidence Interval [CI]: 0.94 to 0.97, P = 1.19E-12). However, a separate analysis of CD and UC showed that this negative association appeared to exist only for T1DM and CD (IVW OR: 0.95, 95% CI: 0.91 to 0.99, P = 0.0063) and not for UC (IVW OR: 1.02, 95% CI: 0.98 to 1.05, P = 0.3315). In contrast, we found no difference in the prevalence of T1DM among patients with IBD, CD, and UC compared to the general population. Conclusions: This study using MR has confirmed that individuals diagnosed with T1DM exhibit a decreased susceptibility to IBD in comparison to the general population，indicating that new therapeutic targets for IBD based on the pathogenesis of T1DM should be explored.

Sarcopenia is characterized by the loss of muscle mass and function. It is well known that sarcopenia is often associated with aging, while in recent years, sarcopenia comorbid with chronic diseases such as cirrhosis has attracted widespread attention, whose underlying molecular mechanisms remain unclear. Since cirrhosis and sarcopenia are assumed to be closely interrelated in terms of pathogenesis, this review innovatively discussed the role of epigenetic modifications and microecological dysregulation in sarcopenia in the context of liver cirrhosis. Here we illustrated the relationship between sarcopenia and cirrhosis in the aspect of epigenetics, dysbiosis, and the crosstalk between gene modifications and intestinal microecology. Furthermore, the alterations in cirrhosis patients with sarcopenia, such as inflammatory response and oxidative stress, are found to present synergistic effects in the pathways of epigenetics and dysbiosis leading to sarcopenia. This review proposes that microbiome-based therapies are promising to break the vicious cycle between epigenetic modification and dysbiosis, providing strong support for the use of intestinal microecological interventions to prevent sarcopenia in cirrhotic patients.

Objective Vitamin D (VD) deficiency was reported to contribute to the progression of Crohn’s disease (CD) and affect the prognosis of CD patients. This study investigated the role of serum VD, body mass index (BMI), and tumor necrosis factor alpha (TNF-α) in the diagnosis of Crohn’s disease. Methods CD patients ( n =76) and healthy subjects ( n =76) were enrolled between May 2019 and December 2020. The serum 25-hydroxyvitamin D [25(OH)D] levels, BMI, and TNF-α levels, together with other biochemical parameters, were assessed before treatment. The diagnostic efficacy of the single and joint detection of serum 25(OH)D, BMI, and TNF-α was determined using receiver operating characteristic (ROC) curves. Results The levels of 25(OH) D, BMI, and nutritional indicators, including hemoglobin, total protein, albumin, and high-density lipoprotein cholesterol, were much lower, and the TNF-α levels were much higher in the CD patients than in the healthy subjects ( P <0.05 for all). The areas under the ROC curve for the single detection of 25(OH)D, BMI, and TNF-α were 0.887, 0.896, and 0.838, respectively, with the optimal cutoff values being 20.64 ng/mL, 19.77 kg/m 2 , and 6.85 fmol/mL, respectively. The diagnostic efficacy of the joint detection of 25(OH)D, BMI, and TNF-α was the highest, with an area under the ROC curve of 0.988 (95%CI: 0.968–1.000). Conclusion The joint detection of 25(OH)D, TNF-α, and BMI showed high sensitivity, specificity, and accuracy in CD diagnosis; thus, it would be effective for the diagnosis of CD in clinical practice.

Abstract Background Unfolded protein response (UPR), an orchestrating adaptive mechanism activated by endoplasmic reticulum (ER) stress, plays an instrumental protumoral roles in several kinds of cancers, and high unfolded protein response is correlated to poorer prognosis and malignant hallmark. Considerable evidence indicates that UPR induced by oncogenic conditions is a distinguishing feature of cancer. Methods Bioinformatics mining was carried out by using the public pancer data of TCGA and other public databases to analyze the differential gene expression profiles of the patients and Cox regression analysis to find out the differentially expressed endoplasmic reticulum stress related genes with prognostic value. ER-stress Potential Index (EPI) was defined to computationally dissect the UPR trends via gene set enrichment analysis using R package ‘GSVA’. Combined with TCGA and GEO databases, the clinical characteristics of EPI were comprehensively analyzed in LIHC. Virtual screening was performed to find out potential compounds targeting STC2, which was a good diagnostic marker and pharmacological target towards endoplasmic reticulum stress in LIHC. Results Pan-cancer analysis results showed that unfolded protein response pathway was generally positive associated with poor prognosis of patients across different cancer types. It would be an important and ubiquitous mechanism in different tumors. High EPI was positive associated with tumor malignant phenotype, including higher death rate, recurrence rate, metastatic risk, larger tumor size and other undesirable aggressive clinical traits. In addition, EPI was also responsible for immune evasion via upregulating the expression of immunosuppressive gene and facilitating the production of pro-inflammatory and immunomodulatory cytokines. Besides, EPI played pivotal role in liver cancers’ resistance of chemotherapy and therapeutic targeting UPR would be enhance the anti-tumor effectiveness. STC2 would be a good diagnostic marker and pharmacological target in LIHC. Through virtual screening, we found that flavonoids compounds could be a good compound targeting STC2. Flavonoids could become a good pharmaceutical therapeutic candidate in unique or adjuvant therapeutic approaches toward LIHC. Conclusion EPI was associated with subtypes and clinical features and providing new insight into tumor biology and can guide efficient pharmalogical intervention of unfolded protein response to help patients.

As microecology research has advanced, the existence of the correlation between microbiota and systemic inflammatory response syndrome (SIRS), has been gradually suggested in recent years. Substantial evidence underscored the critical role of gut microbiota in sepsis and the organ damage brought on by sepsis. New particular metabolites have been found by applications of metabolomics technology, partially filling in the gaps in sepsis prognosis and early warning systems. However, previous study of sepsis with metabolomics were merely used for screening differential metabolites or examining their mechanisms. And the upstream and downstream relationships between the gut microbiota and sepsis were ignored. In this regard, this review suggests combining gut microbiota and metabolites, and exploring the changes and links of “gut microbiota metabolites organism” in the occurrence and development of sepsis, as well as the damage of various organs caused by sepsis. This will jointly provide new possibilities for the diagnosis, prognosis prediction, and individualized treatment of sepsis. Also provide a basis for the treatment of various organ damage caused by sepsis.

Objective:To evaluate modified Lanza score (MLS) of gastric mucosa for predicting the prognosis of geriatric patients with sepsis.Methods:Data of 50 patients with sepsis, who were over 60 years old and underwent gastroscopy for suspected gastrointestinal bleeding in the Department of Geriatric Critical Care Medicine of Guangdong Provincial People's Hospital from January 2019 to April 2022, were retrospectively analyzed. Patients were divided into the death group ( n=32) and the survival group ( n=18) according to their regression within 28 days after gastroscopy. Their gastric mucosa was scored by using MLS system, and the mortality of patients with MLS≥1 was calculated, then the patients were further divided into 2 groups, MLS=0-2 ( n=23, less than 2 regions of lesions ) and MLS=3-5 ( n=27, two or more regions of lesions). The relationship between MLS and acute physiology and chronic health status evaluation (APACHE) Ⅱ score, risk factor of death and mortality in each group were compared. The correlation between MLS and mortality was analyzed. The influence of geriatric sepsis risk factors affecting the prognosis of patients within 28 days were analyzed by using logistic regression. Results:Among the 50 geriatric patients with sepsis, those with gastric mucosal lesions, i.e., MLS ≥1, accounted for 68.00% (34/50), including 84.38% (27/32) patients with MLS≥1 in the death group, which was significantly higher than the 38.89% (7/18) patients with MLS≥1 in the survival group ( χ 2=10.593, P<0.001). Patients with MLS=3-5 had significantly higher APACHE Ⅱ scores (26.09±6.47 VS 18.57±7.66, t=3.527, P=0.001) and higher mortality [85.19% (23/27) VS 39.13% (9/23), χ 2=11.434, P=0.001] compared with MLS=0-2. Correlation analysis showed a significant correlation between MLS and mortality ( r=0.886, P=0.019). Multivariate logistic regression analysis showed that MLS=4-5 was an independent risk factor for death in geriatric patients with sepsis ( OR=17.055, 95% CI: 1.387-209.744, P=0.027). Conclusion:MLS presents high sensitivity in predicting 28-day outcomes for geriatric patients with sepsis. Two or more than 2 regions of gastric mucosal lesions can significantly increase the risk of death in geriatric patients with sepsis.