Objective: ZhiZhu Kuanzhong (ZZKZ) capsule, a Chinese herbal extract, is extensively employed for the clinical management of functional dyspepsia (FD) in China. This study aimed to elucidate the therapeutic efficacy and underlying mechanisms of ZZKZ on the co-morbidity of anxiety and depression of FD. Methods: The FD model was established in Sprague-Dawley rats via neonatal gastric irritation with 0.1% iodoacetamide. Subsequently, FD rats were gavaged with ZZKZ or fluoxetine. Depression-like behaviors were evaluated using the sucrose preference test (SPT) and forced swimming test (FST), while anxiety-like behaviors were assessed via light-dark box (LDB) and open field tests (OFTs). Network pharmacology and molecular docking were conducted to explore the mechanisms of ZZKZ's action. Hippocampal levels of monoamine neurotransmitters and monoaminergic system components were evaluated by HPLC and RT-qPCR, respectively. Serum concentrations of HPA axis hormones were determined by ELISA. Results: ZZKZ administration reversed the deficits in body weight gain and food intake in FD rats. Behaviorally, ZZKZ increased sucrose consumption in SPT and prolonged swimming duration in FST, and it increased duration and entries into the central zone in OFT. According to the prediction of network pharmacology, ZZKZ treatment elevated hippocampal levels of 5-HT/NE/DA, increased expression of TPH2/TH, and decreased expression of MAOA/SERT in FD rats. Molecular docking further confirmed high-affinity binding between core ingredients of ZZKZ and TPH2/TH/MAOA/SERT. Moreover, ZZKZ administration attenuated the stress-induced elevation of serum CRH/ACTH/CORT. Conclusions: ZZKZ effectively ameliorates the disordered gut-brain interaction and mitigates anxiety-like and depression-like behaviors, which might be modulated by the hippocampal monoaminergic system and hypothalamic-pituitary-adrenal axis response.

711 Background: Neoadjuvant therapy is recommended for pancreatic cancer (PC) patients with high-risk features, although no standardized regimen currently exists. The NALIRIFOX regimen (liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin) has shown improved overall survival (OS) compared to gemcitabine plus nab-paclitaxel regimen in metastatic PC. This trial evaluates the efficacy and safety of perioperative NALIRIFOX compared to upfront surgery in patients with high-risk resectable PC. Methods: This randomized controlled, multicenter, open-label trial enrolled patients with high-risk resectable PC, defined by the following criteria: (1) radiologic evidence of resectable PC according to the 2024 NCCN guidelines; (2) CA19-9 levels ≥500 U/mL or a primary tumor diameter >3.0 cm. Patients were randomly assigned to perioperative chemotherapy with NALIRIFOX (Group A) or upfront surgery (Group B). The primary endpoint was 2-year OS rate. Secondary endpoints included resection rate, R0 resection rate, event-free survival (EFS), and safety. Results: As of September 2025, 26 patients were enrolled (Group A: n=14; Group B: n=12). The median age was 60 years (range: 48-69) in Group A and 61 years (42-70) in Group B, with median tumor diameters were 3.3 cm (range: 2.9-7.0) and 3.2 cm (range: 2.2-5.6), respectively. Baseline characteristics were generally balanced. In Group A, 9 patients underwent surgery, with R0 resection achieved in 7 (77.8%) patients. Five patients did not proceed to surgery: 2 continued neoadjuvant therapy, 2 discontinued due to progression, and 1 withdrew consent. In Group B, all 12 patients underwent surgery, with R0 resection in 11 (91.7%) patients. During neoadjuvant therapy, Group A exhibited a disease control rate of 91.7%. Among 7 evaluable patients, 6 (85.7%) achieved >50% reduction in CA19-9 from baseline, including 4 (57.1%) with >70% reduction. Grade ≥3 adverse events included neutropenia (42.9% vs. 33.3% in Groups A and B, respectively), elevated C-reactive protein (14.3% vs. 41.7%), and elevated procalcitonin (14.3% vs. 33.3%). Conclusions: The NALIRIFOX regimen shows a manageable safety profile in the perioperative treatment of high-risk resectable PC. Further follow-up is required to determine the survival benefits between the different treatment strategies. Clinical trial information: NCT06210360 .

[This corrects the article DOI: 10.3389/fonc.2026.1762770.].

Background:Osteosarcoma (OS) is a highly aggressive primary bone malignancy in adolescents, with poor prognosis due to limited diagnostic and therapeutic strategies. Mitochondrial dysfunction is a hallmark of cancer, and mitophagy, the selective clearance of damaged mitochondria, critically maintains cellular homeostasis. However, the specific role of mitophagy in shaping the OS tumor microenvironment (TME) at single-cell resolution remains poorly understood. This study aims to systematically characterize mitophagy patterns within the OS TME and investigate their impact on intercellular communication, tumor progression, and patient prognosis. Methods:We analyzed single-cell RNA sequencing data from OS samples using non-negative matrix factorization to cluster cells based on mitophagy-related genes. We characterized distinct mitophagy-associated subtypes of TME cells. Pseudotime trajectory, cell-cell communication), gene regulatory network, and functional enrichment analyses were performed. Prognostic significance was evaluated using GSVA and Cox regression in bulk RNA-seq cohort. Immunotherapy response was predicted using the TIDE algorithm. Results:We identified diverse mitophagy-activated cellular subtypes within the TME. Mitophagy-active CAFs and macrophages exhibited enhanced angiogenic signaling to endothelial cells. Mitophagy-associated CD8+ T cells displayed marked exhaustion features, while macrophages showed metabolic reprogramming. Clinically, higher infiltration of these mitophagy-related subtypes was consistently associated with poorer overall survival. TIDE analysis indicated that mitophagy patterns potentially correlate with immune checkpoint blockade response. Conclusions:Our findings reveal that mitophagy drives complex intercellular crosstalk in the OS TME, promoting angiogenesis and immunosuppression. Mitophagy-related signatures serve as robust prognostic biomarkers. These insights suggest that targeted inhibition of mitophagy, rather than activation, represents a promising therapeutic strategy, providing a novel framework for improving OS patient outcomes.

Objectives Gut-vascular barrier (GVB) disruption in cirrhotic portal hypertension (PH) exacerbates hepatic and systemic damage via the gut-liver-organ axis, but the underlying mechanism is unclear. The mechanosensitive channel Piezo1, known to regulate endothelial homeostasis, may mediate GVB dysfunction, requiring validation. Methods Carbon tetrachloride (CCl 4 )-induced liver cirrhosis and partial portal vein ligation (PPVL)-induced pre-hepatic PH model were established in Piezo1 flox/flox and endothelial cells (ECs)-specific Piezo1-deficient (Piezo1 △EC ) mice. Portal pressure, GVB permeability, intestinal and systemic inflammation, and Piezo1 expression in mucosal ECs were measured. Cultured intestinal microvascular ECs were treated with the Piezo1 agonist Yoda1 or hydrostatic pressure to investigate Piezo1-mediated endothelial barrier regulation. Results PH induced significant GVB breakdown in CCl 4 and PPVL mice, presented as increased permeability from the gut-to-blood and also leakage from blood-to-gut, accompanied by increased Piezo1 and VEGFR2 expression in ECs, along with systemic and intestinal inflammation and leaky epithelium. These effects were reversed in Piezo1 △EC mice, and Piezo1 knockout in ECs reduced VEGFR2 expression which in turn inhibited intestinal leakage and inflammatory infiltration, and meanwhile improved systemic inflammation. Moreover, Yoda1 or hydrostatic pressure promoted VEGFR2 phosphorylation and ECs monolayer disruption, blocked by siRNA of Piezo1 or Vegfr2 . Conclusion Endothelial Piezo1 contributed to GVB dysfunction in PH via VEGFR2 pathway. The outward and inward hyper-permeability of GVB in PH may initiate the intestinal inflammation and trigger epithelial leakage, and further cause systemic inflammation and injury. Therefore, Piezo1-mediated GVB damage may be a novel explanation and potential therapeutic target for deterioration of liver cirrhosis with PH.

Anxiety is highly comorbid with disorders of gut-brain interaction, including irritable bowel syndrome (IBS). The gut microbiota is implicated in both conditions, yet the underlying mechanisms remain unclear. This study aimed to elucidate the neuropathological basis of anxiety in diarrhea-predominant IBS (IBS-D) and identify potential microbiota-based therapeutic targets. Here, Mendelian randomization analysis established a bidirectional causal relationship between IBS and anxiety. In our clinical cohort, 35.85% of IBS-D patients presented with comorbid anxiety, and GAD-7 anxiety scores correlated significantly with IBS symptom severity. Resting-state functional magnetic resonance imaging (rs-fMRI) revealed that IBS-D patients with comorbid anxiety exhibited significantly altered regional homogeneity (ReHo) in nine brain regions, with the most pronounced reductions observed in the bilateral amygdala. Moreover, bilateral amygdala ReHo could effectively differentiate these patients, with receiver operating characteristic (ROC) analysis yielding area under curve (AUC) of 0.746. To investigate the underlying pathology, we established a water avoidance stress (WAS) mouse model that successfully recapitulated the anxiety-like behaviors and visceral hypersensitivity observed clinically. Critically, these phenotypes were transmissible, as recipient mice colonized with microbiota from the WAS-induced IBS-D group also developed visceral hypersensitivity and anxiety-like behaviors. Phocaeicola vulgatus was determined as a key bacterial strain significantly depleted in both our IBS-D patient cohort and the WAS-induced IBS-D mice, with its abundance negatively correlating with anxiety levels. As anticipated, IBS-D patients with lower abundance of P. vulgatus exhibited reduced amygdala ReHo and Mendelian randomization analysis identified P. vulgatus as a protective factor against anxiety. Correspondingly, therapeutic supplementation with P. vulgatus ameliorated anxiety-like behaviors in WAS-induced IBS-D mice by attenuating neuroinflammation and restoring neuronal morphology in the amygdala. In conclusion, this study provides the first evidence that P. vulgatus can alleviate anxiety in IBS by targeting amygdala-centered neuropathology, presenting a novel psychobiotic strategy for treating emotional comorbidities in disorders of gut-brain interaction.

Objectives: Chronic stress may represent a risk factor for digestive diseases, yet its underlying neural pathways remain unclear. We aimed to examine associations between chronic stress and incident digestive diseases, and to assess whether regional gray matter volume (GMV) alterations mediate these associations. Methods: We analyzed data from 442,143 UK Biobank participants. Chronic stress exposure was defined by the presence of six specific stressful life events. Cox proportional hazards models estimated associations between each stressor and nine digestive disease outcomes. For the GMV associated with chronic stress, mediation analyses were further conducted to evaluate the mediating role of regional GMV in the associations between chronic stress and incident digestive diseases. Results: Chronic stress was significantly associated with increased incidences of gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), gastric and duodenal ulcer (GU&DU), haemorrhoids, and perianal venous thrombosis (H&PVT), and oesophagitis, with clear dose-response patterns for GERD, IBS, H&PVT, and oesophagitis. Of the six stressors, financial difficulties showed the most consistent associations, significantly increasing the incidence of GERD (HR = 1.25, 95%CI: 1.19-1.31), IBS (HR = 1.47, 1.32-1.64), GU&DU (HR = 1.23, 1.03-1.47), and H&PVT (HR = 1.26, 1.17-1.35). Mediation analyses identified nine significant indirect pathways. The strongest mediation effects were observed for financial difficulties through the right posterior superior temporal gyrus for GERD (3.05%), through the right cerebellar VIIIb for IBS (-6.82%) and GU&DU (4.09%), and for serious illness/injury/assault to a close relative through the left postcentral gyrus for H&PVT (4.02%). Positive mediation was observed for GERD, GU&DU, and H&PVT. In contrast, all significant pathways for IBS showed negative mediation, suggesting potential compensatory or buffering neural mechanisms. Conclusions: Chronic stress contributes to digestive disease risk partly via structural alterations in stress-related brain regions. These findings highlight the heterogeneity of stress-brain-gut pathways across digestive phenotypes and suggest that brain remodeling may buffer or amplify the impact of chronic stress on digestive health.

Idiopathic pulmonary fibrosis (IPF), the continuously advancing and frequently lethal idiopathic interstitial pneumonia, is pathologically characterized by abnormal deposition of extracellular matrix constituents, leading to progressive pulmonary scarring. Although substantial research efforts have been devoted to elucidating its pathogenesis, the etiology, molecular mechanisms, and effective treatment strategies for IPF remain inadequately characterized, contributing to a median postdiagnostic survival period of merely three to five years. Epigenetic modifications, particularly DNA methylation, have emerged as a potential missing link between the genetic background and environmental risk factors contributing to the pathogenesis of fibrotic disorders, including IPF. DNA methylation entails the attachment of a methyl group to the cytosine residue, frequently occurring at CpG dinucleotides, which are concentrated in clusters known as CpG islands and orchestrates the target gene expression. In this review, we will explore the mechanism of DNA methylation and provide insights into recent advancements concerning its role in major profibrotic cells within lung tissues during the progression of IPF, and by which, we aim to generate valuable evidence that can facilitate the advancement of antifibrotic therapies for clinical applications.

BackgroundRenal carcinoma is a common, aggressive urinary tract malignancy with notable clinical challenges such as severe treatment toxicity and poor patient outcomes; 18β-glycyrrhetinic acid (18β-GA), an active component of Chinese herb Glycyrrhiza uralensis, has potent anti-tumor activity, while its role and molecular mechanisms in renal cancer remain elusive.AimThis research investigates the mechanism through which 18β-GA suppresses renal cancer cell proliferation.MethodsCombining whole transcriptome sequencing and network pharmacology, we identified 18β-GA-regulated key molecule miR-27a-5p and its core renal cancer targets; Cell assays confirmed 18β-GA-mediated suppression of renal cancer cell proliferation. Lentivirus-mediated miR-27a-5p modulation verified its role in renal cancer proliferation, and Western blot detection of autophagy marker LC3 expression clarified the miR-27a-5p/LC3 axis involvement in the anti-renal cancer effects of 18β-GA.ResultsResearch shows 18β-GA may exert anti-renal cancer effects by targeting HMOX1, HCK, CASP1 and IDO1, with its mechanism linked to the autophagy pathway via functional enrichment analysis; whole transcriptome sequencing identified miR-27a-5p as the most significantly altered by 18β-GA in renal cancer cells. Experimental verification confirmed that 18β-GA downregulates miR-27a-5p to elevate the autophagy marker LC3II/LC3I ratio, activate autophagy, reduce 786-O and ACHN cell viability, promote apoptosis, inhibit colony formation, and thus suppress renal cancer cell proliferation.Conclusion18β-GA induces autophagy and inhibits proliferation of renal cancer cells by down-regulating miR-27a-5p and relieving its inhibition on the LC3-mediated autophagy pathway, suggesting that the miR-27a-5p/LC3 axis may be a key target for 18β-GA in the treatment of renal cancer.

Introduction:The COVID-19 pandemic caused by SARS-CoV-2 has profound implications for global public health. It significantly affects the nervous system and cognitive function. The emergence of long COVID has raised concerns regarding long-term cognitive impairment, particularly among patients who experienced neurological symptoms during the acute phase of infection. Aim:This study investigated the impact of neurological symptoms during acute SARS-CoV-2 infection on subsequent cognitive change and neurological sequelae over a 2-year period. Methods:We enrolled 3,419 hospitalized patients with confirmed infection in Wuhan, China (Dec 2022-Mar 2023), and 2,087 completed follow-ups. Propensity score matching identified 901 patients with acute neurological symptoms and 901 controls. Cognitive decline was measured with the Informant Questionnaire on Cognitive Decline in the Elderly, and cognitive status with the Telephone Interview of Cognitive Status-40. Multivariable regression was used to examine risk factors and cognitive changes, and residual neurological symptoms and new-onset symptoms were also analyzed. Results:Acute neurological symptoms, particularly central nervous system manifestations such as delirium and brain fog, were strongly associated with both cognitive decline (aOR, 2.16; 95% CI, 1.53-3.07) and cognitive impairment (aOR, 2.75; 95% CI, 1.73-4.49). Delirium, brain fog, stroke, numbness, and facial paralysis were associated risk factors (all p < 0.05). After 2 years' follow-up, most acute neurological symptoms had subsided, yet fatigue (8.66%) and brain fog (5.99%) persisted. Comorbidities did not significantly increase the risk of persistent symptoms. For the new-onset symptoms, the proportion of insomnia, tinnitus, blurred vision, movement disorder, palpitation, muscle weakness, and respiratory symptoms were much higher in the neurological symptom group (p < 0.05), with a highest proportion in insomnia (9.99% vs. 5.22%, p < 0.001), compared with the non-neurological symptom group. Conclusion:Acute neurological symptoms, especially central nervous system manifestations, were strongly associated with long-term cognitive decline and new-onset symptoms (mainly insomnia) in COVID-19 survivors. This study uniquely reveals the persistence of high levels in brain fog and fatigue at 2-year's follow up, despite overall subsidence of most acute manifestations, underscoring the need for early intervention and sustained monitoring in this high-risk population.

The purpose of this paper is to explore the mechanism of 18β glycyrrhetinic acid (18β-GRA) in treating gastric cancer. Firstly, the toxicological effects of 18β-GRA were predicted using the ProTox3.0 database. Then, candidate biomarkers for the anti-gastric cancer of 18β-GRA were screened using the weighted gene co-expression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), the support vector machine (SVM), the random forest algorithm combined with the TMT proteomics methods. Additionally, we explored the potential upstream transcription factors and downstream interacting proteins of the biomarkers. The WGCNA method yielded 269 targets, while TMT proteomics analysis identified 6,273 genes. Among these, 12 targets were identical. Using LASSO, SVM, and random forest algorithms, three candidate markers were identified: insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), keratin 6B (KRT6B), and E3 ubiquitin-protein ligase NEDD4-like (NEDD4L). Based on molecular docking and molecular dynamics results, NEDD4L is believed to be a 18β-GRA biomarker, while sodium channel protein type 5 subunit alpha (SCN5A) and early growth response protein 1 (EGR1) are the potential upstream and downstream regulatory proteins, respectively. These findings provide a theoretical basis for future experimental verification.

BACKGROUND:Exhaled volatile organic compound (VOC) profiling is a promising non-invasive tool for disease diagnosis, but its clinical value in general critical illness remains underexplored. This study investigated whether exhaled breath VOC signatures can distinguish critically ill patients from healthy controls, stratify disease severity, and predict short-term prognosis in a heterogeneous intensive care unit (ICU) population. METHODS:We conducted a prospective observational study enrolling 278 consecutive ICU patients and 145 healthy controls. Exhaled VOC profiles were collected via gas chromatography-ion mobility spectrometry (GC-IMS). Differential VOC analysis was performed, and an orthogonal partial least squares-discriminant analysis (OPLS-DA) model was constructed to evaluate diagnostic accuracy, stratification capacity, and prognostic performance. RESULTS:A total of 862 exhaled breath samples were analyzed, identifying 28 of 44 detected VOC signals. Eight of these compounds showed significant abundance alterations in ICU patients relative to controls. The OPLS-DA model achieved an area under the receiver operating characteristic curve (AUC) of 0.97 for distinguishing ICU patients from healthy individuals. VOC profiles also differed significantly between patients stratified by high vs. low APACHE Ⅱ scores. For predicting 30-day all-cause mortality, the model yielded a moderate AUC of 0.73, with 3 specific VOCs (2-Butanone-3-hydroxy-D, ethyl acetate-M, and dimethyl sulfide) showing significant abundance differences between non-survivors and patients with clinical improvement. CONCLUSIONS:Exhaled VOC profiling effectively identifies critical illness and stratifies disease severity. While single-modal VOC profiling has limited prognostic performance due to the heterogeneity of critical illness outcomes, the distinct differential signatures identified here provide a solid foundation for future research.

Acute myocardial infarction (AMI) has become a serious disease that endangers human health, with high morbidity and mortality. Numerous studies have reported histone acetylation can result in the occurrence of cardiovascular diseases. This article aims to explore the potential biomarkers of histone acetylation regulatory genes (ARGs) in AMI patients. Five AMI datasets were downloaded from the Gene Expression Omnibus (GEO) database. Next, ARG-related genes were gathered by gene set variation analysis (GSVA) and Spearman’s correlation analysis. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed to identify the module genes related to histone acetylation regulation. In the GSE60993 and GSE48060 datasets, the common differentially expressed genes (DEGs) between AMI and control samples were screened. Importantly, the intersecting genes were obtained by overlapping ARGs-related genes, common DEGs, and module genes. Then, the biomarkers in AMI were determined by machine learning, receiver operating characteristic (ROC) curves, and quantitative PCR (qPCR). In addition, immune analysis, drug prediction, molecular docking, and the lncRNA-miRNA-mRNA regulatory network targeting the biomarkers were analyzed, respectively. Here, a total of 18 intersecting genes were identified by overlapping 7,349 ARGs-related genes, 5,565 module genes, and 25 common DEGs. Further, five biomarkers (AQP9, HLA-DQA1, MCEMP1, NKG7, and S100A12) were obtained, and a nomogram was constructed and verified based on these biomarkers. Notably, the biomarkers were significantly associated with CD8 T cells and neutrophils. In addition, the drugs related to biomarkers were predicted, and ATOGEPANT with the molecular target (S100A12) had a high binding affinity (docking score = -10 kcal/mol). AQP9, HLA-DQA1, MCEMP1, NKG7, and S100A12 were identified as biomarkers related to ARGs in AMI, which provides a new perspective to study the relationship between ARGs and AMI.

Cobalt (Co) is an important transition metal and widely distributed in the natural environment. Co exposure is associated with an increased risk of diabetes. Epidemiological studies have identified the associations between Co exposure and fasting plasma glucose (FPG) levels. However, the mechanism of cobalt associated with FPG increase is still unclear. In this study, we investigated the relationship between urinary Co and FPG through population surveys and explored the mechanism of Co-induced glucose metabolic disorders in mice and MIHA human normal liver cell line. We found a positive correlation between urinary Co concentrations and FPG levels in investigated population, and the PI3K/Akt signaling pathway was screened out by metabolomics and network toxicology analyses, which might be associated with Co-induced the elevation of FPG. Mechanistically, Co inhibited hepatic glucose uptake and glycogen synthesis and enhanced gluconeogenesis by suppressing PI3K/Akt signaling pathway activation that acted on glucose metabolism by FOXO1, GSK-3β and glucose transporter protein GLUT2. Furthermore, Co upregulated the expression of PTEN, an inhibitory protein of PI3K/Akt signaling, via reduced the miR-148b-3p, leading to the suppression of PI3K/Akt signaling, ultimately induced glucose metabolic disorders in liver. However, Co has no effects on the glucose metabolism of skeletal muscle in mice. Our research results provide a new discovery for Co disrupting glucose metabolic and increasing FPG levels through inhibiting glycogen synthesis and increasing gluconeogenesis, not affecting the glycolytic capacity in liver.

Liver cancer is the third leading cause of death globally, with hepatitis B virus (HBV) infection being identified as the primary risk factor for its development. The occurrence of HBV-related hepatocellular carcinoma (HCC) is attributed to various mechanisms, such as chronic inflammation and liver cell regeneration induced by the cytotoxic immune response triggered by the virus, abnormal activation of oncogenes arising from HBV DNA insertion mutations, and epigenetic alterations mediated by viral oncoproteins. The envelope protein of the HBV virus, known as hepatitis B surface antigen (HBsAg), is a key indicator of increased risk for developing HCC in HBsAg-positive individuals. The HBsAg seroclearance status is found to be associated with recurrence in HCC patients undergoing hepatectomy. Additional evidence indicates that HBsAg is essential to the entire process of tumor development, from initiation to advancement, and acts as an oncoprotein involved in accelerating tumor progression. This review comprehensively analyzes the extensive effects and internal mechanisms of HBsAg during the various stages of the initiation and progression of HCC. Furthermore, it highlights the importance and potential applications of HBsAg in the realms of HCC early diagnosis and personalized therapeutic interventions. An in-depth understanding of the molecular mechanism of HBsAg in the occurrence and development of HCC is provided, which is expected to develop more precise and efficient strategies for the prevention and management of HCC in the future.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting neonates, especially preterm and very low birth weight infants. Recent studies highlight the role of the gut microbiota in neonatal health, with microbial dysbiosis linked to NEC onset. However, bibliometric analyses in this field remain relatively scarce. This study aims to conduct a comprehensive analysis of the literature related to gut microbiota and NEC published between 1996 and 2024, to outline the development of this research area, identify emerging trends, and provide insights for future investigations. Articles and reviews related to gut microbiota and NEC were retrieved through a subject search from Web of Science Core Collection, restricting the document type to articles or reviews and language to English. The relevant literature to be included in the analysis was identified. Subsequently, bibliometric analyses were conducted using Python, CiteSpace, VOSviewer, and the Bibliometrix (R-Tool of R-Studio) software to perform a visualization analysis of basic information and trends regarding journals, countries/regions, influential authors, institutions, keywords, and papers. A total of 555 relevant articles were published between 1996 and 2024. The number of publications has consistently grown, with a notable surge since 2009. The United States and China are the primary contributors to this body of research, with the United States exerting the greatest influence in this field. Prominent journals include Frontiers in Pediatrics, Nutrients, Frontiers in Microbiology, Pediatric Research, and PLOS One. Influential authors in this area include Sangild PT and Neu J. Key research trends focus on the pathogenesis of the neonatal gut microbiota about NEC, the therapeutic potential of breast milk and probiotics, and the identification of multi-omics biomarkers. Recent literature prominently features keywords such as “premature infants,” “pathogenesis,” “breast milk,” “NEC,” “prebiotics,” “probiotics,” and “gut microbiota,” while topics such as “inflammatory bowel disease” and “immune system” highlight a shift in research priorities, with an increasing focus on understanding pathological mechanisms and therapeutic interventions. Our analysis highlights the role of gut microbiota in NEC in preterm infants, identifying probiotics and breast milk as potential therapeutic targets. It emphasizes the need for further research on microbiota-based interventions and their safety in neonates.

BACKGROUND:Electrogenic Na+/HCO3- co-transporter 1 (NBCe1) plays a pivotal role in epithelial bicarbonate transport involved in the maintenance of the intestinal mucus barrier. However, the specific role of NBCe1 in colitis remains unknown. METHODS:NBCe1 was identified by bioinformatics analysis methods including GO/KEGG/GSEA, protein-protein interaction (PPI) network analysis, immune infiltration analysis, and Mendelian randomization (MR) analysis. Expression level of NBCe1 was detected in patients with IBD and in DSS-induced colitis mice. The role of NBCe1 in intestinal mucus barrier and colitis was accessed by S0859 pretreatment in DSS model. The function of NBCe1 and related bicarbonate secretion were evaluated using short-circuit current (Isc) measurements in Ussing chamber system. RESULTS:Bioinformatic analyses indicated that SLC4A4 (NBCe1) was a signature gene in bicarbonate transport implicated in ulcerative colitis (UC) development and was negatively associated with the risk of UC. NBCe1's expression was significantly diminished in colonic mucosa of UC patients and DSS-treated mice. More severe intestinal inflammation and impaired mucus barrier were observed in S0859-treated mice. Moreover, S0859 administration led a significant decrease in mucus secretion rate and an significant increase in Isc of colonic mucosa. The forskolin-induced ΔIsc was also suppressed by S0859 pretreatment. CONCLUSION:NBCe1 has been identified as a valuable signature gene may have a protective effect against the onset of colitis. Function of NBCe1 is diminished in colitis, which is associated with impaired mucus barrier and declined HCO3- secretion both contributing to the development of IBD.

Background:Pneumonia is among the most dangerous complications of infection after intracerebral hemorrhage. We aimed to create a novel nomogram for pneumonia after intracerebral hemorrhage. Methods and Results:The data from the Chinese Cerebral Hemorrhage: Mechanism and Intervention (CHEERY) study was analyzed. Thirty percent of qualified patients were placed in the validation group (n=763) while seventy percent of them were randomly placed in the training group (n=1784). In the multivariate analysis, ten variables were included in the model: age (β= 0.023, P<0.001), hospital days (β=0.392, P<0.001), baseline mRS score (β=0.484, P<0.001), baseline GCS score (β=-0.285, P<0.001), hs-CRP (β=0.328, P<0.001), hematoma volume (β=0.376, P<0.001), brainstem hemorrhage (β=0.956, P=0.002), intraventricular hemorrhage (β=0.629, P=0.001), and β-blocker (β=0.899, P<0.001) In the training subset, the areas under curve were 0.805 (95% CI, 0.773-0.833). The model was subsequently examined in the validation group, with the area under curve 0.767 (95% CI, 0.716-0.807). There was strong agreement between the anticipated and actual survival rates in the nomogram calibration curves for both the training and validation groups. The clinical value of the model is assessed by means of Decision Curve Analysis. In addition, we validated other models with this cohort, which showed that our model had better discrimination. Moreover, the area under the curve of the catboost model established using the above nine variables in the training set and the validation set is 0.87(95% CI, 0.80-0.90) and 0.77(95% CI, 0.72-0.80). Conclusion:We have established a simple and easy predictive tool. By evaluating the incidence of pneumonia after intracerebral hemorrhage, we can identify high-risk groups early. At the same time, our study also suggests that doctors should be cautious in the use of β-blocker in clinical decision-making.

Ethnopharmacological relevance TongXie-Ning (TXN), a traditional Chinese herbal medicine (TCM) that modified from TongXie YaoFang had long been used to treat diarrhea-predominant irritable bowel syndrome (IBS-D). However, the underlying mechanisms require further scientific elucidation. Aim of the study This study aimed to elucidate the multitarget actions of TXN in relieving gut dysfunction against IBS-D. Materials and methods The therapeutic effect of TXN on a postinfectious (PI)-IBS rat model, induced by Trichinella spiralis infection, was assessed. Subsequently, the effects of TXN on intestinal smooth muscle activity, epithelial chloride and fluid secretion, and visceral sensory activity were assessed using isometric muscle contraction assays, transepithelial short-circuit current measurements, and recordings of intestinal mesenteric afferent nerves firing, respectively. Results TXN effectively increased colonic transit time, reduced fecal water content and enhanced visceral pain threshold in PI-IBS rats. Ex vivo, TXN inhibited the spontaneous and induced colonic smooth muscle activity in a concentration-dependent manner. Specially, it suppressed myogenic contraction by blocking extracellular Ca2+ influx and opening K+ channels, and attenuated neurogenic contraction by enhancing nitrergic signaling and adrenergic β2-like effect. Furthermore, TXN reduced intestinal mucosal secretion and fluid outflow, by inhibiting epithelial Cl- secretion via a Ca2+-related way, without affecting Cl- absorption. TXN also alleviated the spontaneous activity of mesenteric afferents and suppressed firing induced by chemical (capsaicin)/mechanical (intraluminal pressure) stimuli. Conclusions As a botanical compound, TXN exhibits multitarget effects on intestinal motility, secretion, and sensation, thereby effectively ameliorating the gut dysfunctions underlying diarrhea and pain in IBS-D. This study provides a scientific basis for the clinical application of TXN and helps developing IBS-D therapeutics based on TXN.