OBJECTIVE To preliminarily investigate the antiasthmatic effect and mechanism of Ephedrae Herba-Armeniacae Semen Amarum herb pair on the respiratory center. METHODS Male SD rats were randomly divided into blank group， model group， dexamethasone group （positive control）， and Ephedrae Herba-Armeniacae Semen Amarum 2∶1， 1∶1 and 1∶2 groups. Rats in each group were administered different ratios of the herb pair decoction [all at 18 g （crude drug）/kg]， dexamethasone suspension （0.5 mg/kg）， or normal saline intragastrically twice daily for seven consecutive days. Forty minutes after the last administration， medicated cerebrospinal fluid was collected to determine the content of effective components entering the brain. One and a half hours after the last administration， the nucleus tractus solitarius （NTS） was located using a stereotaxic apparatus. Histamine phosphate （1 μL） was injected into the NTS region at a constant rate of 1 μL/min using a 10 μL microsyringe to induce excitation of the respiratory center in rats； the blank group was injected with normal saline. The contents of neurotransmitters [nerve growth factor （NGF）， substance P （SP）， norepinephrine （NA）， 5-hydroxytryptamine （5-HT） and acetylcholine （Ach）] in the medulla oblongata brain tissue were detected. The mRNA expressions of neurokinin-1 receptor （NK-1R）， p38 mitogen-activated protein kinase （MAPK）， and c-fos in the medulla oblongata， as well as the protein expressions of NK-1R， p38 MAPK， and c-fos in the NTS region， were determined. RESULTS The main active components of Ephedrae Herba-Armeniacae Semen Amarum herb pair entering the brain were ephedrine， pseudoephedrine， and methylephedrine. Compared with blank group， the contents of NGF， SP， NA， 5-HT and Ach， and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein were significantly increased in the model group （ P ＜0.01）. Compared with model group， Ephedrae Herba-Armeniacae Semen Amarum herb pair groups with different ratios significantly reduced the neurotransmitter contents and the relative expression levels of NK-1R， p38 MAPK， and c-fos mRNA and protein （ P ＜0.01）， with the 2∶1 Ephedrae Herba-Armeniacae Semen Amarum herb pair and 1∶1 mass ratios showing relatively better effects. CONCLUSIONS Ephedrae Herba alkaloids are the main active components in affecting the function of the respiratory center. The herb pair groups with a larger proportion of Ephedrae Herba exhibit stronger effects. Ephedrae Herba-Armeniacae Semen Amarum herb pair can reduce the excitability of the respiratory center by down-regulating the expression of the NK-1R/MAPK/c-fos pathway in the NTS and decreasing the abnormal release of neurotransmitters such as NGF and SP.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9％)and a failed group(6 cases,17.1％)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00％vs.17.24％,P=0.040),history of diabetes(100.00％vs.10.34％,P=0.025),and chronic total occlusion of coronary artery(83.33％vs.17.24％,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67％vs.58.62％,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P＜0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95％CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2％.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.

Objective:To investigate the risk factors influencing mortality in neonates undergoing continuous renal replacement therapy (CRRT).Methods:This retrospective study included 34 neonates with a corrected age of≤28 days who received CRRT at the Affiliated Children's Hospital of Xiangya School of Medicine, Central South University, from January 2019 to December 2023. The neonates were divided into a mortality group ( n=16) and a survival group ( n=18) based on whether they died during CRRT. Pre-CRRT blood biochemical indices, general condition, CRRT treatment modes, parameters, and related complications were analyzed using t-tests, Wilcoxon signed-rank tests, and Chi-square tests. Logistic stepwise regression analysis was used to screen for risk factors associated with CRRT mortality. Results:The mortality rate among the 34 neonates was 48.6% (16/34), with a median CRRT age of 17 days (range: 2-33 days). Eleven neonates (32.3%) were preterm, with the youngest gestational age being 27 weeks and the lowest weight before CRRT initiation being 1 700 g. The mortality group had lower urine output 6-12 hours before CRRT initiation and lower critical illness scores compared to the survival group [0.05 (0.02-1.00) ml/(kg·h) vs. 0.50 (0.20-1.05) ml/(kg·h), (64.50±7.10) scores vs. (77.67±3.65) scores, Z or t values were 10.97 and 3.91, respectively]. However, the vasoactive inotropic score (VIS), proportion of coma, and levels of blood potassium, alanine aminotransferase, aspartate aminotransferase, blood ammonia, blood lactic acid, and activated partial thromboplastin time (APTT) were higher in the mortality group compared to the survival group [ (86.88±15.80) scores vs. (55.56±24.31) scores, 11/16 vs. 1/18, (7.02±1.73) mmol/L vs. (5.88±1.53) mmol/L, 274.55(132.50-664.98) U/L vs. 31.10(19.03-110.70) U/L, 688.20 (449.73-3 618.13) U/L vs. 96.65 (44.15-439.00) U/L, 232.75 (70.33-1 310.85) μmol/L vs.77.70 (49.78-919.05) μmol/L, (11.17±3.36) U/L vs. (7.99±2.67) U/L, and (99.57±39.74) s vs. (60.97±31.25) s, with t, χ2, or Z values of－4.39, 14.81,－2.03,－2.72,－11.81,－3.89,－3.06, and－3.17, respectively] (all P<0.05). Logistic regression analysis revealed that pre-treatment VIS value ( OR=1.150, 95% CI: 1.035-1.278), and blood ammonia level ( OR=1.004, 95% CI: 1.002-1.009) were independent risk factors for mortality (both P<0.05). Conclusions:Neonatal CRRT mortality is associated with pre-treatment VIS scores and blood ammonia levels. Attention should be paid to a rapid decreases in urine output, the intensity of vasopressor support, and elevated levels of blood ammonia, blood lactic acid, transaminases, and APTT at the initiation of treatment.

Objective To explore potential categories of post-stroke depression in acute-phase stroke patients and its correlation with the degree of neurological deficits,and to provide references for healthcare professionals in developing targeted interventions.Methods Using convenience sampling,patients with acute stroke who were hospitalized in neurological ward of 2 tertiary general hospitals in Henan Province from January to April 2024 were selected as the survey participants.The investigation was conducted using the General Information Questionnaire,the National Institute of Health Stroke Scale,and the Patient Health Questionnaire-9.The correlation between potential categories of post-stroke depression and the degree of neurological deficit was analysed using unordered multiclassified logistic regression.Results Post-stroke depression score was 10.22±3.61 in 193 acute-phase stroke patients,and post-stroke depression could be categorized into 3 potential categories,namely"low depressive symptoms"(44.6％),"melancholic depression"(15.0％),and"atypical depression"(40.4％).There was a significant difference in the degree of neurological deficits(H=38.074,P＜0.001).Compared with severe neurological deficits,patients with mild deficits were more likely to be categorized as"melancholic depression"(OR=0.016,P=0.001)and"atypical depression"(OR=0.040,P＜0.001),and patients with moderate deficits were more likely to be classified as"atypical depression"(OR=0.085,P=0.001).Conclusion Post-stroke depression in acute-phase stroke patients has obvious categorization characteristics,and it is recommended that healthcare professionals should pay more attention to patients with different degrees of neurological deficits and adopt targeted interventions according to the different categories of post-stroke depression in order to alleviate their depressive symptoms.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.

Objective To explore the influencing factors of frailty among the health check-up elder-ly participants from our outpatient clinic.Methods A total of 710 elderly individuals(≥60 years old)who taking health check-up in our outpatient department between April and August 2022 were consecutively enrolled,and according to the results of Fried Frailty Phenotype Scale,they were divided into non-frailty group(422 cases),pre-frailty group(225 cases)and frailty group(63 cases).Their general clinical data,laboratory indicators and echocardiographic parameters were collected,and multivariate logistic regression analysis was applied to identify the independent in-fluencing factors for pre-frailty and frailty.Results The overall prevalence of pre-frailty and frail-ty was 31.7％and 8.9％,respectively.The pre-frailty and frailty groups had obviously larger left atrial anterior-posterior diameter and left ventricular end diastolic diameter and lower left ventric-ular ejection fraction when compared with the non-frailty group(P＜0.05).Multivariate logistic regression analysis showed that Hb was a protective factor for pre-frailty in the elderly partici-pants(OR=0.984,95％CI:0.966-0.992,P=0.048),while age(OR=1.064),CCI(OR=1.387)and LAAP(OR=1.059)were risk factors for pre-frailty in them(P＜0.05,P＜0.01).Serum albumin was a protective factor for frailty(OR=0.823,95％CI:0.728-0.931,P=0.002),but age(OR=1.081),CCI(OR=1.458),left atrial anterior-posterior diameter(OR=1.249)and NT-proBNP(OR=1.652)were independent risk factors for frailty(P＜0.05,P＜0.01).Conclusion There are differences in influencing factors for frailty of different severity,and the status of frailty is related to factors such as age,comorbidity,cardiac function and nutritional sta-tus.Therefore,comprehensive interventions should be implemented as early as possible for the elderly occurrence of pre-frailty so as to prevent and reverse frailty at the same time.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.