Short-chain fatty acids （SCFA） are the main metabolic products generated by the fermentation of dietary fiber by gut microbiota. Studies have shown that SCFA not only play a role in energy metabolism， but also act as important signaling molecules， exhibiting a significant potential in alleviating liver and pancreatic fibrosis. The core mechanism of SCFA mainly involves the regulation of various key signaling pathways by activating G protein-coupled receptors and inhibiting the activity of histone deacetylase， thereby suppressing the activation and proliferation of hepatic stellate cell （HSC） and pancreatic stellate cell （PSC）， which is a key link in fibrosis formation. In addition， SCFA can effectively alleviate tissue inflammation response， improve intestinal barrier function， and regulate gut microbiota balance， thus indirectly preventing the process of fibrosis mediated by the “gut-liver/pancreas axis”. Compared with the research on SCFA in liver fibrosis， studies on their role in pancreatic fibrosis are limited. Given that HSC and PSC are highly homologous， the transcription factors and proteins that have been confirmed in liver fibrosis-related studies are also similarly expressed in PSC， suggesting that they may also influence the activation of PSC. This article systematically summarizes the recent advances in the research on SCFA in alleviating liver and pancreatic fibrosis， in order to provide new perspectives for exploring the mechanism of pancreatic fibrosis and developing related interventional strategies.

Plant-derived exosome-like nanovesicles (PELNs), characterized by a natural lipid bilayer membrane, have rapidly emerged as a prominent research frontier in medicine owing to their unique biological properties and robust therapeutic potential. This review comprehensively examines the biological profiles, mechanistic functions, and recent engineering advancements of PELNs. In terms of composition, PELNs are uniquely enriched in plant-specific glycolipids, phosphatidylserine, secondary metabolites, and highly stable 2'-O-methylated miRNAs. This distinct molecular makeup endows them with exceptional biocompatibility, negligible immunogenicity, and the capacity for cross-species molecular communication. Mechanistically, PELNs demonstrate profound anti-inflammatory efficacy by suppressing the NF-κB and NLRP3 inflammasome pathways. They also serve as potent immune modulators, driving macrophage M1/M2 polarization and regulating T cell activity. Additionally, PELNs exhibit promising antitumor capabilities, targeting malignancies via reactive oxygen species (ROS) induction, TRAIL pathway activation, and tumor microenvironment remodeling. Crucially, the plant miRNAs encapsulated within PELNs remain highly stable in the gastrointestinal tract, allowing them to selectively alter gene expression in specific gut microbiota communities. This interaction deeply influences host immunity and metabolism, highlighting the vital role in cross-species regulation. Advancements in bioengineering have further expanded the clinical utility of PELNs. Targeted delivery efficiency can be significantly amplified via surface functionalization (e.g., folate and RGD sequences) and state-of-the-art drug loading technologies such as sonication and electroporation. Consequently, engineered PELNs surpass traditional synthetic nanocarriers in penetrating natural physiological barriers, particularly for oral and transdermal drug administration. Despite these advantages, clinical translation is currently hindered by the lack of standardized isolation protocols, challenges in scalable manufacturing, and the need for robust quality control frameworks. Looking forward, the integration of multi-omics approaches and AI-driven “molecular fingerprinting”—coupled with the design of synthetic biomimetic vesicles—will be instrumental in overcoming these bottlenecks, ultimately establishing PELNs as a next-generation platform for precision medicine and targeted nanotherapeutic delivery.

Chronic pancreatitis （CP） is a common disease in clinical practice characterized by progressive inflammatory fibrosis of the pancreas. Gut microbiota， known as the “second genome” of humans， bidirectionally modulates the progression of fibrosis in CP via the gut-pancreas axis. This article systematically elaborates on the characteristics of gut microbiota during the progression of CP and its molecular mechanism in mediating pancreatic fibrosis through bacterial translocation， metabolites， immune regulatory networks， and microbe-pancreatic stellate cell interactions， with a focus on the pivotal role of short-chain fatty acids and inflammatory cytokine networks in pancreatic stellate cell activation and extracellular matrix deposition. In addition， this article explores the potential value of gut microbiota-targeted interventions in the prevention and treatment of CP fibrosis， such as probiotics， prebiotics， and fecal microbiota transplantation， and discusses the translational potential of using multi-omics technologies to identify diagnostic biomarkers and novel therapeutic targets for CP， in order to provide new ideas for the precise diagnosis and treatment of CP.

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:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To observe the effect of sodium cantharidate assisted bevacizumab in the treatment of advanced non-small cell lung cancer patients.Methods:A total of 120 patients with advanced lung adenocarcinoma from January 2021 to December 2023 were divided into two groups,namely the experimental group and the matched group,each consisting of 60 cases.All patients were treated with AP(cisplatin+pemetrexed)chemotherapy,and bevacizumab(7.5 mg/kg)was administered intravenously at the same time as chemotherapy in the matched group,while sodium bengalate(0.5 mg)was added intravenously in the experimental group on the basis of the matched group,and the patients in the two groups were compared with each other in terms of the clinical efficacy of the two groups in a cycle of 21 d,and the changes in the indicators of the immune function,symptoms and scores of adverse reactions were also compared before and after the 4 consecutive cycles of treatment.After 4 consecutive cycles of treatment,we compared the clinical efficacy,immune function indexes,symptoms,and the incidence of adverse reactions.Results:There was no difference in disease control rate(P＞0.05),and the objective response rate was higher than the matched group(P＜0.05);Pretherapy,tthe levels of natural killer(NK)cells,CD4+/CD8+,immunoglobulin(Ig)G and IgA were different between the test and matched group(P＞0.05).Post-treatment,the levels of NK cells,CD4+/CD8+,IgG,and IgA in the experimental group increased,while there was no significant change in the matched group.The experimental group was higher than the matched group(P＜0.05);Pretherapy,there was no difference in VAS and BFI scores between the experimental group and the matched group(P＞0.05).Post-treatment,the scores of the Simplified Fatigue Scale(BFI)and Visual Analog Scale(VAS)in both groups decreased,and the experimental group was lower than the matched group(P＜0.05);The incidence of grade Ⅰ-Ⅱ gastrointestinal reactions,liver and kidney dysfunction,bone marrow suppression,leukopenia,and grade Ⅲ-Ⅳ bone marrow suppression in the experimental group were all lower than those in the matched group(P＜0.05).Conclusion:Sodium cantharidate assisted bevacizumab therapy has a significant effect on non-small cell lung cancer.Compared with single chemotherapy combined with bevacizumab,it can improve the objective remission rate of patients,improve their immune function level,alleviate pain and cancer-related fatigue symptoms,and assist in reducing the incidence of adverse reactions caused by bevacizumab and chemotherapy.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.