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 explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.

Ventricular assist devices(VADs)have emerged as a pivotal therapeutic option for end-stage heart failure,undergoing significant technological advancements from pneumatic membrane pumps to continuous-flow centrifugal pumps.This review provides a detailed overview of several VAD models,including HeartMate Ⅲ,EVAHEART 2,and Heart Con.The initial generation of VADs established a foundation for subsequent developments,despite the occurrence of frequent complications.The second generation of VADs demonstrated a notable improvement in patient prognosis but carried the risk of ventricular collapse.The third generation of VADs represents a further reduction in size,incorporating magnetic levitation technology to enhance durability and blood compatibility.In the future,the development of VADs will focus on better emulating the physiological function of the native heart,improving pulsatility,and extending device longevity.As technology advances,VADs are expected to offer heart failure patients with a greater range of treatment options and a higher quality of life.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Aim To evaluate the continuous flow exposure sys-tem at the air-liquid interface(ALI)in vitro to provide reference data for in vitro studies on inhalation toxicology,and to conduct a preliminary evaluation of the inhalation toxicity of the com-pound limonene by using the system in conjunction with an ALI culture model of Calu-3 cells.Methods Fluorescein sodium(Na-flu)dosimetry supplemented with quartz microbalance(QCM)was used to evaluate the deposition volume and pore-to-pore homogeneity of the ALI continuous flow exposure system;limonene aerosol was exposed to an ALI-cultured model of Calu-3 cells for 3 h using the ALI continuous flow exposure system at exposure doses of high(0.213 μg·cm-2),medium(0.104μg·cm-2),low(0.064 5 μg·cm-2),clean air exposure was used as a negative control group,and the activity,lactate dehydrogenase(LDH)release,trans-epithelial electrical resist-ance(TEER),mucin MUC5AC and inflammatory factor gene expression of the exposed cells were detected after 24 h to evalu-ate the inhalation toxicity of limonene.Results The deposition of sodium fluorescein in the ALI continuous flow exposure system was 0.085±0.007 μg/30 min/well,and inter-well homogeneity was optimized from the initial 26％to less than 10％after sever-al debugging sessions;compared with the control group,there was no significant change in cellular activity and IL-8 gene ex-pression,but cellular IL-6 gene expression increased after limo-nene aerosol exposure;the mid-exposure dose of limonene pro-moted cellular release of LDH and inflammatory factor gene ex-pression.The medium exposure dose of limonene induced the cells to release LDH＞10％and decreased the expression of cel-lular tumor necrosis factor TNF-α gene;the high exposure dose of limonene decreased the cellular TEER value,impaired the cellular barrier function,and increased the expression of cellular mucin MUC5AC gene.Conclusions The ALI continuous flow exposure system can be used for inhalation toxicity in vitro stud-ies after commissioning;high and medium exposure doses of limonene are inhalation toxic.