This paper explores the therapeutic approach for glaucoma based on the concept of "jueyin （厥阴） as the closing phase" from the perspectives of time and space. In traditional Chinese medicine， jueyin governs inward， converging aspect of qi， representing the crucial turning point between the end of yin and the emergence of yang， as well as the transformation between yin and yang. When the closing and descending function of jueyin operates smoothly， it promotes the inward convergence and smooth descent of qi， enabling the internal retention of blood， spirit， and emotions， which nourishes the internal organs and moistens the meridian-sinews. Conversely， dysfunction of this "closing" mechanism results in a disturbance of yin and yang， a mixture of cold and heat， and disharmony of qi and blood. It is proposed that "failure of jueyin to properly close and descend" is a core pathomechanism of glaucoma. From the perspective of spatiotemporal theory， clinical treatment should focus on "regulating the closing function of jueyin and harmonizing yin and yang". The modified Wumei Pill （乌梅丸） is recommended to adjust the ascending-descending and entering-exiting dynamics of jueyin qi transformation， thereby restoring its free flow， achieving yin and yang balance， and ensuring nourishment to the ocular system.

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Japanese encephalitis virus(JEV)belongs to the genus Flavivirus and the family Flavi-viridae,and is classified as a single-stranded,positive-sense RNA virus.The disease known as Japa-nese encephalitis(JE),which results from JEV infection,is a viral zoonosis that is prevalent worldwide and poses a significant public health concern.JEV infection activates a variety of signa-ling pathways,leading to a series of changes that are crucial to the virus's pathogenesis.Among these pathways,Toll-like receptors(TLRs)are particularly significant,and their diverse range and complex signal transduction mechanisms present substantial challenges for the prevention and con-trol of JEV.Currently,there is no specific treatment for JEV.Although some vaccines have been developed to prevent JE,eradicating JEV remains difficult due to its zoonotic transmission cycle and the limited efficacy of the available vaccines.This article reviews the alterations in various TLR signaling pathways induced by JEV infection in the host,aiming to provide insights into the patho-genic mechanisms of JEV and to identify potential new antiviral targets.

Porcine reproductive and respiratory syndrome virus(PRRSV)is the pathogen of porcine reproductive and respiratory syndrome(PRRS),and its infection mainly causes abortion,stillbirth in sows and piglet respiratory infections,which are widely prevalent in the world and seriously jeopardize the development of the world's animal husbandry industry.PRRSV infection of the host is capable of inducing significant immunosuppression,and in recent years,the study of the mecha-nism of PRRSV immunosuppression has become a hot topic,with studies showing that numerous PRRSV proteins are involved in the regulation of host innate immunity and elucidating the mecha-nism by which PRRSV proteins modulate host innate immunity.In this paper,we reviewed the progress of research on the interaction mechanism between PRRSV proteins and host innate im-munity to provide a theoretical basis for a comprehensive understanding of the pathogenesis of PRRSV and the prevention and control of PRRS.

Objective The effects of carrimycin(CAM)on the biological functions of intrahepatic cholan-giocarcinoma HuCCT1 cells were examined through in vitro experiments,and a preliminary investigation was conducted into its mechanism of action.Methods The intrahepatic cholangiocarcinoma cell line HuCCT1 was selected for the study.The effect of CAM on cell viability was assessed using the CCK-8 assay,and the IC50 concen-tration was determined accordingly.The impact of CAM on cell migration was evaluated through a scratch wound healing assay.In addition,the effect of CAM on clonogenic ability was examined using a colony formation assay.Cell invasion capacity was assessed using a Transwell invasion assay.Flow cytometry was employed to analyze the effect of CAM on cell cycle progression.Furthermore,Western blotting was conducted to evaluate the expression levels of key proteins associated with epithelial-mesenchymal transition and the cell cycle.Finally,the influence of CAM on the AXL/c-Myc/c-Met signaling axis was also investigated.Results Compared with the control group,CAM significantly inhibited the proliferation of HuCCT1 cells in a concentration-dependent manner(P<0.05).Plate cloning assays demonstrated that CAM markedly suppressed the colony-forming ability of HuCCT1 cells(P<0.05).Scratch wound healing assays confirmed that CAM treatment significantly reduced the migration speed and narrowed the migration area of HuCCT1 cells(P<0.05).Flow cytometry analysis revealed that CAM treatment led to a significant increase in the proportion of cells in the G0/G1 phase and a decrease in the S phase(P<0.05).Western blot analysis further confirmed that the expression levels of key regulatory proteins CCND1 and CDK4,which are involved in the G1/S phase transition,were down-regulated,while the expression of p21 was up-regulated(P<0.05).Transwell invasion assays indicated that CAM inhibited the invasive capacity of HuCCT1 cells.Consis-tently,Western blot results showed that E-Cadherin expression was increased(P<0.05),whereas the expression levels of N-Cadherin and Vimentin were decreased(P<0.05).Moreover,Western blot analysis verified that the expression of AXL,c-Met,and c-Myc was up-regulated in HuCCT1 cells treated with AXL recombinant protein(P<0.05).However,co-treatment with CAM and AXL recombinant protein significantly attenuated the expression of these proteins(P<0.05).Conclusions CAM inhibits the proliferation,migration,and invasion of intrahe-patic cholangiocarcinoma HuCCT1 cells,thereby demonstrating antitumor effects,which may be associated with the AXL/c-Met/c-Myc signaling pathway.

Retinopathy caused by myopia is the first cause of irreversible blinding eye disease in China.The TCM methods to prevent and control myopia mainly include Chinese materia medica and TCM appropriate techniques,which have the advantages of good efficacy,simple operation,and few adverse reactions.This paper believed that internal and external pathogenic factors act on the brain and eyes,breaking their homeostasis,leading to rhythmic disorders,and imbalance of essence,qi and blood is the main pathogenesis of myopia.Based on the idea of"nature and human in the same rhythm"and"the same treatment for common diseases",targeting the above pathogenesis,the method of"brain-eye synchronization"was proposed to restore the homeostasis of the brain and eyes to prevent and control myopia in children and adolescents,and the treatment rules were to regulate the rhythms of the time,harmonize the qi and blood,nourish the blood to soften the tendons,and replenish the essence and blood,so as to achieve the effect of brain-eye synchronization and the treatment of the spirit and the body together.This article summarized the theoretical basis of"brain-eye synchronization"and its clinical application in traditional Chinese and Western medicine,with a view to providing new ideas for the prevention and control of myopia in children and adolescents.

To identify clinical viral diseases characterized by reproductive disorders and abortion,a quadruple qPCR method was established for simultaneous detection of PRV,PPV,PCV2 and AS-FV.Four pairs of specific primers and probes were designed according to the conserved genes of four viruses in the NCBI gene bank.The annealing temperature,primer concentration and probe concentration of the reaction were optimized,and the specificity,sensitivity and repeatability of the method were tested.The results showed that the method could not detect other pathogens except the target ones.The minimum detection limit of PRV,PPV,PCV2 and ASFV was 10 copies.Intra-group and inter-group repeatability tests showed that the coefficient of variation of C,values be-tween different batches was less than 3％,indicating that the method was highly specific,sensitive and stable.Establishment of an efficient and sensitive quadruple qPCR method provides technical reference for the clinical prevention and control of porcine pseudorabies virus disease,porcine circo-virus disease,porcine parvovirus disease and African swine fever.

This study investigates the effects of pseudorabies virus(PRV)infection on the antiviral immune signaling pathways and type Ⅰ interferon factors in mouse trigeminal ganglion(TG)cells.In this experiment,primary TG cells were infected with PRV at a multiplicity of infection(MOI)of 1,while mice were infected via a drop-nose method using 106,29 TCID50 of PRV.Real-time fluorescence quantitative PCR(qPCR),Western blot and ELISA were used to assess gene tran-scription,protein expression,and the secretion of IFN-α and IFN-β.The results indicated that PRV infection of mouse TG primary cells led to alterations in the gene and protein expression of RIG-Ⅰ,MAVS,and IRF3,as well as the phosphorylation of IRF3 and IKBα both in vivo and ex vivo.ELISA results showed that PRV infection could regulate the secretion of IFN-α and IFN-β in mouse primary TG cells and mouse TGs.The results of RIG-Ⅰ signaling pathway-related proteins and the secretion of IFN-a and IFN-β were analyzed using Western blot after using siRNA to interfere with RIG-Ⅰ expression in TG cells.The results showed that siRIG-Ⅰ successfully inter-fered with RIG-Ⅰ protein expression in TG cells and caused changes in the expression of down-stream proteins such as MAVS and IRF3,and also regulated the secretion of IFN-α and IFN-β in TG cells.Furthermore,the results indicated that PRV infection induced the expression of RIG-Ⅰ in mouse TG progenitor cells,regulating the antiviral immune response of type Ⅰ interferon factors in TG cells through the RIG-Ⅰ-MAVS-IRF3 signaling axis.Notably,PRV inhibited the expression of IRF3 in TG cells while significantly upregulating the expression of IFN-β during the later stages of infection,which may be an important factor in the important reason for the rapid mortality ob-served in mice during the late stages of PRV infection.This experiment elucidates part of the anti-viral immune mechanism mediated by the RIG-Ⅰ-MAVS-IRF3 signaling pathway in regulating type Ⅰ interferon factor after PRV infection of mouse TG cells,as well as the discovery of differ-ent trends of IRF3 protein changes in vivo and ex vivo,laying the groundwork for future in-depth studies.

Traditional Chinese medicine upholds the unity of nature and humanity as its fundamental principle,asserting that man is in harmony with heaven and earth and corresponds to the sun and moon.Human life processes align with the circadian rhythms of nature,exhibiting periodic temporal changes-concepts that Western medicine defines as biological rhythms.The"opening-closing-pivot"of the three yin and three yang meridians represents the primary mode of interaction between nature and humanity.This mechanism regulates the transformation of yin and yang to qi within the body,ensuring synchronization with the circadian rhythm.Building upon this foundation,the concept of"the harmony of rhythms and states"was proposed to explain human growth and aging."Rhythms"encompass not only circadian cycles but also the movement of qi and blood,as well as the contraction rhythm of muscle fascia,among other physiological processes."States"refer to the dynamic evolution and transformation of qi during the"opening-closing-pivot"stages in both time and space."Harmony"pertains not only to the individual physiological balance of"rhythms"or"states"but also to their coherent interaction.The fundamental cause of myopia is"the disharmony of rhythms and states",considering that rhythm disorders,qi and blood disorders,and fascia imbalances contribute to this disease.Based on this understanding,myopia prevention and treatment should center on"regulating rhythms and states",with adjusting the pivot to brighten the eyes as the core therapeutic principle throughout the entire cycle of myopia.Treatment should be tailored to different disease stages and supplemented with methods such as time-based regulation,qi and blood harmonization,tendon relaxation and collateral dredging,and essence and blood nourishment to prevent and manage myopia effectively.

Yttrium-90(90Y)selective internal radiation therapy(SIRT)is an emerging modality for the treatment of hepatocellular carcinoma(HCC),leveraging the nuclide 90Y to deliver targeted radiation therapy.90Y has a long half-life and can be used to selectively ablate tumor cells by high-energy beta rays.It has high biological effectiveness and robust local control capabilities.In recent years,with the continuous advancement of basic and clinical research,the application of 90Y-SIRT in the conversion treatment of unresectable HCC(uHCC)has made significant progress.However,challenges remain in the clinical application of 90Y-SIRT,including how to improve the efficacy of conversion therapy and how to optimize therapy regimens.This review aims to summarize the research progress of90Y-SIRT in the conversion therapy of uHCC.