ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

Background: Malignant pleural effusion (MPE), a common complication of advanced cancers, is associated with poor prognosis and reduced quality of life. Although host–tumor interactions are known to drive MPE development, the associated immune dynamics during disease progression remain unclear. Using a Lewis lung carcinoma-induced MPE model in C57BL/6JNidfc mice, we systematically evaluated general parameters and immune cell changes at two-day intervals throughout disease progression. Results: The day of Lewis lung carcinoma cell injection into the pleural space was designated as day 0. By day 10 post-injection (p.i.), MPE-bearing mice exhibited ~ 10% body weight loss, marking the experimental endpoint. Pleural tumor mass and pleural effusion volume were minimal up to day 4 p.i. but increased sharply from day 6 onward.CD45⁺ immune cell counts rose over time, and days 6, 8, and 10 p.i. marked key stages of MPE progression. On day 6, B cells, T cells, and natural killer cells, but not macrophages and neutrophils, increased significantly compared to earlier timepoints. By day 8, all immune cell subsets except T cells exceeded day 6 levels, and at day 10, natural killer cell numbers declined while others continued to increase. Besides, the numbers of CD8⁺ T cells, Th1 cells, regulatory T cells, and M2 macrophages progressively increased from day 6 to 10. Based on these data, days 6 and 10 were defined as early and advanced MPE stages, respectively, with distinct immune phenotypes. In advanced MPE, CD8⁺ T cells displayed reduced IFN-γ, TNF-α, Granzyme B, Perforin, FasL, and Ki-67, but upregulated PD-1 and CTLA-4 relative to early stage. Similarly, Th1 cells showed decreased IFN-γ, TNF-α, and IL-2 production along with reduced Ki-67 expression. Advanced-stage M2 macrophages exhibited lower MHC-II levels and impaired phagocytosis, but higher PD-L1 and IL-10 production, while neutrophils showed reduced TNF-α release and phagocytic activity. Conclusions Our findings characterize the temporal immune dynamics associated with MPE progression in a mouse model, revealing a transition from an early immunostimulatory state to a late immunosuppressive state. This study enhances our understanding of MPE immunopathogenesis and provides a foundation for developing precise, stagespecific therapeutic strategies.

Endoscopic transforaminal lumbar interbody fusion (TLIF) offers substantial advantages in the management of degenerative spinal diseases, including accelerated postoperative recovery. However, its technical complexity and steep learning curve pose risks for nerve root injury. Optimizing nerve root protection in full-endoscopic facet-sparing TLIF (FE fs-TLIF) and full-endoscopic facet-resecting TLIF (FE fr-TLIF) is essential for enhancing surgical safety. This study aimed to improve the nerve root protection in FE fs-TLIF and FE fr-TLIF by optimizing cage glider selection and insertion techniques based on the specific cage shape—banana-shaped or bullet-shaped. The goal was to ensure safe cage positioning and mitigate nerve root injury during discectomy, endplate preparation, and cage insertion. These strategies were validated through cadaveric simulations and clinical implementation. In FE fr-TLIF utilizing bullet-shaped (straight) cages, one-tip and two-tip cage gliders effectively protected the traversing nerve root by facilitating medial cage entry, thereby minimizing irritation of the exiting nerve root. Conversely, in FE fr-TLIF with banana-shaped cages, the lateral tilt of the cage holder during implantation required the use of a two-tip cage glider to protect the traversing and exiting nerve roots, thereby mitigating the potential risk of nerve irritation. In FE fs-TLIF, a one-tip cage glider is preferred for safeguarding the exiting nerve root, while the traversing root is inherently protected by the medial wall of the facet joint. The use of a two-tip cage glider in FE fs-TLIF can cause injury to the nerve root during glider insertion. In addition to the selection of cage gliders, improper cage insertion steps can also contribute to postoperative neurapraxia. The appropriate selection of cage gliders with corresponding insertion techniques is critical for nerve root protection in endoscopic TLIF. Tailoring these choices to the specific approach (FE fs-TLIF or FE fr-TLIF) and cage type (banana or bullet) enhances surgical safety and clinical outcomes.

Acquired resistance to the proteasome inhibitor bortezomib(BTZ)poses a significant chal-lenge in the treatment of multiple myeloma(MM).During the acquisition of BTZ resistance,metabolic reprogramming is actively engaged in MM cells.However,the key regulatory genes and molecular mecha-nisms mediating bortezomib resistance through this metabolic rewiring have not been fully elucidated.This study aims to investigate the regulatory role of pyrimidine metabolites in drug resistance of MM and their underlying molecular mechanisms.Screening via CCK-8 assays demonstrated that the pyrimidine metabolite uridine is associated with BTZ resistance in MM(P＜0.05).In vitro experiments,including CCK-8 assays,Western blotting,and flow cytometry,demonstrated that uridine partially suppresses bort-ezomib-induced apoptosis in MM cells(P＜0.05).In vivo,experiments utilizing Vk*MYC mouse mod-els,subcutaneous tumor models,and intramedullary bone marrow transplantation models showed that the combination of BTZ and uridine significantly accelerated tumor growth,exacerbated bone destruction,and increased tumor cell infiltration in tumor-bearing mice(P＜0.05).RNA sequencing analysis re-vealed that uridine primarily affects mitochondrial translation in MM at the transcriptional level.Seahorse energy metabolism assays demonstrated that uridine enhances mitochondrial oxidative phosphorylation without significantly altering glycolysis.Transcriptomic analysis further identified a significant upregula-tion of cytochrome c oxidase subunit 5B(COX5B)transcription in uridine-treated groups(P＜0.05).Functional studies confirmed that COX5B is a key molecule mediating uridine's effects on mitochondrial function in MM cells.In conclusion,uridine promotes BTZ resistance in MM by upregulating COX5B transcription and protein expression,thereby enhancing cytochrome c oxidase activity and regulating mito-chondrial oxidative phosphorylation.This study delineates the role of uridine in the development of borte-zomib resistance in MM and elucidates its COX5B-mediated metabolic reprogramming mechanism,provi-ding a theoretical foundation for developing targeted therapies against relapsed/refractory MM.

Fear of disease progression(FoP)is a common psychological state among patients with coronary heart dis-ease(CHD),which exists throughout the course of disease and seriously affects the prognosis.High level of FoP not only harms the mental health of patients but also do not benefit their rehabilitation after discharge.This concept was first proposed by foreign researchers studying the psychological state of cancer patients.In recent years,there have been numerous studies on the influencing factors and qualitative aspects of FoP in CHD patients,while related inter-vention studies remain few.This paper reviews the concept,scales and related influencing factors of FoP,providing ideas for medical staff to provide targeted interventions for CHD patients.

This study aims to investigate the mechanisms underlying the effects of the combined ac-tion of high-fat diet-induced obesity and the aflatoxin B1(AFB1)on hepatic oxidative stress and inflammatory responses.Thirty-six rats of similar weight and 4 weeks old were randomly divided into 4 groups,with 9 rats in each group:the blank control group(basal diet),the AFB1 group(0.4 mg/kg AFB1+basal diet),the HFD group(high-fat diet),and the HFD+AFB1 group(high-fat diet+0.4 mg/kg AFB1).Histological changes and lipid deposition were observed via hematox-ylin-eosin(HE)staining and Oil Red O staining.Levels of oxidative stress and inflammation-relat-ed factors were measured using commercial assay kits.The relative protein expression levels of factors involved in the Nrf2-Keap1 signaling pathway were assessed by Western blot analysis.The HE staining results showed that in the AFB1 group,the liver cells exhibited widespread watery de-generation,with shrunk and ruptured nuclei,inflammatory cells infiltration,and increased fibrosis.In the HFD group,liver cell fatty degeneration was observed,with cytoplasmic lipid droplet infil-tration.In the portal area,liver fibrosis was seen,with liver cell necrosis and inflammatory cell in-filtration in the fibrotic area,accompanied by lipofuscous granules.When HFD was applied to the AFB1 group,the abnormal state of liver interstitial and interstitial spaces was further aggravated,and a large number of lipid droplets appeared.The Oil Red O staining results showed that there were large numbers of dark red lipid droplets in the liver tissue of the HFD group,which were fused in strands.In the AFB1 group,lipid droplets could also be observed in the liver tissue of rats,but the number and degree were significantly less than those in the HFD group.The number and degree of red lipid droplets in the liver tissue of rats in the HFD+AFB1 group were higher than those in the AFB1 group and the HFD group.HFD exacerbated AFB1-induced oxidative stress by elevating ROS,MDA levels,and decreasing the expression of antioxidant stress factors such as CAT,SOD,Nrf2,HO-1,NQO1,and GCLC.Furthermore,the combined effect of HFD and AFB1 further significantly increased the levels of pro-inflammatory cytokines IL-2,IL-6,TNF-α,and IL-1β in the body.In summary,HFD treatment significantly exacerbated liver oxidative stress and in-flammatory responses in rats exposed to AFB1 through the Nrf2-keap1 signaling pathway.

Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.

To investigate the effect of capsaicin(CAP)on the replication of bovine viral diarrhea vi-rus(BVDV).Bovine nasal turbinate osteoblasts(BT)infected with BVDV served as the research model,and viral gene and protein levels were evaluated using RT-qPCR and Western blot.Moreo-ver,molecular docking,molecular dynamics simulation,and oil red O staining were applied to ana-lyze the mechanism by which CAP inhibits BVDV replication.The results revealed no significant effect of CAP at 6.25,12.5,25,and 50 mg/L on the viability of BT cells.CAP was found to signifi-cantly inhibit BVDV 5′UTR RNA and E2 protein levels,according to the antiviral effect study.Molecular docking and molecular dynamics simulations indicated that CAP could bind with high affinity to the active site of PI3K.Additional mechanistic studies indicated that CAP significantly reduced the activation of the PI3K/AKT signaling pathway triggered by BVDV.Furthermore,CAP notably decreased the mRNA levels of FASN,SREBP-1,and ACC-1,which are crucial fatty acid synthesis enzymes in the downstream PI3K/AKT signaling pathway,as well as the levels of lipid droplets.Interestingly,the addition of exogenous oleic acid greatly diminished the antiviral effec-tiveness of CAP and significantly lowered the mRNA levels of IFN-α and IFN-β.The results reveal for the first time that CAP can inhibit BVDV replication,establishing a foundation for its preven-tion and the development of feed additives.

Objective:To establish a high-performance liquid chromatography method for the determination of related substances in panamivir injection.Methods:The Waters Xbridge Peptide BEH C18(250 mm×4.6 mm,3.5 μm).Phosphate buffer-acetonitrile was used as mobile phase,gradient elution,flow rate 0.8 mL·min-1,column temperature 35℃,detection wavelength 210 nm.Results:Peramivir could be effectively separated from all known impurities,with a limit of quantification of 5.29-18.02 ng and a limit of detection of 1.59-5.41 ng,with a good linear relationship(r＞0.999 0)in the range of 200%of the limit of quantification to the limit concen-tration,and the average recovery rate of each impurity was 99.6%-106.8%(n=12).The results of three batches of peramivir injection samples showed that the known impurities and other largest single impurities were less than 0.2%,and the total impurities were less than 1.0%.Conclusion:Verified by analytical methodology,the method is convenient,fast,specific,sensitive,and accurate,and can be used for the determination of peramivir injection-related substances.

Objective:To explore the effect of multiple modified process management intervention on cardiac func-tion,psychological state,stress level,sleep quality and adverse events in patients with severe coronary atherosclerot-ic heart disease(CHD).Methods:This randomized controlled study enrolled 130 severe CHD patients who were treated in Affiliated Beijing Shijitan Hospital of Capital Medical University between January 2020 and May 2023.Patients were randomly divided into control group(n=65)and intervention group(n=65).Patients in the control group were treated with routine management intervention,while those in the intervention group were given addi-tional multiple modified process management interventions.Both groups were intervened for 4 weeks.Cardiac func-tion,levels of norepinephrine(NE)and cortisol(COR),scores of Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),General Comfort Questionnaire(GCQ),Pittsburgh Sleep Quality Index(PSQI),and the incidence of adverse events during intervention were compared between the two groups.Results:Compared to those in control group after intervention,patients in intervention group had significant higher left ventricular ejection fraction(LVEF)[(57.81±2.15)％vs.(50.11±2.99)％]and GCQ score[(95.88±5.37)points vs.(75.81±6.67)points](P＜0.001 all),and significant lower left ventricular end-diastolic volume(LVEDV)[(109.81±5.37)ml vs.(129.26±5.17)ml],left ventricular end-systolic volume(LVESV)[(50.85±3.08)ml vs.(66.02±3.77)ml],levels of NE[(61.56±5.49)pg/ml vs.(69.86±5.03)pg/ml],COR[(85.63±5.19)ng/ml vs.(92.28±6.57)ng/ml],scores of SAS[(30.06±5.19)points vs.(49.51±5.85)points],SDS[(31.86±4.51)points vs.(40.00±5.10)points]and PSQI[(8.72±1.58)points vs.(13.89±2.40)points],and incidence of ad-verse events(4.69％vs.23.44％)(P＜0.01 all).Conclusion:The multiple modified process management interven-tion may improve the cardiac function,adverse psychological state,stress level,sleep quality and reduce the inci-dence of adverse events in patients with severe CHD.