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.

ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

Atherosclerotic plaques arise within the vessels， yet their morphological evolution parallels that of carbuncles and abscesses. Drawing on the pathomechanism progression of carbuncles and abscesses， this paper proposes a dynamic pathogenesis model of "constraint-putrefaction-ulceration" for atherosclerotic plaques. The formation of atherosclerotic plaque begins with phlegm-turbidity obstruction and qi-blood stagnation （constraint stage）； prolonged constraint transforms into heat that scorches the vessels and forms plaques （putrefaction stage）； ultimately， toxin invades inward and ruptures the vessels， injuring the heart （ulceration stage）. Accordingly， staged differentiation and treatments are proposed. During the constraint stage， the focus is venting constraint and unblocking collaterals， clearing and relieving constraint-heat， for which Yue Jyu Pills （越鞠丸） and Danzhi Xiaoyao Powder （丹栀逍遥散） with modifications can be used. During the putrefaction stage， the method is clearing heat and dispelling abscesses， resolving stasis and dissipating knot， with modified Wuwei Xiaodu Beverage （五味消毒饮） and Xuefu Zhuyu Decoction （血府逐瘀汤）. During the ulceration stage， it is suggested to expell toxin and stasis， benefit qi and nourish yin using modified Gualou Xiebai Banxia Decoction （瓜蒌薤白半夏汤） and Sheng Mai Powder （生脉散）. This framework offers new perspectives for the differentiation and treatment of atherosclerotic plaques in traditional Chinese medicine.

Cough variant asthma is a distinct subtype of asthma characterized by chronic irritant dry cough as the sole or predominant clinical manifestation. It is one of the primary causes of chronic cough in children. In traditional Chinese medicine, it belongs to the category of " spasmodic cough", " wind-induced cough", " chronic cough", and " asthmatic cough". At present, Western medicine treatment approaches mainly focus on symptomatic treatment, but fail to fully deal with its complex systemic mechanisms, and have limitations such as poor control of clinical symptoms and rebound exacerbation upon treatment cessation. Based on the theory of " systemic qi stagnation", this paper proposes that the core pathogenesis of cough variant asthma in children is qi stagnation, intermingling of phlegm and blood stasis, and obstruction of collaterals. Disease progression is fundamentally driven by exogenous pathogen activation of endogenous predispositions, particularly dysregulation of sanjiao qi movement, which serves as the primary disease-inducing factor. During the acute phase, the treatment principle focuses on dispelling wind and ventilating lung to restore physiological qi. As the disease progresses to the progressive phase, the focus shifts toward smoothing liver and purging lung to resolve qi counterflow. In the chronic phase, therapeutic strategy prioritizes dissipating phlegm and eliminating blood stasis to smooth collaterals. Finally, during the remission phase, treatment emphasizes strengthening spleen and kidney to consolidate the foundation and cultivate the vitality. This integrative approach synergizes the external elimination of latent pathogens, internal harmonization of qi movement, and dredging collaterals by dispelling blood stasis. It also incorporates the theory of " gentle dispersion to expel pathogens and moistening dryness to harmonize collaterals", aiming to provide a theoretical basis and effective prescriptions for the integrated traditional Chinese and Western medicine treatment of cough variant asthma in children.

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

Objective To analyze the possible mechanism and drug treatment plan of diffuse alveolar hemorrhage induced by human granulocyte colony-stimulating factor injection, point out medication risks and provide reference for medical treatment and pharmaceutical care of such patients. Methods The abnormal lung conditions of a patient treated with human granulocyte colony-stimulating factor injection was found by clinical pharmacists, who participated in clinical diagnosis and treatment by analyzing of adverse drug reactions, optimization of medical treatment and pharmaceutical care. Results Diffuse alveolar hemorrhage was likely an adverse drug reaction caused by human granulocyte colony-stimulating factor injection. The physician discontinued the medication immediately and provided treatment such as oxygen inhalation, high-dose hormone shock, plasma exchange, etc. The patient’s oxygen saturation was improved, alveolar bleeding was decreased, and the condition was improved. Conclusion Clinical pharmacists participate in patients’ medication treatment, carry out pharmaceutical guardianship, and assist physicians in adjusting treatment plans, which could contribute to the effectiveness and safety of patient treatment.

Objective:To prepare a polyvinyl butyral(PVB)nanofiber membrane loaded with propolis,and to clarify its physicochemical properties,drug release behavior,antibacterial activity,and biocompatibility.Methods:Propolis with a mass fraction of 0.12％was dissolved in 18％(mass fraction)PVB methanol solution.PVB and PVB-propolis(PVB-P)nanofiber membranes were prepared using electrospinning from PVB and PVB-P solutions,respectively.Scanning electron microscope(SEM)was used to observe the microscopic morphology of PVB-P nanofibers,and the Nano Measurer software was used to analyze the fiber diameter distribution.Fourier transform infrared spectroscopy(FTIR)was used to analyze the chemical composition of PVB-P.Water contact angle measurements were used to evaluate the hydrophilicity of PVB-P.UV spectrophotometer was used to detect the cumulative release of propolis at different time points.PVB and PVB-P nanofiber membranes were co-cultured with Staphylococcus aureus(S.aureus),Escherichia coli(E.coli),Candida albicans(C.albicans),Salmonella,and Pseudomonas aeruginosa(P.aeruginosa)and divided into PVB group and PVB-P group.The absorbance method was used to calculate the antibacterial values of PVB and PVB-P against the five types of bacteria.The NIH-3T3 cells were seeded on PVB and PVB-P nanofiber membranes and divided into PVB group and PVB-P group.The CCK-8 method was used to detect the survival rates of NIH-3T3 cells on the nanofiber membranes in PVB group and PVB-P group at 1,3,and 7 d.Results:The SEM results showed that PVB and PVB-P nanofibers were interconnected in a mesh-like porous structure,with uniform thickness and no beads.The Nano Measurer software measurement results showed that the diameter of PVB nanofibers was(0.50±0.10)μm,and the diameter of PVB-P nanofibers was(0.54±0.16)μm.FTIR analysis showed that PVB-P nanofiber membranes exhibited characteristic peaks of PVB(1 140 and 1 002 cm-1)and propolis(1 161 cm-1).The water contact angle measurement results showed that the contact angle of PVB membrane was(144.26°±2.90°)and that of PVB-P membrane was(128.13°±1.36°).The UV spectrophotometer results showed that the cumulative release of propolis was 0.04 mg at 1d,0.07 mg at 3 d,and reached a steady state of 0.79 mg at 7 d.The absorbance method results showed that the antibacterial values of PVB-P nanofiber membranes against S.aureus,E.coli,C.albicans,Salmonella,and P.aeruginosa were 4.39,1.27,5.68,3.16,and 1.87,respectively.The CCK-8 method results showed that the survival rates of NIH-3T3 cells on PVB and PVB-P nanofiber membranes was＞90％at 1,3,and 7 d,and there were no significant differences between various groups(P＞0.05).Conclusion:The diameter of PVB nanofiber membranes loaded with propolis is increased,and these membranes exhibit antibacterial effects against S.aureus and C.albicans,while also achieving sustained release of propolis.

Objective:To explore the effect, postoperative mucosal pathological changes and molecular biological changes of reboot operation for type 2 inflammation chronic rhinosinusitis with nasal polyps（CRSwNP） patients, and to provide theoretical basis for the clinical application of this kind of operation. Methods:We collected 29 patients who were diagnosed with CRSwNP with type 2 inflammatino response and underwent Reboot surgery from June 2022 to August 2023, and 27 patients who were diagnosed with deviated septum and underwent simple submucosal resection of the septum as the control group. We conducted nasal symptom scoring, endoscopic sinusitis scoring, and CT scanning of the sinuses before and after surgery, as well as HE staining, immunohistochemical staining, and detection of inflammatory factors using Elisa kits at the time of surgery, 1, 3, and 6 months postoperatively. We also observed the ultrastructural changes using transmission electron microscopy and scanning electron microscopy, and performed proteomic analysis of the mucosa in the ethmoid sinus area of the sinusitis patients at the time of surgery and 6 months postoperatively. Results:After 6 months of postoperative follow-up, CT scores of the nasal cavity and sinuses had gradually decreased compared with the preoperative period. The VAS score of main symptoms, SNOT-22 score and Lund-Kennedy endoscopic score were decreased after 12 months follow-up. The histological morphology of the mucosa in the area of the screen was significantly improved compared with the preoperative period, with a reduction in the number of eosinophils. The levels of inflammatory factors such as IL-4 and IL-5 et al. in the mucosa of the area of the screen were gradually reduced compared with the preoperative period. The histological morphology, ultrastructure, and cilia structure of the mucosa in the area of the screen were gradually improved compared with the preoperative period, though not recovered completely. The number of CD4⁺T and CD8⁺T cells not changed significantly before and after the surgery yet. By conducting proteomic analysis of the ethmoidal sinus mucosa before and after surgery, differential proteins were selected, and bioinformatics analysis was conducted on the differentially expressed proteins. By using cytoHubba to identify hub genes and intersecting them with the genes related to chronic sinusitis, we found that MMP9 expression increased in non-type 2 CRS and type 2 CRS in sequence, while ACTC1 expression decreased in non-tpye 2 CRS and type 2 CRS in sequence. Conclusion:Reboot surgery can improve the postoperative symptoms and signs of patients, improve the pathological morphology of the mucosa, and influence the expression of protein after surgery. However, the surgery may not have a significant impact on the distribution of T cell subpopulations and inflammation signal pathway in the nasal mucosa.
Humans ; Sinusitis/metabolism* ; Nasal Polyps/metabolism* ; Nasal Mucosa/ultrastructure* ; Chronic Disease ; Rhinitis/complications* ; Inflammation ; Male ; Female ; Postoperative Period ; Adult ; Interleukin-5/metabolism* ; Interleukin-4/metabolism* ; Middle Aged ; Proteomics ; Rhinosinusitis

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.