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.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

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.

Objective To evaluate the therapeutic effect of Shenfu injection in shock patients by using bedside critical ultrasound.Methods A total of 80 shock patients admitted to First Hospital of Nanchang from January 2022 to May 2024 were selected and divided into Shenfu group(45 cases)and control group(35 cases)according to whether Shenfu injection was applied.Patients in control group were given conventional western medical treatment,while patients in Shenfu group were treated with Shenfu injection in addition to control group.The ultrasound measurement indicators and clinical results were recorded on the 1st,3rd,and 7th days of treatment respectively,and left ventricular end diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),peak velocity of early diastolic flow of mitral valve(E)/peak velocity of early diastolic motion of mitral annulus(E'),tricuspid annular plane systolic excusion(TAPSE),right ventricular fractional area change(RVFAC),inferior vena cava variation rate(IVCV),heart rate(HR),mean arterial pressure(MAP),N-terminal pro-brain natriuretic peptide(NT-proBNP),lactic acid(Lac),sequential organ failure assessment(SOFA)score and 30-day survival status of two groups of patients was compared.Results After 1 day,3 days and 7 days of treatment,LVEDD and E/E'of two groups of patients gradually decreased,while LVEF,TAPSE,RVFAC and IVCV gradually increased significantly(P＜0.05).After 7 days of treatment,the LVEF,TAPSE,RVFAC and IVCV of patients in Shenfu group were significantly higher than those in control group(P＜0.05).After 7 days of treatment,the HR,NT-proBNP,Lac and SOFA scores of two groups of patients were significantly lower than those before treatment in same group,and the MAP was significantly higher than that before treatment in same group(P＜0.05).The HR,NT-proBNP,Lac and SOFA scores of patients in Shenfu group were significantly lower than those in control group,the MAP was significantly higher than that in control group,and the mechanical ventilation time and the length of stay in intensive care unit were significantly shorter than those in control group(P＜0.05).Kaplan-Meier survival analysis showed that 30-day survival rate of patients in Shenfu group was significantly higher than that in control group(82.22％vs.54.28％,P＜0.05).Conclusion Bedside critical ultrasound showed that Shenfu injection could effectively improve ventricular systolic and diastolic function in shock patients,providing a valuable real-time assessment tool for shock treatment.

Objective:To evaluate the efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator (short for "3M fixator") for Sanders types II and III calcaneal fractures.Methods:A retrospective case series study was conducted to analyze the clinical data of 26 patients (26 feet) with calcaneal fractures admitted to Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to June 2024, including 21 males and 5 females, aged 27-69 years [(46.5±2.5)years]. Among them, 10 patients had fractures in the left foot and 16 in the right. According to the Sanders classification, the fractures were classified as type II in 16 patients and type III in 10. All the patients were treated with the close reduction with reduction robot system combined with 3M fixator in a minimally invasive procedure. The surgical waiting time, operative duration, and fracture healing time were recorded. The length, width and height of the calcaneus, B?hler′s angle and Gissane′s angle were compared before operation and at 1, 3 months after operation. The visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score before operation and at 1, 3 months after operation and at the last follow-up were detected. The postoperative complications were recorded.Results:All the patients were followed up for 6-12 months [(9.7±1.1)months]. The surgical waiting time was 1-4 days [(2.0±0.8)days]. The operative duration was 36-66 minutes [(53.2±9.5)minutes]. All the fractures achieved primary union with a healing period of 3-4 months [(3.2±0.4)months]. At 1, 3 months after operation, the length of the calcaneus [(83.3±3.7)mm and (83.6±3.6)mm], width of the calcaneus [(44.3±5.8)mm and (44.3±5.7)mm], height of the calcaneus [(50.1±3.8)mm and (50.3±3.6)mm], B?hler′s angle [(29.8±2.9)° and (29.8±3.0)°], and Gissane angle [(121.1±6.7)° and (123.9±5.9)°] were significantly improved compared with those before operation [(79.3±4.5)mm, (53.6±4.1)mm, (46.2±3.7)mm, (18.9±3.8)°, (109.0±7.5)°, respectively] ( P<0.05), with no significant differences between those indicators at 1, 3 months after operation ( P>0.05). The VAS scores were (3.2±0.6)points, (1.9±0.5)points, and (1.6±0.3)points at 1, 3 months after operation and at the last follow-up, which were lower than (7.1±0.5)points preoperatively and decreased with the prolongation of follow-up time ( P<0.05). The AOFAS scores were (73.5±6.9)points, (90.1±4.3)points, and (92.0±3.6)points, which were higher than (32.0±4.6)points preoperatively and increased with the follow-up time ( P<0.05). One patient had lateral calcaneal pain after operation, and was alleviated after rehabilitation. No complications such as infection or nonunion were found after operation. Conclusion:The reduction robot system combined with 3M fixator for Sanders types II and III calcaneal fractures demonstrates significant clinical advantages, such as reduced surgical waiting time and operative duration, promoted fracture healing, early alleviated pain, enhanced ankle joint functional recovery, and decreased complication occurrence.