Objective To explore the effects of Peiyuan Yishen Antai Decoction on cell senescence and decidualization of aged mice with recurrent spontaneous abortion(RSA)based on P53/P21 signaling pathway;To discuss its mechanism in the treatment of RSA.Methods 8-9 month old CBA/J female mice were randomly divided into aging model group(normal saline 0.3 mL/d),Chinese materia medica group(18.72 g/kg)and dydrogesterone group(2.6 mg/kg).6-8 week old CBA/J female mice were assigned to a reproductive age blank group(normal saline 0.3 mL/d),with five mice in each group.After administering the corresponding solutions by gavage for 2 weeks,the reproductive age blank group mice were housed in cages with BALB/c male mice,while the remaining groups were housed in cages with DBA/2 male mice.After confirming the presence of vaginal plug,gavage was continued until the 9th day of pregnancy for sampling.Mice embryo loss rate was observed,HE staining was used to observe the morphology of uterine decidua,immunohistochemistry was used to detect the localization and expression of aging related protein Pi6INK4a in decidua tissue,RT-PCR and Western blot were used to detect the mRNA and protein expressions of P53,P21,insulin-like growth factor binding protein 1(IGFBP-1)and prolactin(PRL)in decidual tissue.Results Compared with the reproductive age blank group,the embryo loss rate of the aging model group significantly increased(P＜0.05),the irregular endometrial cells were vacuolated,the number of glands and blood vessels was reduced,the expression of P16INK4a in decidual tissue significantly increased(P＜0.05),and the expressions of P53,P21 mRNA and protein significantly increased(P＜0.05),the mRNA and protein expressions of IGFBP-1 and PRL significantly decreased(P＜0.05).Compared with the aging model group,the Chinese materia medica group and the dydrogesterone group showed an decreasing trend in embryo loss rate in mice,the arrangement of cells in the decidua tissue was relatively neat,and the number of blood vessels and glands increased,the expression of P16INK4a in decidua tissue was significantly decreased(P＜0.05),the mRNA and protein expressions of P53 and P21 were significantly decreased(P＜0.05),while the mRNA and protein expressions of IGFBP-1 and PRL significantly increased(P＜0.05).Conclusion Peiyuan Yishen Antai Decoction can improve the aging status of endometrial stromal cells in aged RSA model mice by regulating the P53/P21 signaling pathway,promote decidualization process,and thus exert a protective effect on pregnancy.

Objective To investigate the research competency among undergraduate interns of rehabilitation therapy.Methods In July,2024,a total of 81 undergraduate rehabilitation therapy interns from Department of Rehabilitation Medicine,Guangdong Provincial People's Hospital were self-rated the research competency,using research com-petency and activities,level 1 of World Health Organization rehabilitation competency framework.Semi-struc-tured interviews were conducted to investigate the willingness and difficulties to participate in research.Results The self-rated competencies were the lowest in behavior of C2.3 Assists in assessing rehabilitation service user needs and priorities for research,and Activity of A2 Disseminating evidence.For interviews,72 students would participate in researches,primarily motivated by career advancement and postgraduate admission competition.The main difficulties included insufficient faculty mentorship(n=48),limitation in knowledge(n=43)and diffi-culties in formulating scientific questions(n=43).Conclusion Most rehabilitation therapy undergraduates would like to participate in researches,but are suboptimal in re-search competency due to personal and environmental constraints.

In recent years,patient-derived tumor organoid(PDTO)models have rapidly emerged as important tools in cancer research,thanks to their unique ability to preserve the characteristics of primary tumors.These models provide a reliable preclinical research platform for screening individualized chemotherapy and targeted therapies for patients.However,traditional PDTOs lack immune cells and cannot replicate the tumor immune microenvironment,which restricts their utility in evaluating immunotherapies.To address this challenge,researchers have developed composite models that incorporate both tumor cells and immune cells,known as patient-derived immunocompetent tumor organoids(PDITOs).PDITOs have shown excellent performance in the preclinical evaluation of immunotherapies,particularly with PD-1/PD-L1 immune checkpoint inhibitors,with some studies reporting up to 100％accuracy in predicting patient responses to immunotherapy.As a common malignancy of the urinary system,bladder cancer has benefited from the application of PDITOs in drug screening and personalized immunotherapy evaluation,demonstrating significant potential.This paper aims to review the rise and development of PDITOs,and compare the advantages and limitations of using different methods to construct PDITOs,so as to explore their application in the treatment of bladder cancer.

Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

Background: Influenza A viruses (IAVs) are the major pathogens associated with respiratory infections which can result in extensive pathological damage in lungs and serious complications. Isorhamnetin, an abundant natural flavonoid in fruits and medicinal plants, has recently been shown to have strong antioxidative, anti-inflammatory, and antiviral effects. Objective: This study investigated the pharmacological effects of isorhamnetin on viral pneumonia and explored the underlying mechanisms by in vivo and in vitro experiments. Materials and methods: In the present study, the protective effect of isorhamnetin against IAV was evaluated by the cytopathogenic effect assay, cell counting kit-8 assay, real-time polymerase chain reaction, and immunofluorescence assay in vitro. Then the pathological damage associated with pneumonia was examined by calculating the pulmonary index and performing micro-CT and hematoxylin-eosin staining in vivo. Thereafter, the related protein or gene levels of factors in the mitogen-activated protein kinase (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were determined by Western blot and immunofluorescence staining. Results: Isorhamnetin exerted significant anti-influenza effects and inhibited the expression of viral RNA in A549 cells, counteracting oxidative stress and apoptosis by suppressing the production of reactive oxygen species and caspase-3. The in vivo experiment results showed that isorhamnetin (20 and 40 mg/kg) caused a significant decrease in the pulmonary index, ameliorated pathological damage in the lung tissue, decreased viral load and NA activity, and reduced cytokines and nuclear factors. Furthermore, isorhamnetin could counteract the B cell lymphoma-2/B cell lymphoma-2–associated X protein (Bax) imbalance induced by PR8, suppress activation of the MAPK pathway, and upregulate the expression of Nrf2 and HO-1. Conclusions: Isorhamnetin can protect against viral pneumonia by activating the Nrf2/HO-1 pathway and suppressing the MAPK path-way. This study deciphers the pharmacological mechanism of isorhamnetin in alleviating pathological damage in viral pneumonia and provides rationale for the application of isorhamnetin in influenza treatment.

Objective: This study aims to investigate the therapeutic effects and underlying mechanisms of Xuanfei Baidu Decoction (XFBD) in a mouse model of dampness-heat toxin pneumonia. By exploring how XFBD exerts its effects, we seek to deepen our understanding of its role in treating pulmonary diseases and to address the current knowledge gap regarding its mechanisms of action, thereby supporting its clinical application. Methods: Ultra-high-performance liquid chromatography and high-resolution mass spectrometry (HRMS) were employed to analyze the chemical constituents of XFBD. The protective effects of XFBD were evaluated using a dampness-heat toxin-induced mouse model, established through dampness-heat exposure and HCoV-229E infection. XFBD was administered orally, followed by assessments including lung index measurement, micro-CT imaging, viral load quantification, cytokine analysis, and histological evaluation via hematoxylin-eosin staining. Proteomics and single-cell transcriptomic analyses were conducted to explore the potential mechanisms underlying XFBD’s pharmacological effects. A cellular model of HCoV-229E infection was developed to investigate changes in the cAMP/PKA signaling pathway. Molecular docking and surface plasmon resonance (SPR) experiments confirmed the strong binding affinity between key XFBD components and PKA. Finally, PKA activators and inhibitors were applied in vitro to validate these mechanistic findings. Results: In vivo studies demonstrated that XFBD significantly reduced the lung index, improved the structural integrity of lung and tongue tissues, and decreased levels of proinflammatory mediators, including IL-6, IL-8, and TNF-α. Proteomic and single-cell transcriptomic analyses showed that the differentially expressed proteins after XFBD treatment were primarily associated with inflammatory responses and immune regulation. The cAMP/PKA signaling pathway was identified as a key mechanism underlying these therapeutic effects. Notably, Western blot, ELISA, molecular docking, and SPR analyses confirmed that XFBD elevated cAMP levels and p-PKA expression, thereby activating the cAMP/PKA signaling pathway in vitro. Conclusion: This study demonstrated that XFBD significantly alleviates symptoms in mice with dampness-heat toxin pneumonia. Its therapeutic effects are mediated, at least in part, through activation of the cAMP/PKA signaling pathway. These findings provide compelling evidence that XFBD is an effective herbal remedy against HCoV-229E infection.

Background: The global rise in visual impairment, driven by population aging, the increasing prevalence of lifestyle-related chronic diseases, and environmental factors, has made it a critical public health concern, highlighting the urgent need for effective preventive strategies and eye health maintenance. Cuscutae Semen (CS), a traditional Chinese herbal medicine long regarded for its vision-enhancing properties, has been widely used to support ocular health. However, its underlying molecular mechanisms and bioactive constituents remain poorly understood, limiting its modernization and broader clinical application. Objective: This study aims to investigate the restorative effects of CS on visual impairment, elucidate its underlying mechanisms, and identify potential active components. Methods: A zebrafish model of visual impairment was established using mepanipyrim to simulate retinal structural damage and visual dysfunction. The therapeutic effects of CS were systematically evaluated through behavioral analyses and histomorphological observations. To elucidate the underlying mechanisms, an integrated approach was employed, combining transcriptome sequencing (RNA-seq), reverse transcription quantitative polymerase chain reaction validation, and immunofluorescence staining to identify critical genes and pathways involved. Furthermore, macroporous resin column chromatography was employed for the fractionation and screening of potential active components. Results: CS treatment significantly alleviated mepanipyrim-induced ocular abnormalities in zebrafish, restoring approximately 82% of the observed morphological defects. Behavioral assessments revealed that CS-treated zebrafish exhibited markedly increased swimming speed and distance, indicating enhanced visual light sensitivity. Histopathological analysis demonstrated that CS effectively repaired the structure of retinal cell layers. RNA-seq revealed that CS broadly reversed mepanipyrim-induced gene expression disturbances, suggesting a restorative effect on transcriptomic homeostasis. Gene Ontology enrichment analysis identified the phototransduction pathway as a key mediator of CS’s therapeutic effects. This was further supported by reverse transcription quantitative polymerase chain reaction validation of critical genes and immunofluorescence staining, which confirmed the restored expression of Pde6a and Gnat2, key proteins involved in photic signal transmission. Active component screening indicated that high-polar constituents, including chlorogenic acid, may constitute one of the major bioactive fractions responsible for the observed therapeutic effects. Conclusion: This study provides evidence of the vision-protective effects of CS in a zebrafish model, demonstrating that its therapeutic mechanism involves modulation of the phototransduction pathway. Chlorogenic acid was identified as one of the key bioactive constituents contributing to this effect. These findings not only provide scientific validation for the traditional use of CS in ocular protection but also present promising therapeutic prospects for the prevention and treatment of visual impairment.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

En bloc resection of bladder tumor(ERBT),as an innovative procedure for conventional transurethral resection of bladder tumor(cTURBT),has become an important treatment option for non-muscle invasive bladder cancer(NMIBC).Although ERBT has been recommended by international guidelines,its technical standardization,verification of long-term survival benefits and stratification of indications are still the focus of future research.This article first provides an overview of the surgical techniques of ERBT,and then elaborates on the advantages and disadvantages of the three energy sources of ERBT,namely,electrocautery,laser,and Hybridknife.In terms of pathological assessment,current research suggests that the detection of detrusor muscle in surgical specimens can reflect the quality of the surgery.The integrity of pathological specimens and diagnostic consistency have promoted the progress of sub-staging of T1 bladder cancer and have also driven more research on microscopic indicators related to prognosis.Finally,this article reviews whether repeated transurethral resection can be avoided to help optimize individualized treatment for bladder tumor.