The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

A 70-year-old male patient was admitted to a hospital on March 1,2024 due to"muscle soreness in his extremities for over a month".Diagnosis consideration:polymyalgia rheumatica(with a high likelihood,the possi-bility of a tumor needs to be excluded).The patient was treated with methylprednisolone.After discharge from the hospital,the patient's symptoms worsened due to self-withdrawal of medication(methylprednisolone treatment for 20 days),and developed fever and cough.He then revisited the hospital and was confirmed to have Legionella mar-ssiliensis infection through metagenomic sequencing of bronchoalveolar lavage fluid(nucleic acid of all microorga-nisms were extracted from the specimens and compared in the PMDB database to obtain species information of the suspected pathogenic microorganisms).Subsequently,the patient was treated with a combination of 0.75 g levo-floxacin intravenous infusion qd+0.1 g doxycycline enteric-coated capsules orally bid for anti-infective therapy.The patient's symptoms,such as cough and muscle pain,improved significantly after anti-inflammatory and anti-in-fective treatment,and he was discharged on March 18.As the first reported case of Legionella marssiliensis pulmo-nary infection in China,this case highlights that among the multiple species of Legionella,there is another bacte-rium that can infect the human body and cause disease.This case report is beneficial for improving medical staff's understanding on Legionella marssiliensis and providing reference for the diagnosis and treatment of future cases of Legionella marssiliensis infection.

Objective To investigate the effects of miR-23c and its target gene OCT1 on the proliferation,migration and apoptosis of hepatocellular liver cancer.Methods The expression level of miR-23c in normal liver cell line LO2 and hepatocel-lular carcinoma cell lines(including Huh7,HepG2,Hep-3B,SK-HEP1,HCCLM3 and MHCC97H)was detected by real-time flu-orescence quantitative PCR(qRT-PCR).The miR-23c mimics were designed to measure the proliferation status,migration abili-ty and apoptosis level of cells in the hepatocellular carcinoma cell line Huh7 using CCK-8 assay,cell migration assay and flow cytometric analysis.The target relationship between miR-23c and OCT1 was verified by predictive site prediction and dual lucif-erase assay,and the effect of miR-23c overexpression on OCT1 level was analyzed by Western blotting.The effect of miR-23c targeting OCT1 on the proliferation,migration and apoptosis of hepatocellular carcinoma was investigated by rescue as-say.Results Compared with the normal liver cell line LO2,the expression of miR-23c was significantly downregulated in liver cancer cell lines.In comparison with the NC group,Huh7 cells transfected with miR-23c mimics showed reduced proliferation and migration,while apoptosis was significantly enhanced.The interaction between miR-23c and OCT1 was verified.OCT1 pro-tein expression in Huh7 cells was reduced after miR-23c overexpression.The proliferation and migration of Huh7 cells were in-hibited,and apoptosis was promoted after transfection of miR-23c mimics.These effects were reversed by overexpression of OCT1.Conclusion miR-23c can downregulate OCT1,thereby inhibiting proliferation and migration,and promoting apoptosis in hepatocellular liver cancer cells.

Objective Summarize and analyze the core issues in the process of the"three medics"linkage reform in China,and provide optimized paths and countermeasure suggestions for the coordinated development and governance of the"three medics".Methods The problem list of the"three medics"linkage reform in China was summarized through literature analysis and boundary analysis method.The problem system was constructed based on the macro model of the health system,and the prob-lem evaluation was conducted by using the social network analysis method and the entropy weight Topsis method.Results The problem list can be summarized into 4 major categories,with a total of 45 problem topics.Among them,there are 5 items in the external submodule category,18 items in the structure category,17 items in the process category,and 5 items in the result cate-gory.The total frequency proportions are 16.22％,27.15％,43.68％,and 12.95％ respectively.Among the process-related problem themes,"excessive medical treatment"has the highest attention,the entropy weight Topsis comprehensive evaluation value of"lagging information system construction"is the highest,and"insufficient cross-departmental collaboration"is closest to the centrality value and has the greatest correlation.Conclusion Guided by the framework of the theory of holistic governance,it is urgently necessary to construct an information system for the coordinated development of the"three medics",reshape the mechanisms of leadership decision-making,data linkage and information collaboration,and enhance the synergy among depart-ments.Taking the reform of medical service prices as the starting point,by improving the value-oriented medical insurance pay-ment mechanism,the compensation mechanism of public hospitals,the salary system,etc.,we promote the compatibility of in-centives among multiple subjects and form a closed loop of coordinated development of the"three medics"sectors.

Objectives To investigate the clinical efficacy on combined application of ear canal injected administration dispenser and triamcinolone acetonide econazole nitrate cream in the treatment of mycosis externa.Methods Clinical data of 130 patients(166 ears)diagnosed with mycosis externa from January 2023 to December 2023 were collected and randomly divided into two groups.In the observation group,65 cases(86 ears)were treated with ear canal injected administration dispenser combined with triamcinolone acetonide econazole nitrate cream,while in the control group,65 cases(80 ears)applied clean cotton swabs with triamcinolone acetonide econazole nitrate cream to the external auditory canal by themselves to treat mycosis externa.All the patients were treated for 4 weeks and followed up for half a year.The clinical efficacy,recurrence rate and adverse reactions were statistically analyzed and compared.Results The total effective rate of the observation group was 97.67%,which was significantly higher than that of the control group was 73.75%,there was a significant difference between the two groups(P<0.05).There were no obvious adverse reactions in either group.No obvious recurrence was observed in the recovered patients of both groups during the follow-up period.Conclusion The efficacy of combined of ear canal injected administration dispenser and triamcinolone acetonide econazole nitrate cream in the treatment of mycosis externa is significant.Compared with the traditional way of medicine application,the adverse reactions are less.It can improve the cure rate and reduce the recurrence rate,which is worthy in clinical application.

This study investigated the effects and underlying mechanisms of the luteolin-naringenin combination(LN)on liver injury induced by acetaminophen(APAP).Forty-eight Kunming mice were randomly allocated into six groups:a normal control group,an APAP-induced liver injury model group,a positive drug treatment group,and three LN treatment groups with low,medium,and high doses.After the final drug administration,the mice were fasted for 12 hours prior to eu-thanasia for sample collection.Serum transaminase activity,oxidative stress indices,and hematoxy-lin-eosin(HE)staining were assessed to evaluate the effects of LN on APAP-induced hepatic inju-ry.Additionally,Western blot analysis was conducted to examine the expression levels of sphingo-sine kinase 1(SPHK1)and endoplasmic reticulum stress(ERS)-related proteins,thereby elucida-ting the potential mechanisms by which LN mitigates APAP-induced liver injury.The results dem-onstrated that varying concentrations of LN effectively ameliorated serum aminotransferase activi-ty and oxidative stress levels induced by APAP in a dose-dependent manner.Histopathological ex-amination via HE staining revealed significant improvement in APAP-induced liver tissue injury following treatment with different concentrations of LN.Furthermore,Western blot analysis indi-cated that the protein expressions of SPHK1,CHOP,p-IRE1α,ATF6,p-PERK,p-eIF2α,and ATF4 were markedly reduced after administration of various concentrations of LN.The results demonstrate that LN exhibits a significant protective effect against APAP-induced liver injury by inhibiting the SPHK1-mediated aberrant expression of ERS-related molecules.This study high-lights the importance of targeting SPHK1 in the treatment of APAP liver injury and provides a no-vel therapeutic approach through the multi-target and multi-pathway combination of monomers.

Objective To investigate the awareness of female patients with pelvic floor dysfunction regarding minimally invasive laser treatment of the reproductive tract and analyze the factors influencing their decision-making intentions,this study aims to provide a foundation for early treatment of pelvic floor dysfunction and further development in reproductive health management.Methods A convenience sampling method was employed to select 164 female patients with pelvic floor dysfunction who sought treatment at the Pelvic Rehabilitation Center of Dongguan Maternal and Child Health Care Hospital between June 2023 and August 2024.The study utilized the Female Sexual Function Index,Incontinence Quality of Life Questionnaire,and Family Support Self-Assessment Scale to conduct a survey.Binary logistic stepwise regression analysis was conducted to investigate the factors influ-encing patients'inclination towards undergoing genital laser minimally invasive treatment.Results Among the 164 female patients,143(87.2%)expressed an intention to receive treatment,with 22.6%demonstrating a rela-tively clear understanding of genital laser minimally invasive treatment.Logistic regression analysis revealed that occupation significantly influenced treatment intention(P<0.05).Compared to healthcare professionals,individuals in the teaching profession(OR=10.81,95%CI:1.04～112.21),self-employed individuals(OR=20.34,95%CI:3.46～119.43),and those in other professions(OR=16.26,95%CI:4.05～65.29)were more inclined to express willingness for undergoing treatment.Furthermore,a lower score on the Incontinence Quality of Life scale was found to positively correlate with treatment intention(OR=0.96,95%CI:0.93～0.99).Conclusion Although patients express a high intention to undergo minimally invasive genital laser treatment,their overall awareness of the procedure remains insufficient.

Objective To investigate the drivers,stakeholders,core tasks,and differentiated development models of digital transformation in Chinese hospitals,develop a hospital digital transformation model,and propose advancement pathways.Methods Leveraging ROCCIPI theory,socio-technical systems theory,and social network theory,a multiple case study approach was employed to analyze four representative Chinese hospitals,examining the driving factors,social network relationship,and core tasks of digital transformation.Results Hospital digital transformation is a complex process driven by regulations,opportunities,and capabilities,requiring efficient collaboration among stakeholders focused on patient services,clinical operations,hospital management,and security.It identified three development models-ecology-oriented,regional integration,and grassroots enhancement—based on the distinct characteristics of the hospitals.A theoretical model for digital transformation in four Chinese hospitals was developed,along with proposed pathways and strategies.Conclusion It presents a digital transformation model and advancement pathways for hospitals through multiple case analyses,addressing the limited perspectives of existing research and providing a reference for practice.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.