This paper outlines the development of artificial intelligence （AI） and its applications in traditional Chinese medicine （TCM） research， and elucidates the roles and advantages of large language models， knowledge graphs， and natural language processing in advancing syndrome identification， prescription generation， and mechanism exploration. Using spleen-stomach diseases as an example， it demonstrates the empowering effects of AI in classical literature mining， precise clinical syndrome differentiation， efficacy and safety prediction， and intelligent education， highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration， a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed， integrating blockchain-based smart contracts， federated learning， and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases， providing feasible pathways and a technical framework for building a high-quality， trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.

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.

Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.

Purpose To investigate the value of two-dimensional speckle tracking in evaluating right ventricular function in cardiac amyloidosis(CA).Materials and Methods A total of 25 patients with CA,30 patients with hypertrophic cardiomyopathy(HCM)and 30 healthy controls were retrospectively selected from July 2021 to October 2023 in Wuhan Asia Heart Hospital.The regional difference was represented by the formula apical ratio.The parameters of conventional echocardiography,two-dimensional strain and apical ratio of the three groups were analyzed and compared.Results Only segmental strain was different in right ventricular structure and function between CA group and HCM group,and the differences were statistically significant(all P<0.05).In the CA group,the strain gradient of the right ventricle from the apex of the heart to the base was the same as that of the left ventricle,that was,the"apex preservation"pattern,which was not seen in the HCM group and the control group.Comparison of the right ventricular free wall longitudinal strain-apical ratio,right ventricle four-chamber longitudinal strain-apical ratio,left ventride global longitudinal strain-apical ratio among the three groups,it was found that the levels of CA group were higher than HCM group and control group,and the differences were statistically significant(H=40.40,43.18,55.43,all P<0.05).The right ventricular free wall longitudinal strain-apical ratio had the highest CA recognition value,the area under the curve was 0.935,sensitivity was 96%and specificity was 83%.Conclusion Two-dimensional speckle tracking can accurately evaluate the right ventricular function impairment in CA patients and provide a new choice for clinical evaluation and identification of CA patients.

Prostate cancer(PCa)is one of the common malignant tumors of the genitourinary system in men.It is generally believed that the serum prostate-specific antigen(PSA)level exceeding 4.0 ng/mL has potential diagnostic value for PCa.However,there are many cases of PCa with low PSA levels in clinical practice,specifically between 0-4.0 ng/mL.These cases may be missed or even misdiagnosed due to low PSA levels,leading to delays in treatment and missing the optimal clinical window for diagnosis and treatment.This review provides a com-prehensive summary of the clinicopathological characteristics of PCa patients with PSA levels below 4.0 ng/mL,including their baseline and clinical features,histological characteristics,imaging features,neuroendocrine prostate cancer(NEPC)and prognostic factors,aiming to en-hance the understanding of this type of PCa.

Immune checkpoint inhibitors targeting PD-1/PD-L1 are gradually being applied in the treatment of advanced urinary system tumors. Immunohistochemical analysis of PD-L1 expression is the most popular method for screening suitable patients for immunotherapy and predicting therapeutic efficacy. The current application status of PD-L1 detection for urinary system tumors (mainly urothelial carcinoma), methods of the different antibody tests and the precautions, challenges and solutions in the interpretation of immunostaining were summarized in this review.

Objective:To understand the clinicopathological and molecular genetic characteristics of aggressive renal mucinous tubular and spindle cell carcinoma (MTSCC).Methods:The clinical features, histology, immunophenotype, molecular characteristics and prognosis of 4 cases of metastatic/recurrent renal MTSCC that were submitted to the Peking University Third Hospital (2 cases), Institute of Urology, Peking University (one case) and Zhejiang Provincial People′s Hospital (one case) from 2015 to 2020 were retrospectively reviewed and analyzed.Results:Among the four patients, two were male and two were female. The average age was 58 years, ranging from 28 to 77 years. Three patients underwent radical nephrectomy, while one underwent partial nephrectomy. The tumor size was 2-8 cm (mean, 5.6 cm). There were two cases classified as pT3a, one case as pT1b and one case as pT1a. Histologically, the tumors were mainly composed of tubules and spindle cell cords. For nuclear grade, three cases were G3 and one case was G2. Extracellular mucus was present in all four cases. Sarcomatoid features and tumor necrosis were observed in one and three cases, respectively. Immunohistochemistry showed that PAX8 (4/4), AMACR (4/4), CK7 (4/4), CKpan (3/3), vimentin (3/3) and CK8/18 (2/2) were positive in the tumor cells, but CAⅨ (1/4) or CD10 (2/3) were focally positive or negative. Fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and l7 (2/2). Targeted next generation sequencing were performed in all four cases and showed that 3 cases had mutations in Hippo pathway involving MET (2/4), NF2 (1/4) and NTRK1 (1/4) genes. The other potentially pathogenic mutations involved KDM6A, SETD2 and PALB2. The follow-up period was 13 to 99 months. The time between diagnosis and metastasis/recurrence ranged from 6 to 58 months. Two patients died after lung metastasis occurred, one had multi-organ and multi-site lymph node metastases, and one achieved disease-free survival after resection of metastatic/recurrent foci.Conclusions:Renal MTSCC is a rare and distinct entity. The presence of high nuclear grade and pathological stage, high-grade morphology, lymphovascular invasion, and tumor necrosis suggests potential aggressive behaviors. It is thus recommended to report these histological features and conduct active follow-up and surveillance after surgery. The frequent mutations in MET, NF2 and NTRK1 suggest that dysregulation of Hippo pathway may be related to the development and progression of renal MTSCC.

ObjectiveTo analyze the development trajectory， research hotspots， and trends in medical humanities research in China since the new era. MethodsA search was conducted on the CNKI （China National Knowledge Infrastructure） advanced search page using the themes“medical humanities”or “humanistic medicine，”retrieving a total of 5，758 articles. After applying specific screening criteria， 5，095 articles were included in the analysis. Citespace6.1.R6 was used to visualize and analyze the authors， institutions， and keywords of the 5，095 articles. ResultsSince the new era， the volume of publications on medical humanities in China has shown an overall upward trend， with limited collaboration between core institutions and core authors. The research content of medical humanities has evolved from broad to specific， from abstract to concrete， and from theoretical to practical. ConclusionThe development of medical humanities research in China has generally gone through three stages： defining related concepts， integrating medical humanistic spirit into clinical practice， and applying empirical methods. Narrative medicine， ideological and political education in curricula， and medical humanities education are potential future research directions.

BACKGROUND:Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair.However,the mechanism of action and effects of this compound in osteoblasts need to be further explored. OBJECTIVE:To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway. METHODS:Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours,and the optimal intervention concentrations were screened.Osteoblasts were treated with dexamethasone,pinoresinol diglucoside and inhibitor XAV-939.Then,control group,dexamethasone group,XVA-939 group,pinoresinol diglucoside group,pinoresinol diglucoside+XVA-939 group were set up.Cell counting kit-8 assay was used to detect cell activity.Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected.Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation.Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen,respectively. RESULTS AND CONCLUSION:After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours,10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition,and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L.Compared with the dexamethasone group,alkaline phosphatase activity was significantly enhanced(P<0.05)and caspase3/7 enzyme activity was significantly reduced(P<0.05)in the pinoresinol diglucoside group.Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention.The mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups(P<0.05).To conclude,pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention,protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway,which may play a role in delaying steroid-induced osteonecrosis of the femoral head.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.