Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

Yin-Yang theory is one of the core components of the foundational theory of traditional Chinese medicine (TCM), yet its classification as philosophical or scientific has long been controversial. To move beyond the longstanding either-philosophy-or-science debate surrounding Yin-Yang theory in TCM, this article, for the first time, proposes a three-level framework spanning macro, meso, and micro perspectives. At the macro level, Yin and Yang are a theoretical achievement of ancient Chinese natural philosophy, used to explain universal laws governing how the cosmos operates, which constitutes Yin-Yang theory in philosophy; at the meso level, Huangdi Neijing (《黄帝内经》, Inner Canon of Huangdi) translated Yin-Yang from a cosmological framework into medical discourse, making it a core methodological basis for clinical pattern differentiation and treatment, which constitutes Yin-Yang theory in medicine; at the micro level, Yin-Yang theory in TCM has increasingly converged with modern science, showing scientific features that are testable and reproducible, which constitutes Yin-Yang theory in science. The article further demonstrates that Yin-Yang theory in TCM differs markedly from Yin-Yang as a general philosophical doctrine in core application and practical orientation: in the course of its medical transformation, elements related to life phenomena were selectively incorporated, while, within a medical context, abstract propositions such as cosmological speculation were bracketed and rendered concrete, thereby achieving a practice-oriented transition from philosophy to medicine. Based on this, the present study conducts analyses from four aspects, namely philosophical roots, clinical application, modern scientific interpretation, and implications for life sciences; it substantiates the logical basis for Yin-Yang theory in TCM as the overarching framework for clinical pattern differentiation and treatment, reviews modern research progress from perspectives such as systems science and network regulation, and explores its potential value in advancing a new paradigm of state-based medicine. The study suggests that an accurate understanding of Yin-Yang theory in TCM requires moving beyond the either-philosophy-or-science binary and analyzing specific issues on a case-by-case basis. Across different perspectives, Yin-Yang theory in TCM has philosophical, medical, and scientific attributes. Only by grounding the theory in actual clinical efficacy and engaging with modern science can the innovative development of Yin-Yang theory in TCM be promoted, thereby providing valuable Eastern insights for building a life science system with original Chinese contributions.

Objective To investigate the clinical characteristics, diagnosis, treatment and prognosis of rare simultaneous ipsilateral renal multifocal tumors. Methods The clinical data of a patient with clear cell renal cell carcinoma(ccRCC)and primary renal leiomyosarcoma(LMS)with liver metastasis were retrospectively analyzed. Results The 70-year-old male patient was admitted due to space-occupying lesions of the right kidney detected by physical examination for 12 days. CT showed space-occupying lesions in the upper and middle parts of the right kidney, suggestive of renal cell carcinoma or renal angiosarcoma. He underwent radical nephrectomy. Postoperative pathology showed the tumor in the upper pole of the right kidney with morphology of ccRCC(solid acinar clear cells), but immunohistochemical(IHC)results showed CK(+), EMA(+), CD10(-), PAX-8(-)(rare phenotype); the tumor in the middle of the kidney showed LMS characteristics(spindle cells, active mitosis), Vim(+)and SMA(+). Four months after operation, abdominal CT scan revealed liver metastasis. The biopsy confirmed metastatic LMS, with IHC results showing Vim(+), CD10(+), RCC(+), CK8/18(-), CK7(-), SMA(+), and Caldesmon(+). Subsequently, a liver biopsy combined with microwave ablation of the tumor was performed. The patient was treated with tirelizumab and anlotinib, but the tumor still progressed. The patient died 11 months after operation. Conclusion Simultaneous ipsilateral ccRCC and LMS are extremely rare in clinic, and the prognosis is poor. At present, there is no standardized treatment plan. Surgery is the main treatment for simultaneous multifocal tumors. After surgery, the pathological characteristics of the two tumors should be considered to formulate a comprehensive drug treatment strategy targeting at different biological behaviors so as to provide reference for clinical practice.

Objective To investigate the role and related mechanisms of exosomes derived from mesenchymal stem cells (MSCs) in radiation-induced lung injury (RILI). Methods Human umbilical cord-derived MSCs were isolated and cultured for the extraction and identification of exosomes. Eighteen male SD rats were randomly divided into Control group, RILI group and RILI + exosomes group (EXO group), with 6 rats in each group. Except for Control group, the other groups received a single X-ray dose of 30 Gy to the right lung. Immediately after irradiation, the EXO group was administered 2 × 10⁹ exosomes/kg via tail vein injection. Control group and RILI group were given the same volume of normal saline. Eight weeks post-irradiation, the rats were sacrificed, lung tissue and peripheral venous blood were collected. HE and Masson staining were employed to observe the pathological and fibrotic changes of lung tissue. The levels of serum inflammatory factors IL-6, IFN-γ, TNF-α, and IL-10 were detected by ELISA. RT-qPCR was used to assess the mRNA levels of IL-1β, IL-6, Cdh1, and Col1a1 in lung tissue. The expression levels of Vimentin and TGF-β1 in lung tissue were measured by immunohistochemical staining. The expression levels of AMPK, p-AMPK, and TGF-β1 in lung tissue were detected by Western blot. Results MSC-derived exosomes were successfully extracted and identified. Compared with RILI group, EXO group showed significantly reduced pathological changes of lung inflammation and collagen deposition. The levels of serum inflammatory factors IL-6, INF-γ, and TNF-α were significantly decreased (P < 0.05), and the level of anti-inflammatory factor IL-10 was significantly increased (P < 0.05). The mRNA levels of IL-1β, IL-6, and Col1a1 in lung tissue were significantly decreased (P < 0.05 or P < 0.01), and the mRNA level of Cdh1 was significantly increased (P < 0.05 or P < 0.01). The levels of Vimentin and TGF-β1 in lung tissue were significantly reduced, while p-AMPK level was significantly up-regulated (P < 0.05). Conclusion Exosomes derived from MSCs may alleviate RILI by inhibiting inflammatory responses and regulating epithelial-mesenchymal transition mediated by AMPK/TGF-β1 signaling pathway.

Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

Objective To investigate the current situation and risk factors of"socialized hospitalization"in elderly stroke patients.Methods A total of 329 elderly stroke patients who were admitted to No.971 Hospital of PLA Navy from January 2022 to December 2022 were enrolled in this retrospective study.The patients without"socialized hospitalization"were assigned to the control group(n=258),and those with"socialized hospitalization"were assigned to observation group(n=71).The age,gender,admission route,department transfer during hospitalization,hospital-acquired infection,depressive symptoms,cognitive impairment,activity of daily living(ADL)level at discharge were compared between the two groups.Multivariate logistic regression analysis was used to analyze the risk factors of"socialized hospitalization"in elderly stroke patients.Results There were no significant differences in gender,age,route of admission,or department transfer during hospitalization between the two groups(P>0.05).The proportions of patients with hospital-acquired infections,cognitive impairment,depressive symptoms and ADL meeting discharge standards in the observation group were higher than those in the control group(P<0.05).Multivariate logistic regression analysis showed that hospital-acquired infections,depressive symptoms and severe ADL level at discharge were independent risk factors for"socialized hospitalization"in elderly stroke patients(P<0.05).Conclusion There is a high proportion of"socialized hospitalization"in elderly patients with stroke.The main risk factors are hospital-acquired infection,cognitive impairment,depressive symptoms and ADL level at discharge.Active and effective measures should be taken to deal with them.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

BACKGROUND:Exosomes have been confirmed to be closely related to cartilage degeneration in osteoarthritis.However,the role and mechanism of exosome-derived genes in cartilage degeneration of osteoarthritis have not been fully elucidated.OBJECTIVE:Bioinformatics analyses were used to screen the genes related to cartilage degeneration in the synovial exosomes of patients with osteoarthritis,and to determine their biological functions and signaling pathways in order to provide new therapeutic targets for delaying cartilage degeneration in osteoarthritis.METHODS:Firstly,osteoarthritis-related exosome dataset GSE185059 and cartilage degeneration dataset GSE114007 were downloaded from Gene Expression Omnibus(GEO)database to screen exosome-derived cartilage degeneration related genes.GO functional and KEGG pathway enrichment analyses were performed based on the screened exosome-derived cartilage degeneration related genes.Protein-protein interaction network was drawn and Ingenuity Pathway Analysis(IPA)was conducted to screen and obtain key exosome-derived cartilage degeneration-related genes.Finally,qRT-PCR was used to verify the expression of key genes in osteoarthritis cartilage tissue and interleukin-1β stimulated chondrocyte models.RESULTS AND CONCLUSION:(1)There were 831 differentially expressed genes in the GSE185059 dataset and 5 323 differentially expressed genes in the GSE114007 dataset.A total of 94 exosome-derived cartilage degeneration related genes were screened after the intersection of these differentially expressed genes,of which 51 genes were down-regulated and 43 genes were up-regulated.(2)GO functional enrichment analysis showed that the up-regulated genes were mainly involved in the positive regulation of cell-cell adhesion,the positive regulation of T cell activation,and chronic inflammatory response,while the down-regulated genes were mainly involved in biological processes such as cell aggregation,cartilage differentiation and development,and skeletal system morphogenesis.(3)KEGG pathway enrichment analysis showed that exosome-derived cartilage degeneration-related genes were mainly involved in tryptophan enrichment metabolism,vitamin B6 metabolism,and leukocyte transendothelial migration.(4)The constructed protein-protein interaction network confirmed the existence of multiple interaction relationships among exosome-derived cartilage degeneration-related genes.Combined with five algorithms in CytoHubba software,four key exosome-derived cartilage degeneration-related genes were further screened,namely THY1,CYP1A1,NFKB2,and COL6A3.(5)The results of qRT-PCR showed that compared with normal cartilage,the expressions of THY1 and COL6A3 in osteoarthritic cartilage were increased,while the expression of CYP1A1 and NFKB2 was decreased.Similarly,compared with the unstimulated group,the expression of THY1 and COL6A3 in the interleukin-1β induced chondrocytes was upregulated,while the expression of CYP1A1 and NFKB2 was downregulated.(6)These results indicate that THY1,CYP1A1,NFKB2,and COL6A3 are genes related to cartilage degeneration in the exosomes of synovial fluid of patients with osteoarthritis,and may participate in the pathogenesis of osteoarthritis by regulating biological processes such as protein tyrosine kinase activity and lipid metabolism,as well as nuclear factor-κB signaling pathway and focal adhesion signaling pathway.However,the specific regulatory roles and molecular mechanisms of these key genes in cartilage degeneration need to be further verified by experiments.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.