ObjectiveTo study the therapeutic mechanism of Xihuang Wan for hyperplasia of mammary glands based on network pharmacology， molecular docking， and cell experiments. MethodsThe active ingredients and targets of Xihuang Wan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and A Bioinformatics Annotation daTabase for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and supplemented by searching against PubChem and Swiss Target Prediction. The targets of differential metabolites in tissues and urine were obtained from previous metabolomics studies through PubChem and Swiss Target Prediction. GeneCards， Online Mendelian Inheritance in Man （OMIM）， PharmGKB， Therapeutic Target Database （TTD）， Drunbank were searched for the targets of hyperplasia of mammary glands. After the common targets were obtained via Veeny2.1.0， the STRING database was used to analyze the protein-protein interactions， and Cytoscape was used for the core target analysis and visualization. Gene Ontology （GO） and the Kyoto Encyclopedia of Genes and Genomes （KEGG） were employed for enrichment analysis. Molecular docking was carried out in Autodock， and cell experiments were conducted to verify the prediction results. In the cell experiments， estradiol and progesterone （E₂+P） were used to intervene in human mammary epithelial/MCF-10A cells， and thus the MCF-10A cell proliferation model was established. The cells were then treated with Xihuang Wan-medicated serum. The cell counting kit-8 （CCK-8） was used to measure the cell proliferation， and flow cytometry was used to detect apoptosis. The mRNA and protein levels of key factors in MCF-10A cells were determined by real-time PCR and Western blot， respectively. ResultsThe results of network pharmacology showed that 90 active ingredients and 316 common targets were obtained， from which 20 core targets and 38 corresponding active ingredients were screened out. The results of GO and KEGG enrichment analyses showed that Xihuang Wan exerted effect against hyperplasia of mammary glands by regulating a variety of biological processes， which may be related to protein kinase B （Akt）-related molecular functions， estrogen signaling pathway， prolactin signaling pathway and other biological processes. The results of molecular docking showed that estrogen receptor 1 （ESR1）， serine/threonine kinase 1 （Akt1）， non-receptor tyrosine kinase （SRC）， and signal transducer and activator of transcription 3 （STAT3） all had strong binding activity with the nine active ingredients， suggesting that Xihuang Wan exert the effect through the ESR1/SRC/phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway and the Janus kinase （JAK）/STAT3 signaling pathway. The results of cell experiments showed that E₂+P intervention in MCF-10A cells promoted the proliferation of MCF-10A cells （P<0.05）， while the Xihuang Wan-medicated serum inhibited the proliferation of MCF-10A cells exposed to E₂+P （P<0.05）. Flow cytometry showed that the Xihuang Wan-medicated serum promoted the apoptosis of MCF-10A cells exposed to E₂+P （P<0.01）. The results of Real-time PCR showed that the Xihuang Wan-medicated serum down-regulated the mRNA levels of PI3K， Akt， JAK2， and STAT3 in MCF-10A cells treated with E₂+P （P<0.01）. The results of Western blot showed that the Xihuang Wan-medicated serum inhibited the expression of p-PI3K/PI3K， p-Akt/Akt， p-JAK2/JAK2， and p-STAT3/STAT3 in MCF-10A cells treated with E₂+P （P<0.05）. ConclusionXihuang Wan may exert the effect against hyperplasia of mammary glands by inhibiting the proliferation and promoting the apoptosis of MCF-10A cells， which may related to the inhibition of the activation of PI3K/Akt and JAK2/STAT3 signaling pathways.

Objective: To explore whether the long-term and frequent use of citrate anticoagulants negatively affects the bone metabolism balance of female frequent plateletpheresis donors, so as to better protect their health. Methods: A total of 65 female plateletpheresis donors and 55 female whole-blood donors from Guangzhou Blood Center (May to December 2024) were enrolled as experimental and control groups respectively, stratified into age subgroups (18-39 years and 40-60 years). Serum levels of 25-hydroxyvitamin D [25(OH)D], procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and type I collagen carboxy-terminal telopeptide (CTX) were measured. Differences in bone metabolism markers between experimental and control groups across age subgroups were compared. ANOVA was used to analyze dose-response relationships between donation age, annual apheresis donation frequency, and biochemical indicators. Results: In the 40-60 age subgroup, 25(OH)D levels were significantly lower in the experimental group (P<0.05), exhibiting a linear increase with age and a linear decrease with annual donation frequency. No significant differences in CTX or PINP levels were observed between experimental and control groups in either age subgroup. Conclusion: High-frequency plateletpheresis donation does not disrupt bone metabolic balance in female donors. However, it is associated with reduced vitamin D levels in female donors aged >40 years, potentially increasing the risk of osteoporosis. Vitamin D supplementation is recommended for high-frequency female plateletpheresis donors in this age group.

Pan vascular disease （PVD） is a systemic vascular disorder that has become the leading cause of death among the Chinese residents， and there is currently a lack of effective systemic treatment options. Clinical practice has found that the traditional Chinese medicine （TCM） method of kidney tonification can effectively intervene in PVD and target key pathological mechanisms of PVD recognized in Western medicine. Accordingly， this paper conducts research from the following three aspects： First， it clarifies that immune dysregulation， metabolic disorders， and genetic susceptibility constitute the core pathological mechanisms of PVD in Western medicine. Typical pathological manifestations include progressive vascular endothelial injury， lipid deposition， and plaque formation， ultimately leading to multi-organ damage and dysfunction. PVD activates pathways such as the NOD-like receptor thermal protein domain-associated protein 3 （NLRP3） inflammasome， triggering immune dysregulation； it also induces disorders of mitochondrial energy metabolism， water-salt metabolism， and hormonal metabolism， synergizing with genetic susceptibility factors （e.g.， apolipoprotein E gene） to accelerate vascular homeostasis imbalance. Second， this study analyzes the intrinsic relationship between the TCM theory of "kidney deficiency" and the "immune-metabolic-genetic" axis， revealing the theoretical basis for kidney tonification in intervening PVD. The kidney stores essence， governs bones， and produces marrow， which is related to the generation and differentiation of immune cells. It regulates Qi transformation and governs water， overseeing material and energy metabolism. The kidney is the root of congenital essence and governs reproduction， closely related to genetic mechanisms. Third， by integrating modern clinical research， this study elaborates on the unique advantages and clinical value of kidney tonification in targeting the "immune-metabolic-genetic" axis of heart， brain， and kidney organs. Traditional kidney-tonifying formulas and their active ingredients improve immune-inflammatory responses， enhance material and energy metabolism homeostasis， and modulate epigenetic pathways through multiple pathways， targeting various pathways to intervene in PVD. This study systematically elucidates the scientific connotation of kidney tonification in treating PVD， providing theoretical support and practical guidance for integrated TCM-Western medicine approaches and contributing to innovation and improvement in diagnostic and treatment strategies for PVD.

OBJECTIVE To investigate the mechanism of Bushen huoxue formula in improving pregnancy outcomes in mice with antiphospholipid antibody-related recurrent spontaneous abortion （aPL-RSA）. METHODS SPF female BALB/c mice were randomly divided into normal control group， adjuvant control group， model group， and Bushen huoxue formula group. The aPL-RSA mouse model was established by immunization with β 2 glycoproteinⅠcombined with Freund’s adjuvant. From gestational day 0， the Bushen huoxue formula group was administered 1.653 6 g/（kg·d） of the prescription by gavage， while the other three groups received an equal volume of normal saline， twice daily for 15 consecutive days. The uterine appearance of pregnant mice was observed； individual embryo weight was recorded， and the embryo resorption rate was calculated. The proportion of activated CD41 + CD62p + platelets in platelet-rich plasma （PRP） was detected. Serum levels of thromboxane B2 （TXB2） and platelet factor 4 （PF4） were measured. Morphological changes of placental tissue were observed. The cell apoptosis rate of placental tissue was detected. The levels of malondialdehyde （MDA） content， tot al superoxide dismutase （T-SOD） activity， the interleukin-1β （IL-1β） and IL-18， the protein expressions of matrix metalloproteinase-3 （MMP-3）， MMP-9， nuclear proliferation antigen-67 （Ki67）， superoxide dismutase 2 （SOD2）， Nod-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and caspase-1， as well as the mRNA expressions of superoxide dismutase 2（SOD2）， NLRP3， ASC and caspase-1 of placental tissue were detected. RESULTS Compared with the normal control group and adjuvant control group， the model group showed significant decreases in individual embryo weight， T-SOD activity of placental tissue， and relative expression levels of SOD2 mRNA and protein （ P ＜0.05）； while significant increases were observed in embryo resorption rate， proportion of activated CD41 + CD62p + platelets in PRP， serum levels of TXB2 and PF4， placental cell apoptosis rate， MDA content in placental tissue， relative protein expressions of MMP-3， MMP-9 and Ki67， relative protein and mRNA expression levels of NLRP3， ASC and caspase-1 as well as IL-1β and IL-18 levels （ P ＜0.05）. The model group also exhibited irregular uterine morphology with localized atrophy in some uterine horns； placental tissue showed fragmentation of decidual cells， extensive vacuolization and necrosis of trophoblast cells in the labyrinthine zone， accompanied by vascular reduction. After intervention with Bushen huoxue formula， the above indicators were significantly reversed （ P ＜0.05）， and uterine morphology and pathological damage were markedly improved. CONCLUSIONS Bushen huoxue formula can effectively improve pregnancy outcomes in aPL-RSA model mice， and its mechanism may be closely related to inhibiting platelet activation， reducing oxidative stress injury， enhancing trophoblast cell function， and suppressing the inflammatory response mediated by the NLRP3 inflammasome pathway.

Objective To design and fabricate an integrated optoelectrical fiber to enable the simultaneous transmission of high-power laser and electrical current, thereby developing a novel tool for urological surgery.Methods A miniature metal sleeve was installed at the front end of a medical high-energy optical fiber, and corresponding conductive circuits were configured. The fiber was connected to a fiber thulium laser and a bipolar plasma generator simultaneously. Experiments of simulated vaporization were conducted on ex vivo porcine kidney tissues using thulium laser (50 W), plasma (100 W), and thulium laser + plasma (50 W+100 W), respectively. Tissue removal efficiency was calculated using the weighing method:tissue clearance rate (g/min)=[mass before vaporization (g) - mass after vaporization (g)]/vaporization time (min). Lateral tissue thermal damage was assessed with hematoxylin-eosin (HE) staining. One-way analysis of variance and least significant difference test were used for statistical analysis.Results The integrated optoelectrical fiber was successfully constructed, which could simultaneously and continuously transmit thulium laser and plasma electrocision current. The tissue clearance rate of the thulium laser+plasma group was significantly higher than that of the thulium laser group and plasma group [(0.49±0.13) g/min vs. (0.14±0.02) g/min vs. (0.11±0.04) g/min, P＜0.001]. The average lateral thermal damage depth of the thulium laser + plasma group showed no statistically significant difference compared to the thulium laser group [(985.5±178.5) μm vs.(957.5±197.4) μm, P＞0.05], but both were significantly higher than that of the simple plasma group [(499.6±78.0) μm] (P＜0.001). Conclusion The thulium laser + plasma energy transmitted simultaneously by the integrated optoelectrical fiber can vaporize kidney tissue more efficiently without additional thermal damage.

Puerariae Lobatae Radix and Puerariae Thomsonii Radix are the dried roots of Pueraria lobata and Pueraria thomsonii of the Leguminosae family， respectively. Since their separate inclusion in the 2005 edition of Pharmacopoeia of the People's Republic of China， the two herbs have been individually recorded. Although they share the same functions and indications， the required content of puerarin differs by a factor of up to eightfold between them. The current quality standard relies solely on a single indicator， puerarin， which fails to reflect the correlation between chemical constituents and core therapeutic effects. This has resulted in prominent issues of mixed use in clinical practice and production， thereby constraining the high-quality development of the industry. Modern research has demonstrated that Puerariae Lobatae Radix contains a comprehensive range and higher content of isoflavonoid constituents， while Puerariae Thomsonii Radix is rich in starch and polysaccharides. Puerariae Lobatae Radix exhibits stronger effects in antipyresis， cardiovascular and cerebrovascular protection， and central analgesia， while Puerariae Thomsonii Radix demonstrates greater advantages in anti-inflammation， hypoglycemia， and peripheral analgesia. Based on this， the chemical material bases of Puerariae Lobatae Radix and Puerariae Thomsonii Radix at both the macromolecule and micromolecule levels were systematically reviewed and compared. The pharmacodynamic material bases and mechanisms of action underlying their three core therapeutic effects， namely "relieving exterior syndrome and clearing heat"， "promoting fluid production to quench thirst"， and "dredging channels and activating collaterals"， were summarized. The most highly correlated common metabolic pathway shared by both herbs for these three therapeutic effects is the arachidonic acid metabolic pathway， and their common core target is prostaglandin-endoperoxide synthase 2 （PTGS2）. This review provided clinical application recommendations based on the therapeutic differences between the two herbs， elucidated the scientific connotation of their "same origin but different effects"， and， grounded in the quality marker （Q-Marker）， proposed the concept of efficacy-related Q-Marker based on "substance-efficacy-syndrome" association， as well as a novel strategy for efficacy-oriented quality evaluation. Preliminary screening of quality markers associated with different therapeutic effects was also conducted. This study aims to provide critical scientific evidence for the precise clinical application of Puerariae Lobatae Radix and Puerariae Thomsonii Radix， the improvement of quality standards， and the high-quality development of the industry.

This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group， a model group， and a Danshen Tongluo formula （28 mg·kg^-1·d^-1） group. The efficacy was evaluated by examining the cardiac ultrasound， determination of the plasma level of N-terminal pro-brain natriuretic peptide， and pathological staining. After single-cell sequencing， SingleR package， public datasets， and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis， and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide （ NT-proBNP ） level （P<0.05）， ameliorated myocardial cell damage and fibrosis， and increase left ventricular ejection fractions （LVEF） in the rat model of heart failure after myocardial infarction（P<0.05）. Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells， venous endothelial cells， and capillary-arterial endothelial cells， while reducing the proportion of capillary-venous endothelial cells. In addition， this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells， while downregulating Mif-（CD74⁺CXCR44） signaling in endothelium-M1 macrophages and Mif-（CD74⁺CD44） signaling in endothelium-M2 macrophages. It reduced the citric acid cycle， oxidative phosphorylation， and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells， venous endothelial cells， and venous capillary endothelial cells can all regulate oxidative phosphorylation， cell adhesion molecules， and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.