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.

ObjectiveTo investigate the mechanism by which Shenqi Yiliu prescription reverses cisplatin resistance in ovarian cancer cells by regulating the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway-mediated glycolysis. MethodsThe human ovarian cancer A2780 cell line was intervened with progressively increasing doses of cisplatin （1 g·L^-1） to establish the cisplatin-resistant cell line A2780cisR， and the cell sensitivity to cisplatin was examined by the cell counting kit-8 （CCK-8） assay. High， medium， and low （39.9， 19.95， 9.98 g·kg^-1） doses of Shenqi Yiliu prescription-containing sera were used to treat A2780cisR cells for 48 h. Glucose consumption and lactate production were measured by the cuvette assay. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the activities of glucose transporter （GLUT）， phosphofructokinase （PFK）， and pyruvate kinase （PK）. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was used to detect apoptosis. Western blot was employed to quantify the protein levels of phosphorylated （p）-PI3K， p-Akt， p-mTOR， hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， B-cell lymphoblastoma-2 （Bcl-2）， Bcl-2-associated X-protein （Bax）， and B-lymphoblastoma-2 gene-related promoter （Bad）. Real-time PCR was conducted to determine the mRNA levels of HK2， PKM2， Bax， Bcl-2， and Bad. ResultsThe median inhibitory concentration （IC₅₀） of cisplatin on A2780cisR cells was nearly 3 times that on A2780P cells. Compared with A2780P cells， A2780cisR cells showed increased glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax （P<0.05）， and decreased apoptosis rate and Bcl-2 expression （P<0.05）. Compared with A2780cisR cells， medium- and high-dose Shenqi Yiliu prescription reduced the glucose consumption， lactate production， GLUT， PFK， and PK activities， and mRNA and protein levels of p-PI3K， Akt， p-mTOR， HK2， PKM2， Bax， and Bad （P<0.05）， while increasing the apoptosis rate and Bcl-2 expression （P<0.05）. ConclusionShenqi Yiliu prescription can inhibit glycolysis mediated by the PI3K/Akt/mTOR pathway to promote apoptosis， thereby reversing cisplatin resistance in ovarian cancer cells.

Erchentang is a classic formula widely used by medical practitioners throughout history. In this paper，ancient and modern literature of Erchentang were collected， and bibliometrics was employed to analyze its historic evolution，prescription meaning，herbs origin， processing method，preparation methods， and clinical application. A total of 84 pieces of data were collected， and 58 pieces of data involving 53 ancient medical Chinese books were screened， sorted， and processed. Combined with research of modern scholars，the research has found that the Erchentang originated from the Taiping Huimin Huiye Shijie Fang compiled by the Imperial Medical Bureau of the Song Dynasty. The basic information about the origin of the drugs is quite clear. Pinelliae rhizoma in the formula is the dried tuber of Pinellia ternata. Citri exocarpium rubrum is the dried mature peel of Citrus reticulata and its cultivated varieties， with the inner white membrane removed. Poria is the whitest dry sclerotia of Poria cocos； Glycyrrhizae radix et rhizoma is the dried root and rhizome of the Glycyrrhiza uralensis. The dosage is 5.70 g Pinelliae rhizome and Citri exocarpium rubrum， 3.43 g Poria， and 1.69 g Glycyrrhizae radix et rhizoma praeparata cum melle. During the decoction process， the above-mentioned herbs should be chopped， with 300 mL water， 7 g ginger in thick slices， and 2 g Mume fructus added， and it was then simmered together to 180 mL. After removing the medicinal residue， it can be taken warmly. Erchentang has the effect of drying dampness and resolving phlegm， regulating Qi and harmonizing the middle. It can be used in treating the syndrome of phlegm and dampness，as well as symptoms such as frequent cough，white phlegm，fullness in chest and diaphragm，nausea and vomiting，limb drowsiness，anorexia，dizziness，palpitations，white and greasy tongue coating， and slippery pulse. The above results provide reference for future research and development of Erchentang.

As a globally acclaimed emerging technology， the development speed and scale of the brain-computer interfaces have exceeded public expectations. On the one hand， it boasts significant application value in treating brain diseases， promoting the development of the brain-computer interaction industry， enhancing human capabilities， and driving a new round of technological revolution. On the other hand， its inherent uncertainty and ambiguity can trigger a series of complex and unique risks， including threats to individuals’ physical and psychological safety， erosion of individual autonomy， potential risks from the abuse of brain data， as well as latent threats to social justice and national security. Therefore， this study proposed a governance framework for responsible research and innovation， encompassing recommendations such as an open and transparent governance process， flexible regulation to avoid stifling technological innovation， and strengthened international cooperation to restrict military applications.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Houpo Sanwutang， included in the Catalogue of Ancient Classical Prescriptions （Second Batch）， was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining， statistical analysis， and data processing， combined with modern articles， this study employed bibliometrics to investigate the historical origin， composition， decoction methods， clinical application， and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty， it is recommended that 110.4 g Magnolia Officinalis Cortex， 55.2 g Rhei Radix et Rhizoma， and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first， and 1 000 mL should be taken from the decocted liquid. Following this， Rhei Radix et Rhizoma should be added for further decoction， and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL， and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi， relieving stuffiness and fullness， removing food stagnation， and regulating bowels. It can be used in treating abdominal distending pain， guarding， constipation， and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.

Objective To explore the value of CT signs and quantitative parameters of artificial intelligence (AI) in predicting the efficacy of neoadjuvant chemotherapy for colorectal cancer. Methods A total of 349 colorectal cancer patients who received neoadjuvant chemotherapy at Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province from January 2022 to January 2025 were selected and and divided into the effective group (n = 267) and the ineffective group (n = 82) according to the evaluation criteria for the efficacy of solid tumors. Conduct a CT examination and extract AI quantitative parameters from the CT images based on the lesion. The data were analyzed using SPSS21.0 software, Logistic regression was used to screen the influencing factors of ineffective neoadjuvant chemotherapy in patients with colorectal cancer, and separate and combined models of CT signs and AI quantitative parameters were established. The predictive effect of the model was verified by using the ROC curve, calibration curve and decision curve. Results Compared with the effective group, the proportion of regular tumor morphology and the proportion of non-enlarged lymph nodesin the ineffective group were smaller. The tumor volume, peak value and entropy value were larger (P < 0.05). Multivariable analysis showed that irregular shape (OR= 4.216), presence of lymph node enlargement (OR = 8.998), larger tumor volume (OR = 1.109), higher average CT value (OR = 1.120), elevated peak value (OR = 2.528), and increased entropy value (OR = 1.390) were independent risk factors for ineffective neoadjuvant chemotherapy in colorectal cancer (P < 0.05). The areas under the ROC curves of the individual and combined models of CT signs and AI quantitative parameters were 0.777, 0.818, and 0.877, respectively(P < 0.05). The calibration curve showed a Brier score of 0.091. The decision curve showed that the threshold was between 0.10 and 0.85, and the combined model achieved a relatively high net clinical benefit. Conclusion CT signs combined with AI quantitative parameters has a predictive value for the efficacy of neoadjuvant chemotherapy in colorectal cancer. To provide evidence-based basis for clinical screening of the population benefiting from chemotherapy and optimization of treatment strategies.

Heart failure (HF) is a common end-stage clinical manifestation of cardiovascular diseases, imposing substantial health-related burdens worldwide. With its high mortality rates and poor long-term prognosis, there is a pressing need for novel therapies. SIRT1, a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase, has anti-cardiovascular aging properties and other cardioprotective effects, attracting much research attention in recent years. In addition, SIRT1 plays an important role in HF pathophysiology. This review summarized the roles of SIRT1 and its activators in HF, the changes of SIRT1 gene expression in cardiac tissues from animal models and HF patients, and the current status of clinical trials investigating SIRT1 activators as potential therapies for HF. This will provide new ideas for further exploration of pathological mechanisms and the development of clinical prevention strategies for HF.
Heart Failure/metabolism* ; Sirtuin 1/genetics* ; Humans ; Animals

This study aims to elucidate the role and mechanism of clematichinenoside AR(CAR) in protecting bone marrow mesenchymal stem cells(BMSCs) from hypoxia-induced apoptosis. BMSCs were isolated by the bone fragment method and identified by flow cytometry. Cells were cultured under normal conditions(37℃, 5% CO_2) and hypoxic conditions(37℃, 90% N_2, 5% CO_2) and treated with CAR. The BMSCs were classified into eight groups: control(normal conditions), CAR(normal conditions + CAR), hypoxia 24 h, hypoxia 24 h + CAR, hypoxia 48 h, hypoxia 48 h + CAR, hypoxia 72 h, and hypoxia 72 h + CAR. The cell counting kit-8(CCK-8) assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) were employed to measure cell proliferation and apoptosis, respectively. The number of mitochondria and mitochondrial membrane potential were measured by MitoTracker®Red CM-H2XRo staining and JC-1 staining, respectively. The level of reactive oxygen species(ROS) was measured with the DCFH-DA fluorescence probe. The protein levels of B-cell lymphoma-2 associated X protein(BAX), caspase-3, and optic atrophy 1(OPA1) were determined by Western blot. The results demonstrated that CAR significantly increased cell proliferation. Compared with the control group, the hypoxia groups showed increased apoptosis rates, reduced mitochondria, elevated ROS levels, decreased mitochondrial membrane potential, upregulated expression of BAX and caspase-3, and downregulated expression of OPA1. In comparison to the corresponding hypoxia groups, CAR intervention significantly decreased the apoptosis rate, increased mitochondria, reduced ROS levels, elevated mitochondrial membrane potential, downregulated the expression of BAX and caspase-3, and upregulated the expression of OPA1. Therefore, it can be concluded that CAR may exert an anti-apoptotic effect on BMSCs under hypoxic conditions by regulating OPA1 to maintain mitochondrial homeostasis.
Mesenchymal Stem Cells/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Hypoxia/drug effects* ; Homeostasis/drug effects* ; Reactive Oxygen Species/metabolism* ; Rats, Sprague-Dawley ; Membrane Potential, Mitochondrial/drug effects* ; Saponins/pharmacology* ; Caspase 3/genetics* ; Male ; bcl-2-Associated X Protein/genetics* ; Bone Marrow Cells/metabolism* ; Cell Proliferation/drug effects* ; Protective Agents/pharmacology* ; Cells, Cultured