ObjectiveTo investigate the inhibitory effect of Huoluo Xiaolingdan on triple negative breast cancer （TNBC） in mice through its regulation of TCF1⁺CD8⁺ stem cell-like T cells infiltration. MethodsA mouse model of TNBC was established and the mice were randomly divided into the model group， low-dose （3.9 g·kg^-1）， medium-dose （7.8 g·kg^-1） and high-dose （15.6 g·kg^-1） Huoluo Xiaolingdan groups， and anti-PD-1 antibody treatment group. Each group was given a dose of 0.01 mL·g^-1， while the model group and the anti-PD-1 treatment group were also given an equivalent volume of normal saline. The drug was administered for 21 days. In the anti-PD-1 antibody group， mice were intraperitoneally injected with 100 μg of mouse anti-PD-1 antibody twice a week， for a total of five injections. The tumor volume， survival time and tumor mass were measured at different time points. Hematoxylin-eosin （HE） staining was used to observe the histological changes of the tumor. The expression of CD8⁺T cells and TCF1⁺CD8⁺ stem-like T cells in tumor tissues was detected by immunohistochemistry and immunofluorescence staining. Flow cytometry was used to detect the difference of immune cell subsets in tumors and the expression difference of TCF1⁺CD8⁺ stem cell-like T cells in tumors and peripheral blood. The expression level of PD-L1 in tumor tissues was detected by Western blot. ResultsCompared with model group， the tumor volume and mass of in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group were decreased （P<0.05， P<0.01）. The median survival time of mice in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was as follows： 27.00 days （95%CI， 0.45-2.65）， 31.00 days （95%CI， 0.32-1.89）， 34.00 days （95%CI， 0.40-2.33）， and 35.00 days （95%CI， 0.42-2.47）. All of them were higher than that of the model group ［24.50 days （95%CI， 0.37-10.5）］. Flow cytometry showed that compared with the model group， the proportion and number of infiltrating CD8⁺ T cells in tumor were increased in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group （P<0.05， P<0.01）， while the proportion of tumor regulatory T cells （Treg） and M2 macrophages decreased （P<0.05）. Compared with the model group， the proportion of IFN-γ⁺CD8⁺ T and GrzB⁺CD8⁺ T cells in tumors in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was increased （P<0.01）， and the proportion of TCF1⁺CD8⁺ T cells in tumor and peripheral blood was also increased. Immunofluorescence staining further showed that the number of TCF1⁺CD8⁺ T cells in tumor tissues increased in low-， medium- and high-dose Huoluo Xiaolingdan groups. Western blot analysis showed no significant decrease in the PD-L1 protein expression in tumor tissues between the Huoluo Xiaolingdan groups and the model group. ConclusionHuoluo Xiaolingdan can inhibit TNBC in mice by increasing tumor infiltration of TCF1⁺CD8⁺ stem-like T cells， enhancing CD8⁺ T cell activity， and regulating immune cell subgroups such as M2 macrophages and Treg cells to enhance anti-tumor immunity. This study provides a theoretical basis for the clinical application of Huoluo Xiaolingdan in breast cancer treatment and combination therapy.

Objective: To analyze the characteristics and safety risks of preservatives and sweeteners in beverages sold near schools in Anshun City, so as to provide a evidence for formulating targeted regulatory strategies in campus. Methods: From December 2023 to July 2024, 834 beverage samples were collected from sales points near primary and secondary schools in Xixiu District and four surrounding townships of Anshun City by a stratified random sampling method. High performance liquid chromatography was used to detect three preservatives (sorbic acid, benzoic acid and dehydroacetic acid) and four sweeteners (sodium saccharin, acesulfame-K, aspartame, and neotame). Differences were analyzed using the Chi-square test. Results: The overall exceedance rate of preservative was 8.6% (72 samples), with dehydroacetic acid showing the highest exceedance rate (7.0%, 58 samples), significantly higher than sorbic acid (0.6%, 5 samples) and benzoic acid (0.4%, 3 samples) ( χ 2=90.85, P <0.01). The overall exceedance rate of sweetener was 10.4% (87 samples), with sodium saccharin having the highest exceedance rate ( 6.2 %, 52 samples),significantly higher than neotame (2.8%, 23 samples), acesulfame-K (0) and aspartame (0) ( χ 2=262.04, P <0.01). Potential risks were identified due to the co occurrence of multiple additive exceedances, including 0.7% (6 samples) for mixed preservatives and 1.6% (13 samples) for mixed sweetener. No statistically significant differences were found in preservative (7.2%, 26 samples) or sweetener (12.3%, 44 samples) exceedance rates between micro enterprises and large, medium and small enterprises ( χ 2=2.67, 5.16, both P >0.05). Conclusion Systemic misuse risk of food additives in beverages sold near school necessitates a risk traceability based regulatory framework, with emphasis on standardizing enterprise production practices and strengthening oversight of sales outlets near campuses.

With the rapid development of social economy， the number of patients with nervous system diseases has increased， and the incidence of the population has a trend of younger， which has a serious impact on life health and social economy. Artemisinin is an active antimalarial component extracted and isolated from Artemisia annua， a Chinese medicinal material. Artemisinin and its derivatives， in addition to the antimalarial effect， also have anti-parasitic， anti-fungal， anti-viral， hypoglycemic， hypolipidemic， anti-tumor， and anti-inflammatory effects， showing a wide range of pharmacological activities. In the past five years， research on the new pharmacological effects of artemisinin and its derivatives has been deepening， and the efficacy of artemisinin and its derivatives in nervous system diseases has attracted much attention， including anti-neuroinflammation， anti-oxidative stress， maintaining the stability of the blood-brain barrier， regulating the release of neurotransmitters， repairing neuronal damage， and promoting neuronal regeneration. These pharmacological effects indicate that artemisinin and its derivatives are potentially capable of neuroprotection. By sorting out literature on the pharmacological activity of artemisinin and its derivatives in nervous system during 2019－2024， this paper systematically summarized the protective effects of artemisinin and its derivatives against nervous system diseases such as stroke， neurodegenerative diseases， neuroimmunological diseases， neuralgia， and nervous system tumors. This review is expected to provide clues and evidence for new indication expansion of artemisinin drugs， innovative drug development， and clinical treatment of nervous system diseases.

The impact of air pollution on human health has always been a research hotspot in the global health field. Outdoor air pollutants composed of multiple components can enter the human body through various pathways. Cardiovascular diseases are a group of diseases caused by outdoor air pollutants. Studies have shown that the incidence of cardiovascular diseases， including hypertension， arrhythmia， and heart failure， is significantly increased among people exposed to air pollution environments. Air pollutants such as fine particulate matter， nitrogen dioxide， ozone， carbon monoxide， and sulfur dioxide are closely related to the occurrence of cardiovascular diseases， and short-term and long-term exposure causes different cardiovascular risks. By reviewing the relevant research reports from 2019 to 2024， this article summarizes the epidemiological evidence of cardiovascular diseases caused by different air pollutants. It generalizes the pathways through which air pollutants accelerate the progression of cardiovascular diseases. These pathways include oxidative stress， inflammatory response， thrombosis， extracellular vesicle release， endoplasmic reticulum stress， apoptosis， endothelial dysfunction， autonomic nervous system imbalance， and their interactions. Based on the different mechanisms of air pollution on cardiovascular diseases， the article analyzes the main progress in drug intervention and summarizes the roles of various active ingredients and compound prescriptions of traditional Chinese medicine in treating air pollution-related cardiovascular diseases， providing reference for the research on the mechanisms and drug interventions of air pollution-related cardiovascular diseases.

Clustered regularly interspaced short palindromic repeats（CRISPR）/CRISPR associated nuclease 9 （CRISPR/Cas9） is a self-defense system found in bacteria and archaea that enables targeted gene editing based on the principle. Due to its universality， efficiency， and simplicity， CRISPR/Cas9 has been applied in the pathological mechanism and prevention and treatment of diseases in many fields. Cerebrovascular diseases and central nervous system diseases seriously endanger human health. Stroke is related to genetics， unhealthy living habits， chronic diseases， and other factors. The brain tissue structure is complex and the cell types are diverse. It is difficult for a universal gene editing platform to study target genes safely， specifically， and efficiently. Scholars have continuously improved and optimized gene editing technology， explored the potential and research methods of gene editing technology， and promoted the research process of brain science. After a brief introduction to the mechanism of CRISPR/Cas9， this paper mainly summarized the optimization of the system in the fields of cerebral science including delivery methods， adeno-associated virus assembly， and new nanomaterials. Its application in cerebrovascular research including vascular homeostasis， microglial homeostasis， angiogenesis， blood-brain barrier， and drug screening was also summarized. Finally， this paper prospected the development of CRISPR/Cas9 in traditional Chinese medicine， hoping to provide references for related research design.

Objective To investigate the predictive value of preoperative bi-parametric MRI radiomics for the International Society of Urological Pathology(ISUP)grading of prostate cancer(PCa).Methods One hundred and sixty-five patients with PCa confirmed by pathology were analyzed retrospectively.According to the ISUP grading system,PCa patients were divided into five subgroups:G1 group(Gleason score=6),G2 group(Gleason score=3+4),G3 group(Gleason score=4+3),G4 group(Gleason score=8)and G5 group(Gleason score=9 or 10).A total of 3 948 radiomics features were extracted from T2WI,diffusion weighted imaging(DWI),and apparent diffusion coefficient(ADC)images of each patient.Patients were classified into two categories based on Gleason score≥4+3 or ≤3+4.A radiomics signature(Rad-score)was constructed after reduction of dimension by the minimum redundancy maximum relevance(mRMR)and the least absolute shrinkage and selection operator(LASSO).The Spearman rank correlation test was used to evaluate the correlation between Rad-score and ISUP grading groups.The Kruskal-Wallis test was used to compare the difference of Rad-score among the five groups.Results Eleven most valuable features were selected as the Rad-score after reducing the dimension by mRMR and LASSO algorithm.Moderate correlation existed between Rad-score and ISUP grading(r=0.53,P＜0.05).There were significant differences in Rad-score between G1 and G2 groups and G3,G4 and G5 groups(P＜0.05),no significant difference existed between the remained two groups(P＞0.05).The area under the curve(AUC)of receiver operating characteristic(ROC)curve for Rad-score were 0.827,0.762,0.563,0.657,0.698 for G1,G2,G3,G4 and G5 groups,respectively.Conclusion The radiomics based on bi-parametric MRI can be used to predict grade 1,2 PCa patients in the ISUP grading system.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

ObjectiveTo observe the protective effect of Shenlian prescription on acute lung injury induced by particulate matter （PM） exposure in rats and explore the mechanism. MethodFifty male SD rats were randomly divided into the control group， model group， Shenlian low-dose group （4.32 g·kg^-1）， Shenlian high-dose group （8.64 g·kg^-1）， and roflumilast group （3.46 mg·kg^-1）， with 10 in each group. Pre-administration with drugs by gavage was performed for one week. On the 8^th and 11^th days， the control group was instilled with normal saline in the trachea and the other groups with PM suspension to establish a rat model of acute lung injury induced by PM exposure. After modeling， drugs were given continuously until the end of the experiment. Forty-eight hours after the last exposure， the lung function of rats was detected. Then the rats were sacrificed and the lung morphological changes and pathological changes by hematoxylin-eosin （HE） staining were observed. CD68 expression in lung was detected by immunohistochemistry， and the levels of lung injury markers surfactant protein A （SP-A） and Clara cell protein16 （CC16） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of interleukin-1α （IL-1α）， IL-6， IL-18， and monocyte chemoattractant protein-1 （MCP-1） in lung tissue was measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with those in the control group， the rats in the model group had decreased lung function and obvious structural damage of lung tissue， PM deposition， and infiltration of CD68 positive cells. The expressions of IL-1α， IL-6， IL-18， and MCP-1 in lung tissue were increased （P<0.01）. Compared with the model group， Shenlian prescription low and high doses restored the rats' lung function injury（P<0.05，P<0.01）， improved lung morphological and pathological structure， and reduced PM deposition. Infiltration of CD68 positive cells in lung was not significantly decreased. The levels of inflammatory factors IL-1α， IL -6， IL-18， and MCP-1 in lung were lowered （P<0.01）. ConclusionShenlian prescription could protect the rats' lung injury caused by PM exposure， improve lung morphology， and reduce PM deposition and inflammatory factor expression.

Insufficient remyelination due to impaired oligodendrocyte precursor cell (OPC) differentiation and maturation is strongly associated with irreversible white matter injury (WMI) and neurological deficits. We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2 (LCN2) in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1 (EGR1) as the key signals contributing to LCN2-mediated insufficient OPC remyelination. In LCN-knockdown and OPC EGR1 conditional-knockout mice, we discovered enhanced OPC differentiation in developing and injured white matter (WM); consistent with this, the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical, acute WMI due to subarachnoid hemorrhage and typical, chronic WMI due to multiple sclerosis. This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.
Mice ; Animals ; Remyelination/physiology* ; Oligodendrocyte Precursor Cells/metabolism* ; White Matter ; Subarachnoid Hemorrhage/metabolism* ; Lipocalin-2/metabolism* ; Early Growth Response Protein 1/metabolism* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Cell Differentiation/physiology* ; Brain Injuries/metabolism*

Objective:To explore the effect of family supportive nursing on self-perception and outcome events in elderly patients with chronic diseases.Methods:A simple random sampling method was used to select 115 elderly patients with chronic diseases discharged from Henan Provincial People's Hospital from January 2019 to January 2020. They were divided into the observation group (58 cases) and the control group (57 cases) by random number table method. The control group received routine nursing, while the observation group received family support nursing. The self-perception and family function scores of the two groups were compared before the intervention and after 3 and 6 months of the intervention. The medication compliance and readmission rate were compared between the two groups.Results:After 3 months of intervention, scores of Self-Perceived Burden (SPBS) of the observation group and the control group were respectively (25.73±3.85) and (28.14±3.90) and scores of Family Adaptability Cohesion Environment Scale (FACES) were respectively (105.62±12.41) and (96.35±10.05) . After 6 months of intervention, the SPBS scores of the observation group and the control group were respectively (21.89±4.33) and (25.41±4.20) , and the FACES scores were (122.60±14.70) and (112.35±16.32) respectively. Repeated-measures analysis of variance showed that there were statistically significant differences in interaction effect, time effect and between-group effect in the comparison of SPBS and FACES total scores between the two groups (all P<0.01) . After 6 months of intervention, the rate of good medication compliance in the observation group and the control group was respectively 70.69% (41/58) and 50.88% (29/57) , and that of the observation group was higher than the control group, and the difference was statistically significant (χ 2=4.738, P=0.030) . After one-year follow-up after intervention, the readmission rates of the observation group and the control group were respectively 18.87% (10/53) and 39.22% (20/51) , and the observation group was lower than the control group, and the difference was statistically significant (χ 2=5.243, P=0.022) . Conclusions:Family support nursing can reduce the self-perceived burden of elderly patients with chronic diseases, improve their family function, improve medication compliance and reduce readmission.