Triple-negative breast cancer (TNBC) is aggressive, with high recurrence rates and poor prognosis. Paclitaxel (PTX) remains a key chemotherapeutic agent for TNBC, but its efficacy diminishes due to the emergence of drug resistance, largely driven by cancer stem-like cells (CSCs), vasculogenic mimicry (VM) formation and tumor immunosuppressive microenvironment (TIME). Pyruvate kinase M2 (PKM2) is highly expressed in TNBC, and is a potential target for TNBC treatment. In this study, we developed a biomimetic codelivery system using albumin nanoparticles (termed S/P NP) to co-encapsulate PTX and shikonin (SHK), a natural inhibitor of PKM2. By inhibiting PKM2, SHK suppressed β-Catenin signaling, thereby reversing CSC stemness and preventing VM formation. The S/P NP system exhibited tumor-targeting delivery effect and significantly inhibited TNBC growth and lung metastasis. Mechanistically, the treatment reversed epithelial-mesenchymal transition (EMT) and stem-like properties of TNBC cells, suppressed VM formation, and remodeled the TIME. It reduced immunosuppressive cells (M2 macrophages, MDSCs) while promoting anti-tumor immunity (M1 macrophages, dendritic cells, cytotoxic T cells, and memory T cells). This dual-action strategy holds promise for improving TNBC therapy by targeting CSCs, VM, and the immune microenvironment, and for overcoming PTX resistance and reducing metastasis.

OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Objective To study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis(UC).Methods Acer1 knockout mice(Acer1 KO)were constructed,and the UC model was induced by continuous drinking water of sodium dextran sulfate(DSS)for 7 days,and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared.The expression levels of intestinal mucosal barriers(ZO-1,Occludin,Claudin,JAMA)were detected by RT-PCR and immunohistochemistry.Systemic immune response levels(IL-1b、IL-6、IL-23、IL-17、IL-10,and TNF-a)were assessed by ELISA and intestinal inflammatory infiltration levels(TNF-a、IL-1b、IL-6、IL-17、IL-21,etc.)were assessed by RT-PCR.Results There was no significant difference between C57 and Acer1 KO mice in free drinking water.In the DSS induced UC model,compared with C57 mice,the survival rate of Acer1 KO mice decreased,the weight decreased significantly,the mechanical barrier and mucus barrier protein expression levels decreased significantly,the intes-tinal epithelial barrier was seriously damaged,the inflammatory response was strong,and the cytokine infiltration was obvious,with statistical differences(P<0.05).Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier,preventing endotoxin,and delaying the progression of UC.

Objective To analyze the prevalence of dengue fever in Guangzhou based on circuit-qi theory.Methods Data on dengue fever cases in Guangzhou from January 21,2012,to January 19,2024 were collected.And then the incidence of dengue fever was analyzed under the circuit-qi conditions of dominant qi,guest qi,celestial qi,joining of guest qi with dominant qi,and dissimilation of circuit and qi.Results Higher incidence of dengue fever in Guangzhou was presented under the circuit-qi conditions of the fifth qi of the dominant qi in each year,shaoyang minister fire of the guest qi,shaoyin monarch fire of the celestial qi,guest qi restricting dominant qi in the joining of guest qi with dominant qi,shaoyang minister fire(guest qi)joining with yangming dry-metal(dominant qi)in the pattern of guest qi restricting dominant qi.The outbreak of dengue fever under the circuit-qi conditions of dissimilation of circuit and qi showed no statistically significant difference.Conclusion Over the 12-year period from 2012 to 2024,the prevalence of dengue fever in Guangzhou exhibited a 4-5-year cyclical pattern,often with consecutive outbreaks over two years.The prevalence of dengue fever in Guangzhou is associated with the factors of dampness and heat in the theory of five circuits and six qi,while has less relation with dissimilation of circuit and qi.

Objective To investigate the characteristics of traditional Chinese medicine(TCM)syndromes in patients with influenza complicated with pneumonia and to provide references for TCM treatment strategies.Methods A retrospective analysis was conducted on 189 cases of influenza complicated with pneumonia,which were treated in the outpatient or inpatient department of Guangdong Provincial Hospital of Chinese Medicine from January 2016 to December 2023.Frequency analysis,factor analysis,and cluster analysis were performed to summarize the distribution patterns of TCM syndromes in these patients.Results(1)Clinical characteristics:Among the 189 patients,162 were infected with influenza A virus,27 with influenza B virus,and 1 with co-infection of both viruses.There were 93 males(49.2％)and 96 females(50.8％).The age of the patients ranged from 19 to 96 years,with a mean of(68.06±19.08)years.(2)TCM four-examination findings:The top four clinical symptoms were cough,fever,expectoration,and fatigue.Regarding tongue manifestations,the predominant tongue colors were red,dark red,and pale with dark hue,while the primary tongue coatings were yellow greasy and white greasy.The most common pulse patterns were slippery,wiry,and rapid.(3)Syndrome distribution characteristics:Factor analysis revealed that the disease location was primarily lung and spleen,with cold,heat,and phlegm as the main pathological factors.Cluster analysis identified three distinct syndrome types:exterior cold with interior heat syndrome,phlegm-turbidity obstructing internally syndrome,and phlegm-stasis obstructing the lung syndrome.Conclusion The predominant TCM syndromes in influenza complicated with pneumonia are exterior cold with interior heat syndrome,phlegm-turbidity obstructing internally syndrome,and phlegm-stasis obstructing the lung syndrome.The disease primarily affects the lung and spleen,with cold,heat,and phlegm as the major pathological factors.Attention should also be paid to the influence of"stasis"as a pathological factor on these patients.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

OBJECTIVE To explore the epidemiological characteristics of human immunodeficiency virus(HIV)/ac-quired immune deficiency syndrome(AIDS)complicated with anorectal diseases and analyze the clinical character-istics of the HIV-positive patients with perianal abscess.METHODS Totally 152 HIV/AIDS patients who were complicated with anorectal diseases and were treated in The Eighth Hospital of Wuhan from Jan.2020 to Dec.2023 were recruited as the research subjects,36 of whom had perianal abscess.The manifestations of anorec-tal diseases,treatment status and incidence rates of the diseases among the patients with different clinical charac-teristics in the different years were statistically analyzed.The clinical characteristics of the HIV-positive patients with perianal abscess were observed.RESULTS Of the 152 HIV/AIDS patients complicated with anorectal disea-ses,51.97％had mixed hemorrhoid,and 23.68％had perianal abscess.The number of patients with HIV/AIDS complicated with anorectal diseases gradually increased from 2020 to 2023;while the incidence rate of male,aged between 30 and 40 years old,married individuals,those with primary school education or below and famers were relatively high.Among the HIV/AIDS patients complicated with anorectal diseases,139 underwent surgical pro-cedures,and 23 did not.Among the 36 HIV-positive patients with perianal abscess,97.22％were male,50.00％were aged between 20 and 30 years old,and 44.44％were married.CONCLUSIONS The number of HIV/AIDS patients complicated with anorectal diseases is gradually increased from 2020 to 2023;the incidence rates are rela-tively high among the patients who are male,aged between 30 and 40 years old,married,with primary school edu-cation or below and famers.Perianal abscess and mixed hemorrhoid are the major types of anorectal diseases.Sur-gical procedures are recommended for HIV/AIDS patients complicated with anorectal diseases,while the HIV-positive patients with perianal abscess are dominated by the population of male,aged between 20 and 30 years old and married.It is necessary to attach great importance to the detection of pathological characteristics of the HIV-positive patients with perianal abscess so as to take appropriate treatment measures to improve the therapeutic effect.

OBJECTIVE To explore the epidemiological characteristics of human immunodeficiency virus(HIV)/ac-quired immune deficiency syndrome(AIDS)complicated with anorectal diseases and analyze the clinical character-istics of the HIV-positive patients with perianal abscess.METHODS Totally 152 HIV/AIDS patients who were complicated with anorectal diseases and were treated in The Eighth Hospital of Wuhan from Jan.2020 to Dec.2023 were recruited as the research subjects,36 of whom had perianal abscess.The manifestations of anorec-tal diseases,treatment status and incidence rates of the diseases among the patients with different clinical charac-teristics in the different years were statistically analyzed.The clinical characteristics of the HIV-positive patients with perianal abscess were observed.RESULTS Of the 152 HIV/AIDS patients complicated with anorectal disea-ses,51.97％had mixed hemorrhoid,and 23.68％had perianal abscess.The number of patients with HIV/AIDS complicated with anorectal diseases gradually increased from 2020 to 2023;while the incidence rate of male,aged between 30 and 40 years old,married individuals,those with primary school education or below and famers were relatively high.Among the HIV/AIDS patients complicated with anorectal diseases,139 underwent surgical pro-cedures,and 23 did not.Among the 36 HIV-positive patients with perianal abscess,97.22％were male,50.00％were aged between 20 and 30 years old,and 44.44％were married.CONCLUSIONS The number of HIV/AIDS patients complicated with anorectal diseases is gradually increased from 2020 to 2023;the incidence rates are rela-tively high among the patients who are male,aged between 30 and 40 years old,married,with primary school edu-cation or below and famers.Perianal abscess and mixed hemorrhoid are the major types of anorectal diseases.Sur-gical procedures are recommended for HIV/AIDS patients complicated with anorectal diseases,while the HIV-positive patients with perianal abscess are dominated by the population of male,aged between 20 and 30 years old and married.It is necessary to attach great importance to the detection of pathological characteristics of the HIV-positive patients with perianal abscess so as to take appropriate treatment measures to improve the therapeutic effect.