Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

The chemical constituents in dried roots of Atractylodes macrocephala were investigated in this study. Through utilizing normal-phase silica gel and ODS column chromatography, TLC, and semi-preparative HPLC, 4 new sesquiterpenoids were purified from the ethyl acetate extract of A. macrocephala. By various spectroscopic techniques, such as 1D and 2D NMR, HR-ESI-MS, IR, UV, and CD, their structures were identified as atractylmacron A (1), 9β-hydroxyasterolide (2), atractylenolide H (3), atractylenolide J (4). Compound 1 possesses a rare 6/7 bicyclic skeleton.

Nanometal materials have been extensively studied due to their non-toxic,stable,and efficient biological properties.Among them,nano-zinc oxide(ZnO-NPs),which exhibits good biocompatibility,is considered a promising antibacterial material for medical applications due to its broad-spectrum antibacterial effects and photocatalytic activity.The antibacterial mechanism of ZnO-NPs is not yet fully understood,but two widely recognized modes have been proposed:one is a non-contact mechanism dominated by reactive oxygen species(ROS)generated by ZnO-NPs and the release of Zn2+,and the other is a direct contact antibacterial mechanism involving the interaction between ZnO-NPs and bacterial cell wall components.These two distinct antibacterial mechanisms are attributed to the physicochemical properties of ZnO-NPs.As a wide-bandgap semiconductor,the antibacterial efficacy of ZnO-NPs is influenced not only by light exposure but also by factors such as particle size,concentration,morphology,as well as the type and structure of the target bacteria.Therefore,understanding the precise mechanisms is crucial for elucidating the antibacterial functions of ZnO-NPs against bacteria and fungi.This review summarizes the latest research progress on the antibacterial mechanisms of ZnO-NPs and their influencing factors,and provides an overview of the factors affecting the antibacterial performance of ZnO-NPs,offering a basis for a deeper understanding and application of ZnO-NPs in antibacterial therapy.

Photothermal therapy,as a novel anti-tumor treatment strategy,faces many challenges such as insufficient targeting,limited penetration ability,and inability to achieve long-term inhibition when used alone for anti-tumor treatment.Based on this,in this study,macrophage extracellular vesicles(MEVs)were modified onto the surface of a vector carrying CSF1R-siRNA and photothermal agents to form a multifunctional gene delivery vector MEVs@RNPs.It could induce the macrophages to reprogram from M2 type to M1 type,so as to achieve efficient photothermal and immunotherapy for triple negative breast cancer(TNBC).The basic physicochemical properties of each nanocarrier were characterized using nanoparticle size analyzer,UV-vis spectrometer,fluorescence spectrometer,thermal imaging instrument,etc.TNBC cells 4T1,endothelial cells Bend3,and macrophages 264.7 were used as in vitro experimental subjects for measurement of MEVs@RNPs.The ability to target tumor cells,kill tumor cells,and induce macrophage reprogramming in vitro was investigated.With Balb/c mice as the in vivo research object,a subcutaneous transplant tumor model was established in mice,and the changes in tumor volume and body weight of mice in different treatment groups were measured.In addition,further isolation of mouse blood and tumor tissue was performed,and hematoxylin-eosin(HE)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)method,and enzyme-linked immunosorbent assay(ELISA)method were used to determine the apoptosis and cytokine secretion of tumor cells for comprehensive evaluation of MEVs@RNPs.The results showed that the MEVs@RNPs could preferentially target tumor cells and induce stronger TNBC cell killing effect under photothermal conditions.Meanwhile,the results of flow cytometry and ELISA analysis showed that the MEVs@RNPs could promote the transformation of macrophages from M2 type to anti-tumor M1 type,significantly enhancing the secretion levels of anti-tumor cytokines tumor necrosis factor-α(TNF-α)and interleukin-12(IL-12).The in vivo anti-tumor treatment effect assessment of the MEVs@RNPs showed that under laser processing conditions,the MEVs@RNPs could significantly induce pathological necrosis and apoptosis of tumor cells,promote macrophage reprogramming and infiltration of CD4+/CD8+T cells into the tumor site,and enhance the secretion levels of TNF-α and IL-12,thereby comprehensively improving the therapeutic effect of TNBC.

Objective:To explore the molecular mechanism of TCM compound Shengxue Tongbian Granules in improving intestinal injury in septic rats through bioinformatics and experimental validation methods.Methods:The GSE131761 gene set was processed by bioinformatics to screen differential genes, then weighted gene co-expression network analysis (WGCNA) was applied to screen modular genes. The intersection of modular genes and differential genes was taken, and finally, the least absolute shrinkage and selection operator (LASSO) technique was applied to further obtain the key targets of sepsis, which was validated by experiments. Totally 72 SD rats were divided into sham-operation group, model group, dexamethasone group (0.15 mg/kg), Shengxue Tongbian Granules low- (0.3 g/kg), medium- (0.6 g/kg), and high-dosage (1.2 g/kg) groups, with 12 rats in each group. Corresponding drug interventions were administered to each treatment group before and 12 hours after modeling. The sham-operation group and the model group were gavaged daily with equal amounts of saline. Samples were collected after 24 hours. HE staining was used to detect the pathological morphology of intestinal tissues in each group of rats; ELISA was used to detect the levels of TNF-α, diamine oxidase (DAO), IL-6, IL-10, and myeloperoxidase (MPO) in rat serum. Immunohistochemistry was used to detect the protein expressions of MPO and neutrophil elastase (NE/LANE) in intestinal tissue, and Western blot was used to detect the protein expression of peptidyl arginine deaminase (PAD4) in intestinal tissue.Results:Seven final key genes related to sepsis were selected, namely ANXA3, CYP1B1, FCAR, LILRA5, PADI4, NOV, and S100A12. Experimental results showed that drug administration alleviated intestinal injury; compared with the model group, the levels of TNF-α, IL-6, MPO, and DAO decreased in the Shengxue Tongbian Granules high-dosage group ( P<0.05), the levels of ELANE and MPO were reduced in Shengxue Tongbian Granules low-, medium-, and high-dosage groups ( P<0.05), and PAD4 expression was reduced in the Shengxue Tongbian Granules high-dosage group ( P<0.05). Conclusion:Shengxue Tongbian Granules can improve the intestinal injury of septic rats, and the mechanism may be related to the inhibition of PAD4-mediated formation of NETs and the improvement of inflammatory response.

Objective To investigate the therapeutic efficacy of Zhi Long Huoxue Tongyu Capsules combined with Edaravone in the treatment of patients with ischemic cerebrovascular disease(ICVD)of qi deficiency and blood stasis syndrome,and to explore their effect on serum levels of soluble cluster of differentiation 40 ligand(sCD40L),lipoprotein phospholipase A2(Lp-PLA2),and glycated albumin(GA).Methods A total of 117 patients with ICVD of qi deficiency and blood stasis syndrome were randomly divided into control group 1,control group 2,and study group,with 39 patients in each group.The three groups were all given basic treatment with agents of diuretic,lipid regulation,antiplatelet,and antihypertensive,and additionally,control group 1 was given Edaravone,control group 2 was given Zhi Long Huoxue Tongyu Capsules,and the study group was given Zhi Long Huoxue Tongyu Capsules combined with Edaravone.The course of treatment for the three groups covered 14 days.Before and after treatment,the three groups were observed in the changes of National Institutes of Health Stroke Scale(NIHSS)scores for neurological function,modified Barthel Index(MBI)scores for activities of daily living(ADL),cerebral hemodynamics indicators[peak systolic velocity(PSV),end-diastolic velocity(EDV),mean velocity(Vm),pulsatility index(PI),and resistance index(RI)],neurofactors[neuron-specific enolase(NSE),S100β protein(S100β),and myelin basic protein(MBP)],vascular endothelial function indicators[von Willebrand factor(VWF),endothelin 1(ET-1),and nitric oxide(NO)],and levels of serum sCD40L,Lp-PLA2,and GA.After treatment,the clinical efficacy and the incidence of adverse reactions among the three groups of patients were compared.Results(1)After 14 days of treatment,the total effective rate of the study group was 94.87%(37/39),which was significantly higher than that of control group 1[71.79%(28/39)]and control group 2[76.92%(30/39)],the differences being statistically significant(P<0.05).No statistically significant difference was shown between control group 1 and control group 2(P>0.05).(2)After treatment,the cerebral hemodynamics indicators of PSV,EDV,Vm,and PI of the middle cerebral artery(MCA)in the three groups were increased compared with those before treatment(P<0.05),and the RI was decreased compared with that before treatment(P<0.05).The increase of PSV,EDV,Vm,and PI of the MCA and the decrease of RI in the study group were significantly superior to those in control group 1 and control group 2(P<0.05).No statistically significant differences in PSV,EDV,Vm,PI,and RI of MCA were shown between control group 1 and control group 2 after treatment(P>0.05).(3)After treatment,the serum sCD40L,Lp-PLA2,and GA levels in the three groups were decreased compared with those before treatment(P<0.05),and the decrease in the study group was significantly superior to that in control group 1 and control group 2(P<0.05).However,the differences of the serum levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(4)After treatment,the serum levels of neurofactors of NSE,S100β,and MBP in the three groups were all decreased compared with those before treatment(P<0.05),and the decrease of the serum levels in the study group was significantly superior to that in control group 1 and control group 2,while the differences of the serum levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(5)After treatment,the vascular endothelial function indicators of serum vWF and ET-1 levels in the three groups were decreased compared with those before treatment(P<0.05),and the serum NO level was increased compared with that before treatment(P<0.05).The decrease of serum vWF and ET-1 levels and the increase of serum NO level in the study group were significantly superior to those in control group-1 and control group-2(P<0.05),while the difference of serum vWF,ET-1 and NO levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(6)After treatment,the NIHSS scores for neurological function in the three groups were decreased(P<0.05)and the MBI scores for ADL were increased(P<0.05)compared with those before treatment,and the decrease of the NIHSS scores and the increase of the MBI scores in the study group was significantly superior to those in control group 1 and control group 2(P<0.05),while and the differences of NIHSS and MBI scores after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(7)The incidence rate of adverse reactions was 15.38%(6/39)in the study group,7.69%(3/39)in the control group 1,and 12.82%(5/39)in the control group 2,and the pairwise comparison between groups showed that the difference was not statistically significant(P>0.05).Conclusion Zhi Long Huoxue Tongyu Capsules combined with Edaravone exert certain efficacy in the treatment of patients with ICVD of qi deficiency and blood stasis syndrome,and the combined therapy is effective on improving blood circulation,restoring neurological function,enhancing the ADL,with higher safety.Its therapeutic mechanism may be related to the improvement of the vascular endothelial function,and the down-regulation of serum levels of neurofactors of NSE,S100 β,MBP,and serum expression levels of sCD40L,Lp-PLA2,and GA.

The anti-aging Klotho gene can not only delay the aging process but also regulate fibrosis and inflamma-tory responses by influencing inflammatory cells such as monocytes-macrophages,T cells,and B cells.It can regu-late the processes related to fibrosis and inflammatory responses through inflammatory pathways such as fibroblast growth factor(FGF),transforming growth factor-β(TGF-β),Toll-like receptor(TLR),nuclear factor-κB(NF-κB),and the renin-angiotensin system(RAS).Thus,elucidating the molecular mechanisms by which Klotho regulates inflammatory responses and fibrosis,and developing targeted intervention strategies to upregulate Klotho levels based on these mechanisms,may provide new theoretical basis and therapeutic targets for the prevention and treatment of related diseases.