ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective To explore the mechanism of Gualou Xiebai Baijiu Decoction(GXB)in improving atherosclerosis(AS)in mice by regulating the gut microbiota(GM)and its metabolites.Methods Thirty-two male ApoE-/-mice were divided randomly into a Blank group,Model group,atorvastatin(Ato)group,and GXB group(n=8 mice per group).AS was established in all mice,except the Blank group,and the respective treatments were administered by gavage.Aortic plaques were detected by Oil red O staining and pathological changes in aortic tissue were detected by hematoxylin and eosin staining.The GM was analyzed using 16S rRNA gene sequencing technology,and mouse GM metabolites,including trimethylamine oxide(TMAO),short-chain fatty acids(SCFA),and serum levels of triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)were determined.Results Compared with the Blank group,mice in the Model and Ato groups showed an increase in AS plaque area(P＜0.05).Serum levels of TG,TC,and LDL-C were increased(P＜0.001)while levels of HDL-C and NO were decreased(P＜0.01,P＜0.001)in the Model group compared with the Blank group.The plaque area was decreased(P＜0.05),serum levels of TG,TC,and LDL-C were decreased(P＜0.001),and NO levels were increased(P＜0.01)in the Ato and GXB groups,while HDL-C levels were increased in the GXB group(P＜0.05)compared with the Model group.Plaque area was decreased(P＜0.05)and the NO level was increased(P＜0.01)in the GXB group compared with the Ato group.A total of 6345 characteristic sequences were obtained from 16S rRNA analysis.α-Diversity analysis indicated that GXB reduced the richness of the GM in AS mice(P＜0.001)and improved its uniformity(P＜0.05).β-Diversity analysis suggested that the microbial community structure in the GXB group was similar to that in the Blank group.The abundance of microbial communities differed among the groups at the phylum and genus levels.At the phylum level,the abundance of Proteobacteria was increased(P＜0.01)in AS mice,while GXB intervention reduced the abundance of Proteobacteria(P＜0.01)and increased the abundance of Verrucomimicrobiota(P＜0.05).At the genus level,GXB effectively increased the abundance of Akkermansia(P＜0.05).SCFAs were significantly increased(P＜0.01)and TMAO levels were significantly decreased(P＜0.01)in the GXB group compared with the Model group.Conclusions GXB can regulate the intestinal flora and intestinal flora metabolites SCFA and TMAO to improve AS.Akkermansia may be a key bacterial genus of the gut microbiota through which GXB may improve AS.

Background Oral exposure to metals/metalloid elements in drinking water may be harmful to human health. Objective To assess potential health risks of oral exposure to 9 metals/metalloids in drinking water in Zibo City of Shandong Province from 2019 to 2023, and provide reference for the development of local drinking water management policies. Method From 2019 to 2023, a total of 1178 drinking water samples were collected from 261 rural water monitoring sites and 14 urban water monitoring sites in 8 districts and counties of Zibo City. The US Environmental Protection Agency's (EPA) four-step health assessment model was used to evaluate the health risks of oral exposure to 9 metals/metalloids in drinking water for adults. Results A total of 1178 water samples were collected, including 561 urban water samples and 617 rural water samples; 769 samples of tap water and 409 samples of finished water; 634 samples collected in wet season and 544 in dry season. The median carcinogenic risk (CR) of arsenic exposure in drinking water for adults was 3.53×10⁻⁵, and the median hazard quotient (HQ) was 7.85×10⁻². The HQs of arsenic and zinc showed an upward trend in recent years, while the HQ of aluminum showed a downward trend. The stratified analysis results showed that there was no statistically significant difference in the CR of arsenic between males and females or between urban water and rural water. The CR of arsenic in dry season was higher than that in wet season, and the CR of arsenic in tap water was higher than that in finished water (P<0.05). There was no statistically significant difference in the HQs of 9 metals/metalloids in drinking water between males and females. The HQs of aluminum, copper, arsenic, selenium, and cadmium in tap water were higher than those in finished water (P<0.05). In dry season, the HQs of aluminum, manganese, copper, zinc, arsenic, and selenium were higher than those in wet season (P<0.05). The HQs of aluminum, copper, zinc, cadmium, and lead in urban water were higher than those in rural water (P<0.05). Conclusion The overall health risks of 9 metal/metalloid pollutants in drinking water in Zibo City are lower than the maximum acceptable risk recommended by the US EPA, and suggest an acceptable level and no significant harm to adult health. The health risk of arsenic is relatively high and should be given priority by relevant departments in drinking water risk management.

Objective: To explore the impact of cognitive emotion regulation strategies on fear of negative evaluation among college students using a random forest algorithm in order to provide empirical evidence to support mental health improvements. Methods: In March 2024, a convenience sampling method was used to conduct an online survey with 5 750 college students from three universities in Wuhan, Hubei Province. A least squares regression model was employed to analyze whether cognitive emotion regulation strategies significantly influenced fear of negative evaluation. A random forest model was also constructed to identify predictors and rank the importance of various factors affecting fear of negative evaluation. Results: The least squares regression model indicated that cognitive emotion regulation strategies significantly impacted fear of negative evaluation among college students ( β=4.25, 95%CI=3.81-4.68, P <0.05). Family support, including mild impairment ( β=-2.71, 95%CI =-3.36 to -2.06, P <0.05) and severe impairment in the domain ( β=-1.64, 95%CI =-2.27 to -1.01, P <0.05), were associated with increased fear. The random forest model further revealed that cognitive emotion regulation strategies, family support index, and academic ranking were the main factors affecting the fear of negative evaluation among college students. Conclusions Cognitive emotion regulation strategies are key factors influencing fear of negative evaluation among college students. Universities should provide enhanced mental health resources, offer training to strengthen cognitive emotion regulation strategies, and offer additional support to students with low family support.

Objective To investigate the effects of Sacoharomyces boulardii combined with ursodeoxycholic acid on serum levels of gamma-glutamate transpeptidase(γ-GT),insulin like growth factor-1(IGF-1)and retinol binding protein(RBP)in neonates with hyperbilirubinemia.Methods Neonatal hyperbilirubinemia children were divided into control group and treatment group by cohort method.The control group was given ursodeoxycholic acid,5 mg·kg-1 each time,twice a day,and took the tablet powder in warm water;the treatment group was additionally treated with Sacoharomyces boulardii on the basis of the control group,1 bag each time,orally once every 24 h.The clinical efficacy,yellows regression,serum total bilirubin(TBIL),indirect bilirubin(IBIL),transferrin(TRF)levels and serum γ-GT,IGF-1 and RBP levels before and after treatment were compared between the two groups.And evaluated the safety.Results 152 cases in treatment group and 148 cases in control group were enrolled.After treatment,the clinical efficacy of the treatment group and control group was 94.08％(143 cases/152 cases)and 81.76％(121 cases/148 cases);the re-phototherapy rate was 8.55％(13 cases/152 cases)and 20.95％(31 cases/148 cases),the difference was statistically significant(all P＜0.05).The duration of phototherapy in the treatment group and control group were(20.17±5.32)and(26.39±7.69)h;the decolorization time were(3.97±0.60)and(5.59±0.83)d;the hospital stay were(7.17±0.66)and(9.16±0.90)d;the TBIL were(133.26±15.69)and(179.15±17.65)μmol·L-1;the IBIL were(141.88±18.19)and(198.65±19.26)μmol·L-1;the γ-GT were(38.19±3.75)and(50.87±4.25)U·L-1;the RBP were(20.42±3.21)and(25.50±3.43)mg·L-1;the IGF-1 were(20.43±3.06)and(26.51±3.38)ng·L-1;the TRF were(1.98±0.27)and(1.65±0.20)g·L-1,the difference was statistically significant(all P＜0.05).The adverse drug reactions of treatment group and control group were diarrhea,nausea and vomiting,rash.The total incidence of adverse reactions in treatment group and control group was 8.52％(13 cases/152 cases)and 9.46％(14 cases/148 cases),there was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The treatment of neonatal hyperbilirubinemia with yeast burra combined with ursodeoxychonic acid can effectively improve the levels of serum γ-GT,IGF-1 and RBP,and the clinical efficacy is good.

Objective To investigate the effects of Sacoharomyces boulardii combined with ursodeoxycholic acid on serum levels of gamma-glutamate transpeptidase(γ-GT),insulin like growth factor-1(IGF-1)and retinol binding protein(RBP)in neonates with hyperbilirubinemia.Methods Neonatal hyperbilirubinemia children were divided into control group and treatment group by cohort method.The control group was given ursodeoxycholic acid,5 mg·kg-1 each time,twice a day,and took the tablet powder in warm water;the treatment group was additionally treated with Sacoharomyces boulardii on the basis of the control group,1 bag each time,orally once every 24 h.The clinical efficacy,yellows regression,serum total bilirubin(TBIL),indirect bilirubin(IBIL),transferrin(TRF)levels and serum γ-GT,IGF-1 and RBP levels before and after treatment were compared between the two groups.And evaluated the safety.Results 152 cases in treatment group and 148 cases in control group were enrolled.After treatment,the clinical efficacy of the treatment group and control group was 94.08％(143 cases/152 cases)and 81.76％(121 cases/148 cases);the re-phototherapy rate was 8.55％(13 cases/152 cases)and 20.95％(31 cases/148 cases),the difference was statistically significant(all P＜0.05).The duration of phototherapy in the treatment group and control group were(20.17±5.32)and(26.39±7.69)h;the decolorization time were(3.97±0.60)and(5.59±0.83)d;the hospital stay were(7.17±0.66)and(9.16±0.90)d;the TBIL were(133.26±15.69)and(179.15±17.65)μmol·L-1;the IBIL were(141.88±18.19)and(198.65±19.26)μmol·L-1;the γ-GT were(38.19±3.75)and(50.87±4.25)U·L-1;the RBP were(20.42±3.21)and(25.50±3.43)mg·L-1;the IGF-1 were(20.43±3.06)and(26.51±3.38)ng·L-1;the TRF were(1.98±0.27)and(1.65±0.20)g·L-1,the difference was statistically significant(all P＜0.05).The adverse drug reactions of treatment group and control group were diarrhea,nausea and vomiting,rash.The total incidence of adverse reactions in treatment group and control group was 8.52％(13 cases/152 cases)and 9.46％(14 cases/148 cases),there was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion The treatment of neonatal hyperbilirubinemia with yeast burra combined with ursodeoxychonic acid can effectively improve the levels of serum γ-GT,IGF-1 and RBP,and the clinical efficacy is good.