ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

From the theoretical perspective of "body fluids and blood stasis mixing"， environmental microplastics （MPs） are conceptualized as a "novel turbid-toxin". This study aims to elucidate the complete pathogenic pathway through which MPs act as a key driving force （the "crucible" of pathogenesis） in the initiation and progression of atherosclerosis （AS）. By tracing the classical theories in the Chapter The Occurrence of All Diseases of Miraculous Pivot （Ling Shu）， this paper clarifies the core connotations of "body fluids"-it not only refers to endogenous pathological fluids and lipid turbidity but also provides a theoretical basis for incorporating "exogenous turbid fluids"， thereby laying a logical foundation for conceptualizing MPs as a "novel turbid-toxin". Meanwhile， the implications of "blood" （encompassing both blood quality abnormalities and blood stasis） and the dynamic process of "mixing" are elucidated. Drawing upon modern toxicological evidence， this paper demonstrates the high homology between MPs and "exogenous turbid-fluids" from three aspects： Morphology， toxicity， and invasion routes. The micro/nano-scale particle morphology of MPs enables mobility within the bloodstream. The multiple exposure pathways of MPs correspond to the traditional Chinese medicine understanding of pathogens invading through the mouth， nose， and skin. The characteristics of accumulating in vivo while inducing oxidative stress and inflammatory responses of MPs fully embody the pathogenic features-adhesion， binding， and vessel damage-of "turbid-toxin". On this basis， the dynamic pathogenesis of MP-induced AS is systematically interpreted. Initially， MPs with the "turbid-toxin" nature impair nutrient-defense harmony and cause endothelial dysfunction. Subsequently， as the core of "mixing"， they interact with blood lipids and immune cells， generating heat and phlegm to form a major pathological hub of chronic inflammation. Ultimately， this process drives the coalescence of phlegm， stasis， and turbid-toxin into tangible plaques， evolving from stable lesions to vulnerable masses and accumulations. By integrating classical pathogenic model with contemporary environmental medicine， this study establishes an analytical framework that bridges macro-theory and micro-mechanisms for understanding the cardiovascular risks of MPs through an integrative Chinese-Western medicine lens.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

Objective To explore the mediating role of mindfulness between work immersion and professional well-being in clinical nurses. Methods A total of 477 clinical nurses were selected as the research subjects using the convenience sampling method. The levels of mindfulness, work immersion, and professional well-being among the clinical nurses were surveyed using the Mindful Attention Awareness Scale, the Emergency Department Nurse Work Immersion Experience Questionnaire, and the Medical Workers' Professional Well-being Scale, respectively. A structural equation model was constructed using AMOS 26.0 software. Results The total scores of mindfulness level, work immersion, and professional well-being among clinical nurses were (68.9±11.4), (134.1±20.2), and (89.1±12.6) points, respectively. The total score of mindfulness level was positively correlated with work immersion and professional well-being [correlation coefficients (r) were 0.566 and 0.344, respectively, both P<0.01], and the total score of work immersion was positively correlated with professional well-being (r=0.431, P<0.01). The mediating effect of mindfulness in work immersion and professional well-being was 0.059, with a 95% confidence interval of (0.014-0.108), accounting for 19.5% of the total effect. Conclusion The level of mindfulness among clinical nurses is relatively high. Mindfulness plays a partial mediating role between work immersion and professional well-being.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Objective To investigate the potential mechanism of miR-21-5p in alleviating cerebral ischemia-reperfusion injury by targeting STAT3.Methods The HT22 cells were induced by OGD/R to construct a cell model of cerebral ischemia reperfusion injury.The expression of miR-21-5p was detected by RT-qPCR.The CCK-8 assay,TUNEL staining and flow cytometry were respectively used to detect the cell viability and apoptosis.ELISA assay was used to determine the contents of inflammatory factors IL-6,IL-10 and TNF-α in the cell supernatant.Western blot was used to detect the expression levels of p-STAT3/STAT3,Cleaved-Caspase-3,Bax and Bcl-2 proteins.The TargetScan database was used to predict the binding sites of miR-21-5p and STAT3.The dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-21-5p and STAT3.Results The relative expression level of miR-21-5p was down-regulated in HT22 cells which induced by OGD/R(P<0.001).The cell viability(P<0.0001)was decreased and the apoptosis rate(P<0.001)was increased in OGD/R induced-HT22 cells.The contents of pro-inflammatory factors IL-6(P<0.001)and TNF-α(P<0.001)was increased,while the content of anti-inflammatory factor IL-10(P<0.001)decreased.After transfection with miR-21-5p mimic,cell viability was enhanced,apoptosis rate was reduced and neuroinflammation was inhibited.MiR-21-5p could target and bind to STAT3.After miR-21-5p inhibitor transfection,cell viability decreased,apoptosis was promoted,and neuroinflammation occurred;STAT3 inhibitor Stattic could reverse the effect of miR-21-5p inhibitor.Conclusion MiR-21-5p could specifically bind to STAT3 and reduce the neuroinflammation and apoptosis of OGD/R induced-HT22 cells.

AIM To study the chemical constituents from Pyrolae Herba and their activity against pathogenic bacteria associated with sports injuries.METHODS Silica gel and Sephadex LH-20 were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antibacterial activity was detected by filter paper method.RESULTS Twenty five compounds were isolated and identified as manuleoside H(1),5-hydroxy-3,7-dimethoxy-4,-methyl flavone(2),5-hydroxy-3,7,4'-methoxy-flavone(3),5-hydroxy-7,3',4'-trimethoxy-flavone(4),5,7-dihydroxy-3-methoxy-flavone(5),7.5,4'-trihydroxyflavone(6),ethyl vanillate(7),clovandiol(8),hydroxydihydrobovolide(9),zanthopyranone(10),eugenin(11),berchemol(12),3,7-dimethoxy-5,3',4'-trihydroxyflavone(13),2,5-dimethyl-7-hydroxychromone(14),rutalinium(15),formononetin(16),8-hydroxy-4',7-dimethoxy-isoflavones(17),isoline(18),dearabinosyl pneumonanthoside(19),3,5-dihydroxycinnamic acid(20),2,4,6-trihydroxyacetophenone(21),p-isopropyl benzoic acid(22),geraldone(23),ethylsyringin(24),4-hydroxyphenylethyl-2'-hydroxypropionate(25).Compounds 8,10,12,16 and 24 showed bacteriostatic zone on pathogenic bacteria susceptible to sports injuries.CONCLUSION All the compounds are isolated from Pyrolae Herba for the first time.Compounds 8,10,12,16 and 24 have inhibitory activity against pathogenic bacteria susceptible to sports injuries.

Neuroscience,a cutting-edge field in interdisciplinary research,consistently draws considerable research interest,of which quantitatively probing the neurochemical dynamics is essential for brain science research.In vivoelectrochemical analysis,featuring with high sensitivity,high spatiotemporal resolution,free from transfection,and designable electrode/solution interfaces,provides important tools for in vivo neurochemicals sensing.Fast scan cyclic voltammetry combined with microelectrodes can not only enable precise detection of dopamine but also is compatible with existing neurosurgical equipment.This offers new opportunities for the clinical application of in vivo electrochemical analysis and paves new avenues for the diagnosis and treatment of neurological diseases.This review summarized recent progress of in vivo electrochemical techniques for brain neurochemistry and addressed key clinical challenges and their potential solutions.