ObjectiveTo investigate the effects of Xijiao Dihuangtang （XJDHT） on mice with sepsis and cellular models of sepsis and explore its molecular mechanism in alleviating sepsis-induced inflammatory responses via regulating pyruvate kinase M2 （PKM2）-mediated one-carbon metabolism pathway. MethodsForty C57BL/6N mice were randomly divided into four groups： normal group， model group， low-dose XJDHT group （7.7 g·kg^-1）， and high-dose XJDHT group （15.4 g·kg^-1）. After one week of continuous gavage， sepsis was induced using cecal ligation and puncture （CLP） in groups except the normal group. 24 h after the surgery， mortality rates in all groups were recorded， and serum cytokines were measured by enzyme linked immunosorbent assay （ELISA）. Lung histopathology was examined by hematoxylin-eosin （HE） staining. During the in vitro experiment， the human monocytic leukemia cell line （THP-1） was exposed to various concentrations of XJDHT and treated with lipopolysaccharide （LPS） at a final concentration of 2 mg·L^-1 for 24 h. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. Protein levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were measured by Western blot. Transcriptome sequencing was performed to analyze differentially expressed genes in all groups and conduct gene ontology （GO） enrichment. Key genes in the one-carbon metabolism pathway， including pyruvate kinase M2 （PKM2）， 5-methyltetrahydrofolate-homocysteine methyltransferase （MTR）， and phosphoglycerate dehydrogenase （PHGDH）， were verified by Western blot. A PKM2 inhibition model was established using shikonin for further protein expression analysis. ResultsAnimal experiments showed that compared with the normal group， the model group exhibited significantly elevated body temperature and lung pathology （P<0.01） and increased serum TNF-α and IL-1β levels （P<0.01）. High-dose XJDHT reduced body temperature and lung tissue damage （P<0.01） and significantly decreased serum TNF-α and IL-1β levels （P<0.01）. Low-dose XJDHT treatment showed no significant temperature change （P<0.01） but reduced serum TNF-α and IL-1β levels （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Cell experiments demonstrated that compared to the normal group， the model group showed elevated protein expressions of TNF-α and IL-1β in THP-1 cells （P<0.01）， decreased Bcl-2/Bax ratio， and increased apoptosis （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Compared to the model group， high-dose XJDHT significantly increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.01） and effectively reduced cell apoptosis （P<0.01） while down-regulating protein expressions of TNF-α， IL-1β， PKM2， and MTR （P<0.01）. Low-dose XJDHT moderately increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.05）， reduced apoptosis （P<0.05）， and decreased IL-1β and MTR protein levels （P<0.05， P<0.01）， but there were no significant changes in TNF-α and PKM2 expression. After PKM2 inhibition by shikonin in THP-1 cells， the expression of protein related to one-carbon metabolism was detected. Compared with the blank group， the LPS-induced model group showed significantly upregulated PKM2 and MTR protein expression （P<0.01） and downregulated PHGDH expression （P<0.01）. Compared with the model group， shikonin treatment significantly reduced PKM2 expression （P<0.05）， increased PHGDH expression （P<0.01）， and decreased MTR expression （P<0.05）. ConclusionXJDHT can inhibit the release of inflammatory factors in sepsis， and its mechanism is related to the intervention of the PKM2-regulated one-carbon metabolism pathway in macrophages.

OBJECTIVE: To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro. METHODS: Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo. RESULTS: Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05). CONCLUSION Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals ; Sirtuin 1/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Autophagy/drug effects* ; Male ; Intestinal Mucosa/drug effects* ; Rats, Sprague-Dawley ; Epithelial Cells/metabolism* ; Colon/drug effects* ; Humans ; Kidney Failure, Chronic/drug therapy* ; Signal Transduction/drug effects* ; Renal Dialysis ; Rats ; Kidney/drug effects*

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.

Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6％ in trial group and 83.5％ in control group(P=0.657).The difference between the two groups was 2.11(95％CI-7.19-11.41).Given that the lower confidence limit of the 95％CI was greater than-12％,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5％ in trial group and 77.7％ in control group(P=0.970).The difference between the two groups was-0.21(95％CI-10.95-10.54),with the lower bound of the 95％CI exceeding-12％.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95％CI-10.0-0.1).As the lower limit of the 95％CI exceeded-12％,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7％,6.3％,2.7％and 69.4％in trial group,and 22.3％,4.1％,6.6％ and 66.9％ in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7％ in trial group and 7.1％ in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4％ vs.4.7％,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2％ vs.15.0％,P=0.144).There was no significant difference in the incidence of major bleeding(1.7％ vs.0.8％,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective The study aims to investigate the impact of microRNA-874-3p(miR-874-3p)regulation of plakophilin 3(PKP3)on the malignant biological behavior of lung adenocarcinoma cells and its underlying mechanism.Methods Immunohistochemistry and immunocytochemistry were used to detect the expression of PKP3 in lung adenocarcinoma tissue microarray and lung adenocarcinoma cell line A549 cells respectively,and the relationship between PKP3 and clinicopathological features of lung adenocarcinoma patients was analyzed.Select lung adenocarcinoma cell line A549,the experiment was divided into A549 cell group(blank control group),miR-NC group(transfected with miR-NC)and miR-mimics group(transfected with miR-874-3p mimics),sh-NC group(control group transfected with PKP3 silencing plasmid),sh-PKP3 group(transfected with PKP3 silencing plasmid),miR+pcDNA-PKP3 group(transfected with miR-874-3P mimics+pcDNA-PKP3,rescue group)and miR+pcDNA-NC group(transfected with miR-874-3p mimics+pcDNA-NC).The proliferation,invasion,migration and apoptosis of cells in each group were detected.ENCORI database was used to predict the upstream gene of PKP3,and dual luciferase assay was used to detect the targeting relationship between miR-874-3p and PKP3.MAPK/mTOR pathway-related proteins were detected by Western blotting.Results The expression of PKP3 in lung adenocarcinoma tissue was significantly higher than that in adjacent tissues.The high expression of PKP3 was related to clinical stage,tumor size,and lymph node metastasis(P＜0.05).Compared with the human normal lung epithelial cells(BEAS-2B),the expression of PKP3 in A549 cells increased significantly,and the expression of miR-874-3p decreased(P＜0.05).Overexpression of miR-874-3p decreased the PKP3 expression level(P＜0.05).Compared with the control group,both overexpression of miR-874-3p and silenced PKP3 inhibited the cloning and invasion ability of A549 cells,caused cell cycle arrest,and decreased the expression levels of cyclin dependent kinase 4(CDK4),cyclin D1,cyclin E1 proteins in A549 cells(P＜0.05).The expressions of Bax protein and Caspase-3 protein were up-regulated(P＜0.05),and apoptosis increased.Overexpression of PKP3 could reverse the biological behavior of overexpression of miR-874-3p.Overexpression of miR-874-3p and silencing of PKP3 significantly decreased the expressions of P38 MAPK and mTOR phosphorylated proteins.Conclusion MiR-874-3p can negatively regulate PKP3 expression and inhibit the malignant biological behavior of A549 cells through MAPK/mTOR pathway.