Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective This study aimed to investigate the effects of sitagliptin on the proliferation,apoptosis,in-flammation,and osteogenic differentiation of human periodontal ligament stem cells(hPDLSCs)in lipopolysaccharide(LPS)-induced inflammatory microenvironment and its molecular mechanism.Methods hPDLSCs were cultured in vitro and treated with different concentrations of sitagliptin to detect cell viability and subsequently determine the exper-imental concentration of sitagliptin.An hPDLSCs inflammation model was established after 24 h of stimulation with 1 μg/mL LPS and divided into blank,control,low-concentration sitagliptin(0.5 μmol/L),medium-concentration sita-gliptin(1 μmol/L),and high-concentration sitagliptin(2 μmol/L),high-concentrationsitagliptin+stromal cell derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway inhibitor(AMD3100)(2 μmol/L+10 μg/mL)groups.A cell-counting kit-8 was used to detect the proliferation activity of hPDLSCs after 24,48,and 72 h culture.The apoptosis of hPDLSCs cultured for 72 h was detected by flow cytometry.After inducing osteogenic differentiation for 21 days,alizarin red staining was used to detect the osteogenic differentiation ability of hPDLSCs.The alkaline phosphatase(ALP)activity in hPDLSCs was determined using a kit.The levels of inflammatory factors[tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-6]in the supernatant of hPDLSCs culture were detected by enzyme-linked immu-nosorbent assay.The mRNA expressions of osteogenic differentiation genes[Runt-associated transcription factor 2(RUNX2),osteocalcin(OCN),osteopontin(OPN)],SDF-1 and CXCR4 in hPDLSCs were detected by real-time fluores-cence quantitative polymerase chain reaction(RT-qPCR).Western blot analysis was used to determine SDF-1 and CX-CR4 protein expression in hPDLSCs.Results Compared with the blank group,the proliferative activity,number of mineralized nodules,staining intensity,ALP activity,and RUNX2,OCN,OPN mRNA,SDF-1,and CXCR4 mRNA and protein expression levels of hPDLSCs in the control group significantly decreased.The apoptosis rate and levels of TNF-α,IL-1β,and IL-6 significantly increased(P<0.05).Compared with the control group,the proliferative activity,number of mineralized nodule,staining intensity,ALP activity,and RUNX2,OCN,OPN mRNA,SDF-1,and CXCR4 mRNA and protein expression levels of hPDLSCs in low-,medium-,and high-concentration sitagliptin groups in-creased.The apoptosis rate and levels of TNF-α,IL-1β,and IL-6 decreased(P<0.05).AMD3100 partially reversed the effect of high-concentration sitagliptin on LPS-induced hPDLSCs(P<0.05).Conclusion Sitagliptin may promote the proliferation and osteogenic differentiation of hPDLSCs in LPS-induced inflammatory microenvironment by activating the SDF-1/CXCR4 signaling pathway.Furthermore,it inhibited the apoptosis and inflammatory response of hPDLSCs.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.

Carbapenem-resistant Enterobacteriaceae bacteria are widespread worldwide,with carbapenem-resistant Klebsiella pneumoniae being the most obvious,and these bacteria are usually resistant to clinically used antibiotics.In the context of the limited development and application of new drugs,and the unclear effica-cy of combination therapy,this article analyzes the relevant literature on the prevention,single and combina-tion therapy of carbapenem-resistant Klebsiella pneumoniae infection,and delays the occurrence of drug resist-ance through the linkage of prevention and anti-infective therapy in the case of carbapenemase epidemic and increasing antibiotic resistance,so as to provide a new strategy for preventing the spread of drug-resistant bac-teria and anti-infective therapy.

Objective To analyze the correlation between serum levels of long non-coding RNA cyclin-de-pendent kinase inhibitor 2B antisense RNA 1(lncRNA CDKN2B-AS1),and microRNA-184(miR-184)in pa-tients with acute coronary syndrome(ACS)and the occurrence of coronary artery restenosis(RS)after percu-taneous coronary intervention(PCI)treatment.Methods A total of 288 ACS patients who underwent PCI treatment in the hospital from February 2020 to March 2023 were selected.According to the results of follow-up angiography at 6 months after surgery,they were separated into a RS group of 96 cases and a non RS group of 192 cases.The quantitative real-time PCR(qRT-PCR)method was applied to detect the relative expression levels of serum lncRNA CDKN2B-AS1 and miR-184.Pearson correlation was applied to analyze the correlation between serum lncRNA CDKN2B-AS1 and miR-184.The factors affecting the occurrence of RS in ACS pa-tients after PCI were analyzed using multivariate Logistic regression analysis.Receiver operating characteristic(ROC)curve was applied to analyze the evaluation value of serum lncRNA CDKN2B-AS1 and miR-184 for the occurrence of RS in ACS patients after PCI.Results Compared with the non RS group,the serum lncRNA CDKN2B-AS1 level in the RS group was obviously increased,while the miR-184 level was obviously reduced(P＜0.05).There were statistically significant differences in the levels of high-sensitivity C-reactive protein(hs-CRP),interleukin-18(IL-18),total bilirubin(TBIL),and cardiac troponin Ⅰ(cTnⅠ)between the two groups(P＜0.05).Pearson correlation analysis showed that there was a obvious negative correlation(r=-0.427,P＜0.05)between the expression levels of serum lncRNA CDKN2B-AS1 and miR-184 in ACS pa-tients.Multivariate Logistic regression analysis results showed that lncRNA CDKN2B-AS1,hs-CRP,IL-18,and cTnⅠ were risk factors affecting the occurrence of RS in ACS patients after PCI,while miR-184 and TBIL were protective factors affecting the occurrence of RS in ACS patients after PCI(P＜0.05).ROC curve re-sults showed that the area under the curve(AUC)of serum lncRNA CDKN2B-AS1,miR-184,and their com-bination in evaluating the occurrence of RS in ACS patients after PCI was 0.787,0.844,and 0.929,respective-ly,and the AUC of the combined evaluation the occurrence of RS in ACS patients after PCI was obviously higher than those of serum lncRNA CDKN2B-AS1 and miR-184 alone(Zcombination-lncRNACDKN2B-AS1=4.490,Zcombination-miR-184=3.429,all P＜0.05).Conclusion The serum lncRNA CDKN2B-AS1 level in ACS patients is obviously elevated,while miR-184 level is obviously reduced,which is correlated with the occurrence of RS in ACS patients after PCI.Both are factors that affect the occurrence of RS in ACS patients after PCI,and the combination of the two has better evaluation effect on the occurrence of RS in ACS patients after PCI.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

Objective To explore the factors influencing the efficacy of conventional Western medicine treatment for patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD),and to provide a basis for individualized clinical treatment.Methods 100 patients with AECOPD were prospectively included in this study,and all of them were given standard treatment plans according to the guidelines.After 3 months of follow-up observation,53 cases were evaluated as effective and included in the effective group;47 cases were evaluated as having no significant effect and included in the ineffective group.Differences in basic characteristics between the two groups in terms of age,duration of COPD,respiratory rate,lung function and consolidated malignancy were compared,and pre-treatment laboratory test indexes and blood gas analysis data were collected for comparison.Results There were significant differences between the two groups in terms of age,duration of COPD,respiratory rate,ratio of forced expiratory volume in one second to forced vital capacity(FEV1/FVC%),consolidated malignancy,hemoglobin,lymphocytes,C-reactive protein,glutamic-pyruvic transaminase and PaCO2(P<0.05).Univariate logistic regression analysis showed that older age,prolonged COPD duration,increased respiratory rate,decreased FEV1/FVC%,consolidated malignancy,decreased hemoglobin,decreased lymphocyte count,increased C-reactive protein,increased glutamic-pyruvic transaminase,increased lactate,and increased PaCO2 were risk factors for poor treatment outcome in AECOPD.Further multifactorial logistic regression analysis showed that age(P=0.007,OR=1.240),FEV1/FVC%(P=0.014,OR=0.757),hemoglobin(P=0.038,OR=0.954),lymphocyte count(P=0.007,OR=0.488),and lactate(P=0.002 OR=9.964)were independent risk factors affecting the efficacy of AECOPD treatment.ROC curve analysis showed that the AUCs for age,FEV1/FVC%,hemoglobin,lymphocyte count and lactate were 0.728[95%CI(0.627,0.829)],0.681[95%CI(0.576,0.785)],0.686[95%CI(0.582,0.790)],0.629[95%CI(0.520,0.737)]and 0.823[95%CI(0.744,0.902)],respectively,and the combined AUC of the five risk factors for predicting a poor AECOPD treatment outcome was 0.957[95%CI(0.923,0.991).Conclusion Age,FEV1/FVC%,hemoglobin,lymphocyte count and lactate are independent risk factors that influence the treatment outcome of AECOPD patients.The comprehensive analysis of these risk factors can predict the treatment effect of AECOPD more accurately,help clinicians adjust the treatment plan in time,and improve the treatment effect and prognosis.