ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

Hematologic malignancies are a severe threat to human health.CAR-T cell therapy,as a highly effective treatment for hematologic malignancies,has become one of the fastest developing cancer immunotherapies in recent years.To obtain highly effective and low-toxicity CAR-T cells,through continuous development and exploration,CAR-T cell therapy has achieved a series of significant breakthroughs in treating hematologic malignancies,including humanized CAR-T cell technology,dual-target and multitarget CAR-T cell technology,universal CAR-T cell technology,and CAR-T cell combination strategy technology.Humanized CAR-T cell technology reduces immunogenicity through humanized modification.Dual-target and multi-target CAR-T cell technology recognizes two or more tumor antigens,minimizes antigen escape and enhance efficacy.Universal CAR-T cell technology solves problems such as high cost and accessibility issues.The CAR-T cell combination strategy technology effectively deals with CAR-T recurrence and enhances efficacy and safety by combining different treatment methods.Although CAR-T cell therapy has achieved significant breakthroughs in the treatment of hematologic malignancies,it still faces challenges such as drug resistance,antigen escape,cytotoxicity,and posttreatment recurrence.This review presents the significant breakthroughs,existing problems,and solutions for CAR-T cell precise therapy for hematological malignancies.

The host-microbe co-metabolism system, generating diverse exogenous and endogenous bioactive molecules that influence the host's immune and metabolic functions, plays a crucial role in the pathogenesis of atherosclerosis. Recent studies have elucidated the interaction between natural medicines and this co-metabolism system. Upon oral administration, natural medicine ingredients can undergo transformation by gut microbiota, potentially enhancing their bioavailability or anti-atherogenic efficacy. Furthermore, natural medicines can exert anti-atherogenic effects via modulation of endogenous host-microbe co-metabolism. This review presents an updated understanding of the dual association between natural medicines and host-microbe co-metabolites. It explores the critical function of microbial exogenous metabolites derived from natural medicines and uncovers the mechanisms underlying natural medicines' intervention on key nodes of endogenous host-microbe co-metabolism. These insights may offer new perspectives for cardiovascular disease (CVD) treatment and guide future drug discovery efforts.
Humans ; Atherosclerosis/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Biological Products/therapeutic use* ; Animals ; Host Microbial Interactions/drug effects*

Objective:To investigate influences of tetrandrine(Tet)on proliferation,apoptosis and immune escape of melanoma cells by regulating cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)signal pathway.Methods:MV3 cells were divided into NC group,Tet-L group(5 μmol/L),Tet-M group(10 μmol/L),Tet-H group(15 μmol/L),RU.521(cGAS inhibi-tor)group(1 μmol/L),Tet-H+RU.521 group(15 μmol/L+1 μmol/L).Proliferation of MV3 cells was detected by CCK-8 and plate cloning test;apoptosis of MV3 cells was detected by flow cytometry;Western blot was used to detect expressions of proliferating cell nuclear antigen(PCNA),Bcl-2-associated X protein(Bax),TGF-β,cGAS,STING proteins in MV3 cells.Cells in above groups were co-cultured with NK cells for 48 h through Transwell chamber,and named NC co-culture group,Tet-L co-culture group,Tet-M co-culture group,Tet-H co-culture group,RU.521 co-culture group,Tet-H+RU.521 co-culture group,respectively.ELISA was used to detect levels of IFN-γ and Granzyme B in supernatant of co-cultured cells;change of NK cell killing activity was detected.Results:Compared with NC group,A450,cloning rate,PCNA and TGF-β protein expressions of MV3 cells in Tet-L group,Tet-M group and Tet-H group were decreased,apoptosis rate,Bax,cGAS,STING protein expressions were increased,which was in a dose dependent man-ner,change trend of corresponding indexes in RU.521 group was contrary to the above(P<0.05);compared with NC co-culture group,levels of IFN-γ,Granzyme B and NK cell killing activity in supernatant of Tet-L co-culture group,Tet-M co-culture group and Tet-H co-culture group were increased,which was in a dose-dependent manner,change trend of corresponding indexes in RU.521 co-culture group was opposite to the above(P<0.05);RU.521 attenuated inhibition of high-dose Tet on MV3 cell proliferation,immune escape and its promotion on apoptosis.Conclusion:Tet may inhibit melanoma cell proliferation,immune escape and promote cell apoptosis by activating cGAS-STING signal pathway.

The number of maintenance hemodialysis patients in China has been steadily increasing. With the continuous iteration of technological innovations, healthcare has entered a new phase of digital healthcare development. This paper summarizes the overview and development of digital healthcare and its application in patients with maintenance hemodialysis. It also discusses existing challenges and corresponding strategies, aiming to provide references for the development of digital healthcare in hemodialysis.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.

Objective:To explore the chain mediating role of positive coping and health literacy in the relationship between family function and social frailty in patients with diabetic retinopathy (DR) .Methods:A convenience sampling method was used to recruit 320 DR patients who visited the ophthalmology outpatient clinic of Beijing Tongren Hospital, Capital Medical University, from June 2023 to June 2024. Participants completed a general information questionnaire, Family Assessment Device (FAD), Simplified Coping Style Questionnaire (SCSQ), Health Literacy Management Scale (HeLMS), and Social Vulnerability Index (SVI). Spearman correlation analysis was used to examine the pairwise correlations between family function, positive coping, health literacy, and social frailty. The chain mediation model was tested using Model 6 of the PROCESS macro in SPSS 3.5. A total of 320 questionnaires were distributed, and 312 were collected. After excluding those with more than 10% missing items or regular response patterns, 302 valid questionnaires were analyzed, yielding a valid response rate of 94.38% (302/320) .Results:Among the 302 DR patients, the mean scores were as follows: FAD (154.26±9.79), positive coping (18.66±5.21), HeLMS (81.38±10.09), and SVI [13.50 (11.50, 16.00) ]. Univariate analysis revealed that age, gender, education level, employment status, and diabetes duration were significant influencing factors of social frailty ( P<0.05). Spearman correlation analysis showed that family function, positive coping, health literacy, and social frailty were all significantly correlated with each other ( P<0.01). Mediation analysis indicated that family function positively predicted the level of social frailty, with a direct effect value of 0.128, accounting for 65.64% of the total effect. Positive coping and health literacy played a mediating role through three pathways: family function→positive coping→social frailty (effect=0.037, 18.97% of the total effect) ; family function→health literacy→social frailty (effect=0.023, 11.80%) ; and family function→positive coping→health literacy→social frailty (effect=0.007, 3.59%). The total indirect effect was 0.067, accounting for 34.36% of the total effect. Conclusions:Family function affects the level of social frailty in DR patients both directly and indirectly through the mediating roles of positive coping and health literacy. Interventions targeting family function improvement, enhancement of positive coping strategies, and health literacy promotion may help reduce social frailty in this population.

Objective:to investigate age-related changes in high-sensitivity cardiac troponin T(hs-cTnT)levels among middle-aged and elderly individuals, and to establish reference values for the 99th percentile upper reference limit(99th URL)of hs-cTnT within this demographic.Methods:This research is designed as a cross-sectional study.Hs-cTnT test results were collected from outpatients at Beijing Hospital between January 2018 and December 2023.The final sample included 5, 677 outpatients aged 45 to 85 years(65±10), all of whom were free from cardiovascular diseases and other chronic heart-related conditions.Multiple linear regression was utilized to assess the impact of gender and age group on hs-cTnT concentrations within the middle-aged and elderly populations.Furthermore, a generalized additive model for location, scale, and shape(GAMLSS)was employed to generate percentile curves of hs-cTnT by gender in this cohort, with the aim of determining the 99th URLs for both middle-aged and elderly individuals.Results:Multiple linear regression analyses indicated that both gender and age significantly influenced hs-cTnT levels in middle-aged and elderly populations( β60-69 years=1.399, β≥70 years=5.306, βgender=-2.650, all Pvalues<0.001).The hs-cTnT data for both males and females conformed to Box-Cox-Cole-Green(BCCG)distributions, with percentile curves fitted at the 25th, 50th, 75th, and 99th percentiles according to gender.The percentile values of hs-cTnT in both males and females demonstrated a progressive increase with advancing age.Notably, males exhibited higher 99th percentile values than females across all age groups. Conclusions:The GAMLSS approach is employed to establish continuous reference intervals for hs-cTnT in the middle-aged and elderly population.This effort aims to provide a theoretical foundation for reference values specific to this demographic in China and to offer guidance for clinical diagnosis and treatment.