OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

Objective:To define the concept of proactive health behavior.Methods:Literature related to proactive health behavior was retrieved from China National Knowledge Infrastructure, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Embase, and Ovid databases, with a retrieval time frame from database inception to March 1, 2025. Walker and Avant's concept analysis method was used to analyze the concept of proactive health behavior.Results:A total of 46 articles related to proactive health behavior were included. Proactive health behavior encompasses five key attributes: self-initiation, long-term persistence, multidimensional integration, future orientation, and overcoming barriers. Antecedents include individual factors, supportive factors, and environmental factors. Outcomes include promoting individual health and improving quality of life, enhancing personal health literacy, reducing disease burden, and fostering a proactive health atmosphere.Conclusions:The concept attributes of proactive health behavior were clarified through concept analysis. Future researchers may develop proactive health behavior assessment tools and construct intervention strategies based on their connotation.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Objective To explore the relationship between biofilm formation ability and virulence of vari-ous drug-resistant strains of Staphylococcus aureus(SA)in bloodstream infections.Methods A total of 42 strains of bloodstream infection SA were collected and identified and tested for drug sensitivity using the BDM50 automatic bacterial identification drug susceptibility system.The biofilm formation ability was deter-mined by crystal violet staining.The virulence was evaluated by detecting extracellular lipase,extracellular protease,and hemolysin,as well as conducting a toxicity test with Galleria mellonella larvae.Results Among the 42 strains of bloodstream infection SA,there were 16 strains(38.10%)of methicillin-resistant Staphylo-coccus aureus(MRSA).Among the 42 bloodstream infected SA strains,25 strains(59.50%)had the ability to form biofilms,among which there were 18 strains of methicillin-sensitive Staphylococcus aureus(MSSA)and 7 strains of MRSA.Among the 42 SA strains with bloodstream infection,37 strains(88.10%)produced hemolysin,18 strains(42.90%)produced extracellular protease,and no strains produced extracellular lipase.The Galleria mellonella larvae toxicity test showed that MRSA had stronger virulence than MSSA.Conclusion Compared with MSSA,MRSA has a higher proportion of extracellular enzymes produced,stronger virulence,and relatively weaker ability to form biofilms.

The Warburg effect, originally discovered by Otto Warburg, refers to the metabolic reprogramming of tumor cells from aerobic oxidation to glycolysis, enabling rapid energy production to support their growth and metastasis. This process is accompanied by the massive production and accumulation of lactate both intracellularly and extracellularly. The resulting acidic microenvironment impairs the normal physiological functions of immune cells and promotes tumor progression. An increasing number of studies indicate that lactate, a key metabolite in the tumor microenvironment (TME), acts as a pivotal immunosuppressive signaling molecule that modulates immune cell function. This review aims to comprehensively examine lactate's role as an immunosuppressive molecule in TME. It focuses on mechanisms such as membrane receptor binding, functional reshaping of immune cells via lactate shuttle transport, epigenetic regulation of gene expression through histone lactylation, and modulation of protein structure and function through nonhistone lactylation, emphasizing lactate's importance in immune regulation within the TME. Ultimately, this review offers novel insights into immunosuppressive therapies aimed at targeting lactate function.
Humans ; Neoplasms/metabolism* ; Tumor Microenvironment/immunology* ; Lactic Acid/immunology* ; Warburg Effect, Oncologic ; Animals ; Glycolysis ; Epigenesis, Genetic

Objective To analyze the influencing factors of health behaviors in stroke patients,and explore the chain mediating effects of self-efficacy and e-health literacy between the perception of stroke recurrence risk and health behaviors in stroke patients,providing a reference for strengthening the health behavior and reducing recurrence risk in stroke patients.Methods 249 stroke patients were selected as the research objects from March to September 2024 in a tertiary hospital in Shanghai,China.Patients were surveyed using General Information Questionnaire,Stroke Recurrence Risk Perception Scale,Stroke Health Behavior Scale(HBS-SP),Chronic Disease Self-Efficacy Scale(CDSES),and the e-health Literacy Scale(e-HEALS).Pearson correlation analysis was used to explore the correlations among various variables,and SPSS 26.0 software macro program Process Model 6 was used to conduct chain mediation model test.Results The scores of Recurrence Risk Perception,HBS-SP,CDSES and e-HEALS of stroke patients were(42.88±6.48)scores,(68.32±14.13)scores,(6.87±1.55)scores and(27.76±6.06)scores,and all the variables were positively correlated(P<0.01).The mediating effect model showed that self-efficacy and e-health literacy played a chain mediating role in the recurrence risk perception and health behavior in stroke patients,with an effect size of 0.488,accounting for 37.22%of the total effect.Conclusions The recurrence risk perception and health behavior of stroke patients are both at a moderate level.In the future,we can establish a mobile management platform to provide comprehensive health management for stroke patients.Further exploration of strategies to enhance stroke patients'self-efficacy and channels for online health education could be pursued to improve their health behaviors.

Objective:To analyze differences on characteristics of HIV/AIDS knowledge, beliefs and behavior among female college students who reported having sex in Zhejiang Province between 2018 and 2020, and provide reference for HIV/AIDS prevention and control among female college students.Methods:Cross-sectional surveys were conducted in October-November 2018 and November-December 2020 among female college students in 13 universities in 11 cities in Zhejiang Province, and female college students who self-reported having sexual intercourse in the past year were included as study subjects, with sample size estimates of 5 265 and 9 466 for the two surveys, respectively. The factors related to the change of relevant characteristics of the two survey subjects were analyzed. The χ2 test was used for univariate analysis and logistic regression model was used for multivariate analysis.Statistical analyses were performed with SPSS 23.0 software. Results:Of the 17 354 and 20 675 female college students surveyed in 2018 and 2020, respectively, the proportion who self-reported having had sex in the past year was 6.56% (1 139/17 354) and 4.19% (866/20 675). Multivariate logistic regression analysis showed that compared with female college students in 2018, the students who have sexual behaviour, receiving health education class by their university in the past year (a OR=1.57, 95% CI:1.29-1.91), receiving HIV testing promotion by the university in the past year (a OR=2.59,95% CI:2.13-3.14), receiving self-assessment of HIV risk by the university in the past year (a OR=2.97,95% CI:2.43-3.65), high self-efficacyfor condom use (a OR=2.00, 95% CI:1.66-2.41), receiving voluntary counseling and HIV testing (VCT) (a OR=1.81,95% CI: 1.41-2.87), perceived risk of HIV infection (a OR=2.44, 95% CI:1.32-4.54), using condoms whenever having casual sexual behaviour in the past year (a OR=3.35,95% CI:1.66-6.77) were significantly higher in 2020. Conclusions:Compared with female college students in 2018, the proportion of female college students who self-reported sexual activity decreased slightly in 2020, and the proportion of receiving HIV/AIDS lectures or health education classes, the proportion of self-rated at risk of HIV infection, the proportion of receiving VCT, the proportion of using condoms with very high confidence in self-efficacy and condom use had an increased.

Objective:To investigate the disease burden, clinical characteristics and independent risk factors affecting in-hospital outcomes of children with congenital heart disease (CHD) combined with heart failure (HF) in China.Methods:(1) Descriptive study: based on the global burden of disease study 2021, available data on children under 15 years of age with CHD and HF in China from 1990 to 2021 were collected. The prevalence and trends in different age subgroups (<1 year, 1-<2 years, 2-<5 years, 5-<10 years, 10-<15 years) were analyzed, and the annual percentage change (EAPC) was estimated using linear regression. (2) Retrospective cohort study: a total of 1 062 children with CHD and HF from a multicenter study on pediatric HF in China were included. The children were divided into two groups:<2 years group and 2-<18 years group. Data on demographics, clinical features, diagnosis, treatments, and in-hospital outcomes were analyzed. Mann-Whitney U test and chi-square test were used for group comparisons.Multivariable Logistic regression was applied to identify factors influencing outcomes (in-hospital mortality and adverse cardiovascular events). Results:(1) From 1990 to 2021, the number of children with CHD and HF in China increased from 333 000 (95% uncertainty interval ( UI) 271 000-405 000) to 368 000 (95% UI 296 000-459 000), a growth of 10.8% (95% UI 5.0%-16.6%). Concurrently the prevalence rate increased from 104.5 (95% UI 85.1-127.3) per 100 000 to 142.0 (95% UI 114.0-176.8) per 100 000, a growth of 35.9% (95% UI 28.7%-43.0%), with an EAPC of 1.5% (95% CI 1.2%-1.8%). Although the number of cases in the<1 year and 1-<2 years groups decreased by 41.0% and 25.6%, respectively, the prevalence in all age groups showed an upward trend:<1 year EAPC 0.6% (95% CI 0.5%-0.7%); 1-<2 years EAPC 0.9% (95% CI 0.8%-1.0%); 2-<5 years EAPC 1.2% (95% CI 1.0%-1.4%); 5-<10 years EAPC 1.5% (95% CI 1.2%-1.8%); 10-<15 years EAPC 2.1% (95% CI 1.9%-2.3%). (2) The multicenter study revealed that among 1 062 hospitalized children, 528 (49.7%) were male and 534 (50.3%) were female, with the age at admission of 5.4 (2.2,18.2) months. The majority of the children (77.9%, 827/1 062) were under 2 years of age, whereas 22.1% (235/1 062) were aged between 2-<18 years. Children with complex congenital heart defects accounted for the highest proportion (48.6%, 516/1 062), while those with isolated CHD made up 31.5% (335/1 062). Statistically significant differences were observed in several variables in demographics, clinical features, diagnosis, treatments, and outcomes between the two age groups (all P<0.05). The use of renin-angiotensin-aldosterone system inhibitors (41.1%, 436/1 062) and beta-blockers (8.7%, 92/1 062) was lower in hospitalized children with CHD and HF. Logistic regression identified complex CHD ( OR=7.73, 95% CI 2.24-26.63; OR=3.17, 95% CI 1.92-5.23), pulmonary hyperperfusion ( OR=2.15, 95% CI 1.01-4.18; OR=2.00, 95% CI 1.35-2.97), left ventricular ejection fraction<55% ( OR=2.13, 95% CI 1.08-4.21; OR=2.80, 95% CI 1.45-5.56), arterial oxygen partial pressure ( OR=0.99, 95% CI 0.98-0.99; OR=0.99, 95% CI 0.98-0.99), and serum calcium levels ( OR=0.31, 95% CI 0.17-0.58; OR=0.42, 95% CI 0.28-0.62) as independent risk factors for in-hospital mortality and cardiovascular events. Conclusions:The disease burden of CHD combined with HF in China has shown a continuous upward trend from 1990 to 2021, with higher growth rates in older age groups. Complex CHD, pulmonary hyperperfusion, left ventricular ejection fraction <55%, arterial oxygen partial pressure, and serum calcium concentration are independent risk factors for in-hospital mortality and cardiovascular events.