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1.
Mol Ther Nucleic Acids ; 35(2): 102225, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38948332

ABSTRACT

Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

2.
Int J Biol Macromol ; 275(Pt 1): 133474, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945338

ABSTRACT

The Bacillus genus is widely distributed in nature, has bacteriostatic and growth-promoting activities, and has broad application potential in agriculture. An exopolysaccharide (EPS) was extracted and purified from Bacillus velezensis HY23. Structural characterisation of the EPS was performed by chemical and spectroscopic analyses. Methylation analysis showed that the EPS of HY23 was composed of mannose and glucose at a ratio of 82:18 and was identified as glucomannan. Combined with the nuclear magnetic resonance (NMR) analysis, EPS from HY23 had a backbone of →2)-α-D-Manp-(1 â†’ and →2,6)-α-D-Manp-(1 â†’ branched at C-6 with terminal α-(3-O-Me)-D-Manp-(1 â†’ and →6)-α-D-Manp-(1 â†’ residues as the side chain. A certain amount of ß-D-Glcp residues were also present in backbone. Moreover, EPS significantly improved the nitrogen-fixing activity and salt resistance of soybean seedlings by regulating the antioxidant pool and expression of ion transporters. These findings indicate that EPS from B. velezensis HY23 is a potential biostimulant for enhancing plant resistance to salt stress.

3.
PLoS One ; 19(6): e0296196, 2024.
Article in English | MEDLINE | ID: mdl-38935785

ABSTRACT

Sickle cell disease (SCD) decreases the oxygen-carrying capacity of red blood cells. Children with SCD have reduced/restricted cerebral blood flow, resulting in neurocognitive deficits. Hydroxyurea is the standard treatment for SCD; however, whether hydroxyurea influences such effects is unclear. A key area of SCD-associated neurocognitive impairment is working memory, which is implicated in other cognitive and academic skills. The neural correlates of working memory can be tested using n-back tasks. We analyzed functional magnetic resonance imaging (fMRI) data of patients with SCD (20 hydroxyurea-treated patients and 11 controls, aged 7-18 years) while they performed n-back tasks. Blood-oxygenation level-dependent (BOLD) signals were assessed during working memory processing at 2 time points: before hydroxyurea treatment and ~1 year after treatment was initiated. Neurocognitive measures were also assessed at both time points. Our results suggested that working memory was stable in the treated group. We observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- >0-back contrast. Searchlight-pattern classification of the 2 time points of the 2-back tasks identified greater changes in the pattern and magnitude of BOLD signals, especially in the posterior regions of the brain, in the control group than in the treated group. In the control group at 1-year follow-up, 2-back BOLD signals increased across time points in several clusters (e.g., right inferior temporal lobe, right angular gyrus). We hypothesize that these changes resulted from increased cognitive effort during working memory processing in the absence of hydroxyurea. In the treated group, 0- to 2-back BOLD signals in the right angular gyrus and left cuneus increased continuously with increasing working memory load, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. These findings suggest that hydroxyurea treatment helps maintain working memory function in SCD.


Subject(s)
Anemia, Sickle Cell , Hydroxyurea , Magnetic Resonance Imaging , Memory, Short-Term , Humans , Hydroxyurea/therapeutic use , Hydroxyurea/pharmacology , Anemia, Sickle Cell/drug therapy , Anemia, Sickle Cell/physiopathology , Memory, Short-Term/drug effects , Child , Adolescent , Male , Female , Antisickling Agents/therapeutic use , Antisickling Agents/pharmacology , Brain/diagnostic imaging , Brain/drug effects , Brain/physiopathology , Case-Control Studies
4.
Cancer Med ; 13(12): e7372, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923216

ABSTRACT

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety. METHODS: This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome. RESULTS: The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome. CONCLUSION: To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment.


Subject(s)
Immunotherapy, Adoptive , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Multiple Myeloma/immunology , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Receptors, Chimeric Antigen/immunology , Infections/etiology , Risk Factors
5.
Front Microbiol ; 15: 1371877, 2024.
Article in English | MEDLINE | ID: mdl-38591027

ABSTRACT

The resource recovery and reuse of precious metal-laden wastewater is widely recognized as crucial for sustainable development. Superalloy electrolytes, produced through the electrolysis of superalloy scrap, contain significant quantities of precious metal ions, thereby possessing substantial potential for recovery value. This study first explores the feasibility of utilizing fungi to treat Superalloy electrolytes. Five fungi resistant to high concentrations of heavy metals in electrolytes (mainly containing Co, Cr, Mo, Re, and Ni) were screened from the soil of a mining area to evaluate their adsorption characteristics. All five fungi were identified by ITS sequencing, and among them, Paecilomyces lilacinus showed the best adsorption performance for the five heavy metals; therefore, we conducted further research on its adsorption characteristics. The best adsorption effect of Co, Cr, Mo, Re, and Ni was 37.09, 64.41, 47.87, 41.59, and 25.38%, respectively, under the conditions of pH 5, time 1 h, dosage 26.67 g/L, temperature 25-30°C, and an initial metal concentration that was diluted fivefold in the electrolyte. The biosorption of Co, Mo, Re, and Ni was better matched by the Langmuir model than by the Freundlich model, while Cr displayed the opposite pattern, showing that the adsorption process of P. lilacinus for the five heavy metals is not a single adsorption mechanism, but may involve a multi-step adsorption process. The kinetics study showed that the quasi-second-order model fitted better than the quasi-first-order model, indicating that chemical adsorption was the main adsorption process of the five heavy metals in P. lilacinus. Fourier transform infrared spectroscopy revealed that the relevant active groups, i.e., hydroxyl (-OH), amino (-NH2), amide (- CONH2), carbonyl (-C = O), carboxyl (-COOH), and phosphate (PO43-), participated in the adsorption process. This study emphasized the potential application of P. lilacinus in the treatment of industrial wastewater with extremely complex background values.

6.
Cancer Nurs ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38625787

ABSTRACT

BACKGROUND: Physical activity promotes healthy physical and mental development in children with leukemia. However, the level of physical activity in hospitalized children with leukemia and the factors that influence it are unknown. OBJECTIVES: The aims of this study were to understand the physical activity level of hospitalized children with leukemia and to explore the factors influencing it to provide a reference for physical activity assessment and intervention in such children. METHODS: A total of 133 hospitalized children with leukemia completed a general information questionnaire, the Chinese University of Hong Kong Physical Activity Rating for Children and Youth, and the Children's Social Anxiety Scale. A cross-sectional study was used to explore the effects of different variables on the children's activity levels. RESULTS: Among the study participants, 44.4% had a low-intensity activity level, 35.3% had a moderate-intensity activity level, and 20.3% had a high-intensity activity level, with a total physical activity rating of 3 (1, 6). Chemotherapy phase (P = .007), screen time (P = .001), and social anxiety (P = .012) were identified as influential factors. CONCLUSIONS: Our results showed that children with hospitalized leukemia had lower-intensity physical activity levels, especially in the chemotherapy phase of induction remission. Furthermore, screen time and social anxiety had negative effects on the children's activity levels. IMPLICATIONS FOR PRACTICE: According to the physical activity level of the children and the influencing factors, healthcare professionals should gradually improve children's mobility and promote their physical and mental health development through guidance and encouragement, and the development of personalized activity intervention programs.

7.
J Fluoresc ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607530

ABSTRACT

Hypochloric acid (HClO) is a reactive oxygen species (ROS) that functions as a bacteriostatic and disinfectant in food production. Excessive levels of ClO-, however, have been linked to various health issues, including cardiovascular diseases (Halliwell and Gutteridge in Oxford University press, USA, 2015), arthritis, and neurodegenerative diseases (Heinzelmann and Bauer in Biol Chem. 391(6):675-693, 2010). Therefore, synthesizing highly selective and sensitive probes for rapidly detecting endogenous ClO- in daily foods is currently a popular research topic (Kalyanaraman et al. in Redox Biol. 15:347-362, 2018; Winterbourn in Nat Chem Biol. 4(5):278-286, 2008; Turrens in J Physiol. 552(2):335-344, 2003). Thus, we have developed two highly selective ratiometric fluorescent probes (Probe1 and Probe2) based on indole-phenothiazine to detect ClO- in common vegetables, fruits and beverages qualitatively and quantitatively. Moreover, Both Probe1 and Probe2 have shown good specificity and stability, with high fluorescence intensity and long duration (Feng et al. in Adv Sci. 5:1800397, 2018; Wei et al. in Angew Chem. 131(14):4595-4599, 2019; Baruah et al. in J Mater Chem B, 2022).

8.
ACS Appl Mater Interfaces ; 16(12): 15143-15155, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38481099

ABSTRACT

Realizing controllable input of botanical pesticides is conducive to improving pesticide utilization, reducing pesticide residues, and avoiding environmental pollution but is extremely challenging. Herein, we constructed a smart pesticide-controlled release platform (namely, SCRP) for enhanced treatment of tobacco black shank based on encapsulating honokiol (HON) with mesoporous hollow structured silica nanospheres covered with pectin and chitosan oligosaccharide (COS). The SCRP has a loading capacity of 12.64% for HON and could effectively protect HON from photolysis. Owing to the pH- and pectinase-sensitive property of the pectin, the SCRP could smartly release HON in response to a low pH or a rich pectinase environment in the black shank-affected area. Consequently, the SCRP effectively inhibits the infection of P. nicotianae on tobacco with a controlled rate for tobacco black shank of up to 87.50%, which is mainly due to the SCRP's capability in accumulating ROS, changing cell membrane permeability, and affecting energy metabolism. In addition, SCRP is biocompatible, and the COS layer enables SCRP to show a significant growth-promoting effect on tobacco. These results indicate that the development of a stimuli-responsive controlled pesticide release system for plant disease control is of great potential and value for practical agriculture production.


Subject(s)
Pesticides , Pesticides/pharmacology , Delayed-Action Preparations/pharmacology , Delayed-Action Preparations/chemistry , Polygalacturonase , Agriculture , Pectins
9.
Food Sci Nutr ; 12(2): 815-829, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370064

ABSTRACT

Pinobanksin, as one of the flavonoids, has powerful biological activities but has been under-recognized. In this study, we optimized the extraction method of phragmites from peony seed shells by using organic solvent extraction. The yield of PSMS was 10.54 ± 0.13% under the conditions of ethanol volume fraction 70%, extraction temperature 70°C, material-liquid ratio 1:25 g/mL, and extraction time 60 min; the optimized PSMS could be effectively separated in S-8 macroporous resin coupled with C18. The relative content of PSMS was increased from 0.42% in PSMS to 92.53% after C18 purification; the antioxidant activity test revealed that pinobanksin could exert antioxidant ability by binding catalase (CAT) enzyme. Second, it was found that pinobanksin could effectively inhibit the proliferation of SH-SY5Y cells, mainly by binding to BCL2-associated X (BAX), B-cell lymphoma-2 (BCL-2), and cyclin-dependent Kinase 4/6 (CDK4/6) to produce more hydrogen bonds to inhibit their activities. This study confirms the medicinal potential of pinobanksin and provides the basis for the proper understanding of pinobanksin and the development of related products.

10.
Ann Med ; 56(1): 2311227, 2024 12.
Article in English | MEDLINE | ID: mdl-38306095

ABSTRACT

BACKGROUND: While Cardiac Rehabilitation (CR) programs have shown effectiveness in improving cardiac outcomes, there is limited understanding of how patients perceive and adapt to these interventions. Furthermore, alternative modes of delivering CR that have received positive evaluations from participants remain underexplored, yet they have the potential to enhance CR uptake. OBJECTIVES: To explore the patient experience in CR programmes following Acute Myocardial Infarction (AMI) and describe their adaptive processing. PATIENTS AND METHODS: This qualitative study was conducted at a nationally certified centre in China between July 2021 and September 2022, encompassing three stages: in-hospital, centre-based, and home-based CR programs. Purposive sampling was used to select eligible AMI patients for in-depth semi-structured interviews. The interview outline and analytical framework were aligned with the key concepts derived from the middle-range theory of adaptation to chronic illness and the normalization process theory. The findings were reported following the Consolidated Criteria for Reporting Qualitative Research checklist. RESULTS: Forty AMI patients were recruited. Four main themes describing the process of AMI patients normalizing CR intervention were identified, including (1) experiencing CR service driving by role's responsibilities, (2) engaging in collaborative relationship based on interpersonal trust, (3) exploring a personalized rehabilitation plan by complex integration, and (4) expecting a promised outcome to shape decision-making. CONCLUSION: Integrated care interventions for AMI patients could benefit from a collaborative co-designed approach to ensure that CR interventions are normalized and fit into patients' daily lives. Organizational-level CR services should align with the rehabilitation needs and expectations of patients.


Subject(s)
Cardiac Rehabilitation , Myocardial Infarction , Humans , Research Design , China
11.
Waste Manag ; 175: 254-264, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38219463

ABSTRACT

Biogas slurry (BS) is widely considered as a source of organic matter and nutrients for improving soil organic carbon (SOC) sequestration and crop production in agroecosystems. Microbial necromass C (MNC) is considered one of the major precursors of SOC sequestration, which is regulated by soil microbial anabolism and catabolism. However, the microbial mechanisms through which BS application increases SOC accumulation in paddy soils have not yet been elucidated. A 12-year field experiment with four treatments (CK, no fertilizers; CF, chemical fertilizer application; BS1 and BS2, biogas slurry application at two nitrogen rates from BS) was conducted in rice paddy fields. The results showed that long-term BS application had no effect on lignin phenols proportion in SOC relative to CF. In contrast, BS application elevated the MNC contribution to SOC by 15.5-20.5 % compared with the CF treatment. The proportion of fungal necromass C (FNC) to SOC increased by 16.0 % under BS1 and by 25.8 % under BS2 compared with the CF treatment, while no significant difference in bacterial necromass C (BNC) contribution to SOC was observed between the BS and CF treatments. The MNC was more closely correlated with fungal community structures than with bacterial community structures. We further found that fungal genera, Mortierella and Ciliophora, mainly regulated the MNC, FNC and BNC accumulation. Collectively, our results highlighted that fungi play a vital role in SOC storage in paddy soils by regulating MNC formation and accumulation under long-term BS application.


Subject(s)
Mycobiome , Oryza , Soil/chemistry , Carbon , Biofuels , Lignin , Fertilizers/analysis , Soil Microbiology
12.
Heliyon ; 10(2): e24515, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38293362

ABSTRACT

In this study, we investigated the antioxidant properties of dry-cured beef crude peptide (BPH) at different storage periods. The combination characteristics of different concentrations of Phe-Asp-Gly-Asp-Phe (FDGDF) and superoxide dismutase (SOD) at different temperatures were analyzed by ultraviolet-visible spectroscopy, fluorescence spectroscopy, and FT-IR spectroscopy, combined with the detection of a SOD activity detection box. It was found that FDGDF could improve the activity of SOD by changing its secondary structure. Bonds were formed at O32/O40/O52 using quantum chemical simulation calculations, and the Fukui index was higher than that of most atoms, indicating that these atoms were more likely to participate in the reaction. SPR biological force analysis showed that FDGDF and SOD were in a fast binding and dissociation mode. This study revealed the theoretical basis for studying the antioxidant mechanism of dry-cured beef and provided ideas for developing new dry-cured beef products.

13.
Am J Hematol ; 99(4): 662-678, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38197307

ABSTRACT

Chimeric antigen receptor (CAR) T-cell therapy, an innovative immunotherapeutic against relapsed/refractory B-cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR-T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post-pandemic era, marked by the Omicron variant, new and severe threats to CAR-T therapy emerge, necessitating exploration of preventive and treatment measures for COVID-19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR-T product safety and recipient survival.


Subject(s)
Lymphoma, B-Cell , Receptors, Chimeric Antigen , Virus Diseases , Humans , Receptors, Chimeric Antigen/therapeutic use , Immunotherapy, Adoptive/adverse effects , Lymphoma, B-Cell/therapy , Virus Diseases/etiology , Antigens, CD19 , Cell- and Tissue-Based Therapy
15.
medRxiv ; 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38045394

ABSTRACT

Pediatric patients with sickle cell disease (SCD) have decreased oxygen-carrying capacity in the blood and reduced or restricted cerebral blood flow resulting in neurocognitive deficits and cerebral infarcts. The standard treatment for children with SCD is hydroxyurea; however, the treatment-related neurocognitive effects are unclear. A key area of impairment in SCD is working memory, which is implicated in other cognitive and academic skills. N-back tasks are commonly used to investigate neural correlates of working memory. We analyzed functional magnetic resonance imaging (fMRI) of patients with SCD while they performed n-back tasks by assessing the blood-oxygenation level-dependent (BOLD) signals during working memory processing. Twenty hydroxyurea-treated and 11 control pediatric patients with SCD (7-18 years old) performed 0-, 1-, and 2-back tasks at 2 time points, once before hydroxyurea treatment (baseline) and ~1 year after treatment (follow-up). Neurocognitive measures (e.g., verbal comprehension, processing speed, full-scale intelligence quotient, etc.) were assessed at both time points. Although no significant changes in behavior performance of n-back tasks and neurocognitive measures were observed in the treated group, we observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- > 0-back contrast. Through searchlight-pattern classifications in the treated and control groups to identify changes in brain activation between time points during the 2-back task, we found more brain areas, especially the posterior region, with changes in the pattern and magnitude of BOLD signals in the control group compared to the treated group. In the control group, increases in 2-back BOLD signals were observed in the right crus I cerebellum, right inferior parietal lobe, right inferior temporal lobe, right angular gyrus, left cuneus and left middle frontal gyrus at 1-year follow-up. Moreover, BOLD signals elevated as the working memory load increased from 0- to 1-back but did not increase further from 1- to 2-back in the right inferior temporal lobe, right angular gyrus, and right superior frontal gyrus. These observations may result from increased cognitive effort during working memory processing with no hydroxyurea treatment. In contrast, we found fewer changes in the pattern and magnitude of BOLD signals across time points in the treated group. Furthermore, BOLD signals in the left crus I cerebellum, right angular gyrus, left cuneus and right superior frontal gyrus of the treated group increased continuously with increasing working memory load from 0- to 2-back, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. Collectively, these findings suggest that hydroxyurea treatment helped maintain working memory function in SCD.

17.
Front Public Health ; 11: 1254126, 2023.
Article in English | MEDLINE | ID: mdl-37790718

ABSTRACT

Background: Cognitive impairment as a complication in post-stroke patients has high prevalence throughout the world. However, few studies have focused on the older adult stroke survivors and explored their prevalence and factors of post-stroke cognitive impairment (PSCI). The study aims to evaluate the cognitive status of stroke patients in Hunan Province, China and to determine the potential risk factors associated with PSCI in order to identify the older adult population in advance and promote healthy aging. Methods: This cross-sectional study was carried out from August to December, 2021. A total of 520 stroke survivors from 6 tertiary hospitals were randomly selected. The information was collected using the general questionnaire, the Barthel Index Rating Scale and the Mini-mental State Examination (MMSE). Analysis was based on descriptive statistics, chi-square test and the significant variables were included in multivariate logistic regression. The reporting of this cross-sectional study followed the STROBE checklist. Results: A total of 195 older adults (40.37%) were screened for cognitive impairment based on the results of the MMSE score. Patients in the PSCI group had a higher proportion of individuals aged 70 or older (35.90% vs. 24.65%, p<0.001). The potential risk factors for post-stroke cognitive impairment in older adults were being aged between 70 and 79 years old (OR = 3.973, 95% CI, 2.346-6.729, p<0.001), being aged 80 years or older (OR = 3.590, 95% CI, 1.373-9.387, p = 0.009), having a low level of education (OR = 9.183, 95% CI, 5.341-15.789, p<0.001), having hypertension (OR = 1.756, 95% CI, 1.121-2.753, p = 0.014), and having a dominant hemisphere lesion (OR = 1.880, 95% CI, 1.193-2.962, p<0.001). Conclusion: The prevalence of PSCI was high among Chinese older adults, particularly those aged 80 years or older. The factors identified in our study could assist in the early identification of older adults at risk, develop personalized management plans, and promote healthy aging.


Subject(s)
Cognitive Dysfunction , Stroke , Humans , Aged , Cross-Sectional Studies , Prevalence , Stroke/complications , Stroke/epidemiology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Risk Factors
18.
PLoS One ; 18(10): e0292285, 2023.
Article in English | MEDLINE | ID: mdl-37796788

ABSTRACT

BACKGROUND: Coronary Heart Disease (CHD) is one of the most prevalent chronic diseases worldwide. Currently, percutaneous coronary intervention (PCI) with stent implantation is the main clinical treatment for CHD, and patients can achieve better outcomes after stenting. However, adverse cardiovascular events continue to recur, ultimately failing to yield good results. Several symptoms exist after stenting and are associated with health outcomes. Little is known about the symptom patterns of patients during the different postoperative periods. Therefore, this study aims to explore the dynamics of symptoms and clarify the experiences of post-stenting in patients during different periods, which may help the delivery of more specific patient management and improve survival outcomes in the future. METHODS: A mixed method (quantitative/qualitative) design will be adopted. Longitudinal research, including surveys regarding three different periods, will be sued to describe the symptom patterns of patients undergoing PCI with stent implantation, clarifying their focused symptom problems during different time periods or in populations with different features. Qualitative individual interviews aim to understand the feelings, experiences, opinions, and health conditions of patients post-stenting, which can explain and supplement quantitative data. Quantitative data will be analyzed using descriptive statistics, latent class analysis (LCA), and latent translation analysis (LTA). Qualitative data will be analyzed using content analysis. DISCUSSION: This study is the first study to explore the symptom patterns and experiences of patients in various domains after stent implantation using a novel design including quantitative and qualitative methods, which will help the delivery of more specific patient management, reduce the recurrence of adverse cardiovascular events, and improve survival outcomes in the future. It is also meaningful to use PROMIS profile-57 to help patients to proactively focus on their health problems, promote health literacy, and incorporate active patient participation into health management, which is a successful transition from passive medical treatment to active management.


Subject(s)
Coronary Disease , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/methods , Health Promotion , Treatment Outcome , Coronary Disease/etiology , Stents/adverse effects
19.
Bioorg Med Chem Lett ; 96: 129502, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37806498

ABSTRACT

Camptothecin (CPT) and its derivatives are potent candidates for cancer treatment. However, the clinical applications are largely restricted by non-selectivity and severe toxicities. The peptide transporter 1 (PEPT1), which is highly expressed in human intestines, has been found to be overexpressed in several cancer cells. This discovery suggests that PEPT1 has the potential to serve as a therapeutic target for both improving bioavailability and cancer-targeting treatment. Therefore, a prodrug approach for CPT targeting at PEPT1 highly expressed cancer cells was adopted in the present study. Eighteen CPT prodrugs, its peptidic conjugates, were synthesized and the structures were confirmed by NMR and HRMS. The protein expression profiles of PEPT1 in different cell lines were performed using immunofluorescence assay and western blotting analysis. The cytotoxicity of CPT prodrugs and their uptake via competition with Gly-Sar, a typical substrate of PEPT1, were evaluated in both PEPT1-overexpressed and under expressed cells. The results demonstrated that most CPT prodrugs significantly impaired Gly-Sar uptake, suggesting a higher affinity of CPT-peptidic conjugates for PEPT1 and PEPT1 overexpression cells. In addition, these prodrugs demonstrated a higher capability for inhibiting cell growth in PEPT1 highly-expressed cancer cells compared to PEPT1 under expressed cells. These results indicated that this peptidic prodrug strategy might offer great potential for improved tumor selectivity and chemotherapeutic efficacy of CPT.


Subject(s)
Neoplasms , Prodrugs , Humans , Prodrugs/chemistry , Peptide Transporter 1/metabolism , Cell Line , Biological Transport , Camptothecin/pharmacology , Camptothecin/chemistry
20.
Ann Med ; 55(2): 2268109, 2023.
Article in English | MEDLINE | ID: mdl-37851734

ABSTRACT

Objective To explore the heterogenous subtypes and the associated factors of health literacy among patients with metabolic syndrome.Methods A cross-sectional study was conducted, and 337 patients with metabolic syndrome were recruited from Sir Run Run Shaw Hospital in Zhejiang Province from December 2021 to February 2022. The Social Support Questionnaire, Short version of the Health Literacy Scale European Questionnaire (HLS-EU-Q16), and MacArthur Scale of Subjective Social Status were used for investigation. Latent class analysis (LCA) was performed to explore the heterogenous subtypes of health literacy among Metabolic syndrome patients. Univariate analysis and logistic regression were used to identify the predictors of the latent classes.Results The findings of LCA suggested that three heterogeneous subtypes of health literacy among individuals with metabolic syndrome were identified: high levels of health literacy, moderate levels of health literacy, and low levels of health literacy. The multinomial logistic regression results indicated that compared with low levels of health literacy class, the high levels of health literacy class were predicted by age (OR 0.932, 95%CI[0.900-0.966]), socio-economic status (OR 1.185, 95%CI[1.058-1.328]), and social support (OR 1.065, 95%CI[1.012-1.120]). Compared with low levels of health literacy class, the moderate levels of health literacy class were predicted by age (OR 0.964, 95%CI[0.934-0.995]), socio-economic status (OR 1.118, 95%CI[1.006-1.242]), male (OR 0.229, 95%CI[0.092-0.576]).Conclusion The levels of health literacy among patients with metabolic syndrome can be divided into three heterogenous subtypes. The results can inform policy-makers and care professionals to design targeted interventions for different subgroups among patients with metabolic syndrome who are male, at older age, have less social support, and with disadvantaged socio-economic status to improve health literacy.


Subject(s)
Health Literacy , Metabolic Syndrome , Humans , Male , Female , Metabolic Syndrome/epidemiology , Latent Class Analysis , Cross-Sectional Studies , Surveys and Questionnaires
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