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1.
J Affect Disord ; 367: 573-582, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39242042

RESUMO

AIM: To investigate the impact of public health emergencies on the prevalence of suicidal ideation among healthcare workers (HCWs) and medical students. METHODS: The prevalence of suicidal ideation among HCWs and medical students was searched for analysis. The platforms included PubMed, medRVix, bioRvix, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Interrupted time-series analysis was employed to determine whether the COVID-19 pandemic influenced the prevalence and trends of suicidal ideation. To account for autocorrelation and heteroskedasticity, Newey-West standard errors were utilized with a lag of order one. RESULTS: Seventy studies with 145,641 HCWs and medical students from 30 countries were included in the final analysis, with 30 studies before COVID-19 and 40 studies during the pandemic. Before the pandemic outbreak (April 2020), the monthly increasing rate was 0.063 % (95 % CI: -0.009 %, 0.135 %, z = 1.73, P = 0.084). The tendency of suicidal ideation prevalence increased by 1.116 % (95%CI: 0.888 %, 1.344 %, z = 9.60, P < 0.001). In other words, the calculated monthly growth rate of suicidal ideation after the pandemic outbreak is 1.179 % (95%CI: 0.968 %, 1.391 %, z = 10.93, P < 0.001) per month. The overall growing trend of prevalence of suicidal ideation during the pandemic is 1.896 % per month in America; 1.590 % in Europe; 0.443 % (95%CI: 0.213 %, 0.673 %, z = 3.77, P < 0.001) in Asia; 1.055 % in HCWs; and 0.645 % in medical students. CONCLUSION: This study highlights that the COVID-19 pandemic can significantly impact the prevalence of suicidal ideation among HCWs and medical students, and the prevalence showed an upward trend.

2.
J Clin Med ; 13(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39274552

RESUMO

Background: Functional recovery following the surgical fixation of acetabular posterior wall fractures remains a challenge. This study compares outcomes of posterior wall fracture reconstruction using an anatomical posterior acetabular plate (APAP) versus conventional reconstruction plates. Methods: Forty patients with acetabular fractures involving the posterior wall or column underwent surgery, with 20 treated using APAPs (APAP group) and 20 with conventional pelvic reconstruction plates (control group). Baseline patient characteristics, intraoperative blood loss and time, reduction quality, postoperative function, and postoperative complications were compared using appropriate non-parametric statistical tests. A general linear model for repeated measures analysis of variance was employed to analyze trends in functional recovery. Results: No significant differences were observed in baseline characteristics. APAP significantly reduced surgical time by 40 min (186.5 ± 51.0 versus 225.0 ± 47.7, p =0.004) and blood loss (695 ± 393 versus 930 ± 609, p = 0.049) compared to conventional plates. At 3 and 6 months following surgery, the APAP group exhibited higher functional scores (modified Merle d'Aubigné scores 10 ± 1.8 versus 7.8 ± 1.4, p < 0.001; 13.4 ± 2.8 versus 10.1 ± 2.1, p = 0.001), converging with the control group by 12 months (modified Merle d'Aubigné scores 14.2 ± 2.6 versus 12.7 ± 2.6, p = 0.072; OHS 31.6 ± 12.3 versus 30.3 ± 10.1, p = 0.398). Radiologically, the APAP group demonstrated superior outcomes (p = 0.047). Complication and conversion rates to hip arthroplasty did not significantly differ between groups (10% versus 15%, p = 0.633). Conclusions: The use of an APAP in reconstructing the posterior acetabulum significantly reduces surgical time, decreases intraoperative blood loss, and leads to earlier functional recovery compared to conventional reconstruction plates. The APAP provides stable fixation of the posterior wall and ensures the durable maintenance of reduction, ultimately yielding favorable surgical outcomes.

3.
Front Plant Sci ; 15: 1382768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39263418

RESUMO

Introduction: Citrus fruit is rich in important functional constituents such as flavonoids, phenolic acids terpenes and other functional substances that play an important role for treating clinical diseases or controlling major agricultural diseases and pests. Plant secondary metabolites have become one of the most important resources of novel lead compounds, especially young citrus fruits contain multiple functional substances. 'Orah', a type of citrus reticulata, is known for its fine appearance, productivity, delicious sweetness, late-maturing characteristics, and is widely cultivated in China. Fruit thinning and rootstock selection are commonly used agronomic measures in its production to ensure its quality and tree vigor. However, few studies have demonstrated the effects of these agronomic measures on the functional substances of 'Orah'. Methods: In this study, we used HPLC coupled with UV to detect the dynamic changes of fruit quality, 13 main flavonoids, 7 phenolic acids, 2 terpenes, synephrine and antioxidant capacity in both peel and pulp of citrus fruits grafted on four rootstocks (Red orange Citrus reticulata Blanco cv. red tangerine, Ziyang xiangcheng Citrus junos Sieb. ex Tanaka, Trifoliate orange Poncirus trifoliata L. Raf, and Carrizo citrange Citrus sinensis Osb.×P.trifoliate Raf) at six different developmental stages (from 90 DAF to 240 DAF). Results: The results indicated that rootstock can significantly affect the contents of functional constituents and antioxidant capacity in 'Orah'. Additionally, it was found that pruning at either 90 DAF (days after flowering) or 150 DAF produced the most favorable outcomes for extracting functional substances. We also identified rootstock 'Trifoliate orange' has the highest total soluble solids (TSS) and 'Ziyang xiangcheng' to be the optimal in terms of comprehensive sensory of fruit quality, while 'Red orange' and 'Ziyang xiangcheng' are optimal in terms of functional substance quality, and 'Red orange' excels in antioxidant capacity. Discussion: Overall, the findings demonstrate the important role of rootstocks and developmental stage in shaping fruit sensory quality and functional substance synthesis, providing valuable insights for guiding rootstock selection, determining thinning time, and utilizing pruned fruits in a more informed manner.

4.
Integr Cancer Ther ; 23: 15347354241273962, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39223822

RESUMO

BACKGROUND: The traditional Chinese medicine (TCM) Xiaoliu Pingyi recipe (XLPYR) has been clinically used for several decades, demonstrating favorable therapeutic effects. However, the underlying regulatory mechanisms remain unclear. The aim of this study was to explore the anti-tumor effects of XLPYR and its regulatory role in the vascular microenvironment through in vivo and in vitro experiment. MATERIALS AND METHODS: In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution). Tumor volume and weight were then compared among the groups. The impact of XLPYR on the tumor vascular microenvironment was assessed using immunohistochemistry staining. In the in vitro study, XLPYR-containing serum was prepared by oral administration to SD rats. The CCK-8 assay evaluated the effect of the serum on the proliferation of normal lung epithelial BEAS-2B cells and LUAD A549 cells, determining the optimal intervention concentrations. The cell migration and invasion abilities were evaluated using the wound-healing assay and Transwell assay, respectively. Finally, ELISA assay measured VEGF secretion levels in the LUAD cell supernatant, and RT-qPCR and Western Blot were employed to detect differences in HIF-1α, VEGFA, Ang-2, and PI3K/Akt mRNA and protein expression levels in both in vivo and in vitro experiments. RESULTS: In the in vivo study, XLPYR significantly inhibited the growth of mice LUAD allografts, with enhanced anti-tumor effects observed with prolonged drug intervention. Immunohistochemistry staining revealed reduced MVD and increased pericyte coverage in all intervention groups. Regarding vascular function, FITC-Dextran extravasation in the tumor tissues of the Model group was significantly higher than in the intervention groups, particularly with lower extravasation in the COMBI group compared to the PEM group. In the in vitro study, XLPYR demonstrated a time- and concentration-dependent inhibitory effect on LUAD cells, and with greater sensitivity in inhibiting LUAD cells compared to BEAS-2B cells. The wound-healing assay and Transwell assay confirmed that XLPYR significantly suppressed the migration and invasion abilities of LUAD cells. ELISA experiments further revealed a significant decrease in VEGF expression in the supernatant of each intervention group. RT-qPCR and Western Blot results showed consistent findings between the in vivo and in vitro experiments. HIF-1α, VEGFA, and Ang-2 mRNA and protein expression levels were significantly downregulated in the PEM group, XLPYR group, and COMBI group. There were no significant differences in the expression of PI3K and Akt mRNA and total protein, but the expression levels of phosphorylated p-PI3K and p-Akt were notably downregulated. CONCLUSION: XLPYR significantly inhibited C57BL/6J mouse LUAD allograft growth and improved the vascular microenvironment, thereby intervening in tumor angiogenesis and inducing vascular normalization. It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.


Assuntos
Adenocarcinoma de Pulmão , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Microambiente Tumoral , Animais , Medicamentos de Ervas Chinesas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Humanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Masculino , Pemetrexede/farmacologia , Neovascularização Patológica/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos
5.
Ann Med ; 56(1): 2397090, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39221748

RESUMO

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.


Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.


Assuntos
Escores de Disfunção Orgânica , Curva ROC , Humanos , Masculino , Feminino , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Pneumonia/mortalidade , Pneumonia/diagnóstico , Índice de Gravidade de Doença , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/diagnóstico , Sepse/mortalidade , Sepse/diagnóstico , Taxa Respiratória , Idoso de 80 Anos ou mais , Pressão Sanguínea , Valor Preditivo dos Testes , Prognóstico
6.
Plant Cell Environ ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39262278

RESUMO

Plants have developed various resistance mechanisms against herbivorous insects through prolonged coevolution. Plant defence responses can be triggered by specific compounds present in insect saliva. Apyrase, a known enzyme that catalyzes the hydrolysis of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) into adenosine monophosphate (AMP) and inorganic phosphorus, has recently been identified in some herbivorous insects. However, whether insect salivary apyrase induces or inhibits plant responses remains poorly understood. In this study, we identified an apyrase-like protein in the salivary proteome of the fall armyworm, Spodoptera frugiperda, named Sfapyrase. Sfapyrase was primarily expressed in the salivary gland and secreted into plants during insect feeding. Transient expression of Sfapyrase in tobacco and maize enhanced plant resistance and resulted in decreased insect feeding. Knockdown of Sfapyrase through RNA interference led to increased growth and feeding of S. frugiperda. Furthermore, we showed that Sfapyrase activates the jasmonic acid signalling pathway and promotes the synthesis of secondary metabolites, especially benzoxazinoids, thereby enhancing resistance to S. frugiperda. In summary, our findings demonstrated that Sfapyrase acts as a salivary elicitor, inducing maize jasmonic acid defence responses and the production of insect-resistant benzoxazinoids. This study provides valuable insights into plant-insect interactions and offers potential targets for developing innovative insect pest management strategies.

7.
Sci Rep ; 14(1): 18190, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107362

RESUMO

The objective of this work was to investigate the sorption behavior of gases, namely CO2, CH4, and N2, by molecules of coal sampled from Linglu mine under different water inclusion rates. To this end, the adsorption, diffusion, adsorption heat, and potential energy distribution characteristics of the gases in the coal pores at different water inclusion rates were analyzed using molecular dynamics and grand canonical ensemble Monte Carlo methods. The results showed that the adsorption relationship of the coal molecules on CO2, CH4, and N2 exhibited a downtrend followed by an uptrend when the water content was increased from 0 to 3.6%. The adsorption amount of CO2 was approximately twice as much as those of CH4 and N2, indicating that the competitive adsorption advantage of CO2 compared with those of CH4 and N2 was unaffected by the water content. The trend in the average heat of adsorption was generally consistent with the trend in the density of coal molecules under different moisture contents. Under the same conditions, the diffusion coefficient within a coal molecule was negatively related to the water content in the system. The layer spacing of the water molecules (2.875 Å) was greater than the liquid-water layer spacing, indicating the formation of a water molecule layer at this point, which inhibited gas adsorption. This study lays a theoretical foundation for further investigating the microscopic mechanism of coal-water interaction.

8.
Acta Pharmacol Sin ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160244

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.

9.
Technol Cancer Res Treat ; 23: 15330338241277699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161322

RESUMO

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577-1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216-1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion: A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI.


Assuntos
Índice de Massa Corporal , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Feminino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/etiologia , Neoplasias dos Genitais Femininos/epidemiologia , Fatores de Risco , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética
10.
Plants (Basel) ; 13(16)2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39204695

RESUMO

The benefits of citrus fruits are strongly associated with their secondary metabolites. In this study, we conducted widely targeted metabolomics analyses to compare the variability of the ingredients in four scion-rootstock combinations. A total of 376 differential metabolites were obtained by a multivariate statistical analysis, and a KEGG pathway analysis showed that the enriched metabolic pathways were mainly related to the biosynthesis of flavonoids as well as lipid metabolism. The anthocyanin-targeted metabolomic features showed that cyanidin 3-O-glucoside, cyanidin 3-O-(6-O-malonyl-beta-D-glucoside), cyanidin 3-O-sophoroside, and cyanidin 3-O-xyloside were the pigments responsible for the red color of Tarocco. A lipid metabolomics analysis revealed that when Tarocco was hetero-grafted with rootstock H, there was an increase in the content of each lipid subclass, accompanied by an increase in the levels of unsaturated fatty acids, including polyunsaturated linoleic and linolenic acids, thus impacting the ratio of unsaturated fatty acids to saturated fatty acids. Additionally, we determined their antioxidant capacity ('Trifoliate orange' (Z) > 'Citrange' (ZC) > 'Hongju' (H) > 'Ziyang Xiangcheng' (X)) using in vitro assays. Finally, we utilized a network pharmacology analysis to explore the antioxidant mechanisms and potential pharmacological ingredients; we obtained 26 core targets proteins and 42 core metabolites associated with oxidative damage, providing a basis for future preventive and therapeutic applications of these metabolites.

12.
Small ; : e2402141, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953313

RESUMO

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

13.
Front Microbiol ; 15: 1396699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957618

RESUMO

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

15.
Eur J Oncol Nurs ; 71: 102667, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39003843

RESUMO

PURPOSE: To evaluate the associations between frailty and all-cause and cancer-related mortality. Additionally, the objective is to compare the magnitude of these associations between older adults and younger adults. METHODS: We gathered baseline data from NHANES (1999-2018) and developed a cumulative index consisting of 39 items to evaluate frailty. The National Death Index database was utilized to track the survival status of individuals. The Cox regression model was employed to estimate the associations between frailty status and all-cause and cancer-related mortality. RESULTS: Ultimately, 3398 cancer patients were included in the analysis, comprising 910 younger adults and 2488 older adults. Compared to non-frail patients, the elevated all-cause and cancer-related mortality among pre-frail patients was not statistically significant (HRs = 1.312, 95%CI: 0.956-1.800, P = 0.092; HRs = 1.462, 0.811-2.635, P = 0.207). However, a significant elevation of both all-cause and cancer-related mortality risk was observed among frail patients (HRs = 2.213, 1.617-3.030, P < 0.001; HRs = 2.463, 95%CI = 1.370-4.429, P = 0.003). Frailty individuals demonstrated a more pronounced association with the prediction of all-cause mortality in younger (HRs = 2.230, 1.073-4.634, P = 0.032) than in older adults (HRs = 2.090, 1.475-2.960, P < 0.001). Sensitivity analysis consistently revealed robust results. RCS plots suggested a progressively escalating dose-response correlation between frailty and both all-cause and cancer-related mortality risk. CONCLUSIONS: Pre-frailty did not result in an increase in mortality risks compared to non-frailty. However, frailty caused a higher all-cause and cancer-related mortality risk than non-frailty. Identifying those at risk and implementing targeted interventions may contribute to extending healthy life expectancy, regardless of age.


Assuntos
Causas de Morte , Fragilidade , Neoplasias , Humanos , Neoplasias/mortalidade , Masculino , Feminino , Fragilidade/mortalidade , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , Avaliação Geriátrica , Inquéritos Nutricionais , Idoso Fragilizado/estatística & dados numéricos , Fatores Etários , Fatores de Risco
16.
ACS Omega ; 9(28): 30461-30469, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39035886

RESUMO

In order to study the effect of H2S on gas adsorption in a coal seam, the adsorption characteristics of single-component CO2, CH4, N2, and H2S and multicomponent H2S mixed with CO2, CH4, and N2 by anthracite were simulated by using the Grand Canonical Ensemble Monte Carlo (GCMC) method. The results show that the adsorption capacity of CO2, CH4, N2, and H2S in anthracite decreases with increasing temperature and increases with increasing pressure. The isothermal adsorption curves of CO2, CH4, N2, and H2S and different proportions of H2S/CH4, H2S/N2, and H2S/CO2 are highly consistent with the Langmuir equation, and the R 2 is above 0.99. Under different temperature and pressure conditions, the adsorption capacity of H2S and CO2 is stronger than that of coal for N2 and CH4, and the adsorption capacity difference is about 3 mmol/g. There is competitive adsorption among H2S, CO2, CH4, and N2, and H2S has a superior adsorption property. When H2S and other gases exist at the same time, the adsorption capacities of CH4, N2, and CO2 are reduced by 48-60%, 81-91%, and 51-66%, respectively.

17.
Immunology ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39022997

RESUMO

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39044536

RESUMO

Lung cancer is a leading cause of death globally, with lung adenocarcinoma being the most common subtype. Despite advancements in targeted therapy, drug resistance remains a major challenge. This study investigated the impact of Bacillus coagulans on drug resistance in lung adenocarcinoma cells. The cells were pretreated with B. coagulans culture filtrate (BCCF), and functional assays were performed, including cell proliferation, cell cycle, apoptosis, and immunofluorescence staining. Results showed that BCCF induced cell cycle arrest at the S phase, reducing cell proliferation and suppressing drug resistance marker P-glycoprotein expression in BCCF-treated resistant cells rather than BCCF-treated control cells. Moreover, drug-resistant cells exhibited the ability for epithelial-mesenchymal transition, which could contribute to their necrosis through the iron-mediated cell death pathway upon BCCF treatment. Proteomic analysis identified downregulation of DNA mismatch repair protein PMS2 after BCCF treatment. These findings suggest that B. coagulans may modulate the DNA repair pathway, influencing drug resistance in lung adenocarcinoma cells. In conclusion, this study highlights the potential impact of B. coagulans on drug-resistant lung adenocarcinoma cells. Further investigation and understanding of the regulatory mechanisms by which B. coagulans modulates drug resistance in lung adenocarcinoma can aid in the development of more effective treatment strategies to improve the prognosis of lung cancer patients.

20.
Front Oncol ; 14: 1352865, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933440

RESUMO

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.

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