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1.
Nurs Crit Care ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004612

RESUMO

BACKGROUND: Catheter-related thrombosis is a common complication of the peripherally inserted central catheter (PICC) in neonates, leading to unintended tube removal and significantly affecting neonatal health and safety. Despite widespread reporting on the estimated occurrence and factors contributing to neonatal PICC-related thrombosis, these findings have not been synthesized. OBJECTIVES: The purpose of this study was to determine the incidence and risk factors of neonatal PICC-related thrombosis. DESIGN: Systematic literature review and meta-analysis. METHODS: Two independent researchers systematically explored multiple databases-such as PubMed, Medline, Embase and the Cochrane Library-from their inception until October 2023. Our study aggregates and scrutinizes studies specifically addressing the incidence and risk factors of neonatal PICC-related thrombosis. Employing the RevMan 5.3 software, a meta-analysis was executed to determine the incidence of both thrombosis and odds ratios (OR), accompanied by their respective 95% confidence intervals (CI) for the risk factors. RESULTS: A total of 327 articles were screened, and data from 24 studies were used in synthesis. Neonatal PICC-related thrombosis incidence varied from 0.23% to 17.91%. The pooled incidence was 2% (95% CI: 1%-2%; I2 = 94%; p < .0001). The study identified 12 risk factors, including insertion sites in the lower extremities (OR = 0.22; 95% CI: 0.09-0.56; p = .001), gestational age <28 weeks, abdominal pathology, fresh frozen plasma by day 5 > 50 mL/kg, PICC tip location (proximal placement), two lumens, three lumens, prolonged hospital stay, infection, mothers' use of anticoagulants, patients with cardiac insufficiency and being twin-to-twin transfusion syndrome donor. CONCLUSIONS: The analysis indicates an overall pooled incidence of neonatal PICC-related thrombosis of 2%. Twelve factors were identified as risks associated with neonatal PICC-related thrombosis. Understanding the risk factors can provide evidence-based recommendations for improving awareness, control and treatment and better nursing management. RELEVANCE TO CLINICAL PRACTICE: This systematic review and meta-analysis illuminates the incidence and risk factors linked to neonatal PICC-related thrombosis, delivering essential insights pivotal for clinical decision-making and enhancing patient care within neonatal health care settings.

2.
Cell Rep ; 43(7): 114453, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38985677

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) infection, a major cause of hospital- and community-acquired pneumonia, still has a high mortality rate. Extracellular vesicles (EVs), as crucial mediators of intercellular communication, have a significant impact on infectious diseases. However, the role of EVs from alveolar macrophages (AMs) in MRSA pneumonia remains unclear. We report that AMs phagocytose MRSA and release more EVs in mice with MRSA pneumonia. EVs from AMs harboring phagocytosed MRSA exhibit significant proinflammatory effects and induce necroptosis by delivering tumor necrosis factor α (TNF-α) and miR-146a-5p. Mechanically, the upregulated miR-146a-5p in these EVs enhances the phosphorylation of RIPK1, RIPK3, and MLKL by targeting TNF receptor-associated factor 6 (TRAF6), thereby promoting TNF-α-induced necroptosis. The combination of a TNF-α antagonist and an miR-146a-5p antagomir effectively improves the outcomes of mice with MRSA pneumonia. Overall, we reveal the pronecrotic effect of EVs from MRSA-infected AMs and provide a promising target for the prevention and treatment of MRSA pneumonia.

3.
Cell Rep ; 43(7): 114466, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38985681

RESUMO

Meristems are crucial for organ formation, but our knowledge of their molecular evolution is limited. Here, we show that AINTEGUMENTA (MpANT) in the euANT branch of the APETALA2-like transcription factor family is essential for meristem development in the nonvascular plant Marchantia polymorpha. MpANT is expressed in the thallus meristem. Mpant mutants show defects to maintain meristem identity and undergo meristem duplication, while MpANT overexpressers show ectopic thallus growth. MpANT directly upregulates MpGRAS9 in the SHORT-ROOT (SHR) branch of the GRAS family. In the vascular plant Arabidopsis thaliana, the euANT-branch genes PLETHORAs (AtPLTs) and AtANT are involved in the formation and maintenance of root/shoot apical meristems and lateral organ primordia, and AtPLTs directly target SHR-branch genes. In addition, euANTs bind through a similar DNA-binding motif to many conserved homologous genes in M. polymorpha and A. thaliana. Overall, the euANT pathway has an evolutionarily conserved role in meristem development.

4.
J Affect Disord ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009316

RESUMO

BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LIMITATIONS: One of the major limitations is the estimation of 24-hour urinary sodium with spot urine samples. CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

5.
Plant Physiol Biochem ; 214: 108937, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018774

RESUMO

Scopoletin and chlorogenic acid (CGA) are important polyphenols that regulate plant growth, development, and stress resistance. The ERF transcription factor WAX INDUCER1 (WIN1) promotes the biosynthesis of cutin, suberine, and wax. However, its full roles in regulating the accumulation of plant secondary metabolites still remain to be further clarified. In this study, NtWIN1 gene encoding a SHINE-type AP2/ERF transcription factor of the Va subgroup was identified from N. tabacum. NtWIN1 showed high expression levels in tobacco stems, sepals, and pistils. Overexpression (OE) and knock-out of NtWIN1 showed that it promoted the accumulation of total polyphenols and altered their composition. Compare to that of WT plants, the CGA contents significantly increased by 25%-50% in the leaves, flowers, and capsules of OE lines, while the scopoletin contents in the OE plants significantly decreased by 30%-67%. In contrast, the CGA contents in ntwin1 lines reduced by 23%-26%, and the scopoletin contents in ntwin1 increased by 38%-75% compare to that of WT plants. Chromatin immunoprecipitation and Dual-Luc transcription activation assays showed that NtWIN1 could bind to the promoters of NtF6'H1 and NtCCoAMT, thereby modulating their expression. The scopoletin content in ntwin1/ntf6'h1 double mutant was significantly lower than that in ntwin1 and WT plants, but showed no significant differences with that in ntf6'h1 mutant, further indicating that the inhibition of NtWIN1 on scopoletin accumulation depends on the activity of NtF6'H1. Our study illustrates the new roles of NtWIN1, and provides a possible target for regulating the synthesis of polyphenols in tobacco.

6.
Int J Food Microbiol ; 421: 110781, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38852217

RESUMO

This study used hydrogen peroxide (H2O2) treatment to overexpress the gene of nitric oxide synthase (nos) in Staphylococcus vitulinus, which was then inoculated into fermented sausages to observe its effect on colour development. The results showed that a low concentration of H2O2 (50 mM) could up-regulate the expression of nos by increasing the oxidative stress level of S. vitulinus. At 2 h after treatment, the expression of nos in S. vitulinus was the highest (P < 0.05), and the relative enzyme activity was increased to about 1.5 times that of the untreated. The growth of S. vitulinus was not substantially affected by 50-mM H2O2 treatment (P > 0.05). When H2O2-treated S. vitulinus was inoculated into fermented sausages, the content of nitrosomyoglobin was increased, and the a*-value (indicating redness) was not significantly different from that in the group treated with nitrite (P > 0.05). This study provides a potential method to enhance the ability of S. vitulinus for colourising fermented sausage by inducing the overexpression of nos.


Assuntos
Fermentação , Peróxido de Hidrogênio , Produtos da Carne , Óxido Nítrico Sintase , Staphylococcus , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Produtos da Carne/microbiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/enzimologia , Staphylococcus/genética , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase/genética , Estresse Oxidativo , Cor , Microbiologia de Alimentos , Animais
7.
Adv Sci (Weinh) ; : e2402361, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874523

RESUMO

Radiotheranostics is a rapidly growing approach in personalized medicine, merging diagnostic imaging and targeted radiotherapy to allow for the precise detection and treatment of diseases, notably cancer. Radiolabeled antibodies have become indispensable tools in the field of cancer theranostics due to their high specificity and affinity for cancer-associated antigens, which allows for accurate targeting with minimal impact on surrounding healthy tissues, enhancing therapeutic efficacy while reducing side effects, immune-modulating ability, and versatility and flexibility in engineering and conjugation. However, there are inherent limitations in using antibodies as a platform for radiopharmaceuticals due to their natural activities within the immune system, large size preventing effective tumor penetration, and relatively long half-life with concerns for prolonged radioactivity exposure. Antibody engineering can solve these challenges while preserving the many advantages of the immunoglobulin framework. In this review, the goal is to give a general overview of antibody engineering and design for tumor radiotheranostics. Particularly, the four ways that antibody engineering is applied to enhance radioimmunoconjugates: pharmacokinetics optimization, site-specific bioconjugation, modulation of Fc interactions, and bispecific construct creation are discussed. The radionuclide choices for designed antibody radionuclide conjugates and conjugation techniques and future directions for antibody radionuclide conjugate innovation and advancement are also discussed.

8.
J Immunother ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38800996

RESUMO

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.

9.
Environ Int ; 186: 108646, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38615543

RESUMO

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.


Assuntos
Pré-Eclâmpsia , Temperatura , Gravidez , Humanos , Feminino , Pré-Eclâmpsia/epidemiologia , China/epidemiologia , Adulto , Exposição Ambiental/estatística & dados numéricos , Estudos de Coortes , Fatores de Risco , Adulto Jovem , Exposição Materna/estatística & dados numéricos , Exposição Materna/efeitos adversos
10.
Cancer Med ; 13(4): e6962, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38457207

RESUMO

BACKGROUND: Though programmed cell death-ligand 1 (PD-L1) has been used in predicting the efficacy of immune checkpoint blockade (ICB), it is insufficient as a single biomarker. As a key effector of an intrinsically mutagenic microhomology-mediated end joining (MMEJ) pathway, DNA polymerase theta (POLQ) was overexpressed in various malignancies, whose expression might have an influence on genomic stability, therefore altering the sensitivity to chemotherapy and immunotherapy. METHODS: A total of 1304 patients with muscle-invasive bladder cancer (MIBC) from six independent cohorts were included in this study. The Zhongshan Hospital (ZSHS) cohort (n = 134), The Cancer Genome Atlas (TCGA) cohort (n = 391), and the Neo-cohort (n = 148) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n = 234) and the UNC-108 cohort (n = 89) were used for the assessment of immunotherapeutic response. In addition, the relationship between POLQ and the immune microenvironment was assessed, and GSE32894 (n = 308) was used only for the evaluation of the immune microenvironment. RESULTS: We identified POLQhigh PD-L1high patients could benefit more from immunotherapy and platinum-based chemotherapy. Further analysis revealed that high POLQ expression was linked to chromosome instability and higher tumor mutational burden (TMB), which might elicit the production of neoantigens. Further, high POLQ expression was associated with an active tumor immune microenvironment with abundant infiltration of immune effector cells and molecules. CONCLUSIONS: The study demonstrated that high POLQ expression was correlated with chromosome instability and antitumor immune microenvironment in MIBC, and the combination of POLQ and PD-L1 could be used as a superior companion biomarker for predicting the efficacy of immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias da Bexiga Urinária , Humanos , Antígeno B7-H1/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/metabolismo , Biomarcadores , Imunoterapia , Instabilidade Cromossômica , Músculos/metabolismo , Músculos/patologia , Microambiente Tumoral
11.
Immun Inflamm Dis ; 12(3): e1196, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38501542

RESUMO

AIM: We investigated the relationship between the group 2 innate lymphoid cells (ILC2s)-myeloid-derived suppressor cells (MDSCs) axis and obesity-related breast cancer. METHODS: Fifty-eight patients with breast cancer who had first relapse and metastasis between January 2019 and August 2021 were enrolled. The proportions of ILC2s and MDSCs in blood and the levels of cytokines in serum were detected with flow cytometry. Correlation analysis among clinical characteristics (such as body mass index [BMI]), cytokines, ILC2s, and MDSCs was conducted. RESULTS: There was a significant difference in the proportions of ILC2s and MDSCs between the high BMI group and the normal BMI group (p < .05). In the triple-negative breast cancer (TNBC) patients, the proportions of ILC2s and MDSCs in the obese group were significantly higher than those in the nonobese group (p < .05). In all breast cancer patients, there was a positive correlation between BMI and the ILC2s-MDSCs axis (p < .05). However, there was no correlation observed between the number of metastases, progression-free survival, and the ILC2s-MDSCs axis (p > .05). Additionally, ILC2s showed positive correlations with MDSCs, interleukin-5 (IL-5), IL-10, IL-17A, (PD-L1), programmed cell death 2 ligand 2 (PD-L2), and molecular typing (p < .05). Similarly, MDSCs exhibited positive correlations with IL-5, IL-8, IL-9, IL-17A, PD-L1, and PD-L2 (p < .05). In patients with TNBC, there was a positive correlation between BMI and IL-5 (p < .05). CONCLUSION: Conclusively, obesity may enhance the immunosuppressive effect of the ILC2-MDSC axis in advanced breast cancer. IL-5 may play a vital role in the ILC2-MDSC axis and obesity in TNBC.


Assuntos
Células Supressoras Mieloides , Neoplasias de Mama Triplo Negativas , Humanos , Células Supressoras Mieloides/metabolismo , Imunidade Inata , Antígeno B7-H1/metabolismo , Interleucina-17/metabolismo , Interleucina-5/metabolismo , Linfócitos/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Citocinas/metabolismo
12.
Med Rev (2021) ; 4(1): 55-67, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38515779

RESUMO

Stroke is a prevalent, severe, and disabling health-care issue on a global scale, inevitably leading to motor and cognitive deficits. It has become one of the most significant challenges in China, resulting in substantial social and economic burdens. In addition to the medication and surgical interventions during the acute phase, rehabilitation treatment plays a crucial role in stroke care. Robotic technology takes distinct advantages over traditional physical therapy, occupational therapy, and speech therapy, and is increasingly gaining popularity in post-stroke rehabilitation. The use of rehabilitation robots not only alleviates the workload of healthcare professionals but also enhances the prognosis for specific stroke patients. This review presents a concise overview of the application of therapeutic robots in post-stroke rehabilitation, with particular emphasis on the recovery of motor and cognitive function.

13.
Cancer Immunol Immunother ; 73(4): 66, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430246

RESUMO

BACKGROUND: Luminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC. METHODS: This study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC. RESULTS: Among patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy. CONCLUSIONS: We emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética , Músculos/patologia
14.
J Pathol ; 263(2): 139-149, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38380548

RESUMO

TP53 mutation is one of the most common genetic alterations in urothelial carcinoma (UrCa), and heterogeneity of TP53 mutants leads to heterogeneous clinical outcomes. This study aimed to investigate the clinical relevance of specific TP53 mutations in UrCa. In this study, a total of eight cohorts were enrolled, along with matched clinical annotation. TP53 mutations were classified as disruptive and nondisruptive according to the degree of disturbance of p53 protein function and structure. We evaluated the clinical significance of TP53 mutations in our local datasets and publicly available datasets. The co-occurring events of TP53 mutations in UrCa, along with their therapeutic indications, functional effects, and the tumor immune microenvironment, were also investigated. TP53 mutations were identified in 49.7% of the UrCa patients. Within this group, 25.1% of patients carried TP53Disruptive mutations, a genetic alteration correlated with a significantly poorer overall survival (OS) when compared to individuals with TP53Nondisruptive mutations and those with wild-type TP53. Significantly, patients with TP53Disruptive mutations exhibit an increased probability of responding favorably to PD-1/PD-L1 blockade and chemoimmunotherapy. Meanwhile, there was no noteworthy distinction in OS among patients with varying TP53 mutation status who underwent chemotherapy. Samples with TP53Disruptive mutations showed an enriched APOBEC- and POLE-related mutational signature, as well as an elevated tumor mutation burden. The sensitivity to immunotherapy in tumors carrying TP53Disruptive mutation may be attributed to the inflamed tumor microenvironment characterized by increased CD8+T cell infiltration and interferon-gamma signaling activation. In conclusion, UrCa patients with TP53Disruptive mutations have shown reduced survival rates, yet they may respond well to PD-1/PD-L1 blockade therapy and chemoimmunotherapy. By distinguishing specific TP53 mutations, we can improve risk stratification and offer personalized genomics-guided therapy to UrCa patients. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Antígeno B7-H1 , Inibidores de Checkpoint Imunológico , Mutação , Receptor de Morte Celular Programada 1 , Microambiente Tumoral , Proteína Supressora de Tumor p53 , Neoplasias da Bexiga Urinária , Humanos , Proteína Supressora de Tumor p53/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/imunologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/mortalidade , Biomarcadores Tumorais/genética , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Pessoa de Meia-Idade
15.
ACS Nano ; 18(9): 6946-6962, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38377037

RESUMO

Pyroptosis mediated by gasdermin protein has shown great potential in cancer immunotherapies. However, the low expression of gasdermin proteins and the systemic toxicity of nonspecific pyroptosis limit its clinical application. Here, we designed a synthetic biology strategy to construct a tumor-specific pyroptosis-inducing nanoplatform M-CNP/Mn@pPHS, in which a pyroptosis-inducing plasmid (pPHS) was loaded onto a manganese (Mn)-doped calcium carbonate nanoparticle and wrapped in a tumor-derived cell membrane. M-CNP/Mn@pPHS showed an efficient tumor targeting ability. After its internalization by tumor cells, the degradation of M-CNP/Mn@pPHS in the acidic endosomal environment allowed the efficient endosomal escape of plasmid pPHS. To trigger tumor-specific pyroptosis, pPHS was designed according to the logic "AND gate circuit" strategy, with Hif-1α and Sox4 as two input signals and gasdermin D induced pyroptosis as output signal. Only in cells with high expression of Hif-1α and Sox4 simultaneously will the output signal gasdermin D be expressed. Since Hif-1α and Sox4 are both specifically expressed in tumor cells, M-CNP/Mn@pPHS induces the tumor-specific expression of gasdermin D and thus pyroptosis, triggering an efficient immune response with little systemic toxicity. The Mn2+ released from the nanoplatform further enhanced the antitumor immune response by stimulating the cGAS-STING pathway. Thus, M-CNP/Mn@pPHS efficiently inhibited tumor growth with 79.8% tumor regression in vivo. We demonstrate that this logic "AND gate circuit"-based gasdermin nanoplatform is a promising strategy for inducing tumor-specific pyroptosis with little systemic toxicity.


Assuntos
Neoplasias , Piroptose , Humanos , Gasderminas , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias/terapia , Imunoterapia , Lógica
16.
ACS Nano ; 18(9): 7136-7147, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38407021

RESUMO

Tapping into the innate immune system's power, nanovaccines can induce tumor-specific immune responses, which is a promising strategy in cancer immunotherapy. However, traditional vaccine design, requiring simultaneous loading of antigens and adjuvants, is complex and poses challenges for mass production. Here, we developed a tumor nanovaccine platform that integrates adjuvant functions into the delivery vehicle, using branched polyguanidine (PolyGu) nanovaccines. These nanovaccines were produced by modifying polyethylenimine (PEI) with various guanidine groups, transforming PEI's cytotoxicity into innate immune activation. The PolyGu nanovaccines based on poly(phenyl biguanidine ) (Poly-PBG) effectively stimulated dendritic cells, promoted their maturation via the TLR4 and NLRP3 pathways, and displayed robust in vivo immune activity. They significantly inhibited tumor growth and extended mouse survival. The PolyGu also showed promise for constructing more potent mRNA-based nanovaccines, offering a platform for personalized cancer vaccine. This work advances cancer immunotherapy toward potential clinical application by introducing a paradigm for developing self-adjuvanting nanovaccines.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Animais , Camundongos , Nanovacinas , Adjuvantes Imunológicos , Imunoterapia , Neoplasias/terapia
17.
BMC Nurs ; 23(1): 116, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360608

RESUMO

BACKGROUND: The shortage of nurses has been a global human resources problem. A good professional growth environment is essential to developing potential nursing students and attracting nurses to join, and it has great significance in reducing nurse turnover. However, nurses' comprehensive perceptions of professional growth have not yet been examined. METHODS: A cluster sampling method was used to conduct a professional growth questionnaire survey on young nursing talents from a large Chinese public tertiary A hospital in March 2022. RESULTS: The score of professional growth among 243 young nursing talents was 57.92 ± 9.607, with a scoring rate of 77.23%. The scores for dimensions of professional growth, from lowest to highest, were rehabilitation growth, promotion speed, professional goal progress, and professional ability development. Attitudes towards participating in training, service as the quality manager or clinical teacher, self-efficacy, professional title, work-family support, education, and organizational commitment of young nursing talents were significantly associated with professional growth. CONCLUSION: The professional growth of young nursing talents was at a moderate level and needed to be strengthened. Nursing leaders and managers are expected to develop management practices to enhance young nursing talents' professional growth in combination with the related factors.

18.
Int J Nurs Sci ; 11(1): 133-142, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352290

RESUMO

Objective: In intensive care units (ICU), frequent false alarms from medical equipment can cause alarm fatigue among nurses, which might lead to delayed or missed responses and increased risk of adverse patient events. This review was conducted to evaluate the effectiveness of intelligent management interventions to reduce false alarms in ICU. Method: Following the framework of Whitmore and Knafl, the reviewers systematically searched six databases: PubMed, EMBASE, CINAHL, OVID, Cochrane Library, and Scopus, and studies included intelligent management of clinical alarms published in the English or Chinese language from the inception of each database to December 2022 were retrieved. The researchers used the PICOS framework to formulate the search strategy, developed keywords, screened literature, and assessed the studies' quality using the Joanna Briggs Institute-Meta-Analysis of Statistics, Assessment, and Review Instrument (JBI-MAStARI). The review was preregistered on PROSPERO (CRD42023411552). Results: Seven studies met the inclusion criteria. The results showed that different interventions for intelligent management of alarms were beneficial in reducing the number of false alarms, the duration of alarms, the response time to important alarms for nurses, and the alarm fatigue levels among nurses. Positive results were found in practice after the application of the novel alarm management approaches. Conclusion: Intelligent management intervention may be an effective way to reduce false alarms. The application of systems or tools for the intelligent management of clinical alarms is urgent in hospitals. To ensure more effective patient monitoring and less distress for nurses, more alarm management approaches combined with artificial intelligence will be needed in the future to enable accurate identification of critical alarms, ensure nurses are responding accurately to alarms, and make a real difference to alarm-ridden healthcare environments.

19.
Int J Nurs Sci ; 11(1): 91-98, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38352296

RESUMO

Objective: This study aimed to investigate the level and influencing factors of nurses' antimicrobial stewardship (AMS) engagement in China based on the capability, opportunity, motivation, and behavior (COM-B) theory, providing valuable insights for developing effective strategies to improve nursing quality in AMS. Methods: This cross-sectional study was conducted in 17 tertiary hospitals in Hunan, China, from November 2021 to January 2022. A total of 4,514 nurses were selected. The Nurse AMS Engagement Questionnaire (NAEQ), developed using the COM-B theory, was used for evaluation. The questionnaire included capability (14 items), opportunity (7 items), motivation (6 items), and behavior (12 items) four dimensions, 39 items. Results: The total NAEQ score was 155.08 ± 27.12, indicating a moderate level. The score of the capability, opportunity, motivation, and behavior dimensions were 52.33 ± 13.48, 28.64 ± 5.76, 24.57 ± 4.57 and 49.53 ± 8.83, respectively. Significant differences in nurses' AMS engagement were based on professional titles, whether working as a part-time infection control nurse, whether knowing the AMS teams and the defined daily doses of antibiotics, department type, the deployment of clinical pharmacists, and frequency of antimicrobial training and physician-nurse joint rounds (P < 0.05). Nurses with junior titles had higher scores on the NAEQ than nurses with intermediate titles (P < 0.05). Nurses who worked as part-time infection control nurses, knew the AMS team, and the defined daily doses of antibiotics had higher NAEQ scores than those who didn't (P < 0.01). Nurses working in the ICU and infectious disease department had lower NAEQ scores than those in other departments, such as the ear, nose, and throat (ENT) department (P < 0.01). Nurses who had clinical pharmacists deployed in their department had higher NAEQ scores than those without or unclear deployment (P < 0.01). Furthermore, nurses who received more frequent antimicrobial training and participated in physician-nurse joint rounds had higher NAEQ scores (P < 0.01). Conclusion: Multiple strategies, including enhanced education and training and improved multidisciplinary communication and collaboration, are expected to improve nurse AMS engagement. It is important to give more attention to nurses with intermediate professional titles, less experience, and those working in specific departments.

20.
Cancer Sci ; 115(4): 1306-1316, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402640

RESUMO

Muscle-invasive bladder cancer (MIBC) is a disease characterized by molecular and clinical heterogeneity, posing challenges in selecting the most appropriate treatment in clinical settings. Considering the significant role of CD4+ T cells, there is an emerging need to integrate CD4+ T cells with molecular subtypes to refine classification. We conducted a comprehensive study involving 895 MIBC patients from four independent cohorts. The Zhongshan Hospital (ZSHS) and The Cancer Genome Atlas (TCGA) cohorts were included to investigate chemotherapeutic response. The IMvigor210 cohort was included to assess the immunotherapeutic response. NCT03179943 was used to evaluate the clinical response to a combination of immune checkpoint blockade (ICB) and chemotherapy. Additionally, we evaluated genomic characteristics and the immune microenvironment to gain deeper insights into the distinctive features of each subtype. We unveiled four immune-molecular subtypes, each exhibiting distinct clinical outcomes and molecular characteristics. These subtypes include luminal CD4+ Thigh, which demonstrated benefits from both immunotherapy and chemotherapy; luminal CD4+ Tlow, characterized by the highest level of fibroblast growth factor receptor 3 (FGFR3) mutation, thus indicating potential responsiveness to FGFR inhibitors; basal CD4+ Thigh, which could benefit from a combination of ICB and chemotherapy; and basal CD4+ Tlow, characterized by an immune suppression microenvironment and likely to benefit from transforming growth factor-ß (TGF-ß) inhibition. This immune-molecular classification offers new possibilities for optimizing therapeutic interventions in MIBC.


Assuntos
Antígeno B7-H1 , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Linfócitos T , Linfócitos T CD4-Positivos , Músculos , Microambiente Tumoral , Prognóstico
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