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1.
Small ; : e2403345, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39118557

RESUMO

Although brightness and efficiency have been continually improved, the inability to achieve superior efficiency, color stability, and low-efficiency roll-off simultaneously in white organic light-emitting diodes (OLEDs) remains a knotty problem restricting the commercial application. In this paper, emission balance for two different horizontal orientation emitting molecules is maintained by using hole transport materials and bipolar host materials to control carriers' recombination and exciton diffusion. Impressively, the obtained devices exhibit extremely stable white emission with small chromaticity coordinates variation of (0.0023, 0.0078) over a wide brightness range from 1000 to 50000 cd m-2. Meanwhile, the optimal white OLED realizes the power efficiency, current efficiency, and external quantum efficiency up to 70.68 lm W-1, 85.53 cd A-1, and 24.33%, respectively at the practical brightness of 1000 cd m-2. Owing to reduced heterogeneous interfaces and broadening recombination region, this device exhibits a high EQE over 20% under high luminance of 10000 cd m-2, demonstrating slight efficiency roll-off. The operating mechanism of the device is analyzed by versatile experimental and theoretical evidences, which concludes precise manipulation of charges and excitons is the key points to achieve these excellent performances. This work provides an effective strategy for the design of high-performance white OLEDs.

2.
BMC Oral Health ; 24(1): 898, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107736

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. METHODS: 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. RESULTS: This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK. CONCLUSIONS: This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.


Assuntos
Carcinoma de Células Escamosas , Receptores ErbB , Neoplasias Bucais , Receptor ErbB-2 , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Receptor ErbB-2/metabolismo , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Camundongos , Masculino , Apoptose/efeitos dos fármacos , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Pessoa de Meia-Idade , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Aminoquinolinas
3.
Fundam Res ; 4(4): 829-840, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39156577

RESUMO

Since their clinical application in the 1840s, the greatest mystery surrounding general anesthesia (GA) is how different kinds of general anesthetics cause reversible unconsciousness, and the precise neural mechanisms underlying the processes. Over past years, although many studies revealed the roles of cortex, thalamus, brainstem, especially the sleep-wake circuits in GA-induced loss of consciousness (LOC),the full picture of the neural circuit mechanism of GA is still largely unknown. Recent studies have focused on the importance of other brain regions. Here, we report that the activity of glutamatergic (Glu) neurons in the piriform cortex (PC), a critical brain region for odor encoding, began to increase during the LOC of GA and gradually recovered after recovery of consciousness. Chemical lesions of the anterior PC (APC) neurons accelerated the induction time of isoflurane anesthesia. Chemogenetic and optogenetic activation of APCGlu neurons prolonged isoflurane and sevoflurane anesthesia induction, whereas APCGlu neuron inhibition displayed the opposite effects. Moreover, the modification of APCGlu neurons did not affect the induction or emergence time of propofol GA. In addition, odor processing may be partially involved in the induction of isoflurane and sevoflurane GA regulated by APCGlu neurons. In conclusion, our findings reveal a critical role of APCGlu neurons in inhalational GA induction.

4.
Proc Natl Acad Sci U S A ; 121(35): e2322418121, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39159377

RESUMO

The growing world population and increasing life expectancy are driving the need to improve the quality of blood transfusion, organ transplantation, and preservation. Here, to improve the ability of red blood cells (RBCs) for normothermic machine perfusion, a biocompatible blood silicification approach termed "shielding-augmenting RBC-in-nanoscale amorphous silica (SARNAS)" has been developed. The key to RBC surface engineering and structure augmentation is the precise control of the hydrolysis form of silicic acid to realize stabilization of RBC within conformal nanoscale silica-based exoskeletons. The formed silicified RBCs (Si-RBCs) maintain membrane/structural integrity, normal cellular functions (e.g., metabolism, oxygen-carrying capability), and enhance resistance to external stressors as well as tunable mechanical properties, resulting in nearly 100% RBC cryoprotection. In vivo experiments confirm their excellent biocompatibility. By shielding RBC surface antigens, the Si-RBCs provide universal blood compatibility, the ability for allogeneic mechanical perfusion, and more importantly, the possibility for cross-species transfusion. Being simple, reliable, and easily scalable, the SARNAS strategy holds great promise to revolutionize the use of engineered blood for future clinical applications.


Assuntos
Materiais Biocompatíveis , Eritrócitos , Dióxido de Silício , Eritrócitos/metabolismo , Dióxido de Silício/química , Materiais Biocompatíveis/química , Animais , Humanos , Perfusão/métodos , Preservação de Sangue/métodos , Transfusão de Sangue/métodos , Camundongos
5.
Langmuir ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161116

RESUMO

Roxarsone (ROX) is the main form of arsenic pollution in the world, and developing effective methods for its elimination is beneficial to human health and the ecological environment. Herein, we report glutaraldehyde cross-linked chitosan-encapsulated CoCe-LDH (layered double hydroxides) as an outstanding catalyst for the advanced oxidation of ROX and the efficient adsorption of inorganic arsenic. 100% of ROX and more than 98.5% of As(III)/As(V) were eliminated, and over 99.3% of remaining inorganic arsenic was oxidized to low-toxicity As(V) in the peroxymonosulfate (PMS) activation system, and some specific properties of LDH are considered the main reasons. The hierarchical anion exchange has been confirmed to be beneficial for constructing a high-concentration PMS interlayer microenvironment. The unique reverse electron transfer process induced 100% selective production of singlet oxygen. This work not only develops an advanced ROX removal method but also provides a new understanding of the LDH-based advanced oxidation process.

6.
Endocr Relat Cancer ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39162682

RESUMO

This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% confidence intervals (CI). Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = -0.83, 95% CI: -0.92 to -0.74), BC (AAPC = -0.48, 95% CI: -0.56 to -0.39), and TC (AAPC = -0.23, 95% CI: -0.29 to -0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. higher social development index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies.

7.
Cell Mol Life Sci ; 81(1): 349, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136771

RESUMO

Multiple myeloma (MM) is the second most common hematological tumor in adults. Immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide (Len), are effective drugs for the treatment of multiple myeloma. Len can recruit IKZF1 and IKZF3 to cereblon (CRBN), a substrate receptor of the cullin 4-RING E3 ligase (CRL4), promote their ubiquitination and degradation, and finally inhibit the proliferation of myeloma cells. However, MM patients develop resistance to IMiDs over time, leading to disease recurrence and deterioration. To explore the possible approaches that may enhance the sensitivity of IMiDs to MM, in this study, we used the proximity labeling technique TurboID and quantitative proteomics to identify Lys-63-specific deubiquitinase BRCC36 as a CRBN-interacting protein. Biochemical experiments demonstrated that BRCC36 in the BRISC complex protects CRBN from lysosomal degradation by specifically cleaving the K63-linked polyubiquitin chain on CRBN. Further studies found that a small-molecule compound SHIN1, which binds to BRISC complex subunit SHMT2, can upregulate CRBN by elevating BRCC36. The combination of SHIN1 and Len can further increase the sensitivity of MM cells to IMiDs. Therefore, this study provides the basis for the exploration of a possible strategy for the SHIN1 and Len combination treatment for MM.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Lenalidomida , Lisossomos , Mieloma Múltiplo , Ubiquitina-Proteína Ligases , Humanos , Mieloma Múltiplo/patologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Lenalidomida/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Linhagem Celular Tumoral , Ubiquitinação/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/antagonistas & inibidores
9.
Front Pharmacol ; 15: 1423555, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144620

RESUMO

Osteoporosis (OP) is a common and complex chronic metabolic disease with an increasing incidence rate, which has markedly increased the human health burden worldwide. The predominant cause of OP is an imbalance between osteoblasts (OB) and osteoclasts (OC). Studies on the correlation between bone marrow-derived mesenchymal stem cells (BMSCs) and OP have indicated that BMSCs-induced OB differentiation is an important pathway for bone tissue renewal. Chinese medicinal herbs have been used for centuries to treat various types of OPs because they are safer and more effective. The in vivo and in vitro experiments have confirmed that these herbs or their primary phytochemicals may exert therapeutic effects by stimulating BMSCs differentiation, which restores OB and OP balance, inhibits adipocyte differentiation, exerts anti-inflammatory and antioxidant effects, regulates the immune system, etc. This review summarizes the research on how Chinese medicinal herbs or their primary phytochemicals treat OP by stimulating BMSC differentiation and provides a scientifically reliable basis and perspective for their future clinical application.

10.
J Microbiol Methods ; : 107021, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147284

RESUMO

OBJECTIVE: To explore the application value of the second-generation metagenomic next-generation sequencing (mNGS) in the detection of pathogens in patients with pulmonary infection. METHODS: We conducted a retrospective analysis of 65 pulmonary infection cases treated at our institution and the Fifth People's Hospital of Shanghai between January 2021 and May 2023. All subjects were subjected to mNGS, targeted next-generation sequencing (tNGS), and conventional microbiological culture. A comparative analysis was performed to evaluate the diversity and quantity of pathogens identified by these methodologies and to appraise their respective diagnostic capabilities in pulmonary infection diagnostics. RESULTS: The mNGS successfully identified etiological agents in 60 of the 65 cases, compared to tNGS, which yielded positive results in 42 cases, and conventional laboratory cultures, which detected pathogens in 24 cases. At the bacterial genus level, mNGS discerned 9 genera, 11 species, and 92 isolates of pathogenic bacteria, whereas tNGS identified 8 genera, 8 species, and 71 isolates. Conventional methods were less sensitive, detecting only 6 genera, 7 species, and 33 isolates. In terms of fungal detection, mNGS identified 4 fungal species, tNGS detected 4 isolates of the Candida genus, and conventional methods identified 2 isolates of the same genus. Viral detection at the species level revealed 10 species and 46 isolates by mNGS, whereas tNGS detected only 3 species and 7 isolates. The area under the receiver operating characteristic curve (AUC) with 95% confidence intervals for diagnosing pulmonary infections was 0.818 (0.671 to 0.966) for mNGS, 0.668 (0.475 to 0.860) for tNGS, and 0.721 (0.545 to 0.897) for conventional culture.The mNGS demonstrates superior diagnostic efficacy and pathogen detection breadth in critically ill patients with respiratory infections, offering a significant advantage by reducing the time to diagnosis. The enhanced sensitivity and comprehensive pathogen profiling of mNGS underscore its potential as a leading diagnostic tool in clinical microbiology.

11.
Sci Adv ; 10(33): eado7249, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151007

RESUMO

Ferroptosis, caused by disorders of iron metabolism, plays a critical role in various diseases, making the regulation of iron metabolism essential for tissue repair. In our analysis of degenerated intervertebral disc tissue, we observe a positive correlation between the concentration of extracellular iron ions (ex-iron) and the severity of ferroptosis in intervertebral disc degeneration (IVDD). Hence, inspired by magnets attracting metals, we combine polyether F127 diacrylate (FDA) with tannin (TA) to construct a magnetically attracting hydrogel (FDA-TA). This hydrogel demonstrates the capability to adsorb ex-iron and remodel the iron metabolism of cells. Furthermore, it exhibits good toughness and self-healing properties. Notably, it can activate the PI3K-AKT pathway to inhibit nuclear receptor coactivator 4-mediated ferritinophagy under ex-iron enrichment conditions. The curative effect and related mechanism are further confirmed in vivo. Consequently, on the basis of the pathological mechanism, a targeted hydrogel is designed to reshape iron metabolism, offering insights for tissue repair.


Assuntos
Ferroptose , Hidrogéis , Ferro , Ferro/metabolismo , Hidrogéis/química , Humanos , Ferroptose/efeitos dos fármacos , Animais , Taninos/química , Taninos/farmacologia , Degeneração do Disco Intervertebral/metabolismo , Cicatrização/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
Adv Mater ; : e2404393, 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39128130

RESUMO

Intensifying the synergy between confined carbon nanopores and ionic liquids (ILs) and a deep comprehension of the ion behavior is required for enhancing the capacitive storage performance. Despite many theoretical insights on the storage mechanism, experimental verification has remained lacking due to the intricate nature of pore texture. Here, a compressed micropore-rich carbon framework (CMCF) with tailored monolayer and bilayer confinement pores is synthesized, which exhibits a compatible ionophilic interface to accommodate the IL [EMIM][BF4]. By deploying in situ Raman spectroscopy, in situ Fourier-transform infrared spectroscopy, and solid-state nuclear magnetic resonance, the effect of the pore textures on ions storage behaviors is elucidated. A voltage-induced ion gradient filling process in these ionophilic pores is proposed, in which ion exchange and co-ion desorption dominate the charge storage process. Moreover, it is established that the monolayer confinement of ions enhances the capacity, and bilayer confinement facilitates the charging dynamics. This work may guide the design of nanoconfinement carbon for high-energy-density supercapacitors and deepen the understanding of the charge storage mechanism in ionophilic pores.

14.
CNS Neurosci Ther ; 30(8): e14922, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39138640

RESUMO

AIMS: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia. METHODS: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed. RESULTS: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity. CONCLUSIONS: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.


Assuntos
Anestésicos Inalatórios , Isoflurano , Camundongos Endogâmicos C57BL , Bainha de Mielina , Neurônios , Isoflurano/farmacologia , Animais , Anestésicos Inalatórios/farmacologia , Camundongos , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Doenças Desmielinizantes/induzido quimicamente , Eletroencefalografia , Encéfalo/efeitos dos fármacos
15.
Int Immunopharmacol ; 141: 112860, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142002

RESUMO

BACKGROUND: In this study, the relationship between C-reactive protein-albumin-lymphocyte (CALLY) index, a novel composite indicator based on inflammation and nutrition, and major adverse cardiovascular events (MACEs) was investigated in patients with ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: This retrospective study included 438 patients with STEMI who were treated at a single center between January 2017 and December 2020. The CALLY index was calculated for each patient on admission. The predictive value of the CALLY index for short- and long-term MACEs was evaluated using the area under the curve (AUC) analysis, and the corresponding AUC values were calculated. Clinical characteristics were analyzed after categorizing the population based on the optimal cut-off value of the CALLY index. Multivariate Cox regression analysis was used to determine factors independently associated with MACEs, while logistic regression analysis was used to identify factors independently associated with the severity of coronary artery lesions. Kaplan-Meier estimation and log-rank test were used to assess event-free survival rates among different CALLY index groups. Additionally, Spearman's correlation test was used to determine the association between the CALLY index and the Gensini score. RESULTS: The AUC for predicting short-term MACEs in STEMI patients using the CALLY index was 0.758, while the AUC for predicting long-term MACEs was 0.740. Similarly, the AUC values were 0.815 and 0.819, respectively, when evaluating the short- and long-term mortality rates using the CALLY index. Multivariable Cox regression analysis revealed that a high CALLY index (threshold of 1.50) independently reduced the risk of short-term MACEs in patients with STEMI (hazard ratio [HR] = 0.274, 95 % confidence interval [CI] = 0.121-0.621, P=0.002). Multivariable Cox regression also demonstrated that a high CALLY index (threshold > 0.91) independently reduced the occurrence of long-term MACEs during follow-up in STEMI patients (HR=0.439, 95 % CI=0.292-0.659, P<0.001). Furthermore, multivariate logistic regression analysis revealed that a high CALLY index (threshold > 1.13) independently reduced the risk of severe coronary artery lesions in patients with STEMI (odds ratio = 0.299 [95 % CI=184-0.485], P<0.001). A positive correlation was observed between the CALLY index and the Gensini score (P<0.001). CONCLUSION: The CALLY index is a novel, convenient, and valuable prognostic indicator exhibiting a protective effect against both short- and long-term MACEs in patients with STEMI, emphasizing the significance of inflammation/nutrition in this patient population.

16.
BMC Urol ; 24(1): 157, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075438

RESUMO

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficiency and safety of percutaneous nephrolithotomy (PCNL) between flank position and prone position for the treatment of renal stones. METHODS: PubMed, Embase, OVID, and Cochrane Library were comprehensively searched from their inception to Jul 2024. Randomized and nonrandomized trials evaluating renal calculi patients who underwent PCNL via flank position or prone position were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes and complications of both groups were compared in this meta-analysis. RESULTS: This review involved five articles (554 patients). Specifically, four articles were randomized controlled trials, and the remaining publication was prospective cohort study. No significant difference was found in stone-free rate between the flank group and prone group after the PCNL procedure. Similarly, the percutaneous access time, operative time, and hospital stay of flank position had no significant difference compared with the prone group. There was no significant difference in the comparison of complication rates between the flank group and the prone group. Although further analysis indicated that patients in the prone position suffered more hemoglobin drop than the flank group, no significant difference was found in the hemorrhage and blood transfusion rates. CONCLUSIONS: Both surgical positions were appropriate for most PCNL procedures and had shown similar efficacy and safety. In practice, the optimal choice should be made according to the patients' conditions and urologists' acquaintance.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Posicionamento do Paciente , Humanos , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Decúbito Ventral , Posicionamento do Paciente/métodos , Cálculos Renais/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(4): 628-636, 2024 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39019792

RESUMO

Patients with anaplastic lymphoma kinase (ALK) fusion lung adenocarcinoma may develop drug resistance after treatment with ALK-tyrosine kinase inhibitor (ALK-TKI), and the mechanisms of this resistance are not yet fully defined. The Affiliated Hospital of Zunyi Medical University admitted a patient who was resistant to ALK fusion after ALK-TKI treatment, leading to disease progression and subsequent biopsy indicating a transformation to small cell lung cancer in September 2021. The patient, a 54-year-old female, initially presented with symptoms of cough, sputum production, and chest pain for 4 months. Chest CT showed a neoplastic lesion in the posterior segment of the right upper lobe to right lower lobe with obstructive pneumonia, metastasis in the right lower lobe, increased and enlarged mediastinal and right hilar lymph nodes, and thickening of the right hilar soft tissue. Bronchoscopy and pathological biopsy confirmed the diagnosis of lung adenocarcinoma. The results of next-generation sequencing indicated that echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion is associated with tumor protein 53 (TP53) and retinoblastoma 1 (RB1) gene mutations. The patient received second-generation ALK-TKI aletinib, achieving a progression-free survival of 11 months before disease progression suggested aletinib resistance. Subsequently, the third-generation ALK-TKI lorlatinib administered for one month without efficacy, resulting in rapid systemic disease progression. The neuron specific enolase (NSE) was significantly increased, and the patient developed new pleural, pericardial, intracranial, liver, and multiple bone metastases occurred in a short period. A second biopsy indicated small cell lung cancer. Modification of treatment regimen to chemotherapy combined with immunotherapy proved effective. The mechanisms of drug resistance of ALK-TKI treatment for advanced non-small cell lung cancer with ALK fusion are complex, and small cell transformation of pathological type is one such mechanism, although rare. Concurrent TP53 and RB1 gene mutations may be characteristic of this transformation. Elevated NSE can serve as a predictive serum marker for adenocarcinoma transforming to small cell carcinoma. Timely re-biopsy and selection of subsequent treatments based on different resistance mechanisms are crucial for comprehensive disease management.


Assuntos
Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Neoplasias Pulmonares , Humanos , Feminino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Quinase do Linfoma Anaplásico/genética , Proteínas de Fusão Oncogênica/genética , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Proteína Supressora de Tumor p53/genética , Aminopiridinas/uso terapêutico
18.
PLoS One ; 19(7): e0306172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39028682

RESUMO

PURPOSE: We aimed to validate the performance of six available scoring models for predicting hospital mortality in children with suspected or confirmed infections. METHODS: This single-center retrospective cohort study included pediatric patients admitted to the PICU for infection. The primary outcome was hospital mortality. The six scores included the age-adapted pSOFA score, SIRS score, PELOD2 score, Sepsis-2 score, qSOFA score, and PMODS. RESULTS: Of the 5,356 children admitted to the PICU, 9.1% (488) died, and 25.1% (1,342) had basic disease with a mortality rate of 12.7% (171); 65.3% (3,499) of the patients were younger than 2 years, and 59.4% (3,183) were male. The discrimination abilities of the pSOFA and PELOD2 scores were superior to those of the other models. The calibration curves of the pSOFA and PELOD2 scores were consistent between the predictions and observations. Elevated lactate levels were a risk factor for mortality. CONCLUSION: The pSOFA and PELOD2 scores had superior predictive performance for mortality. Given the relative unavailability of items and clinical operability, the pSOFA score should be recommended as an optimal tool for acute organ dysfunction in pediatric sepsis patients. Elevated lactate levels are related to a greater risk of death from infection in children in the PICU.


Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva Pediátrica , Escores de Disfunção Orgânica , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Lactente , Estudos Retrospectivos , Sepse/mortalidade , Sepse/diagnóstico , Adolescente , Estudos de Coortes , Infecções/mortalidade , Infecções/diagnóstico , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/diagnóstico , Fatores de Risco
19.
Adv Sci (Weinh) ; : e2404621, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031006

RESUMO

Three dinuclear Pd(II) complexes (1, 2, and 3) with intense red phosphorescence at room temperature are here synthesized using strong ligand field strength compounds. All three complexes are characterized by nuclear magnetic resonance, high-resolution mass spectrometry, and elemental analyses. Complexes 2 and 3 are characterized by single-crystal X-ray diffraction. The crystalline data of 2 and 3 reveal complex double-layer structures, with Pd-Pd distances of 2.8690(9) Å and 2.8584(17) Å, respectively. Furthermore, complexes 1, 2, and 3 show phosphorescence at room temperature in their solid states at the wavelengths of 678, 601, and 672 nm, respectively. In addition, they show phosphorescence at 634, 635, and 582 nm, respectively, in the 2 wt.% (PMMA) films, and phosphorescence at 670, 675, and 589 nm, respectively, in the deoxygenated CH2Cl2 solutions. Among three complexes, complex 1 shows red emission at 634 nm with phosphorescent quantum yield Ф = 67% in the 2 wt.% PMMA film. Furthermore, complex 1-based organic light-emitting diode is fabricated using a vapor-phase deposition process, and their maximum external quantum efficiency reaches 20.52%, which is the highest percentage obtained by using the dinuclear Pd(II) complex triplet emitters with the CIE coordinates of (0.62, 0.38).

20.
Sci Rep ; 14(1): 16794, 2024 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039115

RESUMO

Acute kidney injury (AKI) is one of the most important lethal factors for patients admitted to intensive care units (ICUs), and timely high-risk prognostic assessment and intervention are essential to improving patient prognosis. In this study, a stacking model using the MIMIC-III dataset with a two-tier feature selection approach was developed to predict the risk of in-hospital mortality in ICU patients admitted for AKI. External validation was performed using separate MIMIC-IV and eICU-CRD. The area under the curve (AUC) was calculated using the stacking model, and features were selected using the Boruta and XGBoost feature selection methods. This study compares the performance of a stacking model using two-tier feature selection with a model using single-tier feature selection (XGBoost: 85; Boruta: 83; two-tier: 0.91). The predictive effectiveness of the stacking model was further validated by using different datasets (Validation 1: 0.83; Validation 2: 0.85) and comparing it with a simpler model and traditional clinical scores (SOFA: 0.65; APACH IV: 0.61). In addition, this study combined interpretable techniques and causal inference to analyze the causal relationship between features and predicted outcomes.


Assuntos
Injúria Renal Aguda , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Humanos , Injúria Renal Aguda/mortalidade , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Área Sob a Curva , Fatores de Risco
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