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Electrocatalytic nitrate reduction is an efficient way to produce ammonia sustainably. Herein, we rationally designed a copper metalloporphyrin-based hydrogen-bonded organic framework (HOF-Cu) through molecular engineering strategies for electrochemical nitrate reduction. As a result, the state-of-the-art HOF-Cu catalyst exhibits high NH3 Faradaic efficiency of 93.8%, and the NH3 production rate achieves a superior activity of 0.65 mmol h-1 cm-2. The in situ electrochemical spectroscopic combined with density functional theory calculations reveals that the dispersed Cu promotes the adsorption of NO3- and the mechanism is followed by deoxidation of NO3- to *NO and accompanied by deep hydrogenation. The generated *H participates in the deep hydrogenation of intermediate with fast kinetics as revealed by operando electrochemical impedance spectroscopy, and the competing hydrogen evolution reaction is suppressed. This research provides a promising approach to the conversion of nitrate to ammonia, maintaining the nitrogen balance in the atmosphere.
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We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone â ¢, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone â ¢, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, ß-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone â ¢ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), ß-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.
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Medicamentos de Ervas Chinesas , Ginsenosídeos , Pós , Benchmarking , Medicamentos de Ervas Chinesas/química , Sacarose , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Mapping the complete molecular composition of a lipidome is considered an important goal of lipidomics for unraveling pathways and mechanisms behind lipid homeostasis. Conventional dissociation methods of mass spectrometry (MS) usually cannot give detailed structural information on lipids such as locations of carbon-carbon double bonds (CâC) in acyl chains. Double-bond derivatization via the Paternò-Büchi (PB) reaction has been demonstrated as a simple and highly efficient method for identification of CâC locations of different classes of lipids when paired with tandem mass spectrometry (MS/MS). In this work, reversed-phase lipid chromatography (RPLC)-MS was coupled with an online PB reaction to achieve enhanced analysis of isomers and isobars of phospholipids. A new acetone-containing mobile phase was developed that showed good elution performance for the separation of phospholipids by C18 columns. An improved flow microreactor was developed, enabling online derivatization of phospholipid CâC in 20 s. The workflow of RPLC-PB-MS/MS was developed and optimized for identification of CâC locations in isobaric ether-linked and diacyl phospholipids, 13C isobars, and acyl chain isomers in biological lipid extracts. Separation and identification of CâC locations of cis/trans phospholipid isomers were achieved for lipid standards. The incorporation of the PB reaction into the RPLC-MS workflow enabled analysis of phospholipid isomers and isobars with high confidence, demonstrating its potential for high-throughput phospholipid identification from complex mixtures.
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Fosfolipídeos/análise , Cromatografia de Fase Reversa , Espectrometria de Massas , Estrutura Molecular , Processos Fotoquímicos , EstereoisomerismoRESUMO
A sandwich-type fluorescent biosensor for the determination of tumor-related exosome was designed. It is based on magnetic nanoparticle (MNP) capture and horseradish peroxidase (HRP) catalysis. MNPs were used as the substrate to capture exosomes by modifying the CD63 antibody on MNPs surface. After that, the biotinylated epithelial cell adhesion molecule (EpCAM) antibody was used to capture the tumor-related exosomes, which specifically express EpCAM. A novel method for the fluorescence measurement of tumor-associated exosome was achieved, with a detection limit as low as 200 (± 9) particles mL-1. The analytical range of this method is from 576 (± 15) particles mL-1 to 5.76 × 107 (± 5.1 × 105) particles mL-1. For the fluorescence measurement, the excitation wavelength was set to 320 nm. Fluorescent spectra were collected at emission wavelength in the range 370 to 550 nm; the data shown in the calibration plot were studied by using the fluorescence intensity at 406 nm. This sensor was also able to successfully detect the exosomes from the plasma of patients with hepatocellular carcinoma (HCC) and healthy humans. Graphical abstract Schematic representation of the sensing process of immunoassay-type biosensor based on magnetic nanoparticle capture and the fluorescence signal formed by the horseradish peroxidase (HRP) catalysis for tumor-related exosome determination.
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Técnicas Biossensoriais , Carcinoma Hepatocelular/sangue , Exossomos/química , Fluorescência , Peroxidase do Rábano Silvestre/metabolismo , Imunoensaio , Neoplasias Hepáticas/sangue , Biocatálise , Calibragem , Carcinoma Hepatocelular/diagnóstico , Exossomos/metabolismo , Células Hep G2 , Peroxidase do Rábano Silvestre/química , Humanos , Neoplasias Hepáticas/diagnóstico , Nanopartículas de Magnetita/química , Tamanho da Partícula , Espectrometria de Fluorescência , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.
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Transformação Celular Neoplásica/genética , Transição Epitelial-Mesenquimal/genética , Predisposição Genética para Doença , RNA Circular , Animais , Biomarcadores Tumorais , Transformação Celular Neoplásica/metabolismo , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais , Transcrição GênicaRESUMO
An electrochemical aptasensing method is described for the determination of the biomarker CA125. It combines aptamer recognition and target-triggered strand displacement amplification. Flower like gold nanostructures were electrodeposited on a screen-printed carbon electrode to increase the sensor surface, to assemble more toehold-containing hairpin probe 1 (Hp1), and to improve the accessibility for DNA strands. Under the optimal conditions, this assay has a linear response in the 0.05 to 50 ngâ¢mL-1 CA125 concentration range, with a low detection limit of 5.0 pgâ¢mL-1. This method is specific and stable. It was successfully applied to the detection of CA125 in spiked biological samples, with recoveries between 82.5% and 104.1%. Graphical abstract.
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Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Antígeno Ca-125/análise , Técnicas Eletroquímicas/métodos , Proteínas de Membrana/análise , Nanopartículas Metálicas/química , Aptâmeros de Nucleotídeos/genética , Antígeno Ca-125/sangue , Antígeno Ca-125/urina , Carbono/química , DNA/química , DNA/genética , Sondas de DNA/química , Sondas de DNA/genética , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Proteínas de Membrana/sangue , Proteínas de Membrana/urina , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico , Saliva/químicaRESUMO
An amperometric aptasensor is reported for the electrochemical determination of the epithelial cell adhesion molecule (EpCAM). It is based on a combination of EpCAM-driven toehold-mediated DNA recycling amplification, the specific recognition of EpCAM aptamer, and its binding to EpCAM. Hairpin probe 1 (Hp1) with a toehold region was modified with a 5'-thiol group (5'-SH) and self-assembled onto the surface of a gold electrode. Upon addition of EpCAM, the probe A (a 15-mer) is liberated from the aptamer/probe A complex and then hybridizes with the toehold domain of Hp1. This results in the exposure of another toehold for further hybridizing with hairpin probe 2 (Hp2) to displace probe A in the presence of Hp2 that was labeled with the electrochemical probe Methylene Blue (MB). Subsequently, liberated probe A is hybridized again with another Hp1 to start the next round of DNA recycling amplification by reusing probe A. This leads to the formation of plenty of MB-labeled DNA strands on the electrode surface and generates an amplified current. This 1:N probe-response amplification results in ultrasensitive and specific detection of EpCAM, with a 20 pg·mL-1 detection limit. The electrode is highly stable and regenerable. It was successfully applied to the determination of EpCAM in spiked human serum, urine and saliva, and thus provides a promising tool for early clinical diagnosis. Graphical abstract Schematic illustration of the electrochemical detection for EpCAM. The method is based on aptamer-based recognition and EpCAM-driven toehold-mediated DNA recycling amplification. Hp1: Hairpin probe 1; Hp2: Hairpin probe 2; MB: Methylene blue; MCH: 6-Mercapto-1-hexanol; EpCAM: Epithelial cell adhesion molecule.
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Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , DNA/química , Molécula de Adesão da Célula Epitelial/análise , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Eletroquímica , Molécula de Adesão da Célula Epitelial/metabolismo , Estudos de Viabilidade , Ouro/química , HumanosRESUMO
Yohimbine is a novel compound for the treatment of erectile dysfunction derived from natural products, and pharmacokinetic study is important for its further development as a new medicine. In this work, we developed a novel PEEK tube-based solid-phase microextraction (SPME)-HPLC method for analysis of yohimbine in plasma and further for pharmacokinetic study. Poly (AA-EGDMA) was synthesized inside a PEEK tube as the sorbent for microextraction of yohimbine, and parameters that could influence extraction efficiency were systematically investigated. Under optimum conditions, the PEEK tube-based SPME method exhibits excellent enrichment efficiency towards yohimbine. By using berberine as internal standard, an online SPME-HPLC method was developed for analysis of yohimbine in human plasma sample. The method has wide linear range (2-1000 ng/mL) with an R2 of 0.9962; the limit of detection was determined and was as low as 0.1 ng/mL using UV detection. Finally, a pharmacokinetic study of yohimbine was carried out by the online SPME-HPLC method and the results have been compared with those of reported methods.
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Cromatografia Líquida de Alta Pressão/métodos , Microextração em Fase Sólida/métodos , Ioimbina/sangue , Ioimbina/farmacocinética , Administração Oral , Animais , Berberina/sangue , Cromatografia Líquida de Alta Pressão/normas , Estabilidade de Medicamentos , Desenho de Equipamento , Limite de Detecção , Masculino , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Microextração em Fase Sólida/instrumentação , Ioimbina/administração & dosagemRESUMO
The equilibrium factor F between radon and its short-lived progenies is an important parameter to estimate radon exposure of humans. Therefore, indoor and outdoor concentrations of radon and its short-lived radon progeny were measured in Beijing area using a continuously measuring device, in an effort to obtain information on the F value. The results showed that the mean values of F were 0.58 ± 0.13 (0.25-0.95, n = 305) and 0.52 ± 0.12 (0.31-0.91, n = 64) for indoor and outdoor, respectively. The indoor F value during haze-fog days was higher than the typical value of 0.4 recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation, and it was also higher than the values of 0.47 and 0.49 reported in the literature. A positive correlation was observed between indoor F values and PM2.5 concentrations (R (2) = 0.71). Since 2013, owing to frequent heavy haze-fog events in Beijing and surrounding areas, the number of the days with severe pollution remains at a high level. Future studies on the impact of the ambient fine particulate matter on indoor radon progeny equilibrium factor F could be important.
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Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Material Particulado/análise , Monitoramento de Radiação/métodos , Produtos de Decaimento de Radônio/análise , Tempo (Meteorologia) , China , Produtos de Decaimento de Radônio/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
ABSTRACT: This study investigated indoor radon concentrations in modern residential buildings in the Cold Area and Severe Cold Area in China. A total of 19 cities covering 16 provinces were selected with 1,610 dwellings measured for indoor radon concentration. The arithmetic mean and geometric mean of indoor radon concentration were 68 Bq m-3 and 57 Bq m-3, respectively. It was found that indoor radon concentrations were much higher in the Severe Cold Area than those in the Cold Area. The indoor radon concentrations showed an increasing trend for newly constructed buildings. It was estimated that the average effective dose from inhalation of indoor radon is 2.15 mSv and 1.60 mSv for the Severe Cold Area and Cold Area, respectively. The more and more rigid energy-saving design for residential buildings in the Severe Cold Area and Cold Area has an obvious impact on the increased trend of indoor radon due to extremely low air exchange rate in China.
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Polycystic ovary syndrome (PCOS) is an endocrine disease, and its pathogenesis and treatment are still unclear. Hexokinase domain component 1 (HKDC1) participates in regulating mitochondrial function and glycolysis. However, its role in PCOS development remains unrevealed. Here, female C57BL/6 mice were intraperitoneally injected with dehydroepiandrosterone (DHEA; 60 mg/kg body weight) to establish an in vivo model of PCOS. In vitro, KGN cells, a human ovarian granular cell line, were used to explore the potential mechanisms. DHEA-treated mice exhibited a disrupted estrus cycle, abnormal hormone levels, and insulin resistance. Dysfunction in mitochondria and glycolysis is the main reason for PCOS-related growth inhibition of ovarian granular cells. Here, we found that the structure of mitochondria was impaired, less ATP was generated and more mitochondrial Reactive Oxygen Species were produced in HKDC1-silenced KGN cells. Moreover, HKDC1 knockdown inhibited glucose consumption and decreased the production of glucose-6-phosphate and lactic acid. Conclusively, HKDC1 protects ovarian granulocyte cells from DHEA-related damage at least partly by preserving mitochondrial function and maintaining glycolysis.
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Síndrome do Ovário Policístico , Feminino , Camundongos , Humanos , Animais , Síndrome do Ovário Policístico/metabolismo , Hexoquinase/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/metabolismo , Granulócitos/metabolismo , Granulócitos/patologiaRESUMO
BACKGROUND AND PURPOSE: Metal-based therapeutic agents are limited by the required concentration of metal-based agents. Hereby, we determined if combination with 17ß-oestradiol (E2) could reduce such levels and the therapy still be effective in type 2 diabetes mellitus (T2DM). EXPERIMENTAL APPROACH: The metal-based agent (vanadyl acetylacetonate [VAC])- 17ß-oestradiol (E2) combination is administered using the membrane-permeable graphene quantum dots (GQD), the vehicle, to form the active GQD-E2-VAC complexes, which was characterized by fluorescence spectra, infrared spectra and X-ray photoelectron spectroscopy. In db/db type 2 diabetic mice, the anti-diabetic effects of GQD-E2-VAC complexes were evaluated using blood glucose levels, oral glucose tolerance test (OGTT), serum insulin levels, homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA-IR] and homeostasis model assessment of ß-cell function [HOMA-ß]), histochemical assays and western blot. KEY RESULTS: In diabetic mice, GQD-E2-VAC complex had comprehensive anti-diabetic effects, including control of hyperglycaemia, improved insulin sensitivity, correction of hyperinsulinaemia and prevention of ß-cell loss. Co-regulation of thioredoxin interacting protein (TXNIP) activation by the combination of metal complex and 17ß-oestradiol contributed to the enhanced anti-diabetic effects. Furthermore, a potent mitochondrial protective antioxidant, coniferaldehyde, significantly potentiates the protective effects of GQD-E2-VAC complexes. CONCLUSION AND IMPLICATIONS: A metal complex-E2 combinatorial approach achieved simultaneously the protection of ß cells and insulin enhancement at an unprecedented low dose, similar to the daily intake of dietary metals in vitamin supplements. This study demonstrates the positive effects of combination and multi-modal therapies towards type 2 diabetes treatment.
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Pyroptosis is an inflammasome-dependent form of programmed cell death that is mediated by caspases-1, -4, -5, and -11, and the gasdermin protein family. It is characterized by the rupture of cell membrane and the subsequent release of cell contents and interleukins, leading to inflammatory reaction and activation of the immune system. Recent studies have suggested that pyroptosis plays a role in the development of gastrointestinal tumors, impeding tumor generation and progression as well as providing a favorable microenvironment for tumor growth. In this review we outlined the current knowledge regarding the implications of pyroptosis in gastrointestinal cancers.
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Neoplasias , Piroptose , Humanos , Caspases/metabolismo , Proteínas de Neoplasias/metabolismo , Trato Gastrointestinal , Microambiente TumoralRESUMO
BACKGROUND: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates. CASE PRESENTATION: A 14-year-old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow-up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis. CONCLUSION: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway.
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Hiperplasia Angiolinfoide com Eosinofilia , Doença de Kimura , Masculino , Humanos , Criança , Pré-Escolar , Adolescente , Doença de Kimura/complicações , Doença de Kimura/tratamento farmacológico , Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Hiperplasia Angiolinfoide com Eosinofilia/tratamento farmacológico , Hiperplasia Angiolinfoide com Eosinofilia/complicações , Esteroides/uso terapêutico , Imunoglobulina ERESUMO
BACKGROUND: Therapeutic approaches based on glycolysis and energy metabolism of tumor cells are new promising strategies for the treatment of cancer. Currently, researches on the inhibition of pyruvate kinase M2, a key rate limiting enzyme in glycolysis, have been corroborated as an effective cancer therapy. Alkannin is a potent pyruvate kinase M2 inhibitor. However, its non-selective cytotoxicity has affected its subsequent clinical application. Thus, it needs to be structurally modified to develop novel derivatives with high selectivity. PURPOSE: Our study aimed to ameliorate the toxicity of alkannin through structural modification and elucidate the mechanism of the superior derivative 23 in lung cancer therapy. METHODS: On the basis of the principle of collocation, different amino acids and oxygen-containing heterocycles were introduced into the hydroxyl group of the alkannin side chain. We examined the cell viability of all derivatives on three tumor cells (HepG2, A549 and HCT116) and two normal cells (L02 and MDCK) by MTT assay. Besides, the effect of derivative 23 on the morphology of A549 cells as observed by Giemsa and DAPI staining, respectively. Flow cytometry was performed to assess the effects of derivative 23 on apoptosis and cell cycle arrest. To further assess the effect of derivative 23 on the Pyruvate kinase M2 in glycolysis, an enzyme activity assay and western blot assay were performed. Finally, in vivo the antitumor activity and safety of the derivative 23 were evaluated by using Lewis mouse lung cancer xenograft model. RESULTS: Twenty-three novel alkannin derivatives were designed and synthesized to improve the cytotoxicity selectivity. Among these derivatives, derivative 23 showed the highest cytotoxicity selectivity between cancer and normal cells. The anti-proliferative activity of derivative 23 on A549 cells (IC50 = 1.67 ± 0.34 µM) was 10-fold higher than L02 cells (IC50 = 16.77 ± 1.44 µM) and 5-fold higher than MDCK cells (IC50 = 9.23 ± 0.29 µM) respectively. Subsequently, fluorescent staining and flow cytometric analysis showed that derivative 23 was able to induce apoptosis of A549 cells and arrest the cell cycle in the G0/G1 phase. In addition, the mechanistic studies suggested derivative 23 was an inhibitor of pyruvate kinase; it could regulate glycolysis by inhibiting the activation of the phosphorylation of PKM2/STAT3 signaling pathway. Furthermore, studies in vivo demonstrated derivative 23 significantly inhibited the growth of xenograft tumor. CONCLUSION: In this study, alkannin selectivity is reported to be significantly improved following structural modification, and derivative 23 is first shown to be able to inhibit lung cancer growth via the PKM2/STAT3 phosphorylation signaling pathway in vitro, indicating the potential value of derivative 23 in treating lung cancer.
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Antineoplásicos , Neoplasias Pulmonares , Naftoquinonas , Humanos , Camundongos , Animais , Piruvato Quinase/metabolismo , Linhagem Celular Tumoral , Naftoquinonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Apoptose , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
BACKGROUND: The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC). METHODS: Multiplex immunofluorescence staining was performed to examine CD68+ TAM, CD4+ T cell, CD8+ T cell, FOXP3+ Treg cell, and PD-L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR). RESULTS: There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68+ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68+ PD-L1- (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68+ PD-L1+ and TILs. The infiltration of CD68+ (p = 0.033), CD68+ PD-L1- (p = 0.033), and CD68+ PD-L1+ (p < 0.001) TAMs in stroma area were significantly associated with poorer disease-free survival rate (DFS) of MIBC patients. CONCLUSION: CD68+ and CD68+ PD-L1- TAMs infiltration levels decreased significantly after NAC and pre-treatment TAM infiltration levels were independent prognostic factors for MIBC patients. While there was no sufficient evidence demonstrating that pre-treatment TILs or TAMs could predict response to NAC in MIBC patients.
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Terapia Neoadjuvante , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Antígeno B7-H1/metabolismo , Neoplasias da Bexiga Urinária/patologia , Macrófagos , Músculos/metabolismo , Linfócitos do Interstício Tumoral , Microambiente TumoralRESUMO
This work is aimed at exploring the nursing strategies and effects of continuous renal replacement therapy (CRRT) for end-stage renal disease (ESRD) with refractory hypotension under the background of smart health. 40 ESRD patients with refractory hypotension who received CRRT treatment were enrolled as the research objects and were randomly rolled into the intervention group and the control group, with 20 cases in each group. Patients in the control group received routine nursing, and those in the intervention group received individualized nursing. The incidence of hypotension, dry body weight, serous cavity effusion, renal function indicators (blood urea nitrogen (BUN) and creatinine (Cre)), and patient satisfaction were compared between the two groups. The results showed that the probability of hypotension in the intervention group was 9.38%, which was lower than that in the control group (34.38%). The probability of early termination of dialysis in the intervention group was 0%, which was lower than that in the control group (18.75%), and the difference was statistically significant (P < 0.05). The decreases of BUN and Cre in the intervention group were significantly greater than those in the control group, and the differences were statistically significant (P < 0.05). The proportion of water growth less than 10% during dialysis in the intervention group was 98.44%, which was greater than that in the control group (93.45%), and the difference was statistically significant (P < 0.05). The ultrafiltration volume after dialysis in the intervention group was 2850 ± 400 mL, which was greater than that in the control group 2350 ± 350 mL. After intervention, the proportion of patients with pleural effusion in the intervention group was 10% less than that in the control group (20%), and the difference was statistically significant (P < 0.05). The satisfaction rate of the intervention group was 97.66%, which was higher than that of the control group (65.63%). In conclusion, individualized nursing was more helpful to the recovery of ESRD patients with refractory hypotension treated with CRRT than routine nursing.
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Injúria Renal Aguda , Hipotensão , Falência Renal Crônica , Humanos , Hipotensão/etiologia , Rim/fisiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Terapia de Substituição Renal/métodosRESUMO
Muscle-invasive bladder cancer (MIBC) is an aggressive disease requiring active management. Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is considered the standard treatment paradigm for MIBC patients, which could result in significant perioperative mortality and morbidity, as well as the significant alteration of the quality of life (QOL). Notably, multimodal bladder-preserving treatment strategies have been recommended for highly selected patients. Pathologic complete response (pCR) after NAC is a powerful prognostic indicator of survival for patients with MIBC. Clinical complete response (cCR) is then introduced as a complementary endpoint for pCR to assess disease status preoperatively. Bladder preservation strategy for patients who achieve cCR following NAC is emerging as a new treatment concept. However, the efficiency of the conservative strategy remains controversial. In this state-of-the-art review, we discuss the advantages and limitations of cCR and the feasibility and safety of bladder preservation strategy in highly selected MIBC patients who achieve cCR following NAC. We conclude that a conservative strategy can be considered a reasonable alternative to RC in carefully selected cCR MIBC patients, leading to acceptable oncological outcomes.
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Herpes zoster is a relatively rare infectious disease in the pediatric population, as compared with adults, which is due to the reactivation of latent Varicella-Zoster virus. We report a 7-year-old child without any history of varicella, who first experienced skin pain and later presented skin lesions in dermatomal distribution. Finally, the patient was diagnosed with herpes zoster. We aim to emphasize that herpes zoster could occur in immunocompetent children and may be due to the reactivation of the vaccine strain or previous subclinical infection.