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PURPOSE: An accurate diagnosis of colorectal carcinoma (CRC) can assist physicians in developing reasonable therapeutic regimens, thereby significantly improving the patient's prognosis. Carcinoembryonic antigen (CEA)-targeted PET imaging shows great potential for this purpose. Despite showing remarkable abilities to detect primary and metastatic CRC, previously reported CEA-specific antibody radiotracers or pretargeted imaging are not suitable for clinical use due to poor pharmacokinetics and complicated imaging procedures. In contrast, radiolabeled nanobodies exhibit ideal characteristics for PET imaging, for instance, rapid clearance rates and excellent distribution profiles, allowing same-day imaging with sufficient contrast. In this study, we developed a novel CEA-targeted nanobody radiotracer, [68 Ga]Ga-HNI01, and assessed its tumor imaging ability and biodistribution profile in preclinical xenografts and patients with primary and metastatic CRC. METHODS: The novel nanobody HNI01 was acquired by immunizing the llama with CEA proteins. [68 Ga]Ga-HNI01 was synthesized by site-specifically conjugating [68 Ga]Ga with tris(hydroxypyridinone) (THP). Small-animal PET imaging and biodistribution studies were performed in CEA-overexpressed LS174T and CEA-low-expressed HT-29 tumor models. Following successful preclinical assessment, a phase I study was conducted on 9 patients with primary and metastatic CRC. Study participants received 151.21 ± 25.25 MBq of intravenous [68 Ga]Ga-HNI01 and underwent PET/CT scans at 1 h and 2 h post injection. Patients 01-03 also underwent whole-body dynamic PET imaging within 0-40 min p.i. All patients underwent [18F]F-FDG PET/CT imaging within 1 week after [68 Ga]Ga-HNI01 imaging. Tracer distribution, pharmacokinetics, and radiation dosimetry were calculated. RESULTS: [68 Ga]Ga-HNI01 was successfully synthesized within 10 min under mild conditions, and the radiochemical purity was more than 98% without purification. Micro-PET imaging with [68 Ga]Ga-HNI01 revealed clear visualization of LS174T tumors, while signals from HT-29 tumors were significantly lower. Biodistribution studies indicated that uptake of [68 Ga]Ga-HNI01 in LS174T and HT-29 was 8.83 ± 3.02%ID/g and 1.81 ± 0.87%ID/g, respectively, at 2 h p.i. No adverse events occurred in all clinical participants after the injection of [68 Ga]Ga-HNI01. A fast blood clearance and low background uptake were observed, and CRC lesions could be visualized with high contrast as early as 30 min after injection. [68 Ga]Ga-HNI01 PET could clearly detect metastatic lesions in the liver, lung, and pancreas and showed superior ability in detecting small metastases. A significant accumulation of radioactivity was observed in the kidney, and normal tissues physiologically expressing CEA receptors showed slight uptakes of [68 Ga]Ga-HNI01. An interesting finding was that strong uptake of [68 Ga]Ga-HNI01 was found in non-malignant colorectal tissues adjacent to the primary tumor in some patients, suggesting abnormal CEA expression in these healthy tissues. CONCLUSION: [68 Ga]Ga-HNI01 is a novel CEA-targeted PET imaging radiotracer with excellent pharmacokinetics and favorable dosimetry profiles. [68 Ga]Ga-HNI01 PET is an effective and convenient imaging tool for detecting CRC lesions, particularly for identifying small metastases. Furthermore, its high specificity for CEA in vivo makes it an ideal tool for selecting patients for anti-CEA therapy.
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Neoplasias Colorretais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Humanos , Anticorpos Monoclonais/metabolismo , Antígeno Carcinoembrionário , Neoplasias Colorretais/diagnóstico por imagem , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/farmacologiaRESUMO
OBJECTIVE: Sepsis is a leading cause of morbidity and mortality after surgery. We aimed to explore the role of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) sponging microRNA-26a-5p in sepsis-induced myocardial injury by regulating regulator of calcineurin 2 (Rcan2). METHODS: HL-1 cells were incubated with lipopolysaccharide (LPS) to induce in vitro cardiomyocyte injury models, which were then treated with silenced MALAT1 vector, miR-26a-5p mimic or Rcan2 overexpression vector. Next, inflammatory factor level and apoptosis of cells were determined. The in vivo mouse models were constructed by intraperitoneal injection of LPS. The modeled mice were injected with relative oligonucleotides and the pathology, apoptosis, and inflammation in mouse myocardial tissues were assessed. Expression of MALAT1, miR-26a-5p and Rcan2 in vivo and in vitro was evaluated. RESULTS: MALAT1 and Rcan2 were upregulated while miR-26a-5p was downregulated in LPS-treated HL-1 cells and mice. MALAT1 silencing or miR-26a-5p upregulation suppressed LPS-induced inflammation and apoptosis of cardiomyocytes in cellular and animal models. These effects of elevated miR-26a-5p could be reversed by upregulating Rcan2, and MALAT1 knockdown-induced ameliorative impacts could be reversed by miR-26a-5p downregulation. CONCLUSION: MALAT1 silencing elevated miR-26a-5p to ameliorate LPS-induced myocardial injury by reducing Rcan2. Our research may provide novel biomarkers for the treatment of sepsis.
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Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/metabolismo , Isquemia Miocárdica/fisiopatologia , RNA Longo não Codificante/metabolismo , Sepse/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/etiologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Sepse/complicações , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
BACKGROUND: LncRNA PVT1 was reported to be elevated in septic myocardial tissue. The underlying mechanism by which PVT1 aggravated sepsis induced myocardial injury needs further investigation. METHODS: Mice was subjected to LPS injection to mimic in vivo sepsis model. HE staining was applied to observe tissue injury. Cardiac function of mice was determined by echocardiography. Bone marrow derived macrophage (BMDM) was used to confirm the regulatory effect of PVT1 in macrophage polarization. Western blotting or qRT-PCR were performed to evaluate protein or mRNA levels, respectively. ELISA was conducted to determine cytokine levels. Interaction between PVT1 and miR-29a, miR-29a and HMGB1 were accessed by dual luciferase assay. RESULTS: Expression of PVT1 was elevated in myocardial tissue and heart infiltrating macrophages of sepsis mice. PVT1 knockdown alleviated LPS induced myocardial injury and attenuated M1 macrophage polarization. The mechanic study suggested that PVT1 targeted miR-29a, thus elevated expression of HMGB1, which was repressed by miR-29a targeting. The effect of PVT1 on M1 macrophage polarization was dependent on targeting miR-29a. CONCLUSION: PVT1 promoted M1 polarization and aggravated LPS induced myocardial injury via miR-29a/HMGB1 axis.
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Polaridade Celular , Técnicas de Silenciamento de Genes , Proteína HMGB1/metabolismo , Macrófagos/metabolismo , MicroRNAs/metabolismo , Miocárdio/patologia , RNA Longo não Codificante/metabolismo , Sepse/genética , Animais , Sequência de Bases , Polaridade Celular/genética , Testes de Função Cardíaca , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Regulação para Cima/genéticaRESUMO
BACKGROUND Sepsis-induced myopathy (SIM) is a complication of sepsis that results in prolonged mechanical ventilation, long-term functional disability, and increased patient mortality. This study aimed to use bioinformatics analysis to identify hub genes and molecular pathways involved in SIM, to identify potential diagnostic or therapeutic biomarkers. MATERIAL AND METHODS The Gene Expression Omnibus (GEO) database was used to acquire the GSE13205 expression profile. The differentially expressed genes (DEGs) in cases of SIM and healthy controls, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the limma R/Bioconductor software package and clusterProfiler package in R, respectively. The protein-protein interaction (PPI) network data of DEGs was retrieved using the STRING database and analyzed using the Molecular Complex Detection (MCODE) Cytoscape software plugin. RESULTS A total of 196 DEGs were obtained in SIM samples compared with healthy samples, including 93 upregulated genes. The DEGs were significantly upregulated in mineral absorption, and the interleukin-17 (IL-17) signaling pathway and 103 down-regulated genes were associated with control of the bile secretion signaling pathway. A protein-protein interaction (PPI) network was constructed with 106 nodes and 192 edges. The top two important clusters were selected from the PPI by MCODE analysis. There were 16 hub genes with a high degree of connectivity in the PPI network that were selected, including heme oxygenase 1 (HMOX1), nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1), and metallothionein (MT)-1E. CONCLUSIONS Bioinformatics network analysis identified key hub genes and molecular mechanisms in SIM.
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Biologia Computacional/métodos , Redes Reguladoras de Genes , Doenças Musculares/etiologia , Doenças Musculares/genética , Sepse/complicações , Transdução de Sinais , Análise por Conglomerados , Regulação para Baixo/genética , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Mapas de Interação de Proteínas/genética , Regulação para Cima/genéticaRESUMO
The objective of this study was to develop a positron emission tomography (PET) probe with hypoxia targeting specificity and a relatively long half-life. The synthesis, (64)Cu-labeling in vitro and in vivo study of the novel 2-nitroimidazole complex (64)Cu-BMS2P2 is presented in this study. The hypoxia targeting capacity of (64)Cu-BMS2P2 in vitro was evaluated and compared with the (64)Cu-BMS181321, and confirmed by PET imaging in vivo and immunohistochemistry for carbonic anhydrase 9 (CA9) in a tumor mouse model. These results suggest that (64)Cu-BMS2P2 is a promising candidate for PET hypoxia imaging and worthy of further investigations in dynamic hypoxia imaging.
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Hipóxia Celular , Complexos de Coordenação/farmacocinética , Radioisótopos de Cobre , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Imagem Molecular , Nitroimidazóis/farmacocinética , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química , Animais , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Marcação por Isótopo , Camundongos , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/patologia , Nitroimidazóis/síntese química , Nitroimidazóis/química , Compostos Radiofarmacêuticos/análise , Compostos Radiofarmacêuticos/químicaRESUMO
The objective of this study was the development of a dual-modality imaging device, namely (111)In-core-cross-linked polymeric micelle (CCPM)-octreotide, for neuroendocrine tumor detection, using near-infrared fluoroscopy (NIRF) and single photon emission computed tomography (SPECT). The tumor targeting ability of the (111)In-labeled CCPM-octreotide was evaluated in a tumor mouse model. SPECT/CT, NIRF and gamma imaging results showed high tumor uptake of (111)In-labeled CCPM-octreotide. In contrast, there was a much lower signal in the same mouse model injected with (111)In-labeled CCPM. The high accumulation of (111)In-labeled CCPM-octreotide in U87 tumor was reduced after co-injection with an excess amount of CCPM-octreotide. These results suggested CCPM-octreotide's potential applications in tumor diagnosis, drug delivery and molecular imaging.
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Reagentes de Ligações Cruzadas/química , Fluoroscopia , Micelas , Octreotida/química , Polímeros/química , Tomografia Computadorizada de Emissão de Fóton Único , Administração Intravenosa , Animais , Diagnóstico por Imagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Camundongos , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Neoplasias/tratamento farmacológico , Compostos RadiofarmacêuticosRESUMO
Procalcitonin (PCT) is a reliable biomarker in the early diagnosis of septicemia, pyemia and stroke-associated pneumonia. In this work, through preparing ß-cyclodextrin/graphene (CD/GN) nanohybrid as carrier and amplifier simultaneously to band antibodies and probe molecules, a simple and innovative sandwich-like voltammetric immunosensor was proposed for the sensitive and effective determination of PCT. Owing to the host-guest recognition property, the antibodies of PCT can enter into the CD cavities to generate a stable complex; meanwhile, aminopyrene (AP) were introduced as the signal probe and it was adsorbed on the surface of GN via aminopyrine π-πinteraction. Based on the signal change from AP as a response signal which exhibits linearity to the concentration of PCT, a highly sensitive sandwich-type voltammetric immunosensor was developed successfully after optimizing various key parameters. The results demonstrated that the developed sensor had a considerably low detection limit (0.003 pg mL-1) and wide linearity of 0.01 pg mL-1 to 20.0 ng mL-1. This work offered a very simple and sensitive sensing strategy for PCT and other biomarkers via altering the specific antibodies simply, showing great potential applications.
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Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Pró-Calcitonina , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Grafite/química , Anticorpos , Limite de Detecção , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Ouro/químicaRESUMO
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a risk factor and important coexisting disease for lung cancer; however, the current status of management of COPD in lung cancer patients is not fully described. This study addressed this issue in a general teaching hospital in China. METHODS: Medical records of hospitalized lung cancer patients in Zhongshan Hospital, Fudan University, between January 2006 and December 2010 were reviewed. The definition of COPD was according to the spirometric criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document. The diagnostic rate (COPD recorded as a discharge diagnosis/spirometry-defined percentage) and conformity to GOLD treatment guidelines were investigated. The factors influencing diagnosis were analysed. RESULTS: During the study period, the prevalence of spirometry-defined COPD in hospitalized lung cancer patients was 21.6% (705/3263). The overall diagnostic rate of COPD was 7.1%, and the treatment conformity for stable and acute exacerbation of COPD was 27.1% and 46.8%, respectively. Respiratory physicians had a higher diagnostic rate than non-respiratory doctors (34.8% vs 2.9%, P < 0.001) and a better treatment conformity for acute exacerbation of COPD (63.6% vs 37.5%, P = 0.048). Patients with COPD as a discharge diagnosis had more chance to receive guideline-consistent treatment. The diagnostic rate of COPD was higher among patients with a history of smoking, respiratory diseases or symptoms. CONCLUSIONS: COPD is substantially underdiagnosed and undertreated in a hospitalized lung cancer population. History of smoking, respiratory diseases and symptoms promotes diagnosis. Education of COPD knowledge among patients and doctors is urgently required in this special population.
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Gerenciamento Clínico , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias Pulmonares/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , China/epidemiologia , Comorbidade , Feminino , Hospitais de Ensino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Retrospectivos , EspirometriaRESUMO
d-Glucosamine (DG) was conjugated to a core-cross linked polymeric micelle (CCPM) system equipped with both a near-infrared fluorophore (NIRF) and a gamma emitter (111In). The resultant nano-scale tumor-targeting imaging tracer, 111In-DG-NIRF-CCPM, selectively accumulated in a human epithelial carcinoma A-431 xenograft model in mice. At 24 hrs post injection, the tumor uptake was 2.62 ± 0.80 % of the injected dose per gram of tissue (%ID/g). Tumors were clearly delineated in both single-photon emission computed tomography (SPECT) and optical imaging. The results suggest that the prepared imaging tracer is a promising agent for tumor diagnosis.
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Glucosamina/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Marcação por Isótopo , Camundongos , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Distribuição TecidualRESUMO
BACKGROUND: Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited. AIM: To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy. METHODS: In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle. RESULTS: Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer. CONCLUSION: Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.
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OBJECTIVE: Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD). METHODS: A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin-eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays. RESULTS: Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression. CONCLUSION: The study highlights XYT's potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement.
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Background: Septic shock patients fundamentally require delicate vasoactive and inotropic agent administration, which could be quantitatively and objectively evaluated by the vasoactive-inotropic score (VIS); however, whether the dynamic trends of high-time-resolution VIS alter the clinical outcomes remains unclear. Thus, this study proposes the term VIS Reduction Rate (VRR) to generalise the tendency of dynamic VIS, to explore the association of VRR and mortality for patients with septic shock. Methods: We applied dynamic and static VIS data to predict ICU mortality by two models: the long short-term memory (LSTM) deep learning model, and the extreme gradient boosting (XGBoost), respectively. The specific target cohort was extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database by the sophisticated structured query language (SQL). Enrolled patients were divided into four groups by VRR value: ≥50%, 0 ~ 50%, -50% ~ 0, and < -50%. Statistical approaches included pairwise propensity score matching (PSM), Cox proportional hazards regression, and two doubly robust estimation models to ensure the robustness of the results. The primary and secondary outcomes were ICU mortality and in-hospital mortality, respectively. Results: VRR simplifies the dosing trends of vasoactive and inotropic agents represented by dynamic VIS data while requiring fewer data. In total, 8,887 septic shock patients were included. Compared with the VRR ≥50% group, the 0 ~ 50%, -50% ~ 0, and < -50% groups had significantly higher ICU mortality [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.17-1.50, p < 0.001; HR 1.79, 95% CI 1.44-2.22, p < 0.001; HR 2.07, 95% CI 1.61-2.66, p < 0.001, respectively] and in-hospital mortality [HR 1.43, 95% CI 1.28-1.60, p < 0.001; HR 1.75, 95% CI 1.45-2.11, p < 0.001; HR 2.00, 95% CI 1.61-2.49, p < 0.001, respectively]. Similar findings were observed in two doubly robust estimation models. Conclusion: The trends of dynamic VIS in ICU might help intensivists to stratify the prognosis of adult patients with septic shock. A lower decline of VIS was remarkably associated with higher ICU and in-hospital mortality among septic shock patients receiving vasoactive-inotropic therapy for more than 24 h.
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Purpose: This study aimed to compare the diagnostic performance of [68Ga]Ga-FAPI-04 PET/CT and [18F]F-FDG PET/CT in primary and metastatic colorectal cancer (CRC) lesions. Methods: This single-center preliminary clinical study (NCT04750772) was conducted at the Peking University Cancer Hospital & Institute and included 61 participants with CRC who underwent sequential evaluation through PET/CT with [18F]F-FDG and [68Ga]Ga-FAPI-04. Their PET/CT images were analysed to quantify the uptake of the two tracers in the form of maximum standardised uptake (SUVmax) values and target-to-background ratio (TBR), which were then compared using Wilcoxon's signed-rank test. The final changes in the tumour-node-metastasis (TNM) stage of all participants were recorded. Results: Of all the participants, 21 were treatment naïve and 40 had been previously treated. In primary CRC lesions, the average TBRs of [68Ga]Ga-FAPI-04 and [18F]F-FDG were 13.3 ± 8.9 and 8.2 ± 6.5, respectively. The SUVmax of [68Ga]Ga-FAPI-04 in signet-ring/mucinous carcinomas (11.4 ± 4.9) was higher than that of [18F]F-FDG (7.9 ± 3.6) (P = 0.03). Both median SUVmax in peritoneal metastases and TBR in liver metastases of [68Ga]Ga-FAPI-04 were higher than those of [18F]F-FDG (5.2 vs. 3.8, P < 0.001; 3.7 vs. 1.9, P < 0.001, respectively). Compared with [18F]F-FDG PET/CT, clinical TNM staging based on [68Ga]Ga-FAPI-04 PET/CT led to upstaging and downstaging in 10 (16.4%) and 5 participants (8.2%), respectively. Therefore, the treatment options were changed in 13 participants (21.3%), including 9 with additional chemo/radiotherapy and/or surgery and others with avoidance or narrowed scope of surgery. Conclusion: [68Ga]Ga-FAPI-04 showed potential as a novel PET/CT tracer to detect lymph nodes and distant metastases, which improved CRC staging, thus prompting the optimisation or adjustment of treatment decisions.
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BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).
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OBJECTIVE: To assess the diagnostic and therapeutic status of non-respiratory physicians managing chronic obstructive pulmonary disease (COPD) for patients with lung cancer at general hospitals to promote a standardized regimen. METHODS: Through a retrospective survey from January 2009 to December 2010 at our hospital, the data of clinical features, pulmonary function test results and information of therapy for lung cancer patients with COPD admitted at non-respiratory departments (mostly of thoracic surgery) were collected. RESULTS: A total of 240 lung cancer patients with COPD were admitted. Five patients were diagnosed as COPD with a diagnostic rate of 2.1%. And 210 cases of patients were stable. According to GOLD guidelines in 2010, only 50 cases were treated with adequate drugs (23.8%). Among another 30 patients with acute exacerbation, the following therapies were administrated: selective bronchodilator (n = 13, 43.3%), antibiotics (n = 26, 86.7%) and glucocorticoids (n = 1, 3.3%). CONCLUSION: Underdiagnosis and inadequate treatment of COPD in lung cancer patients by non-respiratory physicians are too serious to be neglected.
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Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adenocarcinoma/complicações , Adenocarcinoma/terapia , Adenocarcinoma de Pulmão , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos RetrospectivosRESUMO
Against the background of people's increasing awareness of personal safety and property safety, the flame retardancy (FR) of materials has increasingly become the focus of attention in the field of construction engineering. A variety of materials have been developed in research and production in this field. Polymers have many advantages, such as their light weight, low water absorption, high flexibility, good chemical corrosion resistance, high specific strength, high specific modulus and low thermal conductivity, and are often applied to the field of construction engineering. However, the FR of unmodified polymer is not ideal, and new methods to make it more flame retardant are needed to enhance the FR. This article primarily introduces the flame-retardant mechanism of fire retardancy. It summarizes the preparation of polymer flame-retardant materials by adding different flame-retardant agents, and the application and research progress related to polymer flame-retardant materials in construction engineering.
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In this study, rural atmospheric carbon dioxide (CO2) and ozone (O3) were measured from January 2015 to December 2018 to investigate characteristics of greenhouse gases in eastern China. Results showed that the annual average CO2 (O3) concentration in 2018 decreased by 2% (increased by 19%) when compared with that in 2015. CO2 concentrations exhibited monthly variability, peaking in February (443.7 ppm) and reaching their lowest levels in July (363.0 ppm); whereas, monthly O3 showed a bimodal pattern with peaks in June (51.3 ppb) and September (34.5 ppb). Regarding the diurnal variation, the maximum CO2 (O3) concentration occurred at nighttime (in the daytime) and a minimum CO2 (O3) in the daytime (at nighttime). As demonstrated by correlation analysis, CO2 and O3 variations were partly modulated by NOx and PM2.5. Furthermore, CO2 showed significant positive correlations with relative humidity in winter, while O3 showed strong positive correlations with temperature in spring. CO2 was accumulated from local sources under calm conditions (< 2 m s-1) and derived from remote sources at high wind speeds (> 4 m s-1), while O3 concentrations were peaking at medium wind speeds of 2-4 m s-1. CO2 was found to derive from long-distance (short-distance transport) transport in spring (the other three seasons), whereas O3 is mainly from long-distance (short-distance) transport in winter (the other three seasons). This work sheds light on the temporal characteristics of CO2 and O3, which has important implications for implementing practices to mitigate source emissions over cropland areas.
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Levosimendan and dobutamine are extensively used to treat sepsis-associated cardiovascular failure in ICU. Nevertheless, the role and mechanism of levosimendan in patients with sepsis-induced cardiomyopathy remains unclear. Moreover, previous studies on whether levosimendan is superior to dobutamine are still controversial. More importantly, these studies did not take changes (before-after comparison to the baseline) in quantitative parameters such as ejection fraction into account with the baseline level. Here, we aimed to determine the pros and cons of the two medicines by assessing the changes in cardiac function and blood lactate, mortality, with the standardized mean difference used as a summary statistic. Relevant studies were obtained by a thorough and disciplined literature search in several notable academic databases, including Google Scholar, PubMed, Cochrane Library and Embase until November 2020. Outcomes included changes in cardiac function, lactic acid, mortality and length of hospital stay. A total of 6 randomized controlled trials were included in this study, including 192 patients. Compared with dobutamine, patients treated with levosimendan had a greater improvement of cardiac index (ΔCI) (random effects, SMD = 0.90 [0.20,1.60]; I2 = 76%, P < 0.01) and left ventricular stroke work index (ΔLVSWI) (random effects, SMD = 1.56 [0.90,2.21]; I2 = 65%, P = 0.04), a significant decrease of blood lactate (Δblood lactate) (random effects, MD = - 0.79 [- 1.33, - 0.25]; I2 = 68%, P < 0.01) at 24-h after drug intervention, respectively. There was no significant difference between levosimendan and dobutamine on all-cause mortality in ICU (fixed effect, OR = 0.72 [0.39,1.33]; I2 = 0%, P = 0.99). We combine effect sizes related to different measurement parameters to evaluate cardiac function, which implied that septic patients with myocardial dysfunction might have a better improvement of cardiac function by levosimendan than dobutamine (random effects, SMD = 1.05 [0.69,1.41]; I2 = 67%, P < 0.01). This study suggested a significant improvement of CI, LVSWI, and decrease of blood lactate in septic patients with myocardial dysfunction in ICU after 24-h administration of levosimendan than dobutamine. However, the administration of levosimendan has neither an impact on mortality nor LVEF. Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.
Assuntos
Dobutamina/uso terapêutico , Cardiopatias , Ácido Láctico/sangue , Sepse , Simendana/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Intervalo Livre de Doença , Cardiopatias/sangue , Cardiopatias/tratamento farmacológico , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Sepse/sangue , Sepse/tratamento farmacológico , Sepse/mortalidade , Sepse/fisiopatologia , Taxa de SobrevidaRESUMO
ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) contributes significantly to cardiovascular dysfunction during septic shock. We aimed to evaluate the potential role of Xinmailong injection (XMLI), a polypeptide medicine extracted from Periplaneta americana, in reversing the progression of myocardial damage to SIMD in sepsis patients. This was a multicenter, randomized, double-blind, parallel-group trial. We recruited all patients consecutively admitted to intensive care units (ICUs) who were aged 18 to 85 years old and met the sepsis 3.0 criteria. The primary outcome measure was the incidence of sepsis-induced myocardial dysfunction while in the ICU. Of the 192 patients, 96 were assigned to the treatment group, and 96 to the control group. Subsequently, 41 patients [41/96 (42.7%)] in the XMLI group and 61 patients in the placebo group [61/96 (63.5%)] were confirmed to have diastolic dysfunction on the fifth day (D5). The incidence of diastolic SIMD was significantly different between the two groups (Pâ=â0.004). There were 36 deaths in the two groups during the 28-day follow-up, with a general mortality rate of 18.8% (36/192). The 28-day mortality rates were not significantly different between the groups (Pâ=â0.45). However, the brain natriuretic peptide (BNP) plasma concentration trends on D0, D2, and D5 significantly differed between the two groups (Pâ=â0.049). In septic patients, XMLI decreased the occurrence rate of diastolic SIMD more effectively than the placebo. The improvement in serum BNP concentration was also greater in the XMLI group. XMLI may, therefore, effectively and safely improve cardiac function in patients with sepsis.
Assuntos
Cardiomiopatias/epidemiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Sepse/complicações , Sepse/terapia , Idoso , Idoso de 80 Anos ou mais , Animais , Cardiomiopatias/prevenção & controle , Cuidados Críticos , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Periplaneta , Estudos Prospectivos , Sepse/mortalidadeRESUMO
BACKGROUND/AIMS: Intraoperative blood loss more than 400 mL during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (DDAVP) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study was to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery. MATERIALS AND METHODS: A multiple-centers, double-blind clinical trial was conducted, patients who underwent gastrointestinal surgery were recruited from 3 hospitals, randomly assigned to two different groups. Patients in the treatment group received desmopressin 0.3 ug/kg,30 min once a day after surgery, patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 hours after the surgery. And the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety. RESULTS: There were 59 patients enrolled between 1 June 2015 and 1 June 2017. At 24hr.after surgery, a decrease in hemoglobin in the DDAVP group was significantly lower than that in the NS group (-5.0±6.9 g/L vs. -10.2±9.3g/L, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in NS group at 24 hr. (2.56 ±0.59 vs. 1.91 ±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 hr. between two group. CONCLUSION: DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.