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1.
Metabolites ; 12(9)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36144243

RESUMO

Rheumatoid arthritis (RA) is characterized by systemic inflammation and synovial hyperplasia. Pristimerin, a natural triterpenoid isolated from plants belonging to the Celastraceae and Hippocrateaceae families, has been reported to exhibit anti-inflammation and anti-proliferation activities. Our study aims to reveal the antiarthritic effects of pristimerin and explore its potential mechanism using in vitro, in silico, and in vivo methods. In the present study, pristimerin treatment led to a dose-dependent decrease in cell viability and migration in TNF-α stimulated human rheumatoid arthritis fibroblast-like synoviocytes MH7A. Moreover, UPLC-LTQ-Orbitrap-based cell metabolomics analysis demonstrated that phospholipid biosynthesis, fatty acid biosynthesis, glutathione metabolism and amino acid metabolic pathways were involved in TNF-α induced MH7A cells after pristimerin treatment. In addition, the adjuvant-induced arthritis (AIA) rat model was employed, and the results exhibited that pristimerin could effectively relieve arthritis symptoms and histopathological damage as well as reduce serum levels of TNF-α, NO and synovial expressions of p-Akt and p-Erk in AIA rats. Furthermore, network pharmacology analysis was performed to visualize crucial protein targets of pristimerin for RA treatment, which showed that the effects were mediated through the MAPK/Erk1/2, PI3K/Akt pathways and directing binding with TNF-α. Taken together, our study not only offered new insights into the biochemical mechanism of natural compounds for RA treatment, but also provided a strategy that integrated in vitro, in silico and in vivo studies to facilitate screening of new anti-RA drugs.

2.
Front Oncol ; 12: 960481, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081570

RESUMO

Objectives: Colorectal cancer(CRC) is a common malignant tumor. Recent studies have found that lncRNAs play an important role in the occurrence and development of colorectal cancer. Methods: Based on high-throughput sequencing results of fresh CRC tissues and adjacent tissues, we identified lncRNA-ENST00000543604 (lncRNA 604) as the research object by qRT-PCR in CRC tissues and cells. We explored the mechanism of lncRNA 604 action by using luciferin reporter, qRT-PCR and Western blot assays. Kaplan-Meier survival analysis and a Cox regression model were used to analyze the correlation of lncRNA 604 and its regulatory molecules with the prognosis of and chemotherapy efficacy in CRC patients. Results: In this study, we found that the expression levels of lncRNA 604 were increased in CRC. LncRNA 604 could promote CRC cell proliferation and metastasis through the miRNA 564/AEG-1 or ZNF326/EMT signaling axis in vivo and in vitro. LncRNA 604 could predict the prognosis of CRC and was an independent negative factor. LncRNA 604 exerted a synergistic effect with miRNA 564 or ZNF326 on the prognosis of CRC. LncRNA 604 could improve chemoresistance by increasing the expression of AEG-1, NF-κB, and ERCC1. Conclusions: Our study demonstrated that lncRNA 604 could promote the progression of CRC via the lncRNA 604/miRNA 564/AEG-1/EMT or lncRNA 604/ZNF326/EMT signaling axis. LncRNA 604 could improve chemoresistance by increasing drug resistance protein expression.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36082970

RESUMO

Oxidative N-heterocyclic carbene (NHC) organocatalysis, typically leading to the formation of acyl azolium reactive intermediates, constitutes one of the most important activation strategies for the NHC-catalyzed chemical transformations. Here, we report an unprecedented oxidative radical NHC catalysis by using peroxyester as the external single-electron oxidant to realize divergent difunctionalization of olefins. The key to success of this chemistry is the catalytic generation of oxygen radicals that could trigger an intermolecular hydrogen atom transfer to activate the inert C-H bonds, thereby enabling the productive radical relay process. With this protocol, commonly used general chemicals could serve as radical precursors to allow efficient synthesis of value-added products in a straightforward and cost-effective manner. Preliminary mechanistic investigations, including control experiments and DFT calculations, shed light on the NHC organocatalytic radical reaction mechanism.

4.
Heliyon ; 8(9): e10448, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36097471

RESUMO

A 52-year-old woman complained of inguinal lymph node enlargement, low fever and night sweats for 20 days. After pathological biopsy and metagenomic sequencing, she was diagnosed as having Bartonella henselae infection. Her lymph nodes were accompanied by multiple ulcers in the affected area and sinus formation. Azithromycin was administered according to the Sanford Guide to Antimicrobial Therapy 2020, combined with wound repair and partial resection of inguinal lymph nodes. The patient showed good recovery after the operation. In all, lymphadenitis associated with B. henselae infection is difficult to diagnose. Lymphadenitis with suppuration and sinus formation needs multidisciplinary consultation. When the causal pathogen is unknown, metagenomic sequencing is recommended for a definite diagnosis.

5.
Front Mol Neurosci ; 15: 953765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966020

RESUMO

Background and purpose: Trigeminal neuralgia is a common condition that is associated with severe pain, which seriously affects the quality of life of patients. When the efficacy of drugs is not satisfactory or adverse drug reactions cannot be tolerated, minimally invasive interventional therapy has become an important treatment because of its simple operation, low risk, high repeatability and low cost. In recent years, minimally invasive interventional treatments, such as radiofrequency thermocoagulation (RF) of the trigeminal nerve and percutaneous microcompression (PMC), have been widely used in the clinic to relieve severe pain in many patients, however, some related problems remain to be addressed. The Pain Association of the Chinese Medical Association organizes and compiles the consensus of Chinese experts to standardize the development of minimally invasive interventional treatment of trigeminal neuralgia to provide a basis for its clinical promotion and application. Materials and methods: The Pain Association of the Chinese Medical Association organizes the Chinese experts to compile a consensus. With reference to the evidence-based medicine (OCEBM) system and the actual situation of the profession, the Consensus Development Committee adopts the nominal group method to adjust the recommended level. Results: Precise imaging positioning and guidance are the keys to ensuring the efficacy and safety of the procedures. RF and PMC are the most widely performed and effective treatments among minimally invasive interventional treatments for trigeminal neuralgia. Conclusions: The pain degree of trigeminal neuralgia is severe, and a variety of minimally invasive intervention methods can effectively improve symptoms. Radiofrequency and percutaneous microcompression may be the first choice for minimally invasive interventional therapy.

6.
Nat Commun ; 13(1): 4993, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008401

RESUMO

Classification and identification of different phases and the transitions between them is a central task in condensed matter physics. Machine learning, which has achieved dramatic success in a wide range of applications, holds the promise to bring unprecedented perspectives for this challenging task. However, despite the exciting progress made along this direction, the reliability of machine-learning approaches in experimental settings demands further investigation. Here, with the nitrogen-vacancy center platform, we report a proof-of-principle experimental demonstration of adversarial examples in learning topological phases. We show that the experimental noises are more likely to act as adversarial perturbations when a larger percentage of the input data are dropped or unavailable for the neural network-based classifiers. We experimentally implement adversarial examples which can deceive the phase classifier with a high confidence, while keeping the topological properties of the simulated Hopf insulators unchanged. Our results explicitly showcase the crucial vulnerability aspect of applying machine learning techniques in experiments to classify phases of matter, which can benefit future studies in this interdisciplinary field.

7.
Front Oncol ; 12: 985484, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033443

RESUMO

Liver cancer is a generic term referring to several cancer types arising from the liver. Every year, liver cancer causes lots of deaths and other burdens to the people all over the world. Though the techniques in the diagnosis and therapy of liver cancer have undergone significant advances, the current status of treating liver cancer is not satisfactory enough. The improvement of techniques for the prognosis of liver cancer patients will be a great supplement for the treatment of liver cancer. Cuproptosis is a newly identified regulatory cell death type, which may have a close connection to liver cancer pathology. Here, we developed a prognostic model for liver cancer based on the cuproptosis-related mRNAs and lncRNAs. This model can not only effectively predict the potential survival of liver cancer patients, but also be applied to evaluate the infiltration of immune cell, tumor mutation burden, and sensitivity to anti-tumor drugs in liver cancer. In addition, this model has been successfully validated in lots of liver cancer patients' data. In summary, we wish this model can become a helpful tool for clinical use in the therapy of liver cancer.

8.
Ageing Res Rev ; 81: 101725, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36029999

RESUMO

The old people often suffer from circadian rhythm disturbances, which in turn accelerate aging. Many aging-related degenerative diseases such as Alzheimer's disease, Parkinson's disease, and osteoarthritis have an inextricable connection with circadian rhythm. In light of the predominant effects of clock genes on regulating circadian rhythm, we systematically present the elaborate network of roles that clock genes play in aging in this review. First, we briefly introduce the basic background regarding clock genes. Second, we systemically summarize the roles of clock genes in aging and aging-related degenerative diseases. Third, we discuss the relationship between clock genes polymorphisms and aging. In summary, this review is intended to clarify the indispensable roles of clock genes in aging and sheds light on developing clock genes as anti-aging targets.

9.
Sci Rep ; 12(1): 13551, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941277

RESUMO

GDP-mannose 3, 5-epimerase (GME, EC 5.1.3.18), a key enzyme in the ascorbic acid synthesis pathway, catalyzes the conversion of GDP-D-mannose to GDP-l-galactose in higher plants. Here, a homolog of GME was isolated from Chrysanthemum vestitum. The cDNA sequence of CvGME was 1131 bp and contained a complete open reading frame encoding a protein comprising 376 amino acids. Quantitative real-time PCR analysis revealed that CvGME was most highly expressed in the stems and roots. Phylogenetic analysis showed that CvGME was closely related to LsGME from Lactuca sativa. Subcellular localization studies revealed that CvGME was localized in the nucleus. Heterologous expression of CvGME in transgenic tobacco plants increased the ascorbic acid content in the leaves. In addition, overexpression of CvGME reduced the malondialdehyde content and increased superoxide dismutase and peroxidase activity in tobacco leaves compared to those in the wild-type plants under drought stress conditions, explaining the increased drought tolerance of transgenic tobacco lines. These results suggest that CvGME can effectively enhance the tolerance of plants to drought by increasing the ascorbic acid content, which may help improve the drought tolerance of chrysanthemums through molecular breeding.


Assuntos
Chrysanthemum , Tabaco , Ácido Ascórbico/metabolismo , Chrysanthemum/genética , Chrysanthemum/metabolismo , Clonagem Molecular , Secas , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Tabaco/metabolismo
10.
Front Pharmacol ; 13: 862966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774597

RESUMO

Asparagus (ASP) is a well-known traditional Chinese medicine with nourishing, moistening, fire-clearing, cough-suppressing, and intestinal effects. In addition, it exerts anti-inflammatory, antioxidant, anti-aging, immunity-enhancing, and anti-tumor pharmacological effect. The anti-tumor effect of ASP has been studied in hepatocellular carcinoma. However, its action and pharmacological mechanism in colorectal cancer (CRC) are unclear. The present study aimed to identify the potential targets of ASP for CRC treatment using network pharmacology and explore its possible therapeutic mechanisms using in vitro and in vivo experiments. The active compounds and potential targets of ASP were obtained from the TCMSP database, followed by CRC-related target genes identification using GeneCards and OMIM databases, which were matched with the potential targets of ASP. Based on the matching results, potential targets and signaling pathways were identified by protein-protein interaction (PPI), gene ontology (GO) functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, in vitro and in vivo experiments were performed to further validate the anti-cancer effects of ASP on CRC. Network pharmacology analysis identified nine active components from ASP from the database based on oral bioavailability and drug similarity index, and 157 potential targets related to ASP were predicted. The PPI network identified tumor protein 53 (TP53), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and AKT serine/threonine kinase 1 (AKT1) as key targets. GO analysis showed that ASP might act through response to wounding, membrane raft, and transcription factor binding. KEGG enrichment analysis revealed that ASP may affect CRC through the phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway. In vitro, ASP inhibited cell proliferation, migration, and invasion of HCT116 and LOVO cells, and caused G0/G1 phase arrest and apoptosis in CRC cells. In vivo, ASP significantly inhibited the growth of CRC transplanted tumors in nude mice. Furthermore, pathway analysis confirmed that ASP could exert its therapeutic effects on CRC by regulating cell proliferation and survival through the PI3K/AKT/mTOR signaling pathway. This study is the first to report the potential role of ASP in the treatment of colorectal cancer.

11.
Cell Death Discov ; 8(1): 336, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879322

RESUMO

Cytochrome c oxidase subunit VIc (COX6c) is one of the most important subunits of the terminal enzyme of the respiratory chain in mitochondria. Numerous studies have demonstrated that COX6c plays a critical role in the regulation of oxidative phosphorylation (OXPHOS) and energy production. The release of COX6c from the mitochondria may be a hallmark of the intrinsic apoptosis pathway. Moreover, The changes in COX6c expression are widespread in a variety of diseases and can be chosen as a potential biomarker for diagnosis and treatment. In light of its exclusive effects, we present the elaborate roles that COX6c plays in various diseases. In this review, we first introduced basic knowledge regarding COX6c and its functions in the OXPHOS and apoptosis pathways. Subsequently, we described the regulation of COX6c expression and activity in both positive and negative ways. Furthermore, we summarized the elaborate roles that COX6c plays in various diseases, including cardiovascular disease, kidney disease, brain injury, skeletal muscle injury, and tumors. This review highlights recent advances and provides a comprehensive summary of COX6c in the regulation of OXPHOS in multiple diseases and may be helpful for drug design and the prediction, diagnosis, treatment, and prognosis of diseases.

12.
Sci Total Environ ; 846: 157492, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-35870578

RESUMO

A two-phase kitchen waste (KW) fermentation was proposed in the current study to enhance medium-chain fatty acids (MCFAs) production from kitchen waste. In particular, effect of acetate to butyrate ratio (ABR) on MCFAs production was investigated which can be regulated by different pH and organic loading during the acidification phase. Medium ABR (1.00) was obtained when pH is 5.5 and organic loading is 20 g VS/L in FW acidification fermentation. Subsequent chain elongation fermentation demonstrated that the highest yield of caproate 9.67 g/L with selectivity of 79 %, and highest ethanol conversion efficiency of 1.11 was achieved in medium ABR system. Microbial community study showed that medium ABR significantly enrich the functional bacteria especially Clostridium kluyveri. The study provides a new method for chain elongation enhancement without addition of other additives in kitchen waste fermentation system and gives a guide for the regulation of the short-chain fatty acids distribution in its acidification phase.


Assuntos
Elétrons , Etanol , Acetatos , Reatores Biológicos , Ácidos Graxos , Ácidos Graxos Voláteis , Fermentação
13.
Cell Chem Biol ; 29(8): 1248-1259.e6, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35858615

RESUMO

Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have designed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment.


Assuntos
Capsaicina , Sepse , Capsaicina/farmacologia , Proteínas de Transporte , Ciclo-Oxigenase 2 , Humanos , Inflamação/tratamento farmacológico , L-Lactato Desidrogenase , Lipopolissacarídeos/farmacologia , Proteínas de Membrana , Sepse/tratamento farmacológico , Canais de Cátion TRPV , Hormônios Tireóideos
14.
Dis Markers ; 2022: 6362344, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35726235

RESUMO

Sepsis is a common critical clinical disease with high mortality that can cause approximately 10 million deaths worldwide each year. Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common clinical complication of sepsis, which occurs primarily as diffuse alveolar injury, hypoxemia, and respiratory distress. The mortality rate of ALI/ARDS is as high as 30%-40%, which greatly endangers human health. Due to the unclear pathogenesis of ALI/ARDS, its treatment is still a worldwide problem. At present, clinical treatment mainly relies on lung-protective ventilation, prone position ventilation, and fluid management. However, there is a lack of effective and specific treatment measures. In recent years, domestic and foreign scholars have committed to basic research on ALI/ARDS, trying to further clarify its pathogenesis and find new targets and methods for the treatment of ALI/ARDS. In this review, we summarize the signaling pathways related to alveolar injury and repair in sepsis-induced ALI/ARDS and their latest research progress. They include the NF-κB, JAK2/STAT3, mitogen-activated protein kinase (MAPK), mTOR, and Notch signaling pathways. Understanding the molecular mechanisms of these signaling pathways in sepsis-induced ALI/ARDS may provide new targets and ideas for the clinical treatment of this disease.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Sepse , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Humanos , Respiração Artificial , Síndrome do Desconforto Respiratório/etiologia , Sepse/complicações , Transdução de Sinais
15.
Mult Scler J Exp Transl Clin ; 8(2): 20552173221104918, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734229

RESUMO

Background: The effects of pregnancy on multiple sclerosis (MS) inflammatory activity are not well described in women with moderate to severe disabilities. Objective: To quantify the peripartum annualized relapse rate (ARR) in women with MS with an Expanded Disability Status Scale (EDSS) ≥ 3. Methods: We performed a retrospective cohort study of 85 pregnancies in 74 subjects with preconception EDSS ≥ 3. We quantified peripartum ARR and tested for risk factors predictive of peripartum relapses, postpartum brain magnetic resonance imaging activity (new T2 or gadolinium-enhancing lesions), and disability worsening. Results: There were 74 live births, with a 56% operative delivery rate. In subjects with relapsing-remitting MS, ARR decreased to 0.11 during the third trimester of pregnancy compared to 0.59 in the year preconception and increased to 1.22 in the 3 months postpartum. Women with a higher preconception EDSS had higher odds of postpartum relapses and clinically significant worsening of disability as compared to subjects with a lower EDSS. Conclusions: Moderately to severely disabled women with MS have a lower risk of relapse during pregnancy as compared to preconception, followed by a marked increase postpartum. Further studies are needed to identify ways to reduce peripartum inflammatory activity and disability progression in women with MS with moderate to severe disability.

16.
Mil Med Res ; 9(1): 30, 2022 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-35698214

RESUMO

BACKGROUND: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. METHODS: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays. RESULTS: We developed a novel clickable, photo-affinity chloroquine analog probe (CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods. CONCLUSIONS: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.


Assuntos
Antimaláricos , Malária , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Humanos , Malária/tratamento farmacológico , Espectrometria de Massas
17.
Molecules ; 27(11)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35684565

RESUMO

BACKGROUND: Poria cocos (P. cocos) is an important medicinal fungus in traditional Chinese medicine. Poria acid (PA), a triterpenoid compound, is an effective component of traditional Chinese medicine P. cocos. This experiment investigated the anti-gastric cancer biological activity of PA in vitro. METHODS: The effect of PA on the viability of gastric cancer cells was detected by the thiazolyl blue (MTT) assay. Cell adhesion assays were used to detect changes in the adhesion of cells treated after PA (0, 20, 40, and 80 µmol/L). The ability of cell invasion and migration were detected by Transwell assays and wound healing assays. A high-content imaging system was used to dynamically record the motility of the gastric cancer cells after PA (0, 20, 40, and 80 µmol/L) treatment. Western blotting was used to detect the expression of epithelial-mesenchymal transformation (EMT), invasion and migration related proteins. RESULTS: The MTT assay showed that the proliferation of gastric cancer cells was significantly inhibited after PA treatment. Cell adhesion experiments showed that the adhesion of gastric cancer cells was significantly decreased after PA treatment. Compared with the control group, the wound healing area of the gastric cancer cells treated with different concentrations of PA decreased. The Transwell assay showed that the number of gastric cancer cells passing through the cell membrane were significantly reduced after PA treatment. In addition, after PA treatment, the cells' movement distance and average movement speed were significantly lower than those of the control group. Finally, PA can significantly alter the expression of EMT-related proteins E-cadherin, N-cadherin, and Vimentin and decreased the expressions of metastasis-related proteins matrix metalloproteinase (MMP) 2, MMP-9 and tissue inhibition of matrix metalloproteinase (TIMP)1 in the gastric cancer cells. CONCLUSIONS: Triterpenoids from P. cocos have significant biological activity against gastric cancer, and the mechanism may be involved in the process of epithelial-mesenchymal transformation.


Assuntos
Neoplasias Gástricas , Triterpenos , Wolfiporia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Triterpenos/farmacologia , Wolfiporia/química
18.
Pathol Oncol Res ; 28: 1610280, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515016

RESUMO

Background: The diagnostic value of tumor markers in pleural effusion (PE) and serum for malignant pleural effusion (MPE) is still in debate. This study aimed to evaluate the diagnostic value of six tumor markers in PE, serum, and the corresponding PE/serum (PE/S) ratio in distinguishing MPE from benign pleural effusion (BPE). Methods: A total of 1,230 patients with PE (452 MPEs and 778 BPEs) were retrospectively included in the study. PE and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), cytokeratin 19 fragment (CYFRA 21-1), and neuron-specific enolase (NSE) were measured. The area under the curve (AUC) was used to assess the single and combined diagnostic values of the six tumor markers for MPE. Results: The levels of the six tumor markers in PE, serum, and PE/S were significantly higher in MPE than that in BPE, except for serum CA125. PE CEA showed the highest AUC [0.890 (0.871-0.907)] at a cut-off value of 3.7 ng/ml compared to any single tumor marker using receiver operating characteristic (ROC) analysis. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of PE CEA were 74.1%, 95.5%, 90.5%, 86.4%, 16.47, and 0.27, respectively. The combination of PE CEA and serum CYFRA21-1 showed the best diagnostic performance with an AUC of 0.934 (sensitivity, 79.9%; specificity, 95.7%, PPV, 90.5; PLR, 17.35) among all two or three combinations. Besides, serum CYFRA21-1 was the best diagnostic tumor marker in distinguishing cytology-negative MPE from BPE at a cut-off value of 3.0 ng/ml. Conclusion: PE CEA was the best diagnostic tumor marker in distinguishing MPE from BPE. Serum CYFRA21-1 was the best diagnostic tumor marker in distinguishing cytology-negative MPE from BPE. The combination of PE CEA and serum CYFRA21-1 could increase the diagnostic performance in distinguishing MPE from BPE and cytology-negative MPE from BPE.


Assuntos
Derrame Pleural Maligno , Derrame Pleural , Antígenos de Neoplasias , Biomarcadores Tumorais , Carboidratos , Antígeno Carcinoembrionário , Humanos , Queratina-19 , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
19.
Front Oncol ; 12: 845613, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530347

RESUMO

Background: Relatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC). Methods: In this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan-Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776). Results: A total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group. Conclusion: TCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

20.
Respir Res ; 23(1): 134, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35624515

RESUMO

BACKGROUND: Distinguishing tuberculous pleural effusion (TPE) from non-tuberculosis (TB) benign pleural effusion (BPE) remains to be a challenge in clinical practice. The aim of the present study was to develop and validate a novel nomogram for diagnosing TPE. METHODS: In this retrospective analysis, a total of 909 consecutive patients with TPE and non-TB BPE from Ningbo First Hospital were divided into the training set and the internal validation set at a ratio of 7:3, respectively. The clinical and laboratory features were collected and analyzed by logistic regression analysis. A diagnostic model incorporating selected variables was developed and was externally validated in a cohort of 110 patients from another hospital. RESULTS: Six variables including age, effusion lymphocyte, effusion adenosine deaminase (ADA), effusion lactatedehy drogenase (LDH), effusion LDH/effusion ADA, and serum white blood cell (WBC) were identified as valuable parameters used for developing a nomogram. The nomogram showed a good diagnostic performance in the training set. A novel scoring system was then established based on the nomogram to distinguish TPE from non-TB BPE. The scoring system showed good diagnostic performance in the training set [area under the curve (AUC) (95% confidence interval (CI)), 0.937 (0.917-0.957); sensitivity, 89.0%, and specificity, 89.5%], the internal validation set [AUC (95%CI), 0.934 (0.902-0.966); sensitivity, 88.7%, and specificity, 90.3%], and the external validation set [(AUC (95%CI), 0.941 (0.891-0.991); sensitivity, 93.6%, and specificity, 87.5%)], respectively. CONCLUSIONS: The study developed and validated a novel scoring system based on a nomogram originated from six clinical parameters. The novel scoring system showed a good diagnostic performance in distinguishing TPE from non-TB BPE and can be conveniently used in clinical settings.


Assuntos
Derrame Pleural , Tuberculose Pleural , Área Sob a Curva , Estudos de Coortes , Humanos , Derrame Pleural/diagnóstico , Estudos Retrospectivos , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/epidemiologia
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