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1.
BMC Pulm Med ; 24(1): 11, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167022

RESUMEN

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS: This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum ß-D-glucan levels was also evaluated for PCP diagnosis. RESULTS: A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum ß-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum ß-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS: Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum ß-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05701631).


Asunto(s)
Infecciones por VIH , Pneumocystis carinii , Neumonía por Pneumocystis , beta-Glucanos , Humanos , Neumonía por Pneumocystis/diagnóstico por imagen , Estudios Retrospectivos , Radiómica , Infecciones por VIH/complicaciones , Glucanos , Tomografía
2.
J Am Chem Soc ; 145(32): 18115-18125, 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37525426

RESUMEN

We report the first catalyst-controlled regiodivergent method that enables the synthesis of structurally diverse 1,2,3,4-tetrasubstituted conjugated dienes with excellent regio- and stereochemical outcomes from the same set of readily available propargyl esters and diaryliodonium salts. In this diene chemistry, the in situ generated, highly electrophilic aryl-CuIII complex serves not only as a π-Lewis acid catalyst for alkyne activation/acyloxy migration but also as an aryl electrophile equivalent. The competitive arylative 1,2- and 1,3-acyloxy migration patterns are exquisitely dictated by Cu and Au/Cu relay catalyses, respectively, providing a modular and attractive approach to traditionally inaccessible tetrasubstituted 1,3-dienes in a regiodivergent manner. Finally, the synthetic utility of this method is demonstrated by further synthetic derivatization of 1,3-dienes into an array of useful compounds.

3.
Angew Chem Int Ed Engl ; 62(33): e202305510, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37329214

RESUMEN

Transition metal-catalyzed C-S cross-coupling has emerged as an important strategy to furnish thioethers; however, the dominant utilization of noble metal catalysts as well as the construction of challenging C(sp3 )-S bonds by transition metal-catalysis remain highly problematic. Earth-abundant manganese has gathered increasing interest as an attractive catalyst for new reaction development; nevertheless, C(sp3 )-S cross-coupling reaction by manganese catalysis has not been reported. Herein, we disclose a highly efficient manganese-catalyzed redox-neutral thiolation of a broad range of alkyl halides with thioformates as practical sulfuration agents. Strategically, employing easily synthesized thioformates as thiyl radical precursors allows access to various aryl and alkyl thioethers in good to excellent yields. Notably, this redox-neutral method avoids the utilization of strong bases, external ligands, forcing reaction conditions, and stoichiometric manganese, thus presenting apparent advantages, such as broad substrate scope, excellent functional group compatibility, and mild reaction conditions. Finally, the utilities of this method are also illustrated by downstream transformations and late-stage thiolation of structurally complex natural products and pharmaceuticals.

4.
Angew Chem Int Ed Engl ; 62(13): e202218286, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36719253

RESUMEN

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

5.
J Am Chem Soc ; 144(50): 23019-23029, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36480540

RESUMEN

The reaction of common acyl-metal species (acyl anion) with aldehydes to furnish acyloins has received much less attention and specifically was restricted to using preformed stoichiometric acyl-metal reagents. Moreover, the (catalytic) enantioselective variants remain unexplored, and the asymmetric synthesis of chiral acyloins has met significant challenges in organic synthesis. Here, we uncover the highly enantioselective coupling of acid chlorides with α-bromobenzoates by nickel catalysis for producing enantioenriched protected α-hydroxy ketones (acyloins, >60 examples) with high enantioselectivities (up to 99% ee). The successful execution of this enantioselective coupling protocol enables the formation of a key ketyl radical from α-bromoalkyl benzoate in situ generated from corresponding aldehyde and acyl bromide, which finally is captured by chiral acyl-Ni species catalytically in situ formed from acyl chlorides, thus avoiding the use of preformed acyl-metal reagents. The synthetic utility of this chemistry is demonstrated in the downstream synthetic elaboration toward a diverse set of synthetically valuable chiral building blocks and biologically active compounds.


Asunto(s)
Cloruros , Níquel , Bromobenzoatos , Estereoisomerismo , Aldehídos/química , Metales/química , Catálisis
6.
Respir Res ; 23(1): 96, 2022 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-35429974

RESUMEN

BACKGROUND: Clinically differentiating preinvasive lesions (atypical adenomatous hyperplasia, AAH and adenocarcinoma in situ, AIS) from invasive lesions (minimally invasive adenocarcinomas, MIA and invasive adenocarcinoma, IA) manifesting as ground-glass opacity nodules (GGOs) is difficult due to overlap of morphological features. Hence, the current study was performed to explore the diagnostic efficiency of radiomics in assessing the invasiveness of lung adenocarcinoma manifesting as GGOs. METHODS: A total of 1018 GGOs pathologically confirmed as lung adenocarcinoma were enrolled in this retrospective study and were randomly divided into a training set (n = 712) and validation set (n = 306). The nodules were delineated manually and 2446 intra-nodular and peri-nodular radiomic features were extracted. Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Clinical and semantic computerized tomography (CT) feature model, radiomic model and a combined nomogram were constructed and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established nomogram. RESULTS: 16 radiomic features were selected and used for model construction. The radiomic model exhibited significantly better performance (AUC = 0.828) comparing to the clinical-semantic model (AUC = 0.746). Further analysis revealed that peri-nodular radiomic features were useful in differentiating between preinvasive and invasive lung adenocarcinomas appearing as GGOs with an AUC of 0.808. A nomogram based on lobulation sign and radiomic features showed the best performance (AUC = 0.835), and was found to have potential clinical value in assessing nodule invasiveness. CONCLUSIONS: Radiomic model based on both intra-nodular and peri-nodular features showed good performance in differentiating between preinvasive lung adenocarcinoma lesions and invasive ones appearing as GGOs, and a nomogram based on clinical, semantic and radiomic features could provide clinicians with added information in nodule management and preoperative evaluation.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Invasividad Neoplásica/diagnóstico por imagen , Invasividad Neoplásica/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
7.
Angew Chem Int Ed Engl ; 61(23): e202203835, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35322509

RESUMEN

Catalyst-controlled regiodivergent catalysis is a vital chemical tool that allows efficient access to large collections of structurally diverse molecules from a common precursor but remains a challenge. We report a catalyst-controlled, tunable, and predictable regiodivergency in transforming the internal aliphatic propargyl esters into diverse libraries of highly substituted 1,3-dienyl and allyl products by Pd-catalysis. Depending on the ligand employed, the palladium catalyst can involve two typical approaches: electrophilic palladium catalysis and a sequential oxidative addition-reductive elimination pathway. This regiodivergent protocol endows facile access to four regioisomers with high regio- and stereoselectivity from the common propargyl esters. In terms of synthetic utility, a notable feature of this protocol is amenable to structural diversification of bioactive relevant molecules, enabling rapid assembly of many useful structural analogs of pharmaceutical candidates.


Asunto(s)
Compuestos Alílicos , Paladio , Compuestos Alílicos/química , Catálisis , Ésteres/química , Ligandos , Paladio/química , Estereoisomerismo
8.
Cytotherapy ; 23(10): 918-930, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34272174

RESUMEN

BACKGROUND AIMS: Acute lung injury (ALI) secondary to sepsis is a complex disease associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) and their conditioned medium have been demonstrated to reduce alveolar inflammation, improve lung endothelial barrier permeability and modulate oxidative stress in vivo and in vitro. Recently, MSCs have been found to release small extracellular vesicles (sEVs) that can deliver functionally active biomolecules into recipient cells. The authors' study was designed to determine whether sEVs released by MSCs would be effective in sepsis-induced ALI mice and to identify the potential mechanisms. METHODS: A total of 6 h after cercal ligation and puncture, the mice received saline, sEV-depleted conditioned medium (sEVD-CM) or MSC sEVs via the tail vein. RESULTS: The administration of MSC sEVs improved pulmonary microvascular permeability and inhibited both histopathological changes and the infiltration of polymorphonuclear neutrophils into lung tissues. In addition, the activities of antioxidant enzymes were significantly increased in the group treated with sEVs compared with the saline and sEVD-CM groups, whereas lipid peroxidation was significantly decreased. Furthermore, sEVs were found to possibly inhibit phosphorylation of the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) pathway and degradation of IκB but increase the activities of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1. CONCLUSIONS: These findings suggest that one of the effective therapeutic mechanisms of sEVs against sepsis-induced ALI may be associated with upregulation of anti-oxidative enzymes and inhibition of MAPK/NF-κB activation.


Asunto(s)
Lesión Pulmonar Aguda , Vesículas Extracelulares , Células Madre Mesenquimatosas , Sepsis , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/terapia , Animales , Vesículas Extracelulares/metabolismo , Humanos , Pulmón/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Sepsis/complicaciones , Sepsis/terapia
9.
BMC Microbiol ; 20(1): 177, 2020 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-32576241

RESUMEN

BACKGROUND: The rapid identification of pathogenic bacteria is important for determining an appropriate antimicrobial therapy for pneumonia, but traditional bacterial culture is time-consuming and labourious. The aim of this study was to develop and evaluate a DNA microarray assay for the simultaneous detection of fifteen bacterial species directly from respiratory tract specimens in patients with pneumonia. These species included Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Mycoplasma pneumoniae, Enterococcus faecalis, Enterococcus faecium, Enterobacter cloacae, Stenotrophomonas maltophilia, Burkholderia cepacia, Legionella pneumophila and Chlamydia pneumoniae. The 16S rDNA genes and other specific genes of each pathogen were chosen as the amplification targets, amplified via multiplex polymerase chain reaction (PCR), and hybridized to oligonucleotide probes in a microarray. RESULTS: The DNA microarray detection limit was 103 copies/µL. Nineteen standard strains and 119 clinical isolates were correctly detected with our microarray, and 3 nontarget species from 4 clinical isolates were not detected. Additionally, bacterial pathogens were accurately identified when two or three bacterial targets were mixed together. Furthermore, the results for 99.4% (156/157) of clinical specimens were the same as those from a conventional assay. CONCLUSIONS: We developed a DNA microarray that could simultaneously detect various bacterial pathogens in pneumonia. The method described here has the potential to provide considerable labour and time savings due to its ability to screen for 15 bacterial pathogens simultaneously.


Asunto(s)
Bacterias/clasificación , ADN Bacteriano/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neumonía/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , ADN Ribosómico/genética , Humanos , Límite de Detección , Reacción en Cadena de la Polimerasa Multiplex , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Especificidad de la Especie
10.
Nature ; 515(7525): 100-3, 2014 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-25373679

RESUMEN

Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest. Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions. In such systems, photoactivated sensitizers initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion. Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the 'green' synthesis of non-racemic chiral molecules.

11.
Med Sci Monit ; 26: e921430, 2020 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-32304567

RESUMEN

BACKGROUND Squamous cell lung cancer is the main cause of cancer-associated mortality. The discovery of promising prognostic biomarkers for predicting the survival of patients with squamous cell lung cancer remains a challenge. MATERIAL AND METHODS Gene expression profiles of GSE33479 and GSE51855, including 42 squamous cell lung cancer tissues and 17 normal tissues, from the GEO database were assessed to find common differentially expressed genes (DEGs) via the GEO2R online tool and Venn diagram software. Then, gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses were conducted. The key protein-protein interaction (PPI) network within those common DEGs was subsequently illustrated through a combination of Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape software. Finally, core genes associated with survival and levels of immune infiltration were demonstrated by the Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) online database, respectively. RESULTS In total, 483 DEGs were involved, including 216 upregulated genes enriched in "cell division", "DNA replication", and "DNA repair pathway" and 267 downregulated genes enriched in "cell adhesion", "oxidation-reduction process", and "cell-cell signaling". The 75 core genes were selected by Molecular Complex Detection applied in Cytoscape. Four genes - MND1, FOXM1, CDC6, and POLE2 - were found to be significantly associated with survival. Further analysis of the KEEG pathway and TIMER database revealed that only POLE2 was enriched in "DNA replication" and its higher expression was negatively associated with survival and immune infiltration. CONCLUSIONS Higher expression of POLE2 is a prognosis-related biomarker for worse survival and is negatively associated with immune infiltration in squamous cell lung cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , ADN Polimerasa II/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Células Escamosas/inmunología , Biología Computacional/métodos , ADN Polimerasa II/metabolismo , Bases de Datos Genéticas , Células Epiteliales/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Redes Reguladoras de Genes/genética , Humanos , Neoplasias Pulmonares/patología , Pronóstico , Mapeo de Interacción de Proteínas/métodos , Mapas de Interacción de Proteínas/genética , Programas Informáticos , Transcriptoma/genética
12.
Acta Biochim Biophys Sin (Shanghai) ; 52(4): 371-381, 2020 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-32188965

RESUMEN

As a subtype of non-small-cell lung cancer, lung squamous cell carcinoma (LUSC) accounts for one-fifth of all lung cancers. Unfortunately, no specific targetable aberration has yet been identified. Hence, it is of huge urgency and potential to identify aberrantly regulated genes in LUSC. Here, five pairs of LUSC samples and their corresponding adjacent tissues were subject to whole transcriptome sequencing. Our results showed that CTD-2562J17.6 and FENDRR were significantly downregulated while MIR205HG, LNC_000378, RP11-116G8.5, RP3-523K23.2, and RP5-968D22.1 were significantly upregulated in all five LUSC samples. Importantly, MIR205HG was upregulated in LUSC clinical samples as well as in LUSC cell lines. Interestingly, our results demonstrated that the expression level of MIR205HG is positively correlated with the malignancy. In addition, MIR205HG is required for LUSC cell growth and cell migration. Most importantly, our results showed that MIR205HG prohibits LUSC apoptosis via regulating Bcl-2 and Bax. Taken together, our data shed lights on the lncRNA regulatory nexus that controls the carcinogenesis of LUSC and provided potential novel diagnostic markers and therapeutic targets for LUSC.


Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Perfilación de la Expresión Génica , Neoplasias Pulmonares/metabolismo , ARN Largo no Codificante/metabolismo , ARN Neoplásico/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , ARN Largo no Codificante/genética , ARN Neoplásico/genética
13.
Crit Care ; 23(1): 300, 2019 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-31484582

RESUMEN

RATIONALE: Our pilot study suggested that noninvasive ventilation (NIV) reduced the need for intubation compared with conventional administration of oxygen on patients with "early" stage of mild acute respiratory distress syndrome (ARDS, PaO2/FIO2 between 200 and 300). OBJECTIVES: To evaluate whether early NIV can reduce the need for invasive ventilation in patients with pneumonia-induced early mild ARDS. METHODS: Prospective, multicenter, randomized controlled trial (RCT) of NIV compared with conventional administration of oxygen through a Venturi mask. Primary outcome included the numbers of patients who met the intubation criteria. RESULTS: Two hundred subjects were randomized to NIV (n = 102) or control (n = 98) groups from 21 centers. Baseline characteristics were similar in the two groups. In the NIV group, PaO2/FIO2 became significantly higher than in the control group at 2 h after randomization and remained stable for the first 72 h. NIV did not decrease the proportion of patients requiring intubation than in the control group (11/102 vs. 9/98, 10.8% vs. 9.2%, p = 0.706). The ICU mortality was similar in the two groups (7/102 vs. 7/98, 4.9% vs. 3.1%, p = 0.721). Multivariate analysis showed minute ventilation greater than 11 L/min at 48 h was the independent risk factor for NIV failure (OR, 1.176 [95% CI, 1.005-1.379], p = 0.043). CONCLUSIONS: Treatment with NIV did not reduce the need for intubation among patients with pneumonia-induced early mild ARDS, despite the improved PaO2/FIO2 observed with NIV compared with standard oxygen therapy. High minute ventilation may predict NIV failure. TRIAL REGISTRATION: NCT01581229 . Registered 19 April 2012.


Asunto(s)
Ventilación no Invasiva/efectos adversos , Síndrome de Dificultad Respiratoria/complicaciones , Lesión Pulmonar Inducida por Ventilación Mecánica/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ventilación no Invasiva/métodos , Proyectos Piloto , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Lesión Pulmonar Inducida por Ventilación Mecánica/terapia
14.
Respiration ; 97(5): 416-427, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30554211

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a leading cause of morbidity and mortality in China, with tobacco smoke, air pollution, and occupational biohazards being the major risk factors. OBJECTIVES: The REACH trial is a multicenter, prospective, randomized controlled trial undertaken in China to assess the safety and effectiveness of the Spiration® Valve System (SVS) compared to standard medical care in COPD patients with severe emphysema. METHODS: Patients with severe airflow obstruction, hyperinflation, and severe dyspnea with interlobar fissure integrity were evaluated for enrollment. A total of 107 subjects were randomized in a 2: 1 allocation ratio to either the treatment group (SVS valves and medical management) or the control group (medical management alone). RESULTS: The 3-month primary endpoint showed statistically significant improvement in forced expiratory volume in 1 s in the treatment group compared to the control group (0.104 ± 0.18 vs. 0.003 ± 0.15 L, p = 0.001), with the difference being durable through 6 months. Statistically significant target lobe volume reduction was achieved at 3 months (mean change 684.4 ± 686.7 mL) and through 6 months (757.0 ± 665.3 mL). Exercise function and quality of life measures improved in the treatment group, but showed a deterioration in the control group. The serious adverse event (SAE) rate was 33% in the treatment group and 24.2% in the control group. The predominance of SAEs were acute exacerbations of COPD in both groups. There was 1 death in the control group and no deaths in the treatment group. CONCLUSION: The SVS represents a novel approach for the treatment of severe emphysema with a clinically acceptable risk-benefit profile.


Asunto(s)
Broncoscopía/métodos , Disnea , Neumonectomía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfisema Pulmonar , Calidad de Vida , Progresión de la Enfermedad , Disnea/etiología , Disnea/psicología , Tolerancia al Ejercicio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonectomía/efectos adversos , Neumonectomía/instrumentación , Neumonectomía/métodos , Diseño de Prótesis , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/prevención & control , Enfisema Pulmonar/terapia , Pruebas de Función Respiratoria/métodos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
15.
Respiration ; 97(5): 484-494, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30970361

RESUMEN

Malignant central airway stenosis refers to airway stenosis caused by primary or metastatic malignant tumors which may lead to different levels of dyspnea or asphyxia in patients. With the rapid development of interventional pulmonology, therapeutic bronchoscopy has become one of the main methods for the diagnosis and treatment of malignant central airway stenosis. However, the level of diagnosis and treatment of respiratory intervention techniques in China is uneven at present, the treatment methods are not uniform, the treatment effects vary greatly, and some treatments even lead to serious complications. The interventional treatment technology for malignant central airway stenosis in China needs to be standardized. Therefore, the relevant experts of the Beijing Health Promotion Association Respiratory and Oncology Intervention and Treatment Alliance have formulated this consensus after several rounds of full discussion.


Asunto(s)
Técnicas de Ablación , Obstrucción de las Vías Aéreas , Broncoscopía , Disección , Neoplasias Pulmonares , Técnicas de Ablación/instrumentación , Técnicas de Ablación/métodos , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/terapia , Broncoscopía/instrumentación , Broncoscopía/métodos , China , Dilatación/instrumentación , Dilatación/métodos , Disección/instrumentación , Disección/métodos , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Índice de Severidad de la Enfermedad , Stents/clasificación , Tiempo de Tratamiento
16.
Angew Chem Int Ed Engl ; 58(32): 10956-10960, 2019 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-31250959

RESUMEN

A method for the construction of boron-substituted quaternary carbons or diarylquaternary carbons by arylboration of highly substituted alkenylarenes is presented. A wide range of alkenes and arylbromides can participate in this reaction thus allowing for a diverse assortment of products to be prepared. In addition, a solvent dependent regiodivergent arylboration of 1,2-disubstituted alkenylarenes is presented, thus greatly increasing the scope of products that can be accessed.

17.
J Am Chem Soc ; 140(34): 10653-10657, 2018 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-30125098

RESUMEN

A three-component coupling of aryl bromides, arylboron reagents, and alkenylarenes is presented. The method tolerates a variety of substitution patterns on all of the components. In particular, 1,2-disubstituted alkenylarenes are suitable and undergo highly diastereoselective diarylation.


Asunto(s)
Alquenos/química , Derivados del Benceno/química , Níquel/química , Alquenos/síntesis química , Derivados del Benceno/síntesis química , Catálisis , Técnicas de Química Sintética/métodos , Estereoisomerismo
18.
J Am Chem Soc ; 139(12): 4568-4573, 2017 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-28266852

RESUMEN

Because of both their synthetically challenging and stereochemically complex structures and their wide range of often clinically relevant biological activities, nonaromatic polyketide natural products have for decades attracted an enormous amount of attention from synthetic chemists and played an important role in the development of modern asymmetric synthesis. Often, such compounds are not available in quantity from natural sources, rendering analogue synthesis and drug development efforts extremely resource-intensive and time-consuming. In this arena, the quest for ever more step-economical and efficient methods and strategies, useful and important goals in their own right, takes on added importance, and the most useful syntheses will combine high levels of step-economy with efficiency and scalability. The nonaromatic polyketide natural product zincophorin methyl ester has attracted significant attention from synthetic chemists due primarily to the historically synthetically challenging C(8)-C(12) all-anti stereopentad. While great progress has been made in the development of new methodologies to more directly address this problem and as a result in the development of more highly step-economical syntheses, a synthesis that combines high levels of step economy with high levels of efficiency and scalability has remained elusive. To address this problem, we have devised a new synthesis of zincophorin methyl ester that proceeds in just nine steps in the longest linear sequence and proceeds in 10% overall yield. Additionally, the scalability and practicability of the route have been demonstrated by performing all of the steps on a meaningful scale. This synthesis thus represents by a significant margin the most step-economical, efficient, and practicable synthesis of this stereochemically complex natural product reported to date, and is well suited to facilitate the synthesis of analogues and medicinal chemistry development efforts in a time- and resource-efficient manner.


Asunto(s)
Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/química , Conformación Molecular
19.
Mycopathologia ; 181(7-8): 485-95, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26994763

RESUMEN

OBJECTIVES: To investigate the distribution of Candida spp., predictors of mortality, and effects of therapeutic measures on outcomes of nosocomial bloodstream infection (BSI) due to Candida spp. METHODS: This retrospective, population-based study enrolled adult patients with Candida nosocomial BSI from January 2010 to December 2014 in one tertiary care hospital. The demographics, comorbidities, species distribution, risk factors, and effects of antifungal treatment were assessed. RESULTS: In total, 190 episodes of Candida BSI were identified. The most prevalent species was C. albicans (38.9 %), followed by C. parapsilosis (23.2 %) and C. tropicalis (20.5 %). In vitro susceptibility testing showed that 88.9 % of Candida isolates were susceptible to fluconazole. The 30-day hospital mortality was 27.9 %, while the early mortality (within 7 days) was 16.3 %. In a multivariate regression analysis, the Acute Physiology and Chronic Health Evaluation II score [odds ratio (OR) 1.23; 95 % confidence interval (CI) 1.080-1.390; P = 0.002] and severe sepsis or septic shock (OR 15.35; 95 % CI 2.391-98.502; P = 0.004) were independently correlated with early mortality. Severe sepsis or septic shock (OR 24.75; 95 % CI 5.099-120.162; P < 0.001) was an independent risk factor for 30-day mortality, while proven catheter-related candidemia (OR 0.16; 95 % CI 0.031-0.810; P = 0.027) was a positive factor for 30-day mortality. Early central venous catheter removal and adequate antifungal treatment were closely related to decreased mortality in patients with primary candidemia. CONCLUSION: The proportion of candidemia caused by C. albicans was lower than that caused by non-albicans species. The severity of illness influenced early mortality, and the origin of the central venous catheter remarkably affected 30-day mortality.


Asunto(s)
Antifúngicos/uso terapéutico , Candida/clasificación , Candida/aislamiento & purificación , Candidemia/epidemiología , Candidemia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Candidemia/tratamiento farmacológico , Candidemia/microbiología , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Centros de Atención Terciaria , Resultado del Tratamiento , Adulto Joven
20.
Cancer ; 121 Suppl 17: 3080-8, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26331814

RESUMEN

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer.


Asunto(s)
Neoplasias Pulmonares/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , China , Manejo de la Enfermedad , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/terapia , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Enfermedad Pulmonar Obstructiva Crónica/terapia , Factores de Riesgo
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