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1.
BMC Infect Dis ; 24(1): 326, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500041

RESUMEN

BACKGROUND: Currently, culture methods are commonly used in clinical tests to detect pathogenic fungi including Candida spp. Nonetheless, these methods are cumbersome and time-consuming, thereby leading to considerable difficulties in diagnosis of pathogenic fungal infections, especially in situations that respiratory samples such as alveolar lavage fluid and pleural fluid contain extremely small amounts of microorganisms. The aim of this study was to elucidate the utility and practicality of microfluidic chip technology in quick detection of respiratory pathogenic fungi. METHODS: DNAs of clinical samples (mainly derived from sputa, alveolar lavage fluid, and pleural fluid) from 64 coastal patients were quickly detected using microfluidic chip technology with 20 species of fungal spectrum and then validated by Real-time qPCR, and their clinical baseline data were analyzed. RESULTS: Microfluidic chip results showed that 36 cases infected with Candida spp. and 27 cases tested negative for fungi, which was consistent with Real-time qPCR validation. In contrast, only 16 cases of fungal infections were detected by the culture method; however, one of the culture-positive samples tested negative by microfluidic chip and qPCR validation. Moreover, we found that the patients with Candida infections had significantly higher rates of platelet count reduction than fungi-negative controls. When compared with the patients infected with C. albicans alone, the proportion of males in the patients co-infected with multiple Candidas significantly increased, while their platelet counts significantly decreased. CONCLUSIONS: These findings suggest that constant temperature amplification-based microfluidic chip technology combined with routine blood tests can increase the detection speed and accuracy (including sensitivity and specificity) of identifying respiratory pathogenic fungi.


Asunto(s)
Micosis , Infecciones del Sistema Respiratorio , Masculino , Humanos , Microfluídica , Hongos/genética , Micosis/diagnóstico , Candida/genética , Candida albicans , Sensibilidad y Especificidad , Infecciones del Sistema Respiratorio/diagnóstico
2.
Medicine (Baltimore) ; 101(9): e27759, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35244034

RESUMEN

ABSTRACT: A global public health crisis caused by the 2019 novel coronavirus disease (COVID-19) leads to considerable morbidity and mortality, which bring great challenge to respiratory medicine. Hydrogen-oxygen therapy contributes to treat severe respiratory diseases and improve lung functions, yet there is no information to support the clinical use of this therapy in the COVID-19 pneumonia.A retrospective study of medical records was carried out in Shishou Hospital of Traditional Chinese Medicine in Hubei, China. COVID-19 patients (aged ≥ 30 years) admitted to the hospital from January 29 to March 20, 2020 were subjected to control group (n = 12) who received routine therapy and case group (n = 12) who received additional hydrogen-oxygen therapy. The clinical characteristics of COVID-19 patients were analyzed. The physiological and biochemical indexes, including immune inflammation indicators, electrolytes, myocardial enzyme profile, and functions of liver and kidney, were examined and investigated before and after hydrogen-oxygen therapy.The results showed significant decreases in the neutrophil percentage and the concentration and abnormal proportion of C-reactive protein in COVID-19 patients received additional hydrogen-oxygen therapy.This novel therapeutic may alleviate clinical symptoms of COVID-19 patients by suppressing inflammation responses.


Asunto(s)
COVID-19/terapia , Hidrógeno/uso terapéutico , Oxígeno/uso terapéutico , Adulto , China/epidemiología , Femenino , Humanos , Inflamación , Masculino , Registros Médicos , Persona de Mediana Edad , Terapia por Inhalación de Oxígeno , Estudios Retrospectivos , SARS-CoV-2 , Resultado del Tratamiento
3.
Elife ; 112022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35258453

RESUMEN

Reproductive synchrony generally occurs in various group-living animals. However, the underlying mechanisms remain largely unexplored. The migratory locust, Locusta migratoria, a worldwide agricultural pest species, displays synchronous maturation and oviposition when forms huge swarm. The reproductive synchrony among group members is critical for the maintenance of locust swarms and population density of next generation. Here, we showed that gregarious female locusts displayed more synchronous sexual maturation and oviposition than solitarious females and olfactory deficiency mutants. Only the presence of gregarious male adults can stimulate sexual maturation synchrony of female adults. Of the volatiles emitted abundantly by gregarious male adults, the aggregation pheromone, 4-vinylanisole, was identified to play key role in inducing female sexual maturation synchrony. This maturation-accelerating effect of 4-vinylanisole disappeared in the females of Or35-/- lines, the mutants of 4-vinylanisole receptor. Interestingly, 4-vinylanisole displayed a time window action by which mainly accelerates oocyte maturation of young females aged at middle developmental stages (3-4 days post adult eclosion). We further revealed that juvenile hormone/vitellogenin pathway mediated female sexual maturation triggered by 4-vinylanisole. Our results highlight a 'catch-up' strategy by which gregarious females synchronize their oocyte maturation and oviposition by time-dependent endocrinal response to 4-vinylanisole, and provide insight into reproductive synchrony induced by olfactory signal released by heterosexual conspecifics in a given group.


Since 2019, a plague of flying insects known as migratory locusts has been causing extensive damage to crops in East Africa. Migratory locusts sometimes live a solitary lifestyle but, if environmental conditions allow, they form large groups containing millions of individuals known as swarms that are responsible for causing locust plagues.Locusts are able to maintain such large swarms because they can aggregate and synchronize. When they live in swarms, individual locusts produce odors that are sensed by other individuals in the group. For example, an aggregation pheromone, called 4-vinylanisole, is known to help keep large groups of locusts together. However, it is less clear how odors synchronize the reproductive cycles of the females in a swarm so that they are ready to mate with males and lay their eggs at the same time. To address this question, Chen et al. examined when female locusts reached sexual maturity after they were exposed to odors produced by other locusts living alone or in groups. The experiments found that only 4-vinylanisole, which was abundantly released by adult male locusts living in groups, stimulated female locusts to reach sexual maturity at the same time. This odor increased the levels of a hormone known as juvenile hormone in less-developed females to help them reach sexual maturity sooner. These findings demonstrate that when migratory locusts are living in swarms, male locusts promote the female locusts to reach sexual maturity at the same time by promoting less-developed females to 'catch up' with other females in the group. A next step will be to investigate the neural and molecular mechanisms underlying the 'catch up' effect induced by 4-vinylanisole.


Asunto(s)
Saltamontes , Locusta migratoria , Animales , Femenino , Locusta migratoria/fisiología , Masculino , Feromonas/metabolismo , Maduración Sexual , Estirenos/metabolismo
4.
Nature ; 584(7822): 584-588, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32788724

RESUMEN

Locust plagues threaten agricultural and environmental safety throughout the world1,2. Aggregation pheromones have a crucial role in the transition of locusts from a solitary form to the devastating gregarious form and the formation of large-scale swarms3,4. However, none of the candidate compounds reported5-7 meet all the criteria for a locust aggregation pheromone. Here, using behavioural assays, electrophysiological recording, olfactory receptor characterization and field experiments, we demonstrate that 4-vinylanisole (4VA) (also known as 4-methoxystyrene) is an aggregation pheromone of the migratory locust (Locusta migratoria). Both gregarious and solitary locusts are strongly attracted to 4VA, regardless of age and sex. Although it is emitted specifically by gregarious locusts, 4VA production can be triggered by aggregation of four to five solitary locusts. It elicits responses specifically from basiconic sensilla on locust antennae. We also identified OR35 as a specific olfactory receptor of 4VA. Knockout of OR35 using CRISPR-Cas9 markedly reduced the electrophysiological responses of the antennae and impaired 4VA behavioural attractiveness. Finally, field trapping experiments verified the attractiveness of 4VA to experimental and wild populations. These findings identify a locust aggregation pheromone and provide insights for the development of novel control strategies for locusts.


Asunto(s)
Locusta migratoria/efectos de los fármacos , Locusta migratoria/fisiología , Feromonas/metabolismo , Feromonas/farmacología , Estirenos/metabolismo , Estirenos/farmacología , Envejecimiento , Migración Animal/efectos de los fármacos , Animales , Ecosistema , Femenino , Control de Insectos , Locusta migratoria/química , Masculino , Densidad de Población , Receptores Odorantes/deficiencia , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Sensilos/fisiología
5.
PLoS Genet ; 16(4): e1008762, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32348297

RESUMEN

Animals often exhibit dramatically behavioral plasticity depending on their internal physiological state, yet little is known about the underlying molecular mechanisms. The migratory locust, Locusta migratoria, provides an excellent model for addressing these questions because of their famous phase polyphenism involving remarkably behavioral plasticity between gregarious and solitarious phases. Here, we report that a major insect hormone, juvenile hormone, is involved in the regulation of this behavioral plasticity related to phase change by influencing the expression levels of olfactory-related genes in the migratory locust. We found that the treatment of juvenile hormone analog, methoprene, can significantly shift the olfactory responses of gregarious nymphs from attraction to repulsion to the volatiles released by gregarious nymphs. In contrast, the repulsion behavior of solitarious nymphs significantly decreased when they were treated with precocene or injected with double-stranded RNA of JHAMT, a juvenile hormone acid O-methyltransferase. Further, JH receptor Met or JH-response gene Kr-h1 knockdown phenocopied the JH-deprivation effects on olfactory behavior. RNA-seq analysis identified 122 differentially expressed genes in antennae after methoprene application on gregarious nymphs. Interestingly, several olfactory-related genes were especially enriched, including takeout (TO) and chemosensory protein (CSP) which have key roles in behavioral phase change of locusts. Furthermore, methoprene application and Met or Kr-h1 knockdown resulted in simultaneous changes of both TO1 and CSP3 expression to reverse pattern, which mediated the transition between repulsion and attraction responses to gregarious volatiles. Our results suggest the regulatory roles of a pleiotropic hormone in locust behavioral plasticity through modulating gene expression in the peripheral olfactory system.


Asunto(s)
Antenas de Artrópodos/metabolismo , Conducta Animal/efectos de los fármacos , Hormonas Juveniles/farmacología , Conducta Social , Transcriptoma/efectos de los fármacos , Animales , Antenas de Artrópodos/efectos de los fármacos , Genes de Insecto , Saltamontes , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Metopreno/farmacología , Metiltransferasas/genética , Metiltransferasas/metabolismo
6.
BMC Biotechnol ; 18(1): 61, 2018 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-30285700

RESUMEN

BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) has been wildly used to generate gene knockout models through inducing indels causing frame-shift. However, there are few studies concerning the post-transcript effects caused by CRISPR-mediated genome editing. RESULTS: In the present study, we showed that gene knockdown model also could be generated using CRISPR-mediated gene editing by disrupting the boundary of exon and intron in mice (C57BL/6 J). CRISPR induced indel at the boundary of exon and intron (5' splice site) caused alternative splicing and produced multiple different mRNAs, most of these mRNAs introduced premature termination codon causing down expression of the gene. CONCLUSIONS: These results showed that alternative splicing mutants were able to generate through CRISPR-mediated genome editing by deleting the boundary of exon and intron causing disruption of 5' splice site. Although alternative splicing was an unexpected outcome, this finding could be developed as a technology to generate gene knockdown models or to investigate pre-mRNA splicing.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Técnicas de Silenciamiento del Gen/métodos , Ratones/genética , Precursores del ARN/genética , Empalme del ARN , Animales , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Exones , Mutación INDEL , Intrones , Ratones Endogámicos C57BL
8.
BMC Biotechnol ; 18(1): 60, 2018 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-30253761

RESUMEN

BACKGROUND: The CRISPR/Cas9 system has been widely used to generate gene knockout/knockin models by inducing frameshift mutants in cell lines and organisms. Several recent studies have reported that such mutants can lead to in-frame exon skipping in cell lines. However, there was little research about post-transcriptional effect of CRISPR-mediated gene editing in vivo. RESULTS: We showed that frameshift indels also induced complete or stochastic exon skipping by deleting different regions to influence pre-mRNA splicing in vivo. In the migratory locust, the missing 55 bp at the boundary of intron 3 and exon 4 of an olfactory receptor gene, LmigOr35, resulted in complete exon 4 skipping, whereas the lacking 22 bp in exon 4 of LmigOr35 only resulted in stochastic exon 4 skipping. A single sgRNA induced small insertions or deletions at the boundary of intron and exon to disrupt the 3' splicing site causing completely exon skipping, or alternatively induce small insertions or deletions in the exon to stochastic alter splicing causing the stochastic exon skipping. CONCLUSIONS: These results indicated that complete or stochastic exon skipping could result from the CRISPR-mediated genome editing by deleting different regions of the gene. Although exon skipping caused by CRISPR-mediated editing was an unexpected outcome, this finding could be developed as a technology to investigate pre-mRNA splicing or to cure several human diseases caused by splicing mutations.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica/métodos , Saltamontes/genética , Empalme del ARN , Migración Animal , Animales , Exones , Mutación del Sistema de Lectura , Saltamontes/fisiología , Mutación INDEL , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Eliminación de Secuencia
9.
Artículo en Inglés | MEDLINE | ID: mdl-29661084

RESUMEN

OBJECTIVE: To identify common practices of noninvasive ventilation (NIV) use among ALS specialists and how they follow respiratory status in their patients. METHODS: A 25-item questionnaire on NIV indications/initiation was sent via SurveyMonkey® to ALS specialists identified through membership in NEALS (114 sites in the US) and ENCALS (39 sites in Europe). Descriptive statistics and Cochran-Mantel-Haenszel test for general association were performed. RESULTS: In their initial evaluation, US and European specialists (n = 186) use upright forced vital capacity (FVC) most (92.8% vs 91.1%; p = 0.752). Upright FVC results are most important for US respondents when deciding to prescribe NIV; European respondents consider symptoms of orthopnea and/or dyspnea as most important. European respondents use overnight pulse oximetry (69.8% vs 7.9%; p < 0.001) and arterial blood gas analyses (62.8% vs 3.2%; p < 0.001) more than US respondents. Insurance regulations/national health care coverage impact NIV initiation more in the US than in Europe (70.0% vs 47.5%; p = 0.025). When asked if insurance/other financial constraints affects when they prescribe NIV, more US respondents answered positively (77.2% vs 15.4%; p < 0.001). In patients with no respiratory symptoms, most US specialists (68.3%) initiated NIV at VC <50% predicted; European responses showed greater variability. CONCLUSIONS: Given the impact of NIV on respiratory function and the importance of respiratory function to quality of life and survival, understanding differences that influence NIV prescribing is critical. This information may inform future study design and identify areas warranting additional research to develop best practices for NIV implementation.


Asunto(s)
Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/diagnóstico , Ventilación no Invasiva/métodos , Insuficiencia Respiratoria/etiología , Esclerosis Amiotrófica Lateral/psicología , Análisis de los Gases de la Sangre , Europa (Continente) , Femenino , Encuestas Epidemiológicas , Humanos , Cooperación Internacional , Masculino , Oximetría , Calidad de Vida , Factores de Tiempo , Estados Unidos
10.
Methods Mol Biol ; 1572: 467-488, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28299706

RESUMEN

Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.


Asunto(s)
Inmunoensayo/instrumentación , Inmunoensayo/métodos , Técnicas Analíticas Microfluídicas/instrumentación , Microfluídica/instrumentación , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Técnicas de Amplificación de Ácido Nucleico/métodos , Diseño de Equipo , Dispositivos Laboratorio en un Chip , Técnicas de Diagnóstico Molecular/instrumentación , Técnicas de Diagnóstico Molecular/métodos
11.
Insect Biochem Mol Biol ; 79: 27-35, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27744049

RESUMEN

Locusts are important agricultural pests worldwide and regarded as study models for entomology. However, the absence of targeted gene manipulation systems for locusts has restricted their applications for research. Herein, we report the successful use of the CRISPR/Cas9 system to induce a targeted heritable mutagenesis of the migratory locust, Locusta migratoria. The target sequence of gRNA was designed to disrupt the gene encoding the odorant receptor co-receptor (Orco) and examine the roles of the odorant receptor pathway in the locust. Microinjection of the mixture of Cas9-mRNA and Orco-gRNA into the locust eggs resulted in efficient target-gene editing at a rate of 71.7% in G0 animals and achieved a germline efficiency of up to 88.1% in G1 animals. By a crossing strategy, we successfully established stable Orco mutant lines. EAGs and SSRs indicated that the fourth-instar nymphs of the Orco mutants showed severely impaired electrophysiological responses to multiple odors. The Orco mutant locusts lost an attraction response to aggregation pheromones under the crowding conditions. The locomotor activity and body coloration of the Orco mutant locusts did not significantly differ from those of the two other genotypes. This study provides an easy and effective approach by using the CRISPR/Cas9 system for generating loss-of-function mutants for functional genetic studies of locusts and for managing insect pests.


Asunto(s)
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Locusta migratoria/fisiología , Percepción Olfatoria/genética , Receptores Odorantes/genética , Olfato/genética , Animales , Secuencia de Bases , Locusta migratoria/genética , Mutagénesis , Receptores Odorantes/metabolismo
12.
Insect Sci ; 23(5): 728-38, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25783997

RESUMEN

The Asian larch bark beetle, Ips subelongatus, is considered to be the major pest of larch within its natural range. We investigated the electrophysiological and behavioral characteristics as well as mitochondrial DNA cytochrome oxidase subunit I sequences of I. subelongatus from 13 geographic populations throughout northeastern China in order to explore population divergence of aggregation pheromone responses and the extent of potential genetic divergence. Electrophysiological analyses showed that antennae of I. subelongatus from all the six tested populations responded strongly to (S)-(-)-ipsenol (100% detection; 0.35-0.73 mV) in gas chromatography (GC)-electroantennographic detection (EAD) analyses, while its antipode, (R)-(+)-ipsenol was antennally inactive. I. subelongatus populations varied in their responses to (R)-(-)- and (S)-(+)-ipsdienol in GC-EAD analyses. Behavioral bioassays demonstrated that (S)-(-)-ipsenol alone was significantly attractive at all the tested sites, supporting its status as a key pheromone component of I. subelongatus, whereas (S)-(+)-ipsdienol was inactive alone. Adding (S)-(+)-ipsdienol to (S)-(-)-ipsenol did not have any effect on the trap catches from some populations in Inner Mongolia. However, (S)-(+)-ipsdienol showed a strong synergistic effect on (S)-(-)-ipsenol from several populations in Jilin and Liaoning Provinces, and a weak synergistic effect from some transition populations in Heilongjiang Province. Furthermore, 27 mitochondrial haplotypes were found among the 13 populations (intraspecific nucleotide divergence, 0.1%-1.1%). Analyses of molecular variance and haplotype networks indicated that different geographic populations have developed some genetic variation but did not form completely independent groups. From an applied point of view, a universal synthetic binary blend of racemic ipsenol and (S)-(+)-ipsdienol might have a potential for monitoring or even mass-trapping of I. subelongatus across northeastern China, even though some populations only use (S)-(-)-ipsenol alone as their active pheromone component.


Asunto(s)
Alcoholes/farmacología , Monoterpenos/farmacología , Octanoles/farmacología , Feromonas/farmacología , Gorgojos/genética , Monoterpenos Acíclicos , Animales , Antenas de Artrópodos/efectos de los fármacos , Conducta Animal/efectos de los fármacos , China , ADN Mitocondrial/genética , Femenino , Masculino , Feromonas/genética , Gorgojos/efectos de los fármacos
13.
Cell Mol Life Sci ; 72(22): 4429-43, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26265180

RESUMEN

Locusts represent the excellent model of insect olfaction because the animals are equipped with an unusual olfactory system and display remarkable density-dependent olfactory plasticity. However, information regarding receptor molecules involved in the olfactory perception of locusts is very limited. On the basis of genome sequence and antennal transcriptome of the migratory locust, we conduct the identification and functional analysis of two olfactory receptor families: odorant receptors (ORs) and ionotropic receptors (IRs). In the migratory locust, there is an expansion of OR family (142 ORs) while distinctly lower number of IR genes (32 IRs) compared to the repertoires of other insects. The number of the locust OR genes is much less than that of glomeruli in antennal lobe, challenging the general principle of the "one glomerulus-one receptor" observed in other insects. Most OR genes are found in tandem arrays, forming two large lineage-specific subfamilies in the phylogenetic tree. The "divergent IR" subfamily displays a significant contraction, and most of the IRs belong to the "antennal IR" subfamily in the locust. Most ORs/IRs have olfactory-specific expression while some broadly- or internal-expressed members are also found. Differing from holometabolous insects, the migratory locust contains very similar expression profiles of ORs/IRs between nymph and adult stages. RNA interference and behavioral assays indicate that an OR-based signaling pathway, not IR-based, mediates the attraction of locusts to aggregation pheromones. These discoveries provide insights into the unusual olfactory system of locusts and enhance our understanding of the evolution of insect olfaction.


Asunto(s)
Proteínas de Insectos/genética , Locusta migratoria/genética , Bulbo Olfatorio/metabolismo , Receptores Odorantes/genética , Secuencia de Aminoácidos , Animales , Antenas de Artrópodos/metabolismo , Antenas de Artrópodos/fisiología , Femenino , Perfilación de la Expresión Génica , Proteínas de Insectos/clasificación , Proteínas de Insectos/fisiología , Locusta migratoria/fisiología , Masculino , Datos de Secuencia Molecular , Familia de Multigenes/genética , Bulbo Olfatorio/fisiología , Filogenia , Isoformas de Proteínas/clasificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Receptores Ionotrópicos de Glutamato/genética , Receptores Ionotrópicos de Glutamato/fisiología , Receptores Odorantes/clasificación , Receptores Odorantes/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Olfato/genética , Olfato/fisiología , Transcriptoma/genética
14.
Oncologist ; 18(3): 273-80, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23485622

RESUMEN

BACKGROUND: Hypertension is associated with antivascular endothelial growth factor treatment, but the clinical implications of hypertension are uncertain. To assess the prognostic and predictive value of bevacizumab-related hypertension, a comprehensive analysis of whether hypertension and efficacy outcomes are associated was conducted on seven company-sponsored placebo-controlled phase III studies of bevacizumab. METHODS: Patient-specific data were available from 6,486 patients with metastatic colorectal, breast, non-small cell lung, pancreatic, and renal cell cancers. Primary hypertension endpoint was a blood pressure (BP) increase of >20 mmHg systolic or >10 mmHg diastolic within the first 60 days of treatment. Additional endpoints included other predefined thresholds of change in BP and severity of hypertension graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events. To analyze the general prognostic importance of an early BP increase, multivariate Cox regression models were used to assess the correlation between BP changes and progression-free (PFS) and overall survival (OS) outcomes in the control groups. To analyze whether early BP increases could predict for benefit from bevacizumab, similar analyses were conducted in the bevacizumab-treated and control groups. RESULTS: In six of seven studies, early BP increase was neither predictive of clinical benefit from bevacizumab nor prognostic for the course of the disease. For study AVF2107g, early increased BP was associated with longer PFS and OS times in the bevacizumab group but shorter OS time in the control group. CONCLUSIONS: Early treatment-related BP increases do not predict clinical benefit from bevacizumab based on PFS or OS outcomes. BP increases do not appear to have general prognostic importance for patients with advanced cancer.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Hipertensión/inducido químicamente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Supervivencia sin Enfermedad , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos
15.
Ups J Med Sci ; 118(1): 9-15, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23039019

RESUMEN

BACKGROUND: The risk factors for No. 12p and No. 12b lymph node (LN) metastases in advanced gastric cancer (GC) remain controversial. The aim of this study was to investigate the risk factors for No. 12p and No. 12b LN metastases in advanced GC. METHODS: From January 1999 to December 2005, a retrospective analysis of 163 patients with advanced GC who underwent D2 lymphadenectomy in addition to No. 12p and No. 12b LN dissections was conducted. Potential clinicopathological factors that could influence No. 12p and No. 12b LN metastases were statistically analyzed. RESULTS: There were 15 cases (9.2%) with No. 12p LN metastases and 5 cases (3.1%) with synchronous No. 12b LN metastases. A logistic regression analysis revealed that the Borrmann type (III/IV versus I/II, P = 0.029), localization (lesser/circular versus greater, P = 0.025), and depth of invasion (pT4 versus pT2/pT3, P = 0.009) were associated with 11.1-, 3.8-, and 5.6-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. A logistic regression analysis also showed that No. 5 (P = 0.006) and No. 12a (P = 0.004) LN metastases were associated with 6.9- and 11.3-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. In addition, significant differences in 5-year survival of patients with and without No. 12p and No. 12b LN metastases were observed (13.3% versus 35.1%, P = 0.022). CONCLUSION: We conclude that Borrmann type, localization, and depth of invasion are significant variables for identifying patients with No. 12p and No. 12b LN metastases. Individuals with No. 5 or No. 12a LN metastases should be on high alert for the possibility of additional metastases to the No. 12p and No. 12b LNs.


Asunto(s)
Neoplasias Gástricas/patología , Adulto , Anciano , China , Femenino , Humanos , Modelos Logísticos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Factores de Riesgo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Tasa de Supervivencia
16.
Clin Cancer Res ; 19(4): 929-37, 2013 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-23169435

RESUMEN

PURPOSE: We evaluated the prognostic and predictive use of circulating VEGF-A levels in phase III trials of bevacizumab in colorectal cancer, lung cancer, and renal cell carcinoma. METHODS: Baseline plasma samples from 1,816 patients were analyzed for VEGF-A using an ELISA, which recognizes the major isoforms with equivalent sensitivity. HR and 95% confidence intervals (CI) for study end points were estimated using Cox regression analysis. A subset of matched archival tumor samples was analyzed for VEGF-A expression using in situ hybridization. RESULTS: Higher VEGF-A levels showed trends toward adverse prognostic significance in the control arms of multiple trials, reaching statistical significance for overall survival (OS) in AVF2107 (highest vs. lowest 50%: HR = 1.76; 95% CI, 1.28-2.41), AVAiL (HR = 1.52; 95% CI, 1.16-2.00), and AVOREN (HR = 1.67; 95% CI, 1.18-2.36). In predictive analyses, the HRs for progression-free survival were similar across low and high VEGF-A subgroups and favored bevacizumab-containing treatment. In the low VEGF-A subgroups, HRs (95% CIs) were 0.61 (0.43-0.87) in AVF2107, 0.71 (0.43-1.16) in E4599, 0.74 (0.59-0.94) in AVAiL (low-dose), 0.89 (0.70-1.13) in AVAiL (high-dose), and 0.56 (0.40-0.78) in AVOREN. Analyses of OS data have shown similar results. No correlation between primary tumor VEGF-A expression and plasma VEGF-A levels was observed. CONCLUSIONS: In this comprehensive evaluation, pretreatment total circulating VEGF-A was prognostic for outcome in metastatic colorectal, lung, and renal cell cancers, but it was not predictive for bevacizumab-based treatment benefit.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Biomarcadores de Tumor/sangre , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab , Carcinoma de Células Renales/sangre , Ensayos Clínicos Fase III como Asunto , Neoplasias Colorrectales/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
17.
Clin Anat ; 26(4): 476-85, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22411712

RESUMEN

The complexity of liver reconstruction has limited partial right lobe living donor liver transplantation. It is largely due to the difficulty of dealing with the middle hepatic vein. We sought to define the anatomic features of hepatic veins. Forty-one fresh adult livers, 43 formalin-fixed adult cadaver livers, and 91 adult liver corrosion casts were used for the study. We determined the number of branches, the maximum diameter, the whole length, the extrahepatic length of the hepatic veins, and the deviation of the middle hepatic vein from the main portal fissure. Nakamura and Tsuzuki's classification of hepatic vein types was used. Type A, B, and C accounted for 59.4, 27.8, and 12.8% of all specimens in this study, respectively. The middle and left hepatic veins formed a common trunk in 60.3% of the specimens, and the length of the common trunk was 1.12 ± 0.62 cm. The degree of deviation to the right of the middle hepatic vein from the main portal fissure was 14.11° ± 12.65°. The frequency of hepatic vein types and the degree of deviation to the right of the middle hepatic vein in this study is markedly different from that reported in other literature. The anatomic features of the hepatic veins in this study suggest that right lobe living donor liver transplantation is more suitable for Chinese.


Asunto(s)
Venas Hepáticas/anatomía & histología , Trasplante de Hígado , Hígado/irrigación sanguínea , Donadores Vivos , Adulto , Pueblo Asiatico , Cadáver , Hepatectomía , Humanos , Hígado/cirugía
18.
Kaohsiung J Med Sci ; 28(2): 115-9, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22313540

RESUMEN

Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.


Asunto(s)
Carcinoma de Células Pequeñas/diagnóstico , Epiplón/patología , Carcinoma de Células Pequeñas/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Ultrasonografía
19.
Hepatogastroenterology ; 59(117): 1366-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22115803

RESUMEN

BACKGROUND/AIMS: To investigate the effectiveness and safety of vascular exclusion by preserving tumor-contralateral branch of hepatic artery in hepatectomy in treatment liver cancer with cirrhosis. METHODOLOGY: The clinical data of 10 cases treated with hepatectomy for liver cancer were analyzed retrospectively. Vascular exclusion by preserving tumor-contralateral branch of hepatic artery was applied to control bleeding. Blood loss, operative time and postoperative hepatic function were observed. RESULTS: The average blood loss was 515mL, the operative time was 191 minutes and the mean time of exclusion was 30.20 minutes. There is no significant difference between hepatic function (serum total bilirubin, alanine transaminase) of postoperative day 7 and that of pre-operation. CONCLUSIONS: Vascular exclusion by preserving tumor-contralateral branch of hepatic artery could effectively control bleeding and preserve hepatic function and is proved to be applicable to patients of liver cancer with cirrhosis.


Asunto(s)
Pérdida de Sangre Quirúrgica , Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Hígado/irrigación sanguínea , Adulto , Anciano , Volumen Sanguíneo , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/complicaciones , Femenino , Arteria Hepática , Humanos , Hígado/fisiopatología , Hígado/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
20.
Sens Actuators B Chem ; 160(1): 1529-1535, 2011 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-22125359

RESUMEN

A portable, small footprint, light, general purpose analyzer (processor) to control the flow in immunoassay cassettes and to facilitate the detection of test results is described. The durable analyzer accepts disposable cassettes that contain pouches and reaction chambers for various unit operations such as hydration of dry reagents, stirring, and incubation. The analyzer includes individually controlled, linear actuators to compress the pouches in the cassette, which facilitates the pumping and mixing of sample and reagents, and to close diaphragm-based valves for flow control. The same types of actuators are used to compress pouches and actuate valves. The analyzer also houses a compact OEM scanner/reader to excite fluorescence and detect emission from labels. The analyzer is hydraulically isolated from the cassette, reducing the possibility of cross-contamination. The analyzer facilitates programmable, automated execution of a sequence of operations such as pumping and valving in a timely fashion, reducing the level of expertise required from the operator and the possibility for errors. The analyzer's design is modular and expandable to accommodate cassettes of various complexities and additional functionalities. In this paper, the utility of the analyzer has been demonstrated with the execution of a simple, consecutive, lateral flow assay of a model biological system and the test results were detected with up converting phosphor labels that are excited at infrared frequencies and emit in the visible spectrum.

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