Gentiopicroside injection promotes the healing of pressure injury wounds by upregulating the expression of bFGFR1.

OBJECTIVE: To observe the therapeutic effect of gentiopicroside, as the main component of Gentianaceae, on wounds in pressure injury (PI) model rats and explore its mechanism. METHOD: Male Sprague Dawley rats were randomly divided into control group, model group and gentiopicroside groups (50, 100 and 200 mg·kg-1·d-1 for 9 consecutive days). The mice's skeletal muscle fibroblast line NOR-10 cells were collected after being treated with gentiopicroside (0.2~5.0 M) and basic fibroblast growth factor receptor 1 (bFGFR1) inhibitor (5.0 M SU5402) for 7 days. RESULTS: Compared to the model group, the gentiopicroside groups showed significantly increased wound healing rates, reduced inflammatory cells in the wound tissues, and significantly increased expression levels of proliferating cell nuclear antigen (PCNA) and bFGFR1, accompanied by increased proliferation of new myofibroblasts. Gentiopicroside upregulated the mRNA expression of bFGFR1 and PCNA in NOR-10 cells in a dose-dependent manner; however, SU5402 reversed the effect of gentiopicroside. CONCLUSION: Gentiopicroside may promote myofibroblast proliferation by upregulating the expression of bFGFR1 and PCNA and ultimately accelerating the healing of PI wounds.

Gentiopicroside injection promotes the healing of pressure injury wounds by upregulating the expression of bFGFR1 / A injeção de gentiopicrosídeo promove a cicatrização de feridas de lesão por pressão pela suprarregulação da expressão de bFGFR1 / La inyección de gentiopicrósido promueve la cicatrización de heridas de lesión por presión al aumentar la expresión de bFGFR1

ABSTRACT Objective: To observe the therapeutic effect of gentiopicroside, as the main component of Gentianaceae, on wounds in pressure injury (PI) model rats and explore its mechanism. Method: Male Sprague Dawley rats were randomly divided into control group, model group and gentiopicroside groups (50, 100 and 200 mg·kg-1·d-1 for 9 consecutive days). The mice's skeletal muscle fibroblast line NOR-10 cells were collected after being treated with gentiopicroside (0.2~5.0 M) and basic fibroblast growth factor receptor 1 (bFGFR1) inhibitor (5.0 M SU5402) for 7 days. Results: Compared to the model group, the gentiopicroside groups showed significantly increased wound healing rates, reduced inflammatory cells in the wound tissues, and significantly increased expression levels of proliferating cell nuclear antigen (PCNA) and bFGFR1, accompanied by increased proliferation of new myofibroblasts. Gentiopicroside upregulated the mRNA expression of bFGFR1 and PCNA in NOR-10 cells in a dose-dependent manner; however, SU5402 reversed the effect of gentiopicroside. Conclusion: Gentiopicroside may promote myofibroblast proliferation by upregulating the expression of bFGFR1 and PCNA and ultimately accelerating the healing of PI wounds.

RESUMO Objetivo: Observar o efeito terapêutico do gentiopicrosídeo como principal componente das Gentianáceas em feridas de lesão por pressão (LP) em modelos de ratos e explorar seu mecanismo. Métodos: Ratos Sprague Dawley machos foram divididos aleatoriamente em grupo controle, grupo modelo e grupos gentiopicrosídeo (50, 100 e 200 mg·kg-1·d-1 por 9 dias consecutivos). As células NOR-10 da linha de fibroblastos do músculo esquelético de camundongos foram coletadas após serem tratadas com gentiopicrosídeo (0,2~5,0 μM) e inibidor do receptor 1 do fator de crescimento fibroblástico básico (bFGFR1) (5.0 μM SU5402) por 7 dias. Resultados: Em comparação com o grupo modelo, os grupos gentiopicrosídeo apresentaram taxas de cicatrização de feridas significativamente maiores, menos células inflamatórias nos tecidos da ferida e níveis de expressão de antígeno nuclear de proliferação celular (PCNA) e bFGFR1 significativamente maiores, acompanhados por aumento da proliferação de novos miofibroblastos. O gentiopicrosídeo regulou positivamente a expressão de mRNA de bFGFR1 e PCNA em células NOR-10 de maneira dependente da dose, enquanto o SU5402 reverteu o efeito do gentiopicrosídeo. Conclusão: O gentiopicrosídeo pode promover a proliferação de miofibroblastos, suprarregulando a expressão de bFGFR1 e PCNA e, em última análise, acelerando a cicatrização de feridas de LP.

RESUMEN Objetivo: Observar el efecto terapéutico del gentiopicrósido como componente principal de la Gentianaceae en heridas por lesión por presión (LP) en modelos de ratas y explorar su mecanismo. Método: Se dividieron aleatoriamente ratas macho Sprague Dawley en grupo control, grupo modelo y grupos gentiopicrósido (50, 100 y 200 mg·kg-1·d-1 durante 9 días consecutivos). Se recogieron células NOR-10 de la línea de fibroblastos de músculo esquelético de ratón después de ser tratadas con gentiopicrósido (0.2~5.0 μM) y un inhibidor del receptor 1 del factor de crecimiento de fibroblastos básico (bFGFR1) (5.0 μM SU5402) durante 7 días. Resultados: En comparación con el grupo modelo, los grupos de gentiopicrósido mostraron tasas de curación de heridas significativamente más altas, menos células inflamatorias en los tejidos de la herida y niveles de expresión significativamente mayores del antígeno nuclear de proliferación celular (PCNA) y bFGFR1, acompañados de una mayor proliferación de nuevos miofibroblastos. El gentiopicrósido podría regular positivamente la expresión de ARNm de bFGFR1 y PCNA en células NOR-10 de manera dependiente de la dosis, sin embargo, SU5402 revirtió el efecto del gentiopicrósido. Conclusión: El gentiopicrósido puede promover la proliferación de miofibroblastos al aumentar la expresión de bFGFR1 y PCNA y, en última instancia, acelerar la cicatrización de las heridas de LP.

Characteristic of decreased bacterial diversity in psoriasis / [Característica da diminuição da diversidade bacteriana na psoríase]

Disturbance of commensal intestinal microbiota is related to chronic inflammatory dermatosis. We analyzed the diversity of the gut microbiota to characterize the biological variation of psoriasis (Ps). Significant differences of gut microbiome profiles were revealed in murine model with psoriasis by sequencing 16S rRNA V3-V4 variable region. Group comparisons included the imiquimod cream (IMQ group, n=8), the imiquimod cream and antibiotics (ATB) (PC+IMQ group, n=8) and the healthy control (CTRL group, n=8). The gut microbiota existed in Ps groups including IMQ group and PC+IMQ group encompassed less diversity than controls, which were attributed to decreased presence of several taxa. The two Ps groups were characterized by significant reduction in firmicutes. In this study, microbiota of psoriasis was defined by an increase presence of Bacteroides. After treated with ATB, we found substantial increase of Lactobacillales but significant decrease of Clostridiales and Coriobacteriales. Relative lower abundance of multiple intestinal bacteria was observed in Ps groups. Although part of genera were concomitantly reduced in both IMQ and PC+IMQ conditions, we discovered the specialty of PC+IMQ group samples was that contained lower abundance of beneficial taxa. Characteristics of gut microbiota profiles in Ps mice were comparable to profiles in patients with Ps, which were related to alteration of specific inflammatory proteins in disease groups but were significantly different from control group. Thus, this study emphasizes the role of intestinal microbiota in the pathogenesis of Ps and provides new insight for investigating association between intestinal microbes and immune inflammation.

A perturbação da microbiota intestinal comensal está relacionada à dermatose inflamatória crônica. Analisamos a diversidade da microbiota intestinal para caracterizar a variação biológica da psoríase (Ps). Diferenças significativas do perfil microbiológico intestinal foram reveladas no modelo murino com psoríase pelo sequenciamento da região variável 16S rRNA V3-V4. As comparações de grupo incluíram o creme imiquimod (grupo IMQ, n=8), o creme imiquimod e antibióticos (ATB) (grupo PC+IMQ, n=8) e o controle saudável (grupo CTRL, n=8). A microbiota intestinal existia nos grupos Ps, incluindo o grupo IMQ e o grupo PC+IMQ englobava menos diversidade do que os controles, que foram atribuídos à diminuição da presença de vários taxa. Os dois grupos de Ps caracterizavam-se por uma redução significativa nos firicutes. Neste estudo, a microbiota da psoríase foi definida por um aumento da presença de bacteroides. Após o tratamento com ATB, encontramos um aumento substancial de Lactobacillales mas uma diminuição significativa de Clostridiales e Coriobacteriales. Uma menor abundância relativa de bactérias intestinais múltiplas foi observada nos grupos de Ps. Embora parte dos gêneros tenha sido concomitantemente reduzida tanto em condições IMQ como PC+IMQ, descobrimos que a especialidade das amostras do grupo PC+IMQ era que continham menor abundância de taxas benéficas. As características dos perfis de microbiota intestinal em ratos de Ps eram comparáveis aos perfis em pacientes com Ps, que estavam relacionados à alteração de proteínas inflamatórias específicas em grupos de doenças, mas eram significativamente diferentes do grupo controle. Assim, este estudo enfatiza o papel da microbiota intestinal na patogênese do Ps e fornece novos conhecimentos para investigar a associação entre micróbios intestinais e inflamação imunológica.

Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins.

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants with, or at Risk of, Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To investigate the efficacy and safety of sildenafil added to inhaled nitric oxide (iNO) for newborn infants with persistent pulmonary hypertension of newborn (PPHN) or hypoxic respiratory failure (HRF) at risk of PPHN. STUDY DESIGN: Part A of a multinational, randomized, double-blind, placebo-controlled trial. Infants ≤96 hours' old, >34 weeks of gestation, receiving iNO (10-20 ppm on ≥50% FiO2) for PPHN or HRF at risk of PPHN, and oxygen index >15 to <60, were randomized (1:1) to intravenous (IV) sildenafil (loading: 0.1 mg/kg, over 30 minutes; maintenance: 0.03 mg/kg/h) or placebo, for up to 14 days. Coprimary end points were treatment failure rate (day 14/discharge) and time on iNO without treatment failure. Secondary end points included time on ventilation and oxygenation measures. RESULTS: Of 87 infants screened, 29 were randomized to IV sildenafil and 30 to placebo; 13 discontinued treatment (sildenafil, n = 6; placebo: n = 7), including 3 deaths (sildenafil: n = 2; placebo: n = 1). Treatment failure rates did not differ with sildenafil (27.6%) vs placebo (20.0%; P = .4935). Mean time on iNO was not different with sildenafil (4.1 days) vs placebo (4.1 days; P = .9850). No differences were noted in secondary end points. Most common adverse events (AEs) with sildenafil (≥10% infants) were hypotension (n = 8/29), hypokalemia (n = 7/29), anemia, drug withdrawal syndrome (n = 4/29, each), and bradycardia (n = 3/29). One serious AE (hypotension) was considered treatment-related. CONCLUSIONS: IV sildenafil added to iNO was not superior to placebo in infants with PPHN or HRF at risk of PPHN. A review of AEs did not identify any pattern of events indicative of a safety concern with IV sildenafil. Infants will have developmental follow-up (Part B). TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01720524.

Nicotine promotes the development of oral leukoplakia via regulating peroxiredoxin 1 and its binding proteins

Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.

Volatile Compounds of Different Fresh Wet Noodle Cultivars Evaluated by Headspace Solid-Phase Microextraction-Gas Chromatography-Mass Spectrometry.

This study was carried out to determine the volatile compounds from four samples of fresh wet noodles and the changes in the volatile compound composition during the storage process. The volatile compounds from four samples of fresh wet noodles were characterized by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS). The compositions of the volatile compounds varied among fresh and cooked wet noodles made from the raw potato/wheat flour or wheat flour. A total of 194 volatile compounds were detected in the raw potato noodles, main volatiles including aldehydes, alcohols, ketones, esters and organic acids. The total volatile compounds in the potato/wheat flour noodle samples contained mainly aldehyde compounds and were greater than those in the wheat noodles. The total volatile compounds in the cooked noodle samples were greater than those in raw noodle samples. Alcohols and ketones were the least common types of volatile substances in the samples at 0 h. During storage time, alcohols and ketones were increased in volatile substances, and the amount of acids increased dramatically. The results indicated that the aroma of fresh wet noodles was affected by the storage process.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC)

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.(AU)

Role of Adiponectin in prostate cancer

ABSTRACT Obesity is defined as a chronic and excessive growth of adipose tissue. It has been associated with a high risk for development and progression of obesity-associated malignancies, while adipokines may mediate this association. Adiponectin is an adipose tissue-derived adipokines, with significant anti-diabetic, anti-inflammatory, anti-atherosclerotic and anti-proliferative properties. Plasma adiponectin levels are decreased in obese individuals, and this feature is closely correlated with development of several metabolic, immunological and neoplastic diseases. Recent studies have shown that prostate cancer patients have lower serum adiponectin levels and decreased expression of adiponectin receptors in tumor tissues, which suggests plasma adiponectin level is a risk factor for prostate cancer. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. In this review, we focus on the potential role of adiponectin and the underlying mechanism of adiponectin in the development and progression of prostate cancer. Exploring the signaling pathways linking adiponectin with tumorigenesis might provide a potential target for therapy.

CBS promoter hypermethylation increases the risk of hypertension and stroke.

OBJECTIVES: Cystathionine ß-synthase is a major enzyme in the metabolism of plasma homocysteine. Hyperhomocysteinemia is positively associated with hypertension and stroke. The present study was performed to examine the possible effects of Cystathionine ß-synthase promoter methylation on the development of hypertension and stroke. METHODS: Using quantitative methylation-specific PCR, we determined the Cystathionine ß-synthase methylation levels in 218 healthy individuals and 132 and 243 age- and gender-matched stroke and hypertensive patients, respectively. The relative changes in Cystathionine ß-synthase promoter methylation were analyzed using the 2-ΔΔCt method. The percent of the methylated reference of Cystathionine ß-synthase was used to represent the Cystathionine ß-synthase promoter methylation levels. RESULTS: In this study, the Cystathionine ß-synthase promoter methylation levels of hypertensive and stroke participants were both higher than that of the healthy individuals (median percentages of the methylated reference were 50.61%, 38.05% and 30.53%, respectively, all p<0.001). Multivariable analysis showed that Cystathionine ß-synthase promoter hypermethylation increased the risk of hypertension [odds ratio, OR (95% confidence interval, CI)=1.035 (1.025-1.045)] and stroke [OR (95% CI)=1.015 (1.003-1.028)]. The area under the curve of Cystathionine ß-synthase promoter methylation was 0.844 (95% CI: 0.796-0.892) in male patients with hypertension and 0.722 (95% CI: 0.653-0.799) in male patients with stroke. CONCLUSION: Cystathionine ß-synthase promoter hypermethylation increases the risk of hypertension and stroke, especially in male patients.

Role of Adiponectin in prostate cancer.

Obesity is defined as a chronic and excessive growth of adipose tissue. It has been associated with a high risk for development and progression of obesity-associated malignancies, while adipokines may mediate this association. Adiponectin is an adipose tissue-derived adipokines, with significant anti-diabetic, anti-inflammatory, anti-atherosclerotic and anti-proliferative properties. Plasma adiponectin levels are decreased in obese individuals, and this feature is closely correlated with development of several metabolic, immunological and neoplastic diseases. Recent studies have shown that prostate cancer patients have lower serum adiponectin levels and decreased expression of adiponectin receptors in tumor tissues, which suggests plasma adiponectin level is a risk factor for prostate cancer. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. In this review, we focus on the potential role of adiponectin and the underlying mechanism of adiponectin in the development and progression of prostate cancer. Exploring the signaling pathways linking adiponectin with tumorigenesis might provide a potential target for therapy.

CBS promoter hypermethylation increases the risk of hypertension and stroke

OBJECTIVES: Cystathionine β-synthase is a major enzyme in the metabolism of plasma homocysteine. Hyperhomocysteinemia is positively associated with hypertension and stroke. The present study was performed to examine the possible effects of Cystathionine β-synthase promoter methylation on the development of hypertension and stroke. METHODS: Using quantitative methylation-specific PCR, we determined the Cystathionine β-synthase methylation levels in 218 healthy individuals and 132 and 243 age- and gender-matched stroke and hypertensive patients, respectively. The relative changes in Cystathionine β-synthase promoter methylation were analyzed using the 2-ΔΔCt method. The percent of the methylated reference of Cystathionine β-synthase was used to represent the Cystathionine β-synthase promoter methylation levels. RESULTS: In this study, the Cystathionine β-synthase promoter methylation levels of hypertensive and stroke participants were both higher than that of the healthy individuals (median percentages of the methylated reference were 50.61%, 38.05% and 30.53%, respectively, all p<0.001). Multivariable analysis showed that Cystathionine β-synthase promoter hypermethylation increased the risk of hypertension [odds ratio, OR (95% confidence interval, CI)=1.035 (1.025-1.045)] and stroke [OR (95% CI)=1.015 (1.003-1.028)]. The area under the curve of Cystathionine β-synthase promoter methylation was 0.844 (95% CI: 0.796-0.892) in male patients with hypertension and 0.722 (95% CI: 0.653-0.799) in male patients with stroke. CONCLUSION: Cystathionine β-synthase promoter hypermethylation increases the risk of hypertension and stroke, especially in male patients.

Audiological Assessment of Word Recognition Skills in Persons With Aphasia.

PURPOSE: The purpose of this study was to evaluate the ability of persons with aphasia, with and without hearing loss, to complete a commonly used open-set word recognition test that requires a verbal response. Furthermore, phonotactic probabilities and neighborhood densities of word recognition errors were assessed to explore potential underlying linguistic complexities that might differentially influence performance among groups. METHOD: Four groups of adult participants were tested: participants with no brain injury with normal hearing, participants with no brain injury with hearing loss, participants with brain injury with aphasia and normal hearing, and participants with brain injury with aphasia and hearing loss. The Northwestern University Auditory Test No. 6 (NU-6; Tillman & Carhart, 1966) was administered. Those participants who were unable to respond orally (repeating words as heard) were assessed with the Picture Identification Task (Wilson & Antablin, 1980), permitting a picture-pointing response instead. Error patterns from the NU-6 were assessed to determine whether phonotactic probability influenced performance. RESULTS: All participants with no brain injury and 72.7% of the participants with aphasia (24 out of 33) completed the NU-6. Furthermore, all participants who were unable to complete the NU-6 were able to complete the Picture Identification Task. There were significant group differences on NU-6 performance. The 2 groups with normal hearing had significantly higher scores than the 2 groups with hearing loss, but the 2 groups with normal hearing and the 2 groups with hearing loss did not differ from one another, implying that their performance was largely determined by hearing loss rather than by brain injury or aphasia. The neighborhood density, but not phonotactic probabilities, of the participants' errors differed across groups with and without aphasia. CONCLUSIONS: Because the vast majority of the participants with aphasia examined could be tested readily using an instrument such as the NU-6, clinicians should not be reticent to use this test if patients are able to repeat single words, but routine use of alternative tests is encouraged for populations of people with brain injuries.

A simple and rapid identification method for newly emerged porcine Deltacoronavirus with loop-mediated isothermal amplification.

BACKGROUND: Porcine Deltacoronavirus (PDCoV) is a newly emerged enteropathogenic coronavirus that causes diarrhea and mortality in neonatal piglets. PDCoV has spread to many countries around the world, leading to significant economic losses in the pork industry. Therefore, a rapid and sensitive method for detection of PDCoV in clinical samples is urgently needed. RESULTS: In this study, we developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay specific for nucleocapsid gene to diagnose and monitor PDCoV infections. The detection limit of RT-LAMP assay was 1 × 101 copies of PDCoV, which was approximately 100-fold more sensitive than gel-based one-step reverse transcription polymerase chain reaction (RT-PCR). This assay could specifically amplify PDCoV and had no cross amplification with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKoV), porcine astrovirus (PAstV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), and porcine circovirus type 2 (PCV2). By screening a panel of clinical specimens (N = 192), this method presented a similar sensitivity with nested RT-PCR and was 1-2 log more sensitive than conventional RT-PCR in detection of PDCoV. CONCLUSIONS: The RT-LAMP assay established in this study is a potentially valuable tool, especially in low-resource laboratories and filed settings, for a rapid diagnosis, surveillance, and molecular epidemiology investigation of PDCoV infections. To the best of our knowledge, this is the first work for detection of newly emerged PDCoV with LAMP technology.

Episodic angioedema associated with eosinophilia.

We report a 12-year-old girl who presented with recurrent angioedema on the face, trunk, and extremities, and concomitant marked weight gain for 5 years. During the episode, her white blood cell count increased to 47.7×109/L with 89.9% eosinophils, followed by elevated serum level of IL-5, IgE, IgM, and LDH. Histopathology showed perivascular eosinophilic infiltration and diffuse eosinophilic infiltration throughout the dermis. Possible causes of hypereosinophilia and eosinophilic infiltration of vital organs were ruled out. We also tested the FIP1L1/PDGFRa and ETV6/PDGFRb fusion gene to exclude the possibility of myeloid and lymphatic vessel neoplasms. The patient was treated with methylprednisolone and discharged with an oral prednisolone taper, which resulted in complete remission of the edema and normalization of peripheral blood eosinophil count, serum IL-5 level, IgE, IgM, and LDH.

Episodic angioedema associated with eosinophilia

Abstract: We report a 12-year-old girl who presented with recurrent angioedema on the face, trunk, and extremities, and concomitant marked weight gain for 5 years. During the episode, her white blood cell count increased to 47.7×109/L with 89.9% eosinophils, followed by elevated serum level of IL-5, IgE, IgM, and LDH. Histopathology showed perivascular eosinophilic infiltration and diffuse eosinophilic infiltration throughout the dermis. Possible causes of hypereosinophilia and eosinophilic infiltration of vital organs were ruled out. We also tested the FIP1L1/PDGFRa and ETV6/PDGFRb fusion gene to exclude the possibility of myeloid and lymphatic vessel neoplasms. The patient was treated with methylprednisolone and discharged with an oral prednisolone taper, which resulted in complete remission of the edema and normalization of peripheral blood eosinophil count, serum IL-5 level, IgE, IgM, and LDH.

A simple and rapid identification method for newly emerged porcine Deltacoronavirus with loop-mediated isothermal amplification

BACKGROUND: Porcine Deltacoronavirus (PDCoV) is a newly emerged enteropathogenic coronavirus that causes diarrhea and mortality in neonatal piglets. PDCoV has spread to many countries around the world, leading to significant economic losses in the pork industry. Therefore, a rapid and sensitive method for detection of PDCoV in clinical samples is urgently needed. RESULTS: In this study, we developed a single-tube one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay specific for nucleocapsid gene to diagnose and monitor PDCoV infections. The detection limit of RT-LAMP assay was 1 × 101 copies of PDCoV, which was approximately 100-fold more sensitive than gel-based one-step reverse transcription polymerase chain reaction (RT-PCR). This assay could specifically amplify PDCoV and had no cross amplification with porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine kobuvirus (PKoV), porcine astrovirus (PAstV), porcine reproductive and respiratory syndrome virus (PRRSV), classic swine fever virus (CSFV), and porcine circovirus type 2 (PCV2). By screening a panel of clinical specimens (N = 192), this method presented a similar sensitivity with nested RT-PCR and was 1-2 log more sensitive than conventional RT-PCR in detection of PDCoV. CONCLUSIONS: The RT-LAMP assay established in this study is a potentially valuable tool, especially in low-resource laboratories and filed settings, for a rapid diagnosis, surveillance, and molecular epidemiology investigation of PDCoV infections. To the best of our knowledge, this is the first work for detection of newly emerged PDCoV with LAMP technology.

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

ABSTRACT PURPOSE: To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. METHODS: Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO2), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot. RESULTS: Compared to the LPD group, the AB192 group showed higher PO2, lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups. CONCLUSION: Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

PURPOSE:To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4.METHODS:Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO2), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot.RESULTS:Compared to the LPD group, the AB192 group showed higher PO2, lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups.CONCLUSION:Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.(AU)

Transmissibility of the Influenza Virus during Influenza Outbreaks and Related Asymptomatic Infection in Mainland China, 2005-2013.

We collected 2768 Influenza-like illness emergency public health incidents from April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting System. After screening by strict inclusion and exclusion criteria, there were 613 outbreaks analyzed with susceptible-exposed-infectious/asymptomatic-removed model in order to estimate the proportion of asymptomatic individuals (p) and the effective reproduction number (Rt). The relation between Rt and viral subtypes, regions, outbreak sites, populations, and seasons were analyzed. The mean values of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up to 0.94. Different subtypes, provinces, regions, and sites of outbreak had statistically significantly different Rt. In particular, the southern region also manifested different Rt by affected population size and seasonality. Our results provide China and also the rest of the world a reference to understand characteristics of transmission and develop prevention and control strategies.