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1.
Nat Commun ; 11(1): 2186, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32367034

RESUMO

Diabetic cardiomyopathy is a progressive disease in diabetic patients, and myocardial insulin resistance contributes to its pathogenesis through incompletely-defined mechanisms. Striated muscle preferentially expressed protein kinase (SPEG) has two kinase-domains and is a critical cardiac regulator. Here we show that SPEG is phosphorylated on Ser2461/Ser2462/Thr2463 by protein kinase B (PKB) in response to insulin. PKB-mediated phosphorylation of SPEG activates its second kinase-domain, which in turn phosphorylates sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (SERCA2a) and accelerates calcium re-uptake into the SR. Cardiac-specific deletion of PKBα/ß or a high fat diet inhibits insulin-induced phosphorylation of SPEG and SERCA2a, prolongs SR re-uptake of calcium, and impairs cardiac function. Mice bearing a Speg3A mutation to prevent its phosphorylation by PKB display cardiac dysfunction. Importantly, the Speg3A mutation impairs SERCA2a phosphorylation and calcium re-uptake into the SR. Collectively, these data demonstrate that insulin resistance impairs this PKB-SPEG-SERCA2a signal axis, which contributes to the development of diabetic cardiomyopathy.

2.
Zhongguo Zhong Yao Za Zhi ; 45(2): 285-289, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237310

RESUMO

Poverty alleviation by Chinese herbal medicine industry is an important way to implement the major strategic plan of the government and to effectively alleviate poverty and increase income of poor farmers in areas with high resource's endowment of Chinese medicinal materials. Based on the analysis of the existing achievements and problems in poverty alleviation by Chinese herbal medicine industry, this paper proposes that improving the comprehensive benefits of Chinese herbal medicine industry is an important direction for poverty alleviation in the poverty-stricken areas with the high endowment of traditional Chinese medicine resources in the future. Then, based on the concept of resource recycling of traditional Chinese medicinal materials, the feasibility and strategies of utilizing by-products in the production process of Chinese medicinal materials and expanding the ways of poverty alleviation were analyzed and discussed. The aim of all these works was to provide the support for enhancing the comprehensive competitiveness of the industry in poverty-stricken regions, enlarging the poverty alleviation effect of Chinese herbal medicine industry, and consolidating the achievements of poverty alleviation.

3.
Zhongguo Zhong Yao Za Zhi ; 45(4): 890-895, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237490

RESUMO

The solid wastes of Chinese materia dedica industrialization represented by Salvia miltiorrhiza residues have a strong small-molecule bio-recalcitrance in the process of high-value utilization of biotransformation. Highly tolerant strains were bred to break bio-recalcitrance of Salvia miltiorrhiza residues and produce high-value added cellulose, which has a significant significance for recycling and industrial utilization of solid waste. In this study, a strain of fungus, Penicillium expansum SZ13, was found with small-molecule antibacterial substance tanshinone contained in Salvia miltiorrhiza residues by a biological method. The optimal enzyme production process and peak period of SZ13 were determined. It was found that SZ13 could maintain peak enzyme production for 5 days by degrading residues under the conditions of temperature 35 ℃, rotation speed 180 r·min~(-1), 5% of residues addition, and 5% seed solution addition. Meanwhile, the ability of SZ13 to degrade the enzyme production of multiple types of residues was explored. The results showed a high enzyme activity and stable enzyme production of SZ13 in the process of degrading residues. SZ13 could efficiently utilize various types of Chinese medicine residues, such as Salvia miltiorrhiza residues, to realize the high-value utilization of cellulose in multiple types of residues.

4.
Sex Transm Infect ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188771

RESUMO

OBJECTIVE: The rapid expansion of the recreational drug market becomes a global health concern. It is worrying that the bacterial and viral infection epidemics linking to drug use may worsen accordingly. This study aimed to estimate the impacts of changing trend and behaviours of using heroin only, synthetic drug (SD) only and polydrug (using SD and heroin concurrently) on HIV, hepatitis C virus (HCV) and syphilis epidemics among people who use drugs in China by 2035. METHODS: We constructed a compartmental model to estimate HIV, HCV and syphilis epidemics in the dynamic drug-use trend by three scenarios: SD-only use, heroin-only use and polydrug use based on Monte Carlo simulations. The parameters for the model were collected from a comprehensive literature search. RESULTS: Our model estimated that polydrug use led to the highest HIV and HCV prevalence among three drug-use patterns. The prevalences were projected to increase from 10.9% (95% CI 10.2% to 11.5%) and 61.7% (95% CI 59.4% to 62.5%) in 2005 to 19.0% (95% CI 17.3% to 20.7%) and 69.1% (95% CI 67.3% to 69.5%), respectively, in 2035 among people using polydrug. Similarly, HIV and HCV prevalence in the SD-only group were projected to increase from 0.4% (95% CI 0.3% to 0.4%) and 19.5% (95% CI 19.4% to 21.7%) to 1.8% (95% CI 1.4 to 2.1%) and 33.7% (95% CI 33.2% to 34.9%) in 2005-2035. Conversely, HIV prevalence in the heroin-only group was projected to decrease from 8.0% (95% CI 7.6% to 8.1%) to 2.2% (95% CI 2.0% to 2.3%) in 2005-2035. Syphilis prevalence was estimated to remain unchanged in all population groups within this time frame. It was projected that the proportion of HIV transmitted by sexual transmission will increase compared with unsafe injection transmission in all people who use drugs from 2005 to 2035. CONCLUSION: Our modelling suggests that polydrug use is projected to lead to the highest HIV and HCV disease burden by 2035, and the proportion of HIV transmitted by sexual transmission will increase. Current HIV intervention among people using heroin seems effective according to our estimation.

5.
Biomed Pharmacother ; 125: 109926, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028239

RESUMO

The spontaneous db/db mice were used to elucidate the biological effects and mechanisms of Rehmannia glutinosa leaves total glycoside (DHY) on kidney injury through biochemical indicators, kidney pathological section analysis, metabolic profiling, intestinal flora analysis and in vitro Human renal tubular epithelial (HK-2) cell model induced by high glucose. It was found that DHY can decrease the blood sugar level (insulin, INS; fasting blood glucose, FBG), blood lipid level (Total Cholesterol, T-CHO; Triglyceride, TG) significantly and improve kidney injury level (blood urea nitrogen, BUN; urine microalbumin, mALB; serum creatinine, Scr). It can also alleviate kidney tubular epithelial cell oedema and reduce interstitial connective tissue hyperplasia of the injury kidney induced by high glucose. 13 endogenous metabolites were identified in serum, which involved of ether lipid metabolism, sphingolipid metabolism, glyoxylic acid and dicarboxylic acid metabolism and arachidonic acid metabolism. High glucose can also lead to the disorder of intestinal flora, especially Firmicutes and Bacteroides. Meanwhile, DHY also inhibited the expression of α-SMA, TGF- ß1, Smad3 and Smad4 in the kidney tissues of db/db mice and HK-2 cells. To sum up, DHY may restore the dysfunctional intestinal flora to normal and regulate glycolipid level of db/db mice as well as TGF-ß/Smad signalling pathway regulation to improve early kidney damage caused by diabetes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31944535

RESUMO

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non-cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture-based next-generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm-level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non-cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.

7.
Sci Rep ; 10(1): 1075, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974510

RESUMO

Evidence showed preventive impacts of the highly active antiretroviral therapy (HAART) on the Human Immunodeficiency Virus (HIV) transmission amomg heterosexual population, however, that is of deficit among men who have sex with men (MSM). The aim was to systematically examine the efficacy of HAART on HIV transmission and the association between the HAART initiation and unprotected anal intercourse (UAI) in MSM population. Three electronic databases were fully searched for articles published in peer-reviewed journals between 1996 and 2017. Of 1616 identified articles, fifteen articles were eligible for meta-analyses. The summary incidence rate (IR) of HIV was 6.63/100 person-year (95%CI 2.06-11.20/100 person-year)(p = 0.004). The pooled per-contact rate (PCR) of HIV was 0.42% (95% CI 0.21-0.63%)(p < 0.05). The HAART initiation (vs non-HAART) was not associated with engaging in UAI, with odds ratio (OR) 1.09 (95% CI 0.90-1.34)(p > 0.05). In the stratified analysis, participants with no less than 6 months recall period was slightly more likely to engage in UAI (OR 1.32; 95% CI 1.01-1.74)(p < 0.05). It indicated that HAART has potential efficacy on reducing infectivity of HIV positive individuals in anal intercourses. The relationship between the HAART initiation and UAI was not significant and may be influenced by some social-demographic factors. Consistent condom use and education on safe sex among MSM are crucial.

8.
Int J Biochem Cell Biol ; 120: 105681, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31884111

RESUMO

Arginine methylation plays essential roles in post-transcriptional modification and signal transduction. Dysregulation of protein arginine methyltransferases (PRMTs) has been reported in human cancers, yet the expression and biological function of PRMT6 in endometrial cancer (EMC) remains unclear. Here, we show that PRMT6 is upregulated in EMC and exhibits oncogenic activities via activation of AKT/mTOR pathway. The expression of PRMT6 in EMC is much higher than that in the adjacent nontumorous tissues. Elevated PRMT6 expression is significantly associated with higher histological tumor grade and unfavorable prognosis in two independent cohorts consisting of a total of 564 patients with EMC. In vitro data demonstrate that PRMT6 expression was identified as a downstream target of miR-372-3p. Ectopic expression of miR-372-3p downregulates PRMT6. Overexpression of PRMT6 promotes EMC cell proliferation and migration, whereas knockdown of PRMT6 leads to opposite phenotypes. Mechanistically, PRMT6 induces the phosphorylation of AKT and mTOR in EMC cells. Inhibition of AKT/mTOR signaling by MK2206 or rapamycin attenuates the PRMT6-mediated EMC progression. In clinical samples, high expression of PRMT6 was correlated to low expression of miR-372-3p and high expression of phosphorylated AKT. Collectively, our findings suggest PRMT6 may function as an oncogene to promote tumor progression, and be of prognostic value to predict disease-free survival of patients with EMC. The newly identified miR-372-3p/PRMT6/AKT/mTOR axis represents a new promising target for EMC management.

9.
J Invest Surg ; 33(1): 79-93, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29856663

RESUMO

Purpose/Aim: Lumbar degenerative diseases (LDDs) cause pain and disability and are treated with lumbar fusion surgery. The aim of this study was to evaluate the efficacy of lumbar fusion surgery with ISOBAR devices versus posterior lumbar interbody fusion (PLIF) surgery for alleviating LDD-associated pain and disability. Materials and Methods: We performed a literature review and meta-analysis conducted in accordance with Cochrane methodology. The analysis included Group Reading Assessment and Diagnostic Evaluation assessments, Jadad Quality Score evaluations, and Risk of Bias in Non-randomized Studies of Interventions assessments. We searched PubMed, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, ProQuest, the Airiti Library, and the China Academic Journals Full-text Database for relevant randomized controlled trials and cohort studies published in English or Chinese between 1997 and 2017. Outcome measures of interest included general pain, lower back pain, and disability. Results: Of the 18 studies that met the inclusion criteria, 16 examined general pain (802 patients), 5 examined lower back pain (274 patients), and 15 examined disability (734 patients). General pain, lower back pain, and disability scores were significantly lower after lumbar fusion surgery with ISOBAR devices compared to presurgery. Moreover, lumbar fusion surgery with ISOBAR devices was more effective than PLIF for decreasing postoperative disability, although it did not provide any benefit in terms of general pain or lower back pain. Conclusions: Lumbar fusion surgery with ISOBAR devices alleviates general pain, lower back pain, and disability in LDD patients and is superior to PLIF for reducing postoperative disability. Given possible publication bias, we recommend further large-scale studies.


Assuntos
Doença , Fusão Vertebral , China , Humanos , Região Lombossacral , Pacientes
10.
J Clin Neurosci ; 72: 466-468, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874812

RESUMO

MRI signal changes in the corpus callosum can be seen in 8.3% of patients following shunt insertion for obstructive hydrocephalus. Several causes have been hypothesised, including mechanical compression, decompression associated oedema and ischaemia, and overshunting. We present a case of a patient with a pineal tumour of intermediate differentiation (WHO grade III), which had caused long-term obstructive hydrocephalus due to compression of the tectal plate and cerebral aqueduct. Following insertion of a shunt, prominent changes in the corpus callosum became evident on CT and MRI characterised by oedema and swelling, particularly affecting the dorsal surface of the corpus callosum. This pattern of signal change, although dramatic, should not be mistaken for other pathologies.

11.
Mol Imaging Biol ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828718

RESUMO

PURPOSE: Externalization of phosphatidylethanolamine (PE) in dying cells makes the phospholipid an attractive target for apoptosis imaging. However, no ideal PE-targeted positron emission tomography (PET) radiotracer was developed. The goal of the study was to develop a novel PE-targeted radiopharmaceutical to imaging apoptosis. PROCEDURE: In this study, we have radiolabeled PE-binding polypeptide duramycin with fluorine-18 for PET imaging of apoptosis. Al[18F]F-NOTA-PEG3-duramycin was synthesized via chelation reaction of NOTA-PEG3-duramycin with Al[18F]F. PE-binding capacity of Al[18F]F-NOTA-PEG3-duramycin was determined in a competitive radiometric PE-binding assay. The pharmacokinetic profile was evaluated in Kunming mice. The apoptosis imaging capacity of Al[18F]F-NOTA-PEG3-duramycin was evaluated using in vitro cell uptake assay with camptothecin-treated Jurkat cells, along with in vivo PET imaging using erlotinib-treated nude mice. RESULTS: The total synthesis procedure lasted for 30 min, with a decay-uncorrected radiochemical yield of 21.3 ± 2.6 % (n = 10). Compared with the control cells, the binding of Al[18F]F-NOTA-PEG3-duramycin with camptothecin-induced apoptotic cells resulted in a tripling increase. A competitive radiometric PE-binding assay strongly confirmed the binding of Al[18F]F-NOTA-PEG3-duramycin to PE. The biodistribution study showed rapid blood clearance, prominent kidney retention, and low liver uptake. In the in vivo PET/CT imaging, Al[18F]F-NOTA-PEG3-duramycin demonstrated 2-fold increase in erlotinib-treated HCC827 tumors in nude mice. CONCLUSION: Considering the facile preparation and improved biological properties, Al[18F]F-NOTA-PEG3-duramycin seems to be a promising PET tracer candidate for imaging apoptosis in the monitoring of cancer treatment.

12.
Front Public Health ; 7: 327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781529

RESUMO

Objectives: We aimed to conduct a comprehensive evaluation of the population impact of methadone maintenance treatment (MMT) for its future program planning. Methods: We conducted a literature review of the effects of MMT in China on HIV and HCV disease burden, injecting, and sexual behaviors and drug-related harm during 2004-2015. Data synthesis and analysis were conducted to obtain the pooled estimates of parameters for a mathematical model which was constructed to evaluate the effectiveness and cost-effectiveness of the program. Results: Based on a review of 134 articles, this study demonstrated that MMT is highly effective in reducing crime-related, high risk sexual, and injecting behaviors. The model estimated US$1,037 m which was invested in MMT from 2004 to 2015 has prevented 29,463 (15,325-43,600) new HIV infections, 130,563 (91,580-169,546) new HCV infections, 10,783 (10,380-11,187) deaths related to HIV, HCV and drug-related harm, and 338,920.0 (334,596.2-343,243.7) disability-adjusted life years (DALYs). The costs for each prevented HIV infection, HCV infection, death, and DALY were $35,206.8 (33,594.8-36,981.4), $7,944.7 ($7,714.4-8,189.2), $96,193.4 (92,726.0-99,930.2), and $3,060.6 ($3,022.0-3,100.1) respectively. Conclusion: The Chinese MMT program has been effective and cost-effective in reducing injecting, injecting-related risk behaviors and adversities due to HIV/HCV infection and drug-related harm among drug users.

13.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683684

RESUMO

Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1ß (IL-1ß), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-Ò¡B)/(NF-Ò¡B), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3α-acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto-ß -boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.

14.
Clin Nurs Res ; : 1054773819883171, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625397

RESUMO

To clarify the effectiveness of music intervention for improving the well-being of patients undergoing coronary procedures for coronary heart disease, we conducted full-text searches of various databases (MEDLINE, Cochrane Library, CINAHL, ProQuest, and Airiti Library; 1966-2019) to identify randomized controlled trials and quasi-experimental studies of music intervention in recipients of angiography or percutaneous coronary intervention. Outcome measures included anxiety, discomfort, pain, heart rate, and blood pressure. The Cochrane methodology, Jadad Quality Score, and ROBINS-I were employed to evaluate evidence from 10 studies. Music intervention reduced anxiety (effect size: Z = 2.15, p = .03; six studies) and discomfort of lying (Z = 2.40, p = .02; two studies), but did not affect pain (Z = 0.94; two studies), heart rate (Z = 0.94; five studies), or blood pressure (systolic, Z = 1.27; diastolic, Z = 1.32; four studies) (all p > .05). The heterogeneity among studies was high. Large-scale, transcultural, high-quality trials are warranted to confirm the benefit of music intervention in patients undergoing coronary procedures.

15.
Clin Nurs Res ; : 1054773819880297, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617405

RESUMO

Although studies have evaluated the quality of life (QoL) of patients undergoing permanent pacemaker (PPM) placement, their results are inconsistent. To assess arrhythmia perceptions and QoL in bradyarrhythmia patients following PPM implantation, 137 patients completed demographic, arrhythmia perception, and QoL questionnaires before and six months after implantation. Before implantation, they reported fatigue (74.1%), dizziness (72.9%), dyspnea (64.7%), chest pain (62.4%), and heart fluttering (54.1%). After implantation, arrhythmia perceptions and QoL showed significant improvement (p < .05), except vitality (p > .05). However, patients with arrhythmia for more than three years, three or more PPM implants, two or more comorbidities, or were 41-50 years showed no significant QoL improvement. Doctors and hospital educators, rather than nurses, provided the most PPM information to patients. Since nurses provide primary in-hospital care to PPM patients, they should impart more patient education while considering individual characteristics in caring situations to enhance patients' QoL.

16.
Molecules ; 24(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533325

RESUMO

In the present study, a new strategy including the combination of external appearance, chemical detection, and biological analysis was proposed for the comprehensive evaluation of safflowers in different producing areas. Firstly, 40 batches of safflower samples were classified into class I and II based on color measurements and K-means clustering analysis. Secondly, a rapid and sensitive analytical method was developed for simultaneous quantification of 16 chromaticity-related characteristic components (including characteristic components hydroxysafflor yellow A, anhydrosafflor yellow B, safflomin C, and another 13 flavonoid glycosides) in safflowers by ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UPLC-QTRAP®/MS2). The results of the quantification indicate that hydroxysafflor yellow A, anhydrosafflor yellow B, kaempferol, quercetin, and safflomin C had significant differences between the two types of safflower, and class I of safflower had a higher content of hydroxysafflor yellow A, anhydrosafflor yellow B, and safflomin C as the main anti-thrombotic components in safflower. Thirdly, chemometrics methods were employed to illustrate the relationship in multivariate data of color measurements and chromaticity-related characteristic components. As a result, kaempferol-3-O-rutinoside and 6-hydroxykaempferol-3-O-ß-d-glucoside were strongly associated with the color indicators. Finally, anti-thrombotic analysis was used to evaluate activity and verify the suitability of the classification basis of safflower based on the color measurements. It was shown that brighter, redder, yellower, more orange-yellow, and more vivid safflowers divided into class I had a higher content of characteristic components and better anti-thrombotic activity. In summary, the presented strategy has potential for quality evaluation of other flower medicinal materials.


Assuntos
Carthamus tinctorius/química , Fenômenos Químicos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Animais , Carthamus tinctorius/classificação , Cromatografia Líquida de Alta Pressão , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Geografia , Espectrometria de Massas em Tandem , Peixe-Zebra
17.
Appl Environ Microbiol ; 85(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31420346

RESUMO

The present study aimed to isolate Aeromonas from fish sold in the markets as well as in sushi and seafood shops and compare their virulence factors and antimicrobial characteristics with those of clinical isolates. Among the 128 fish isolates and 47 clinical isolates, Aeromonas caviae, A. dhakensis, and A. veronii were the principal species. A. dhakensis isolates carried at least 5 virulence genes, more than other Aeromonas species. The predominant genotype of virulence genes was hlyA lip alt col ela in both A. dhakensis and A. hydrophila isolates, alt col ela in A. caviae isolates, and act in A. veronii isolates. A. dhakensis, A. hydrophila, and A. veronii isolates more often exhibited hemolytic and proteolytic activity and showed greater virulence than A. caviae isolates in Caenorhabditis elegans and the C2C12 cell line. However, the link between the genotypes and phenotypes of the studied virulence genes in Aeromonas species was not evident. Among the four major clinical Aeromonas species, nearly all (99.0%) A. dhakensis, A. hydrophila, and A. veronii isolates harbored bla CphA, which encodes a carbapenemase, but only a minority (6.7%, 7/104) were nonsusceptible to carbapenem. Regarding AmpC ß-lactamase genes, bla AQU-1 was exclusively found in A. dhakensis isolates, and bla MOX3 was found only in A. caviae isolates, but only 7.6% (n = 6) of the 79 Aeromonas isolates carrying bla AQU-1 or bla MOX3 exhibited a cefotaxime resistance phenotype. In conclusion, fish Aeromonas isolates carry a variety of combinations of virulence and ß-lactamase resistance genes and exhibit virulence phenotypes and antimicrobial resistance profiles similar to those of clinical isolates.IMPORTANCE Aeromonas species can cause severe infections in immunocompromised individuals upon exposure to virulent pathogens in the environment, but the characteristics of environmental Aeromonas species remain unclear. Our study showed that several pathogenic Aeromonas species possessing virulence traits and antimicrobial resistance similar to those of Aeromonas isolates causing clinical diseases were present in fish intended for human consumption in Tainan City, Taiwan.

18.
Lancet Infect Dis ; 19(9): 1001-1012, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399378

RESUMO

BACKGROUND: Patients who are immunocompromised because of malignancy have an increased risk of herpes zoster and herpes zoster-related complications. We aimed to investigate the efficacy and safety of an inactivated varicella zoster virus (VZV) vaccine for herpes zoster prevention in patients with solid tumour or haematological malignancies. METHODS: This phase 3, two-arm, randomised, double-blind, placebo-controlled, multicentre trial with an adaptive design was done in 329 centres across 40 countries. The trial included adult patients with solid tumour malignancies receiving chemotherapy and those with haematological malignancies, either receiving or not receiving chemotherapy. Patients were randomly assigned (1:1) to receive four doses of VZV vaccine inactivated by γ irradiation or placebo approximately 30 days apart. The patients, investigators, trial site staff, clinical adjudication committee, and sponsor's clinical and laboratory personnel were masked to the group assignment. The primary efficacy endpoint was herpes zoster incidence in patients with solid tumour malignancies receiving chemotherapy, which was assessed in the modified intention-to-treat population (defined as all randomly assigned patients who received at least one dose of inactivated VZV vaccine or placebo). The primary safety endpoint was serious adverse events up to 28 days after the fourth dose in patients with solid tumour malignancies receiving chemotherapy. Safety endpoints were assessed in all patients who received at least one dose of inactivated VZV vaccine or placebo and had follow-up data. This trial is registered (NCT01254630 and EudraCT 2010-023156-89). FINDINGS: Between June 27, 2011, and April 11, 2017, 5286 patients were randomly assigned to receive VZV vaccine inactivated by γ irradiation (n=2637) or placebo (n=2649). The haematological malignancy arm was terminated early because of evidence of futility at a planned interim analysis; therefore, all prespecified haematological malignancy endpoints were deemed exploratory. In patients with solid tumour malignancies in the modified intention-to-treat population, confirmed herpes zoster occurred in 22 of 1328 (6·7 per 1000 person-years) VZV vaccine recipients and in 61 of 1350 (18·5 per 1000 person-years) placebo recipients. Estimated vaccine efficacy against herpes zoster in patients with solid tumour malignancies was 63·6% (97·5% CI 36·4 to 79·1), meeting the prespecified success criterion. In patients with solid tumour malignancies, serious adverse events were similar in frequency across treatment groups, occurring in 298 (22·5%) of 1322 patients who received the vaccine and in 283 (21·0%) of 1346 patients who received placebo (risk difference 1·5%, 95% CI -1·7 to 4·6). Vaccine-related serious adverse events were less than 1% in each treatment group. Vaccine-related injection-site reactions were more common in the vaccine group than in the placebo group. In the haematological malignancy group, VZV vaccine was well tolerated and estimated vaccine efficacy against herpes zoster was 16·8% (95% CI -17·8 to 41·3). INTERPRETATION: The inactivated VZV vaccine was well tolerated and efficacious for herpes zoster prevention in patients with solid tumour malignancies receiving chemotherapy, but was not efficacious for herpes zoster prevention in patients with haematological malignancies. FUNDING: Merck & Co, Inc.

19.
West J Nurs Res ; : 193945919858715, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31313649

RESUMO

Hip fractures may increase mortality and decrease mobility in elderly patients. Effectiveness of comprehensive geriatric care (CGC) has not been verified. A systematic review and a meta-analysis were conducted by searching full-text databases (1988-2018) of Cochrane Library, Clinical Key, Embase, MEDLINE, CINAHL, and ProQuest for randomized controlled trials (RCTs) of CGC following hip fractures. Outcome measures were mortality, activities of daily living, hospital stay, and discharge to institutional setting. Cochrane RoB 2.0, Jadad Quality Score, and Group Reading Assessment were used for analysis. Of the 11 studies included, 8 examined mortality (effect size Z = 2.51, p = 0.01), 5 examined daily activities (effect size Z = 3.31, p = 0.0009), 7 examined length of hospital stay (effect size Z = 0.18, p = 0.85), and 5 examined discharged to an institutional setting (effect size Z = 0.81, p = 0.42). Results showed that CGC decreased mortality and improved daily living activities.

20.
Lancet Oncol ; 20(9): 1239-1251, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345627

RESUMO

BACKGROUND: Pembrolizumab improved progression-free survival and overall survival versus ipilimumab in patients with advanced melanoma and is now a standard of care in the first-line setting. However, the optimal duration of anti-PD-1 administration is unknown. We present results from 5 years of follow-up of patients in KEYNOTE-006. METHODS: KEYNOTE-006 was an open-label, multicentre, randomised, controlled, phase 3 study done at 87 academic institutions, hospitals, and cancer centres in 16 countries. Patients aged at least 18 years with Eastern Cooperative Oncology Group performance status of 0 or 1, ipilimumab-naive histologically confirmed advanced melanoma with known BRAFV600 status and up to one previous systemic therapy were randomly assigned (1:1:1) to intravenous pembrolizumab 10 mg/kg every 2 weeks or every 3 weeks or four doses of intravenous ipilimumab 3 mg/kg every 3 weeks. Treatments were assigned using a centralised, computer-generated allocation schedule with blocked randomisation within strata. Exploratory combination of data from the two pembrolizumab dosing regimen groups was not protocol-specified. Pembrolizumab treatment continued for up to 24 months. Eligible patients who discontinued pembrolizumab with stable disease or better after receiving at least 24 months of pembrolizumab or discontinued with complete response after at least 6 months of pembrolizumab and then progressed could receive an additional 17 cycles of pembrolizumab. Co-primary endpoints were overall survival and progression-free survival. Efficacy was analysed in all randomly assigned patients, and safety was analysed in all randomly assigned patients who received at least one dose of study treatment. Exploratory assessment of efficacy and safety at 5 years' follow-up was not specified in the protocol. Data cutoff for this analysis was Dec 3, 2018. Recruitment is closed; the study is ongoing. This study is registered with ClinicalTrials.gov, number NCT01866319. FINDINGS: Between Sept 18, 2013, and March 3, 2014, 834 patients were enrolled and randomly assigned to receive pembrolizumab (every 2 weeks, n=279; every 3 weeks, n=277), or ipilimumab (n=278). After a median follow-up of 57·7 months (IQR 56·7-59·2) in surviving patients, median overall survival was 32·7 months (95% CI 24·5-41·6) in the combined pembrolizumab groups and 15·9 months (13·3-22·0) in the ipilimumab group (hazard ratio [HR] 0·73, 95% CI 0·61-0·88, p=0·00049). Median progression-free survival was 8·4 months (95% CI 6·6-11·3) in the combined pembrolizumab groups versus 3·4 months (2·9-4·2) in the ipilimumab group (HR 0·57, 95% CI 0·48-0·67, p<0·0001). Grade 3-4 treatment-related adverse events occurred in 96 (17%) of 555 patients in the combined pembrolizumab groups and in 50 (20%) of 256 patients in the ipilimumab group; the most common of these events were colitis (11 [2%] vs 16 [6%]), diarrhoea (ten [2%] vs seven [3%]), and fatigue (four [<1%] vs three [1%]). Any-grade serious treatment-related adverse events occurred in 75 (14%) patients in the combined pembrolizumab groups and in 45 (18%) patients in the ipilimumab group. One patient assigned to pembrolizumab died from treatment-related sepsis. INTERPRETATION: Pembrolizumab continued to show superiority over ipilimumab after almost 5 years of follow-up. These results provide further support for use of pembrolizumab in patients with advanced melanoma. FUNDING: Merck Sharp & Dohme.

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