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1.
Artigo em Inglês | MEDLINE | ID: mdl-32734755

RESUMO

INTRODUCTION: Dance therapy is a non-conventional aerobic exercise in cardiovascular rehabilitation. This meta-analysis aimed to update and assess evidence from randomized controlled trials of dance therapy on patients with hypertension. EVIDENCE ACQUISITION: PubMed, web of science, EBSCO, EMBESE, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases in English or Chinese were searched and randomized controlled trials were conducted for this meta-analysis to investigate the effects of dance therapy on blood pressure in hypertension patients. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed by I2 test. EVIDENCE SYNTHESIS: Five studies were included according to the eligibility criteria. Dance therapy could significantly reduce the systolic、diastolic pressure of hypertension individuals (SBP : WMD -11.07mmHg; 95%CI, -14.3 to -8.12mmHg, p<0.00001;DBP:WMD-4.16mmHg;95% CI, -6.44to-1.88mmHg, p=0.0004) when compared with the control group. low heterogeneity was observed in this research (P =0.65; I2=0% to SBP; P =0.57; I2 =0% to DBP). Subgroup analysis results showed that the subgroup of less than 12 weeks intervention group reduce the blood pressure more than those of 12 weeks intervention. Dance therapy reduce the SPB of hypertension individuals in African region better than Europe and America hypertension population. CONCLUSIONS: Despite the limited number of studies and people involved, the meta-analysis further demonstrated that dance therapy could reduce SBP and DBP in patients with hypertension. The effect of dance therapy intervention on hypertension might be related to duration of intervention and population gene.

2.
Leukemia ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651542

RESUMO

To investigate progression-free survival (PFS) and event-free survival (EFS) as early efficacy endpoints in diffuse large B-cell lymphoma (DLBCL), this systematic review included phase III randomized controlled trials (RCTs), phase II trials, and retrospective studies in newly diagnosed DLBCL receiving rituximab-containing chemotherapy through databases search up to 2019. Quality control was performed, where studies with high risk of bias were excluded. Prediction models were first established using the RCTs, and then externally validated in the phase II and retrospective populations. Trial-level surrogacy analysis was conducted by correlating the logarithmic (log) hazard ratio (HR) for PFS or EFS and log HR for OS. Correlation analysis at treatment arm-level was performed between 1-, 2-, 3-, and 5-year PFS or EFS rates and 5-year OS. The correlation was evaluated using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. Sensitivity analyses were performed to assess the consistency of predictive model by leaving one subgroup of trials out at a time. Twenty-six phase III RCTs, 4 phase II trials and 47 retrospective studies were included. In trial-level surrogacy, PFS (r, 0.772; 95% confidence interval [CI], 0.471-0.913) or EFS (r, 0.838; 95% CI, 0.625-0.938) were associated with OS. For rituximab immunochemotherapy treatment arms in RCTs, there was a linear correlation between 1 and 5-year PFS (r, 0.813-0.873) or EFS (r, 0.853-0.931) and 5-year OS. Sensitivity analysis demonstrated reasonable overall consistency. The correlation between PFS and OS was externally validated using independent phase II, and retrospective data (r, 0.795-0.897). We recommend PFS and EFS as earlier efficacy endpoints in patients with DLBCL primarily treated with rituximab-containing immunochemotherapy.

3.
Theranostics ; 10(14): 6245-6260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483451

RESUMO

Although the enzyme catalytic nanoreactors reported so far have achieved excellent therapeutic efficacy, how to accurately exert enzyme activity in the tumor microenvironment to specifically kill tumor cells and avoid systemic oxidative damage would be an inevitable challenge for catalytic nanomedicine. At the present study, we fabricate an advanced biomimetic nanoreactor, SOD-Fe0@Lapa-ZRF for tumor multi-enzyme cascade delivery that combined specifically killing tumor cells and protect cells from oxidative stress. Methods: We first synthesized the FeNP-embedded SOD (SOD-Fe0) by reduction reaction using sodium borohydride. Next, SOD-Fe0 and Lapa cargo were encapsulated in ZIF-8 by self-assembly. In order to protect the cargo enzyme from digestion by protease and prolong blood circulating time, SOD-Fe0@Lapa-Z was further cloaked with RBC membrane and functionalized with folate targeting, resulting in the final advanced biomimetic nanoreactor SOD-Fe0@Lapa-ZRF. Results: Once internalized, ZIF-8 achieves pH-triggered disassembly in weakly acidic tumor microenvironment. The released SOD-Fe0 and Lapa were further endocytosed by tumor cells and the Lapa produces superoxide anion (O2 -•) through the catalysis of NQO1 that is overexpressed in tumor cells, while O2 -• is converted to H2O2 via SOD. At this time, the released ferrous ions from SOD-Fe0 and H2O2 are further transformed to highly toxic hydroxyl radicals (•OH) for specifically killing tumor cells, and there was no obvious toxicological response during long-term treatment. Importantly, SOD-Fe0@Lapa-ZRF enhanced the normal cell's anti-oxidation ability, and thus had little effect on the secretion of TNF-α, IL-6 and IL-1ß pro-inflammatory cytokines, while effectively reversed the decreased activity of T-SOD and GSH-Px and remained stable MDA content after tumor treatment. In vitro and in vivo results indicate that the tumor microenvironment-responsive release multi-enzyme cascade have high tumor specificity and effective anti-tumor efficacy, and can protect cells from oxidative stress damage. Conclusion: The biomimetic nanoreactor will have a great potential in cancer nanomedicine and provide a novel strategy to regulate oxidative stress.

4.
Curr Org Synth ; 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32562526

RESUMO

BACKGROUND: The sulfinic esters are important and useful building blocks in organic synthesis. OBJECTIVE: The aim of this study was to develop a simple and efficient method for the synthesis of sulfinic esters. METHOD: Constant current electrolysis from thiols and alcohols was selected as the method for the synthesis of sulfinic esters. RESULTS: A novel electrochemical method for the synthesis of sulfinic esters from thiophenols and alcohols has been developed. Up to 27 examples of sulfinic esters have been synthesized using current methods. This protocol shows good functional group tolerance as well as high efficiency. In addition, this protocol can be easily scaled up with good efficiency. Notably, heterocycle-containing substrates including pyridine, thiophene and benzothiazole gave the desired products in good yields. A plausible reaction mechanism is proposed. CONCLUSION: This research not only provides a green and efficient method for the synthesis of sulfinic esters but also shows new applications of electrochemistry in organic synthesis. We consider that this green and efficient synthetic protocol used to prepare sulfinic esters will have good applications in future.

5.
ACS Nano ; 14(6): 7462-7474, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32453543

RESUMO

Cell-based therapy is a promising clinic strategy to address many unmet medical needs. However, engineering cells faces some inevitable challenges, such as limited sources of cells, cell epigenetic alterations, and short shelf life during in vitro culture. Here, the worm-like nanocell mimics are fabricated to engineer effectively the tumor cells in vivo through the synergistic combination of nongenetic membrane surface engineering and inside encapsulation using in situ cell membrane fusion. The specific targeting and deformability of nanocell mimics play a vital role in membrane fusion mechanisms. The engineered primary tumor cells improved the tumor penetration of therapeutic cargoes via extracellular vesicles, while the engineered circulating tumor cells (CTCs) can capture the homologous cells to form the CTC clusters in the bloodstream and eliminate the CTC clusters in the lung, thus achieving excellent antitumor and antimetastasis efficacy. Above all, we find an intriguing phenomenon, in situ cell membrane fusion by the worm-like nanocell mimics, and our finding of in situ cell membrane fusion inspired us to engineer tumor cells in vivo. The present study would be a particularly meaningful strategy to directly engineer cells in vivo for cell-based therapy.

6.
Mol Genet Metab ; 130(3): 209-214, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32418857

RESUMO

PURPOSE: Successful diagnosis of Fabry disease is often delayed or missed in patients, especially females, due to clinical heterogeneity and a lack of disease awareness. We present our experience testing for Fabry disease in high risk populations and discuss the relative sensitivities of α-galactosidase A (α-Gal A) enzyme activity in blood, plasma lyso-globotriaosylceramide (lyso-Gb3) biomarker, and GLA gene sequencing as diagnostic tests for Fabry disease in both males and females. METHODS: Patients with a clinical suspicion of Fabry disease were evaluated with enzyme analysis, biomarker analysis, and GLA sequencing. All three assays were performed from a single tube of EDTA blood. α-Gal A activity was determined in dried blood spots using a fluorometric assay, plasma lyso-Gb3 by UPLC-MS/MS, and GLA analysis by Sanger sequencing. RESULTS: Peripheral blood samples were received from 94 males and 200 females, of which 29% of males and 22% of females had a positive family history of Fabry disease. A likely pathogenic or pathogenic variant was identified in 87 (30%) patients (50 males, 37 females), confirming a diagnosis of Fabry disease. Of the remaining patients, 178 (61%) were determined to be unaffected based on normal enzyme activity (males) or normal lyso-Gb3 and negative sequencing results (females). A VUS was identified in 29 (10%) patients. The positive and negative predictive value of plasma lyso-Gb3 was 100% and 97% in males and 100% and 99% in females, respectively. This compares with 84% and 100% in males, and 58% and 50% in females for α-Gal A activity testing, respectively. CONCLUSIONS: Plasma lyso-Gb3 has high sensitivity and specificity for Fabry disease in males and females, and provides supportive diagnostic information when gene sequencing results are negative or inconclusive. α-Gal A activity in dried blood spots (DBS) has high sensitivity, but lower specificity for Fabry disease in males, as not all males with low α-Gal A activities were confirmed to have Fabry disease. Therefore, reflexing to gene sequencing and plasma lyso-Gb3 is useful for disease confirmation in males. For females, we found that first tier testing consisting of GLA sequencing and plasma lyso-Gb3 analysis provided the greatest sensitivity and specificity. Enzyme testing has lower sensitivity in females and is therefore less useful as a first-tier test. Enzyme analysis in females may still be helpful as a second-tier test in cases where molecular testing and plasma lyso-Gb3 analysis are uninformative and in vitro enzyme activity is low. SUMMARY: Sex-specific testing algorithms that prioritize tests with high specificity and sensitivity offer an effective means of identifying individuals with Fabry disease.

7.
Biomed Res Int ; 2020: 8030972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190681

RESUMO

Introduction. Environmental exposure of the developing offspring to cigarette smoke or nicotine is an important predisposing factor for many chronic respiratory conditions, such as asthma, emphysema, pulmonary fibrosis, and so forth, in the exposed offspring. Studies showed that electroacupuncture (EA) applied to maternal "Zusanli" (ST36) acupoints during pregnancy and lactation protects against perinatal nicotine exposure- (PNE-) induced lung damage. However, the most effective time period, that is, prenatal vs. postnatal, to attain this effect has not been determined. Objective: To determine the most effective developmental timing of EA's protective effect against PNE-induced lung phenotype in the exposed offspring. Methods: Pregnant rats were given (1) saline ("S" group); (2) nicotine ("N" group); (3) nicotine + EA, exclusively prenatally ("Pre-EA" group); (4) nicotine + EA, exclusively postnatally ("Post-EA," group); and (5) nicotine + EA, administered both prenatally and postnatally ("Pre- and Post-EA" group). Nicotine was injected once daily (1 mg/kg, 100 µl) and EA was administered to bilateral ST36 acupoints once daily during the specified time-periods. At the end of the experimental periods, key hypothalamic pituitary adrenal (HPA) axis markers in pups and dams, and lung function, morphometry, and the central molecular markers of lung development in the offspring were determined. Results: After nicotine exposure, alveolar mean linear intercept (MLI) increased, but mean alveolar number (MAN) decreased and lung PPARγ level decreased, but glucocorticoid receptor (GR) and serum corticosterone (Cort) levels increased, in line with the known PNE-induced lung phenotype. In the nicotine exposed group, maternal hypothalamic corticotropin releasing hormone (CRH) level decreased, but pituitary adrenocorticotropic hormone (ACTH) and serum Cort levels increased. In the "Pre- and Post-EA" groups, PNE-induced alterations in lung morphometry, lung development markers, and HPA axis were blocked. In the "Pre-EA" group, PNE-induced changes in lung morphometry, GR, and maternal HPA axis improved; lung PPARγ level decreased, but glucocorticoid receptor (GR) and serum corticosterone (Cort) levels increased, in line with the known PNE-induced lung phenotype. In the nicotine exposed group, maternal hypothalamic corticotropin releasing hormone (CRH) level decreased, but pituitary adrenocorticotropic hormone (ACTH) and serum Cort levels increased. In the "Pre- and Post-EA" groups, PNE-induced alterations in lung morphometry, lung development markers, and HPA axis were blocked. In the "Pre-EA" group, PNE-induced changes in lung morphometry, GR, and maternal HPA axis improved; lung PPAR. Conclusions: Maternal EA applied to ST36 acupoints during both pre- and postnatal periods preserves offspring lung structure and function despite perinatal exposure to nicotine. EA applied during the "prenatal period" affords only limited benefits, whereas EA applied during the "postnatal period" is ineffective, suggesting that the EA's effects in modulating PNE-induced lung phenotype are limited to specific time-periods during lung development.

8.
Arch Med Res ; 51(3): 245-253, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32192759

RESUMO

OBJECTIVE: We aimed to identify and characterize a SCN1B variant, A197V, associated with Brugada Syndrome (BrS). METHODS: Whole-exome sequencing was employed to explore the potential causative genes in 8 unrelated clinically diagnosed BrS patients. A197V variant was only detected in exon 4 of SCN1B in a 46 year old patient, who was admitted due to syncope. Wild type (WT) and mutant (A197V) genes were co-expressed with SCN5A in human embryonic kidney cells (HEK293 cells) and studied using whole-cell patch clamp and immunodetection techniques. RESULTS: Coexpression of 5A/WT + 1B/A197V resulted in a marked decrease in current density compared to 5A/WT + 1B/WT. The activation velocity was decelerated by A197V mutation. No significant changes were observed in recovery from inactivation parameters. Cell surface protein analyses confirmed that Nav1.5 channel membrane distribution was affected by A197V mutation. CONCLUSIONS: The current study is the first to report the functional analysis of SCN1B/ A197V, serving as a substrate responsible for BrS.

10.
Neurosci Bull ; 36(6): 570-584, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32144612

RESUMO

Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.

11.
Biosci Rep ; 40(2)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32043523

RESUMO

AIMS: Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays vital roles in carcinogenesis by influencing cell division and proliferation and by inhibiting apoptosis. However, the prognostic significance of BIRC5 remains unclear in breast cancer. METHODS: BIRC5 expression and methylation status were evaluated using the Oncomine and The Cancer Genome Atlas (TCGA) databases. The relevance between BIRC5 and different clinicopathological features as well as survival information was analyzed using the bc-GenExMiner database and Kaplan-Meier Plotter. BIRC5-drug interaction network was obtained using the Comparative Toxicogenomics Database. RESULTS: Based on the results from databases and own hospital data, BIRC5 was higher expressed in different breast cancer subtypes compared with the matched normal individuals. Hormone receptors were negatively correlated with BIRC5 expression, whereas the Scarff-Bloom-Richardson (SBR) grade, Nottingham Prognostic Index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to BIRC5 level in breast cancer samples with respect to normal tissues. High BIRC5 expression was responsible for shorter relapse-free survival, worse overall survival, reduced distant metastasis free survival, and increased risk of metastatic relapse event. BIRC5-drug interaction network indicated that several common drugs could modulate BIRC5 expression. Furthermore, a positive correlation between BIRC5 andcell-division cycle protein 20 (CDC20) gene was confirmed. CONCLUSION: BIRC5 may be adopted as a promising predictive marker and potential therapeutic target in breast cancer. Further large-scale studies are needed to more precisely confirm the value of BIRC5 in treatment of breast cancer.

12.
Biomed Res Int ; 2020: 3901528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090085

RESUMO

Background: Maternal smoking and/or exposure to environmental tobacco smoke continue to be significant factors in fetal and childhood morbidity and are a serious public health issue worldwide. Nicotine passes through the placenta easily with minimal biotransformation, entering fetal circulation, where it results in many harmful effects on the developing offspring, especially on the developing respiratory system. Objectives: Recently, in a rat model, electroacupuncture (EA) at maternal acupoints ST 36 has been shown to block perinatal nicotine-induced pulmonary damage; however, the underlying mechanism and the specificity of ST 36 acupoints for this effect are unknown. Here, we tested the hypothesis that compared with EA at ST 36, EA at LU 5 acupoints, which are on lung-specific meridian, will be equally or more effective in preventing perinatal nicotine-induced pulmonary changes. Methods: Twenty-four pregnant rat dams were randomly divided into 4 groups: saline ("S"), nicotine ("N"), nicotine + ST 36 (N + ST 36), and nicotine + LU 5 (N + LU 5) groups. Nicotine (1 mg/kg, subcutaneously) and EA (at ST 36 or LU 5 acupoints, bilaterally) were administered from embryonic day 6 to postnatal day 21 once daily. The "S" group was injected saline. As needed, using ELISA, western analysis, q-RT-PCR, lung histopathology, maternal and offspring hypothalamic pituitary adrenal axes, offspring key lung developmental markers, and lung morphometry were determined. Results: With nicotine exposure, alveolar count decreased, but mean linear intercept and septal thickness increased. It also led to a decrease in pulmonary function and PPARγ and an increase of ß-catenin and glucocorticoid receptor expression in lung tissue and corticosterone in the serum of offspring rats. Electroacupuncture at ST 36 normalized all of these changes, whereas EA at LU 5 had no obvious effect. Conclusion: Electroacupuncture applied to ST 36 acupoints provided effective protection against perinatal nicotine-induced lung changes, whereas EA applied at LU 5 acupoints was ineffective, suggesting mechanistic specificity and HPA axis' involvement in mediating EA at ST 36 acupoints' effects in mitigating perinatal nicotine-induced pulmonary phenotype. This opens the possibility that other acupoints, besides ST 36, can have similar or even more robust beneficial effects on the developing lung against the harmful effect of perinatal nicotine exposure. The approach proposed by us is simple, cheap, quick, easy to administer, and is devoid of any significant side effects.

13.
Theranostics ; 10(5): 2201-2214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104504

RESUMO

Biomineralization of enzymes for in vivo diagnosis and treatment of diseases remain a considerable challenge, due to their severe reaction conditions and complicated physiological environment. Herein, we reported a biomimetic enzyme cascade delivery nanosystem, tumor-targeted erythrocyte membrane (EM)-cloaked iron-mineralized glucose oxidases (GOx-Fe0@EM-A) for enhancing anticancer efficacy by self-activated in vivo cascade to generate sufficient high toxic •OH at tumor site. Methods: An ultra-small Fe0 nanoparticle (Fe0NP) was anchored in the inner cavity of glucose oxidase (GOx) to form iron-mineralized glucose oxidase (GOx-Fe0) as a potential tumor therapeutic nanocatalyst. Moreover, erythrocyte membrane cloaking delivery of GOx-Fe0 in vivo was designed to effectively accumulate ultra-small GOx-Fe0 at tumor site. Results: GOx-Fe0@EM-A had satisfactory biocompatibility and light-trigged release efficiency. Erythrocyte membrane cloaking of GOx-Fe0@EM-A not only prolongs blood circulation but also protects in vivo enzyme activity of GOx-Fe0; Tumor targeting of GOx-Fe0@EM-A endowed preferential accumulation at tumor site. After NIR light irradiation at tumor site, erythrocyte membrane of GOx-Fe0@EM-A was ruptured to achieve light-driven release and tumor deep penetration of ultra-small nanosize GOx-Fe0 by the photothermal effect of ICG. Then, GOx-Fe0 occurred self-activated in vivo cascade to effectively eradicate tumor by producing the highly cumulative and deeply penetrating •OH at tumor site. Conclusion: Tumor-targeted erythrocyte membrane-cloaked iron-mineralized glucose oxidase (GOx-Fe0@EM-A) exhibits a promising strategy for striking antitumor efficacy by light-driven tumor deep penetration and self-activated therapeutic cascade.

14.
Chem Commun (Camb) ; 56(10): 1497-1500, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31915758

RESUMO

The direct photocatalyzed para-selective CAr-H difluoroalkylation of aromatic aldehyde derivatives has been accomplished using a newly explored catalytic system. In addition, when using para-substituted benzaldehydes as substrates, ortho-selective CAr-H difluoroalkylation was also accomplished. It is worth noting that all the above site-selectivity is opposite to traditional Friedel-Crafts reactions of aromatic aldehydes. The preliminary mechanistic investigations indicate that an electrophilic difluoroalkyl radical is involved in the catalytic cycle.

15.
Chin Med J (Engl) ; 133(4): 452-461, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31985503

RESUMO

BACKGROUND: Clinical features and outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) remain controversial. Thus, we systematically reviewed literatures of clinical research to assess and analyze characteristics and prognosis of patients with HFmrEF. METHODS: PubMed, Embase, and Web of Science were searched for cohort studies up to April 23, 2019. Clinical features and multivariate adjusted hazard ratios (HRs) of endpoints of short-term all-cause mortality (SAM), long-term all-cause mortality (LAM), long-term cardiovascular death (LCD) and long-term HF rehospitalization (LHR) among patients with HFmrEF and HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) were well addressed. The primary outcome was LAM. RESULTS: Totally 19 studies were included in this study with 164,678 patients enrolled. The follow-up time of LAM was 3.6 ±â€Š2.5 years. HRs of LAM, SAM, LCD, LHR indicated that the risks of patients with HFmrEF were higher than HFpEF patients but lower than HFrEF patients, as for LAM, HFmrEF:HFpEF (reference) HR: 1.07, 95% confidence interval (CI): 1.00-1.15 (I = 63%, P = 0.0005); HFmrEF:HFrEF (reference) HR: 0.80, 95% CI: 0.73-0.88 (I = 70%, P < 0.0001). However, HFmrEF patients had the lowest rate in LAM (30.94%), SAM (2.73%), LCD (17.45%), LHR (26.36%) compared with the other two groups. CONCLUSIONS: This systematic review and meta-analysis compared features and prognosis between patients with HFmrEF and HFpEF, HFrEF by HRs. There appeared a special "separation phenomenon" showing rates of endpoints were inconsistent with their hazards in patients with HFmrEF compared with HFpEF patients.

16.
JCI Insight ; 5(4)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-31990680

RESUMO

BACKGROUNDLiver disease in urea cycle disorders (UCDs) ranges from hepatomegaly and chronic hepatocellular injury to cirrhosis and end-stage liver disease. However, the prevalence and underlying mechanisms are unclear.METHODSWe estimated the prevalence of chronic hepatocellular injury in UCDs using data from a multicenter, longitudinal, natural history study. We also used ultrasound with shear wave elastography and FibroTest to evaluate liver stiffness and markers of fibrosis in individuals with argininosuccinate lyase deficiency (ASLD), a disorder with high prevalence of elevated serum alanine aminotransferase (ALT). To understand the human observations, we evaluated the hepatic phenotype of the AslNeo/Neo mouse model of ASLD.RESULTSWe demonstrate a high prevalence of elevated ALT in ASLD (37%). Hyperammonemia and use of nitrogen-scavenging agents, 2 markers of disease severity, were significantly (P < 0.001 and P = 0.001, respectively) associated with elevated ALT in ASLD. In addition, ultrasound with shear wave elastography and FibroTest revealed increased echogenicity and liver stiffness, even in individuals with ASLD and normal aminotransferases. The AslNeo/Neo mice mimic the human disorder with hepatomegaly, elevated aminotransferases, and excessive hepatic glycogen noted before death (3-5 weeks of age). This excessive hepatic glycogen is associated with impaired hepatic glycogenolysis and decreased glycogen phosphorylase and is rescued with helper-dependent adenovirus expressing Asl using a liver-specific (ApoE) promoter.CONCLUSIONOur results link urea cycle dysfunction and impaired hepatic glucose metabolism and identify a mouse model of liver disease in the setting of urea cycle dysfunction.TRIAL REGISTRATIONThis study has been registered at ClinicalTrials.gov (NCT03721367, NCT00237315).FUNDINGFunding was provided by NIH, Burroughs Wellcome Fund, NUCDF, Genzyme/ACMG Foundation, and CPRIT.

17.
J Gastroenterol Hepatol ; 35(1): 165-169, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31334888

RESUMO

BACKGROUND AND AIM: A few small retrospective studies recently found that endoscopic retrograde cholangiopancreatography (ERCP) in asymptomatic compared with symptomatic common bile duct stones (CBDSs) patients appeared to increase the risk of post-ERCP pancreatitis (PEP). This study aimed to determine the risk of ERCP in asymptomatic CBDS patients. METHODS: A total of 327 consecutive patients with native papilla were invited to participate into the study and divided into two groups: 53 in the asymptomatic group and 274 in the symptomatic group, who underwent CBDS removal by ERCP. Patient's characteristics and outcomes were analyzed. RESULTS: A total of 46 (14.1%) patients had ERCP-related complications, including PEP, cholangitis, perforation, and bleeding. The overall complication rate in the asymptomatic group was higher than in the control group (26.4% vs 11.7%, P < 0.01). PEP was the most common complication (30/327, 9.2%). Of the 30 cases of PEP, 25 (83.3%) were mild, and the severity in both groups was similar (9/1/1 vs 16/2/1, P > 0.05). The incidence rate of PEP in the asymptomatic group was higher than in the symptomatic group (20.8% vs 6.9%, P < 0.01). Multivariate regression analysis identified asymptomatic CBDSs (odds ratio = 0.241, 95% confidence interval: 0.092-0.628) as being independently associated with PEP occurrence. CONCLUSION: Asymptomatic CBDSs were associated with increased incidence of PEP compared with symptomatic CBDSs.

18.
Appl Biochem Biotechnol ; 190(3): 1092-1105, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31701376

RESUMO

Agro-industrial wastes are excellent sources for solid-state culture to produce spores of microorganisms, whereas microbial co-cultivation is not fully exploited in solid-state culture. In this work, the co-cultivation of different strains of Bacillus subtilis, and three microbes of B. subtilis, Bacillus mucilaginosus, and Paecilomyces lilacinus was studied using a solid medium only composed of water and tobacco waste residue after extraction of nicotine and solanesol. The influences of matrix thickness, moister, temperature, and ratio of three microbes in seed on the cell growth and spore formation were studied. The maximum viable cells and spores of each microbe reached 1013 cfu/g when cultured alone at 30 °C in a medium containing 58.3% moisture. Co-cultivation of microbes stimulated cell growth and maximum viable cells of each microbe reached 1014 cfu/g, while spore production was inhibited and decreased to 1011 cfu/g. With decreasing amount of P. lilacinus in seed, total amount of spores was increased. When the seed with a ratio of 6:3:1 for B. mucilaginosus, B. subtilis, and P. lilacinus was inoculated, the total amount of spores reached 4.14 × 1012 cfu/g and the ratio was 1.7:0.7:1. These results indicate the potential of solid-state cultivation in the high production of spores from tobacco waste residue at low cost.


Assuntos
Bacillus subtilis/crescimento & desenvolvimento , Bacillus/crescimento & desenvolvimento , Resíduos Industriais , Paecilomyces/metabolismo , Tabaco , Meios de Cultura , Fertilizantes , Esporos Bacterianos
19.
Rev. esp. enferm. dig ; 111(12): 935-940, dic. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-190537

RESUMO

Background To observe the outcome of endoscopic papillary large balloon dilation (EPLBD) with minor sphincterotomy (mEST) for periampullary diverticular papilla related to stone removal. Methods Patients with confirmed periampullary diverticulum (PAD) during stone removal from May 2016 to April 2018 were reviewed retrospectively. The Chi-square test with Yates correction or Fisher's exact test was used for the analysis of categorical data and a normality test was applied for continuous data. Results A total of 154 consecutive patients (89 males and 65 females, aged 51-87 years) with confirmed PAD during stone removal were included in the study. Cases were divided into the conventional EST group (n = 79) and the mEST plus EPLBD group (n = 75). The number of patients with an initial treatment success was greater in the EPLBD+mEST group compared with the EST group (96% vs 86.1%, p=0.03) and the procedure time for EPLBD+mEST was shorter than that for EST alone (46.1+/-13.7 min vs 53.3+/-11.6 min, p=0.01). The rate of complications in the EPLBD+mEST group was lower than in the EST group (17.3% vs 32.9%, p=0.04). When PAD was >15 mm, the initial success rate was higher (92.6% vs 73.9%, p=0.04) and the rate of overall complications was lower (14.8% vs 41.7%, p=0.03) in the EPLBD+mEST group than those in the EST group. Although, this was similar when PAD was <15 mm. Conclusion EPLBD+mEST might be safer and more effective than conventional EST alone for stone removal in the presence of PAD


No disponible


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Diverticulares/cirurgia , Ampola Hepatopancreática/cirurgia , Esfinterotomia Endoscópica/métodos , Pancreatite/cirurgia , Enteroscopia de Balão/métodos , Dilatação/métodos , Pancreatite/complicações , Resultado do Tratamento , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Coledocolitíase/complicações
20.
Opt Express ; 27(26): 37150-37163, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31878500

RESUMO

Recently, optical neural networks (ONNs) integrated into photonic chips have received extensive attention because they are expected to implement the same pattern recognition tasks in electronic platforms with high efficiency and low power consumption. However, there are no efficient learning algorithms for the training of ONNs on an on-chip integration system. In this article, we propose a novel learning strategy based on neuroevolution to design and train ONNs. Two typical neuroevolution algorithms are used to determine the hyper-parameters of ONNs and to optimize the weights (phase shifters) in the connections. To demonstrate the effectiveness of the training algorithms, the trained ONNs are applied in classification tasks for an iris plants dataset, a wine recognition dataset and modulation formats recognition. The calculated results demonstrate that the accuracy and stability of the training algorithms based on neuroevolution are competitive with other traditional learning algorithms. In comparison to previous works, we introduce an efficient training method for ONNs and demonstrate their broad application prospects in pattern recognition, reinforcement learning and so on.

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