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ABSTRACT: Testicular descent occurs in two consecutive stages: the transabdominal stage and the inguinoscrotal stage. Androgens play a crucial role in the second stage by influencing the development of the gubernaculum, a structure that pulls the testis into the scrotum. However, the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated. To identify the androgen-regulated genes, we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout (Lhcgr KO) mice, an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency. We found that the expression of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (Smoc1) was the most severely suppressed at both the transcript and protein levels, while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice. The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist, flutamide. In addition, in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells. In the cultures of myogenic differentiation medium, both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7 (Pax7) and myogenic factor 5 (Myf5). After short-interfering RNA-mediated knocking down of Smoc1, the expression of Pax7 and Myf5 diminished, and testosterone alone did not recover, but additional SMOC1 did. These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.
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OBJECTIVES: We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC. METHODS: We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507. RESULTS: Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1-penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group's OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P= 5.678e-07) was poorer than that of low-risk groups' (HR, 1.675; 95% CI, 1.037 to 2.713; P= 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p= 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score. CONCLUSIONS: The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC.
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Biomarcadores Tumorais , MicroRNAs , RNA Longo não Codificante , RNA Mensageiro , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , RNA Longo não Codificante/genética , Prognóstico , RNA Mensageiro/genética , MicroRNAs/genética , Masculino , Feminino , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Nomogramas , Perfilação da Expressão Gênica , Idoso , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , TranscriptomaRESUMO
PHYTOCHROME INTERACTING FACTORS (PIFs) integrate light and temperature signs to control plant growth and development. However, little is known about PIFs in crop plants such as cotton. Here, we identified 68 PIF proteins and their coding genes from an allotetraploid and three diploid ancestors. Cotton PIFs contain typical ACTIVEPHYA-BINDING (APA) and ACTIVE PHYB-BINDING (APB) motifs by which they bind to phytochrome phyA and phyB, respectively, and have a BASIC HELIX-LOOP-HELIX (bHLH) domain and a nuclear localization sequence necessary for bHLH-type transcription factors. Bioinformatics analysis showed that the promoter of each PIF gene contains multiple cis-acting elements and that the evolution of cotton genomes probably underwent loss, recombination, and tandem replication. Further observations indicated that the sensitivity of cotton PIF expression to high temperature was significantly different from that to low temperature. We found that allotetraploid Gossypium hirsutum PIF4a (GhPIF4a) was induced by high temperature. GhPIF4a promotes flowering in cotton and Arabidopsis and binds to the promoter of GhFT (G. hirsutum FLOWERING LOCUS T), and binding increased with increasing temperature. Our work identifies the evolutionary and structural characteristics and functions of PIF family members in cotton.
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Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Fitocromo/genética , Fitocromo/metabolismo , Gossypium/genética , Gossypium/metabolismo , Temperatura , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Background: Acute radiation-induced esophagitis (ARIE) is one of the most debilitating complications in patients who receive thoracic radiotherapy, especially those with esophageal cancer (EC). There is little known about the impact of the characteristics of gut microbiota on the initiation and severity of ARIE. Materials and Methods: Gut microbiota samples of EC patients undergoing radiotherapy (n = 7) or concurrent chemoradiotherapy (n = 42) were collected at the start, middle, and end of the radiotherapy regimen. Assessment of patient-reported ARIE was also performed. Based on 16S rRNA gene sequencing, changes of the gut microbial community during the treatment regimen and correlations of the gut microbiota characteristics with the severity of ARIE were investigated. Results: There were significant associations of several properties of the gut microbiota with the severity of ARIE. The relative abundance of several genera in the phylum Proteobacteria increased significantly as mucositis severity increased. The predominant genera had characteristic changes during the treatment regimen, such as an increase of opportunistic pathogenic bacteria including Streptococcus. Patients with severe ARIE had significantly lower alpha diversity and a higher abundance of Fusobacterium before radiotherapy, but patients with mild ARIE were enriched in Klebsiella, Roseburia, Veillonella, Prevotella_9, Megasphaera, and Ruminococcus_2. A model combining these genera had the best performance in prediction of severe ARIE (area under the curve: 0.907). Conclusion: The characteristics of gut microbiota before radiotherapy were associated with subsequent ARIE severity. Microbiota-based strategies have potential use for the early prediction of subsequent ARIE and for the selection of interventions that may prevent severe ARIE.
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The adjustment of stomatal density and clustered ratio on the epidermis is the important strategy for plants to respond to drought, because the stoma-based water loss is directly related to plant growth and survival under drought conditions. But the relevant adjustment mechanism still needs to be explored. 1-Aminocyclopropane-1-carboxylate (ACC) is disclosed to promote stomatal development, while in vivo ACC levels depend on activation of ACC synthase (ACS) family members. Based on the findings of ACS expression involving in drought response and several ACS activity inhibitors reducing stomatal density and cluster in drought response, here we examined how ACS activation is involved in the establishment of stomatal density and cluster on the epidermis under drought conditions. Preliminary data indicated that activation of ACS2 and/or ACS6 (ACS2/6) increased stomatal density and clustered ratio on the Arabidopsis leaf epidermis by accumulating ACC under moderate drought, and raised the survival risk of seedlings under escalated drought. Further exploration indicated that, in Arabidopsis seedlings stressed by drought, the transcription factor SPEECHLESS (SPCH), the initiator of stomatal development, activates ACS2/6 expression and ACC production; and that ACC accumulation induces Ca2+ deficiency in stomatal lineage; this deficiency inactivates a subtilisin-like protease STOMATAL DENSITY AND DISTRIBUTION 1 (SDD1) by stabilizing the inhibition of the transcription factor GT-2 Like 1 (GTL1) on SDD1 expression, resulting in an increases of stomatal density and cluster ratio on the leaf epidermis. This work provides a novel evidence that ACS2/6 activation plays a key role in the establishment of stomatal density and cluster on the leaf epidermis of Arabidopsis in response to drought.
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The prevalence of dementia has been widely reported, and its potential risk and protective factors are well-characterized. However, there is a scarcity of related information regarding mild cognitive impairment (MCI). Thus this population-based study aimed to determine the prevalences of MCI and its subtypes, as well as to identify the risk and protective factors for MCI in the Chinese elderly population of Singapore. Results showed that the overall prevalence of MCI was 12.5%, while the gender-adjusted prevalence of MCI was 12.3%. Gender was found to be significantly associated with the subtypes of MCI, with males more likely to have amnestic MCI and females more likely to have non-amnestic MCI. Older age, lower educational levels, lower social activity levels, depression, hypertension, hyperlipidemia, diabetes and stroke were found to be risk factors for MCI in univariate analysis. However, multivariable analysis showed that only hypertension and stroke were the significant risk factors for MCI. Higher educational levels and active social engagements were significant protective factors for MCI in multivariable analysis. Age and depression had boundary significant associations with the prevalence of MCI. After adjusting for gender, the influence of hypertension, stroke, social engagement, age and depression on MCI remained unchanged, except that education became a boundary significant lower risk factor of MCI development. In conclusion, this study presented the prevalence, risk and protective factors for MCI among Singaporean Chinese older adults, which facilitates the screening of vulnerable groups for MCI.
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BACKGROUND: Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6-12 h after symptom onset is effective and safe in these patients is unknown. METHODS: A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6-12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0-1 at 90 days) was estimated using multivariable logistic regression analysis. RESULTS: A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05-2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation. CONCLUSIONS: Early combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits. TRIAL REGISTRATION: Our study is a retrospectively registered trial.
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Arteriosclerose Intracraniana , Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral Lacunar , Arginina/análogos & derivados , Quimioterapia Combinada , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/tratamento farmacológico , Ácidos Pipecólicos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Sulfonamidas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Inflammation plays an important role in the pathophysiology of stroke. The aim of the present study was to investigate the association between various inflammatory risk markers and ischemic stroke outcome and subtype. METHODS: A total of 3,013 ischemic stroke patients who were admitted to our hospital from 01/01/2016 to 12/30/2018 were retrospectively studied. Stroke subtypes were defined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Levels of five common inflammatory markers including white blood cell (WBC) count, neutrophil, lymphocyte, serum C-reactive protein (CRP), and interleukin-6 (IL-6) were measured, and eleven conventional risk factors were further evaluated in the prediction of overall mortality as well as three functional outcomes defined by the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI). Independent predictors of outcome were identified by multivariate logistic regression, and an importance score measured by the area under the receiver operating characteristics curve for each predictor using a Naive Bayes model was reported. RESULTS: Neutrophil and WBC were significantly higher in large-artery atherosclerosis (LAA) and cardioembolism (CE) subtype. In contrast, lymphocyte was significantly higher in small-artery occlusion (SAO). Neutrophil-lymphocyte ratio and CRP level were the best independent predictors, after adjustment for traditional risk factors and TOAST subtype for all four types of outcomes. CONCLUSION: Inflammatory risk markers including neutrophil, lymphocyte, and CRP may have strong independent prediction values for stroke outcome.
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Isquemia Encefálica , Acidente Vascular Cerebral , Teorema de Bayes , Biomarcadores , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Left atrial enlargement is associated with increased risk for stroke. However, few studies that evaluated the correlation between left atrial size and ischemic stroke severity. In this study, we aim to evaluate the association between left atrial size and stroke severity, especially with cardioembolic and cryptogenic stroke in the Chinese population. METHODS: A total of 1271 patients with acute ischemic stroke were included in this study. Echocardiographic left atrial diameter was measured and indexed to height. Stroke severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Moderate-to-severe neurologic deficit was defined as NIHSS greater than or equal to 5. Patients were divided into mild, moderate, or severe abnormal left atrial size by tertile distribution. Binary logistic regression analysis was used to identify independent predictors of severe stroke after adjustment. RESULTS: Among all enrolled patients, 328 (25.8%) were classified into moderate-to severe stroke severity (NIHSS ≥ 5). In the multivariable model, compared with the lowest tertile of left atrial size, the odds ratio for moderate-to-severe neurologic deficit was 0.902 (95% CI, 0.644-1.264, P = .550) when left atrial size was the highest tertile. Of all patients, 190 patients were further categorized as cardioembolic and cryptogenic subtypes, and 70 (36.8%) were classified into moderate-to-severe stroke severity. After adjusting for confounders, compared with the lowest tertile, the top tertile of left atrial size was significantly associated with moderate-to-severe stroke (3.156, 95% CI, 1.143-8.711, P = .027). CONCLUSION: Left atrial enlargement was associated with more severe initial neurologic deficits of embolic subtypes (cardioembolic and cryptogenic stroke) in patients with acute ischemic stroke.
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Função do Átrio Esquerdo , Remodelamento Atrial , Átrios do Coração/fisiopatologia , Cardiopatias/complicações , Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , China , Avaliação da Deficiência , Ecocardiografia , Átrios do Coração/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologiaRESUMO
BACKGROUND: The efficacy of high-dose atorvastatin pretreatment in reducing the incidence of contrast-induced nephropathy in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) has been examined in some randomized studies. However, the results across the trials remain controversial. OBJECTIVE: This study sought to perform a meta-analysis to evaluate the effect of high-dose atorvastatin in the prevention of contrast-induced nephropathy (CIN) while undergoing CAG or PCI. MATERIALS AND METHODS: Comprehensive literature searches for randomized controlled trials (RCTs) comparing high-dose atorvastatin vs. low-dose statin or placebo pretreatment for prevention of contrast-induced acute kidney injury in patients undergoing CAG were performed using PubMed, Embase, and the Cochrane library updated to June 2017. The primary outcome was the incidence of CIN. RESULTS: A total of 11 RCTs were included in this analysis. The high-dose atorvastatin treatment can significantly reduce the incidence of CIN (OR 0.46, 95% CI 0.35 - 0.62, p < 0.00001). The benefit was consistent in comparison with the low-dose group (OR 0.41, 95% CI 0.25 - 0.66, p = 0.0003) and the placebo group (OR 0.50, 95% CI 0.26 - 0.98, p = 0.04). CONCLUSION: Our study demonstrates that high-dose statin pretreatment shows a benefit specifically in reducing the incidence of contrast-induced acute kidney injury in patients undergoing CAG, especially compared with low-dose statin pretreatment.
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Injúria Renal Aguda/prevenção & controle , Atorvastatina/uso terapêutico , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Humanos , IncidênciaRESUMO
TIPE1, which acts as a cell death regulator, has emerged as a tumor suppressor in the process of carcinogenesis. However, our recent research demonstrated that it serves as an oncogene in the pathogenesis of cervical cancer, indicating that the role of TIPE1 in carcinogenesis needs to be further evaluated. In this study, we show that TIPE1 is able to inhibit breast cancer cell growth both in vivo and in vitro. Functionally, TIPE1 inhibits cancer cell proliferation preferentially by downregulating ERK phosphorylation. Furthermore, the expression of TIPE1 is decreased in breast cancer tissues compared to matched adjacent tissues, and its expression is positively correlated with patients' lifespan. These data indicate that TIPE1 suppresses breast cancer proliferation by inhibiting the ERK signaling pathway. This study also suggests that TIPE1 could serve as a potential therapeutic target and a diagnostic biomarker for breast cancer.
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The present study aims to investigate the mechanism of miR-15a-5p in the atherosclerotic (AS) inflammatory response and arterial injury improvement in diabetic rats by regulating fatty acid synthase (FASN). Initially, bioinformatics tools were applied to evaluate miRNAs and genes correlating with AS, and the target relation between miRNAs and FASN was measured using the Dual-Luciferase Reporter Assay. Subsequently the diabetic AS rat model was established and the surviving rats were divided into: negative control (NC), miR-15a-5p mimic, miR-15a-5p inhibitor, sh-FASN and miR-15a-5p + sh-FASN groups. Then a series of experiments were performed to examine the degree of AS in each group. The results revealed that compared with the NC group, the expressions of C-reactive protein (CRP), interleukin 6 (IL-6), intercellular cell adhesion molecule-1 (ICAM1) in rat arterial tissue, as well as the levels of low-density lipoprotein cholesterol (LDL-C), blood glucose (BG), triglycerides (TG), total cholesterol (TC) and Homocysteine (Hcy) in rat serum, were increased after inhibiting miR-15a-5p, while the level of high-density lipoprotein cholesterol (HDL-C) was decreased and the fat storage area was enlarged after this treatment (P<0.05). In the miR-15a-5p mimic and sh-FASN groups, serum HDL-C levels were increased and the fat storage areas in arteries were reduced. The levels of CRP, IL-6, ICAM1 in rat arterial tissue, along with the levels of LDL-C, BG, TG, TC and Hcy in rat serum, were decreased (P<0.05). Hematoxylin and Eosin (HE) staining and transmission electron microscopy (TEM) results showed AS lesions to be apparent in the arteries of rats in both the NC and miR-15a-5p inhibitor groups, but that in miR-15a-5p and sh-FASN group were improved, the miR-15a-5p mimic + sh-FASN group showed the most obvious improvement. Taken together, miR-15a-5p alleviates the inflammation response and arterial injury in diabetic AS rats by targeting FASN.
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Aterosclerose/genética , Diabetes Mellitus Experimental/genética , Ácido Graxo Sintase Tipo I/genética , Inflamação/genética , MicroRNAs/genética , Animais , Apoptose/efeitos dos fármacos , Artérias/efeitos dos fármacos , Artérias/lesões , Artérias/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/terapia , Ácido Graxo Sintases/genética , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , MicroRNAs/antagonistas & inibidores , RatosRESUMO
In recent years, a growing body of evidence has provided support for the important role of microRNAs (miRNAs) in the progression of human cancers. A recent study showed that a novel miRNA miR-3650 expression was significantly decreased in hepatocellular carcinoma (HCC). However, the precise role of miR-3650 in HCC have remained poorly understood. In this study, we found that miR-3650 expression was frequently decreased in HCC tissues. Low expression of miR-3650 is positively associated with tumor metastasis and poor survival of HCC patients. Forced expression of miR-3650 significantly inhibited the migration and epithelial-mesenchymal transition (EMT) of HCC cells. Through bioinformatic analysis and luciferase assays, we confirmed that neurofascin (NFASC) is a directly target mRNA of miR-3650. Rescue experiment demonstrated that NAFSC overexpression could partially counteracted the inhibitory effect of miR-3650 in HCC metastasis and EMT. In conclusion, our findings are the first time to demonstrate that reduced expression of miR-3650 in HCC was correlated with tumor metastasis and poor survival. MiR-3650 repressed HCC migration and EMT by directly targeting NFASC. Our findings suggested that miR-3650 may serve as a potential prognostic marker and promising application in HCC therapy.
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Carcinoma Hepatocelular/metabolismo , Moléculas de Adesão Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Metástase Neoplásica/genética , Fatores de Crescimento Neural/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/genética , Movimento Celular/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Fatores de Crescimento Neural/genéticaRESUMO
Biochemical processes have been associated with the pathogenesis of mild cognitive impairment (MCI) and dementia, including chronic inflammation, dysregulation of membrane lipids and disruption of neurotransmitter pathways. However, research investigating biomarkers of these processes in MCI remained sparse and inconsistent. To collect fresh evidence, we evaluated the performance of several potential markers in a cohort of 57 MCI patients and 57 cognitively healthy controls. MCI patients showed obviously increased levels of plasma TNF-α (p = 0.045) and C-peptide (p = 0.004) as well as decreased levels of VEGF-A (p = 0.042) and PAI-1 (p = 0.019), compared with controls. In addition, our study detected significant correlations of plasma sTNFR-1 (MCI + Control: B = -6.529, p = 0.020; MCI: B = -9.865, p = 0.011) and sIL-2Rα (MCI + Control: B = -7.010, p = 0.007; MCI: B = -11.834, p = 0.003) levels with MoCA scores in the whole cohort and the MCI group. These findings corroborate the inflammatory and vascular hypothesis for dementia. Future studies are warranted to determine their potential as early biomarkers for cognitive deficits and explore the related mechanisms.
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Disfunção Cognitiva/sangue , Inflamação/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores/sangue , Cognição/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
BACKGROUND: The elevated calcium and phosphorus levels in patients undergoing hemodialysis may increase the risk of all-cause mortality. Paricalcitol, as a new vitamin D receptor activator (VDRA), seemed to be effective in reducing the calcium and phosphorus levels. OBJECTIVES: The aim of this study was to compare the efficacy and safety of paricalcitol with other VDRAs in patients undergoing hemodialysis. METHODS: PubMed, Embase, and Web of Science database were systematically reviewed. SELECTION CRITERIA: Studies that focused on the use of paricalcitol for hemodialysis patients were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two independent investigators performed the literature search, data extraction, and assessment of methodological quality. The outcomes were expressed with standard mean difference (SMD), HR, or risk ratio (RR) with 95% CI. RESULTS: Thirteen studies involving 112,695 patients were included in this meta-analysis. Among these studies, four studies were cohort studies and nine studies were randomized controlled trials (RCTs). For cohort studies, they were regarded as being of high quality; for RCTs, only one was classified as being at low risk of bias; and the remaining eight studies were at being unclear risk of bias. Compared with other VDRAs, paricalcitol significantly improved the overall survival (HR =0.86, 95% CI: 0.80, 0.92; P<0.001) and reduced the intact parathyroid hormone (iPTH) (SMD =-0.53, 95% CI: -0.90, -0.17; P=0.004). Paricalcitol offered similar effect with other VDRAs in the control of calcium (SMD =0.32, 95% CI: -0.04, 0.67; P=0.078) and phosphorus (SMD =0.06, 95% CI: -0.26, 0.37; P=0.727) levels. However, the serum change in calcium phosphate product was greater in the paricalcitol group than in the other VDRA group (SMD =2.13, 95% CI: 0.19, 4.07; P=0.031). There was no significant difference in the incidence of adverse events between the two groups (RR =1.02, 95% CI: 0.93, 1.12; P=0.674). CONCLUSION: Paricalcitol was crucial in reducing the mortality in patients undergoing hemodialysis. Moreover, both paricalcitol and other VDRAs were effective in control of the serum iPTH, calcium, and phosphorus levels. Given the potential limitations in this study, more prospective large-scale, well-conducted RCTs are needed to confirm these findings.
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Ergocalciferóis/efeitos adversos , Ergocalciferóis/uso terapêutico , Hiperparatireoidismo/prevenção & controle , Falência Renal Crônica/terapia , Diálise Renal , Estudos de Coortes , Ergocalciferóis/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The aim of the present study is to determine the association of serum lipid level in the above 55-year-old age elderly with ischemic stroke (IS) in Xinjiang regions, China. METHODS: 408 patients with IS and 347 healthy individuals as control in the ≥55-year-old elderly were selected for the present study in Xinjiang province of China from July 2010 to July 2012. Patients were divided into different groups according to the IS subtypes (large-artery atherosclerosis, LAA; cardio-aortic embolism CE; small-artery occlusion, SAO), plague stability, hypertension and diabetes. The serum lipid level including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), Lipoprotein(a) (Lp(a)) and their ratios(TC/HDL, LDL/HDL, ApoA1/ApoB) were measured. RESULTS: Patients in LAA group had higher ratio of TC/HDL, ApoA1/ApoB and lower level of ApoA1 than SAO group(p<0.05); higher level of TC, HDL, LDL, TC/HDL, LDL/HDL, ApoA1/ApoB and lower level of ApoB compared with CE group. Patients in SAO group had higher level of LDL, ApoA1, ApoB, TC/HDL, LDL/HDL and ApoA1/ApoB than CE group. Patients with stable plaque had higher level of HDL and low level of LDL, ApoB, Lp(a), TC/HDL, LDL/HDL and ApoA1/ApoB than unstable plaque group. Patients with hypertension had higher level of TG, ApoB, Lp(a), LDL/HDL and ApoA1/ApoB than non-hypertensive group. Patients with diabetes had higher level of TC, TG, ApoB, TC/HDL, LDL/HDL, ApoA1/ApoB and low level of ApoA1 than non-diabetic group. Multiple logistic regression analysis revealed that high LDL, ApoB, LDL/HDL and ApoA1/ApoB might be the risk factors for ischemic stroke. CONCLUSION: An abnormal serum lipid level of the patients with IS in older Xinjiang population is significantly associated with the stroke subtypes, plaque stability, hypertension and diabetes.
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This systematic review was designed to evaluate the overall efficacy of angiography-guided drug-eluting stent (DES) implantation vs intravascular ultrasound-guided (IVUS) implantation for percutaneous coronary intervention. The electronic databases CENTRAL, PubMed, Cochrane, and EMBASE were searched for systematic reviews to investigate angiography-guided and IVUS-guided DES implantation. We measured the following six parameters in each patient: cardiovascular death, stent thrombosis, target lesion revascularisation (TLR), myocardial infarction (MI), major adverse cardiac events (MACEs), and all-cause death. Twelve studies involving 6268 subjects were included, with 2984 receiving IVUS-guided DES implantation and 3284 using angiography-guided DES implantation. With regard to MACEs, TLR, MI, cardiovascular death, and all-cause death, the IVUS-guided DES implantation group had remarkably improved clinical outcomes. However, there was no significant statistical difference in stent thrombosis between the two groups. Dramatic decrease in MACEs through IVUS guidance was presented by trial sequential analysis. Remarkably improved clinical outcomes, including MACEs, cardiovascular death, all-cause death, and TLR, were identified through IVUS-guided DES implantation in comparison with angiography-guided DES implantation. Nonetheless, the effect on stent thrombosis and MI required further confirmation. In this meta-analysis, eligible randomised clinical trials were warranted to verify the findings and to determine the beneficial effect of IVUS guidance for patients.
Assuntos
Angiografia/métodos , Stents Farmacológicos , Procedimentos Endovasculares/métodos , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: With the wide use of sildenafil in kidney-transplanted patients, it is vital to recognize the effectiveness and safety in clinical practice. METHODS: Full-text articles involving the application of sildenafil after renal transplantation searched out in multiple databases were reviewed. All the meta-analyses were performed with Review Manager 5.0 software and bias analysis of the studies were conducted to examine the quality of articles. In addition, to estimate possible publication bias, funnel plot and the Egger's test were used. RESULT: Finally 7 articles eventually satisfied the inclusion criteria. The penetration ability and maintenance frequency in sildenafil group were much larger than those of control group. Except orgasmic function, domains of the International Index of Erectile Function have showed larger scores in sildenafil group than those of control group. No significant difference of the concentration of cyclosporine was observed between sildenafil and control group. CONCLUSION: In conclusion, this study showed that treatment with sildenaï¬l in renal allograft recipients with erectile dysfunction is a valid and safe option.
Assuntos
Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Transplante de Rim/efeitos adversos , Ereção Peniana/efeitos dos fármacos , Complicações Pós-Operatórias/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico , Ciclosporina/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Masculino , Citrato de Sildenafila/efeitos adversos , Resultado do Tratamento , Vasodilatadores/efeitos adversosRESUMO
In this article, we propose a 3-dimensional graphical representation of protein sequences based on 10 physicochemical properties of 20 amino acids and the BLOSUM62 matrix. It contains evolutionary information and provides intuitive visualization. To further analyze the similarity of proteins, we extract a specific vector from the graphical representation curve. The vector is used to calculate the similarity distance between 2 protein sequences. To prove the effectiveness of our approach, we apply it to 3 real data sets. The results are consistent with the known evolution fact and show that our method is effective in phylogenetic analysis.
RESUMO
The guilt by association (GBA) principle has been widely used to predict gene functions, and a networkbased approach may enhance the confidence and stability of the analysis compared with focusing on individual genes. Fetal growth restriction (FGR), is the second primary cause of perinatal mortality. Therefore, the present study aimed to predict the optimal gene functions for FGR using a networkbased GBA method. The method was comprised of four parts: Identification of differentiallyexpressed genes (DEGs) between patients with FGR and normal controls based on gene expression data; construction of a coexpression network (CEN) dependent on DEGs, using the Spearman correlation coefficient algorithm; collection of gene ontology (GO) data on the basis of a known confirmed database and DEGs; and prediction of optimal gene functions using the GBA algorithm, for which the area under the receiver operating characteristic curve (AUC) was obtained for each GO term. A total of 115 DEGs and 109 GO terms were obtained for subsequent analysis. All DEGs were mapped to the CEN and formed 6,555 edges. The results of GBA algorithm demonstrated that 78 GO terms had a good classification performance with AUC >0.5. In particular, the AUC for 5 of the GO terms was >0.7, and these were defined as optimal gene functions, including defense response, immune system process, response to stress, cellular response to chemical stimulus and positive regulation of biological process. In conclusion, the results of the present study provided insights into the pathological mechanism underlying FGR, and provided potential biomarkers for early detection and targeted treatment of this disease. However, the interactions between the 5 GO terms remain unclear, and further studies are required.