RESUMEN

Aging is characterized by a functional decline in organism fitness over time due to a complex combination of genetic and environmental factors [ 1-4]. With an increasing elderly population at risk of age-associated diseases, there is a pressing need for research dedicated to promoting health and longevity through anti-aging interventions. The roundworm Caenorhabditis elegans is an established model organism for aging studies due to its short life cycle, ease of culture, and conserved aging pathways. These benefits also make the worm well-suited for high-throughput screening (HTS) methods to study biomarkers of the molecular changes, cellular dysfunction, and physiological decline associated with aging. Within this review, we offer a summary of recent advances in HTS techniques to study biomarkers of aging in C. elegans.

Asunto(s)

RESUMEN

Minimally invasive puncture combined with urokinase is widely used in the treatment of hypertensive intracerebral hemorrhage (HICH). However, the appropriate frequency of urokinase following minimally invasive puncture in patients is still unclear. In total, 55 patients were enrolled in this study. According to the frequency of urokinase (10.0 â€‹× â€‹104 units) administration, 30 patients received urokinase at Q4h, while the other 25 patients received urokinase at Q8h. In the univariate analysis, preoperative GCS (p â€‹= â€‹0.0002), postoperative GCS (p â€‹= â€‹0.0007), the volume of residual hematoma (p â€‹= â€‹0.0179), and the frequency of urokinase (p â€‹= â€‹0.0110) were associated with unfavorable outcomes in patients with HICH in the basal ganglia. The multivariate analysis revealed that the frequency of urokinase was independently associated with unfavorable outcomes in patients with HICH in the basal ganglia (p â€‹= â€‹0.038, 1.109-35.380). The drainage time was significantly shorter in the Q4h group (14.17 â€‹± â€‹0.86 â€‹h) than in the Q8h group (27.36 â€‹± â€‹1.39 â€‹h) (p â€‹< â€‹0.0001). The GOS (4.37 â€‹± â€‹0.18), BI (75.52 â€‹± â€‹2.39), and mRS (1.67 â€‹± â€‹0.24) in the Q4h group were significantly ameliorated compared to those in the Q8h group (GOS 3.56 â€‹± â€‹0.18, BI 64.13 â€‹± â€‹2.22, and mRS 2.64 â€‹± â€‹0.28, respectively) (p â€‹= â€‹0.0004, p â€‹= â€‹0.0002, and p â€‹= â€‹0.0018) at 3 months of follow-up. Thus, minimally invasive puncture combined with urokinase is safe and efficient. Increasing the frequency of urokinase administration can produce faster and better postoperative recovery for patients with HICH in the basal ganglia.

Asunto(s)

RESUMEN

Background: Differences in microRNA (miRNA) expression after hypertensive intracerebral hemorrhage (HICH) have been reported in human and animal models. miRNA-145 plays an important role in vascular endothelial cells. The purpose of this work was to determine the role of miR-145-5p in HICH and the molecular mechanisms by which it acts. Methods: In this study, we constructed a model of hemoglobin-induced HICH in rats and used thrombin-treated human brain microvascular endothelial cells (hBMECs) to create a HICH cell model. To determine brain damage, we tested the rats' neurological performance and measured the cerebral water level of their brain tissue. Cell counting kit 8 (CCK8) was used to determine the viability of cells. Apoptosis was detected using the terminal TdT-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry (FCM). Starbase and TargetScan were used to predict and confirm target genes. Luciferase reporter gene experiments were used to confirm the predictions. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to identify the associated genes and proteins. Results: We observed a reduction in miRNA-145-5p expression in both the HICH cell model and the rat model. miRNA-145-5p overexpression increased cell survival and preserved newly created blood vessels and vascular permeability in hBMECs. MiRNA-145-5p has been predicted to target matrix metalloproteinase 2 (MMP2). Additionally, MMP2 was identified as a miR-145-5p target gene and shown to be substantially expressed in the thrombin-treated hBMECs. MMP2 overexpression suppressed miR-145-5p-mediated effects and increased hBMECs' malfunction. In comparison with controls, the HICH + AAV-miR-145-5p group performed better on behavioral tests and had less brain water. Additionally, miR-145-5p injection increased ZO-1 and occludin expressions, as determined by immunohistochemical staining in the HICH rat model. Conclusions: miRNA-145-5p protects against brain injury following HICH by targeting MMP2, suggesting a possible therapeutic mechanism for HICH.

RESUMEN

BACKGROUND: Recently, minimal invasive surgery (MIS) has been applied as a common therapeutic approach for treatment of hypertensive intracerebral hemorrhage (HICH). However, the efficacy and safety of MIS is still controversial compared with conservative medical treatment or conventional craniotomy. This meta-analysis aimed to systematically assess the safety and efficacy of MIS compared with conservative method and craniotomy in treating HICH patients. METHODS: PubMed, Embase, Web of Science, and Cochrane Controlled Trials Register were used to identify relevant studies on MIS treatment of HICH up to November 2017. This study evaluated Glasgow Outcome Scale (GOS) score, Activities of Daily Living (ADL) score, pulmonary infection rate, mortality rate, and rebleeding rate for patients who underwent MIS, or conservative method, or craniotomy. Subgroup analyses were performed to compare randomization versus non-randomization and large hematoma versus small or mild hematoma. Begg's test and Egger's test were used to determine the potential presence of publication bias. RESULTS: Sixteen studies consisting of 1912 patients were included in this study to compare the efficacy and safety of MIS to conservative method or craniotomy. MIS contributed to a significant improvement on the prognosis of the patients comparing with conservative group or craniotomy group. Patients undergoing MIS had a lower mortality rate when compared to those receiving conservative method. Also, MIS led to a notable reduction of rebleeding rate and an effective improvement of the patient's quality of life by contrast with craniotomy. No obvious difference was found in terms of the pulmonary infection rate among the comparisons of three treatment methods. Randomization is not the potential source of heterogeneity, but hematoma volume may be a risk factor for post-operative mortality rate. No statistical evidence of publication bias among studies was found under most of comparison models. CONCLUSION: This meta-analysis suggests that minimal invasive surgery is an efficient and safe method for the treatment of hypertensive intracerebral hemorrhage, which is associated with a low mortality rate and rebleeding rate, as well as a significant improvement of the prognosis and the quality life of patients when compared with conservative medical treatment or craniotomy.

Asunto(s)

RESUMEN

BACKGROUND: LncRNA-FENDRR is a kind of endothelial genes critical for vascular development. Moreover, miR-126 and vascular endothelial growth factor A (VEGFA) are also involved in the physiological process of vascular endothelial cells. This study aimed to the underlying mechanism of FENDRR involving miR-126 and VEGFA in hypertensive intracerebral hemorrhage (HICH). METHODS: C57BL/6 mice were chosen to establish HICH model. The expression of FENDRR, miR-126, and VEGFA at mRNA level was determined by qRT-PCR. The protein expression of VEGFA was assessed using Western blot. RIP assay and RNA pull-down assay were used to the relationship between FENDRR and miR-126. Flow cytometry was used to analyze cell apoptosis. RESULTS: The levels of FENDRR and VEGFA were increased, and miR-126 expression was decreased in vascular endothelial cells (VECs) from the right brain of model mice and human brain microvascular endothelial cells (HBMECs) treated by thrombin. Overexpression of FENDRR promoted the apoptosis of HBMECs. FENDRR regulating VEGFA participated in HBMECs apoptosis through targeting miR-126. Downregulation of FENDRR was indicated to relieve the HICH in mice. CONCLUSIONS: FENDRR could promote the apoptosis of HBMECs via miR-126 regulating VEGFA in HICH.

Asunto(s)

RESUMEN

OBJECTIVE The goal of this study was to investigate the effectiveness and practicality of endoscopic surgery for treatment of supratentorial hypertensive intracerebral hemorrhage (HICH) compared with traditional craniotomy. METHODS The authors retrospectively analyzed 151 consecutive patients who were operated on for treatment of supratentorial HICH between January 2009 and June 2014 in the Department of Neurosurgery at Chinese PLA General Hospital. Patients were separated into an endoscopy group (82 cases) and a craniotomy group (69 cases), depending on the surgery they received. The hematoma evacuation rate was calculated using 3D Slicer software to measure the hematoma volume. Comparisons of operative time, intraoperative blood loss, Glasgow Coma Scale score 1 week after surgery, hospitalization time, and modified Rankin Scale score 6 months after surgery were also made between these groups. RESULTS There was no statistically significant difference in preoperative data between the endoscopy group and the craniotomy group (p > 0.05). The hematoma evacuation rate was 90.5% ± 6.5% in the endoscopy group and 82.3% ± 8.6% in the craniotomy group, which was statistically significant (p < 0.01). The operative time was 1.6 ± 0.7 hours in the endoscopy group and 5.2 ± 1.8 hours in the craniotomy group (p < 0.01). The intraoperative blood loss was 91.4 ± 93.1 ml in the endoscopy group and 605.6 ± 602.3 ml in the craniotomy group (p < 0.01). The 1-week postoperative Glasgow Coma Scale score was 11.5 ± 2.9 in the endoscopy group and 8.3 ± 3.8 in the craniotomy group (p < 0.01). The hospital stay was 11.6 ± 6.9 days in the endoscopy group and 13.2 ± 7.9 days in the craniotomy group (p < 0.05). The mean modified Rankin Scale score 6 months after surgery was 3.2 ± 1.5 in the endoscopy group and 4.1 ± 1.9 in the craniotomy group (p < 0.01). Patients had better recovery in the endoscopy group than in the craniotomy group. Data are expressed as the mean ± SD. CONCLUSIONS Compared with traditional craniotomy, endoscopic surgery was more effective, less invasive, and may have improved the prognoses of patients with supratentorial HICH. Endoscopic surgery is a promising method for treatment of supratentorial HICH. With the development of endoscope technology, endoscopic evacuation will become more widely used in the clinic. Prospective randomized controlled trials are needed.

Asunto(s)

RESUMEN

BACKGROUND: Previous studies reported that the mild hypothermia therapy (MHT) could significantly improve the clinical outcomes for patients with hypertensive intracerebral hemorrhage (HICH). Therefore, this meta-analysis was conducted to systematically assess whether the addition of local MHT (LMHT) could significantly improve the efficacy of minimally invasive surgery (MIS) in treating HICH. METHODS: Randomized clinical trials on the combined application of MIS and LMHT (MIS+LMHT) vs MIS alone for treating HICH were searched up to September 2016 in databases. Response rate and mortality rate were the primary outcomes, and the neurologic function and Barthel index were the secondary outcomes. Side effects were also analyzed. RESULTS: Totally, 28 studies composed of 2,325 patients were included to compare the efficacy of MIS+LMHT to MIS alone. The therapeutic effects of MIS+LMHT were significantly better than MIS alone. The pooled odds ratio of response rate and mortality rate was 2.68 (95% confidence interval [CI]=2.22-3.24) and 0.43 (95% CI=0.32-0.57), respectively. In addition, the MIS+LMHT led to a significantly better improvement in the neurologic function and activities of daily living. The incidence of pneumonia was similar between the two treatment methods. CONCLUSION: These results indicated that compared to MIS alone, the MIS+LMHT could be more effective for the acute treatment of patients with HICH. This treatment modality should be further explored and optimized.

RESUMEN

BACKGROUND: Hypertension is the most common cause of intracerebral haemorrhages (ICHs), yet the short-term impact factors associated with hypertensive intracerebral haemorrhages (HICHs) in patients who undergo different surgical treatments are still unknown. MATERIALS AND METHODS: All consecutive patients with acute HICHs admitted to our hospital from January 2012 to March 2015 were enrolled in the study. Patients were either randomly divided or assigned according to their family's preference into three groups (those undergoing minimally invasive aspiration, keyhole craniotomy or haematoma aspiration with extended pterional and decompressive craniotomy). Patients' information and clinical characteristics were collected to identify risk factors influencing the short-term effects of the procedures. RESULTS: There were significant differences among the groups: haematoma aspiration with extended pterional and decompressive craniotomy was the optimal method, resulting in fewer complications, higher Glasgow Outcome Scale (GOS) scores and better short-term outcomes. Surgical treatment, Glasgow Coma Scale (GCS) scores, haemorrhage volume and degree of midline shift were risk factors for the short-term effects associated with HICH. CONCLUSIONS: Haematoma aspiration with extended pterional and decompressive craniotomy is suitable for treating HICH patients. Surgical treatment, GCS score, haemorrhage volume and degree of midline shift influence the short-term effects observed following HICH surgery.

Asunto(s)

RESUMEN

OBJECT: The prevalence of patients with asymptomatic unruptured intracranial aneurysms (UIAs) increases with the advancing age of the general population. The goal of the present study was to identify risk factors for the growth of UIAs detected with serial MR angiography (MRA) in patients 70 years of age or older. METHODS: This prospective study enrolled 79 patients (age range 70-84 years) with 98 UIAs. Patients were followed up every 4 months, including an assessment of the aneurysm diameter and morphological changes on MRA, neurological status, and other medical conditions. Aneurysm growth was categorized into two different patterns on the basis of the MRA findings: 1) maximum increase in aneurysm diameter of 2 mm or more; and 2) obvious morphological change, such as the appearance of a bleb. RESULTS: The mean duration of follow-up was 38.5 months (250.2 patient-years). Aneurysm rupture did not occur, but aneurysm growth was observed in 8 aneurysms (8 patients) during the study period. Univariate analysis showed that female sex, patient age ≥ 75 years, and an aneurysm location in the internal carotid artery (ICA) or middle cerebral artery (MCA) were associated with aneurysm growth (p = 0.04, p = 0.04, and p < 0.001, respectively). Multivariate analysis demonstrated that female sex was the only independent predictor of aneurysm growth (p = 0.0313, OR 2.3, 95% CI 1.3-30.2). CONCLUSIONS: Female sex is an independent risk factor for the growth of UIAs in elderly patients. In addition, an age ≥ 75 years and aneurysm location in the ICA or MCA are characteristics that may warrant additional attention during follow-up imaging.

Asunto(s)

RESUMEN

BACKGROUND: Mental disorders are commonly observed among surgically treated patients with hypertensive intracerebral hemorrhage (HICH), leading to serious negative impacts on the patient's treatment, rehabilitation, and prognosis. The study aimed to establish the prevalence rates and risk factors for mental disorders following the surgical treatment of HICH. METHODS: This was a prospective study. Surgically treated patients with HICH were assessed 6 months following surgical treatment. The sociodemographic data were obtained from each subject, and clinical characteristics were collected for each patient from his or her hospital records. Mental disorder-related risk factors were examined using unpaired t-tests for continuous variables and χ(2) for categorical data, respectively, followed by multiple logistic regression analysis. RESULTS: A total of 96 patients were recruited for this study. The incidence of mental disorders following surgical treatment of HICH was 32.3%. Univariate analysis revealed that the occurrence of postoperative mental disorders was correlated with gender, income, social interaction, relationship between family members, hematoma localization, hematoma volume, preoperative Glasgow Coma Scale (GCS) score, surgical approach, Barthel Index, hospitalization time, and discharged patients' caregivers. Multivariate logistic regression analysis indicated that female patients, social barriers, surgical treatment with a craniotomy, and bad relationship between family members were the independent risk factors for mental disorders following surgical treatment of HICH. CONCLUSIONS: Postoperative mental disorders in patients with HICH were more likely to occur in female patients and patients who faced social barriers, those who were treated with a craniotomy, and those who experienced bad relationships between their family members. More attention and supports should be provided to this group of patients.

Asunto(s)