Long Noncoding RNA H19 Overexpression Protects against Hypoxic-Ischemic Brain Damage by Inhibiting miR-107 and Up-Regulating Vascular Endothelial Growth Factor.

Long noncoding RNAs play critical roles in cellular homeostasis, and long noncoding RNA H19 (H19) is implicated in several pathologic conditions. The putative role of H19 in the pathogenesis and progression of hypoxic-ischemic brain damage (HIBD) is not yet understood. Therefore, a series of in vivo and in vitro experiments were designed to investigate the potential roles of H19 in neuronal apoptosis and cognitive dysfunction in HIBD. H19 expression was decreased in HIBD rat models established by partial occlusion of carotid artery. H19 bound to and decreased the expression of miR-107, which also increased VEGF expression. H19 overexpression reduced neuronal apoptosis and alleviated cognitive dysfunction in HIBD rats. The up-regulation of miR-107 reversed the protective effects conferred by H19. In addition, the cell model of HIBD was established by oxygen-glucose deprivation in neuronal cells used. H19 overexpression in oxygen-glucose deprivation neurons increased B-cell lymphoma-2 and decreased B-cell lymphoma-2-associated X, total and cleaved caspase-3 expressions. Taken together, the results showed that H19 expresses at a low level in HIBD. H19 overexpression decreased miR-107 and increased VEGF expression, which resulted in repressed neuronal apoptosis and alleviated cognitive dysfunction. Thus, H19 may serve as a molecular target for translational research for HIBD therapy.

MicroRNA-22-3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5.

Cell death after spinal cord ischemia/reperfusion (I/R) can occur through necrosis, apoptosis, and autophagy, resulting in changes to the immune environment. However, the molecular mechanism of this immune regulation is not clear. Accumulating evidence indicates that microRNAs (miRs) play a crucial role in the pathogenesis of spinal cord I/R injury. Here, we hypothesized miR-22-3p may be involved in spinal cord I/R injury by interacting with interferon regulatory factor (IRF) 5. Rat models of spinal cord I/R injury were established by 12-min occlusion of the aortic arch followed by 48-hr reperfusion, with L4-6 segments of spinal cord tissues collected. MiR-22-3p agomir, a lentivirus-delivered siRNA specific for IRF5, or a lentivirus expressing wild-type IRF5 was injected intrathecally to rats with I/R injury to evaluate the effects of miR-22-3p and IRF5 on hindlimb motor function. Macrophages isolated from rats were treated with miR-22-3p mimic or siRNA specific for IRF5 to evaluate their effects on macrophage polarization. The levels of IL-1ß and TNF-α in spinal cord tissues were detected by ELISA. miR-22-3p was down-regulated, whereas IRF5 was up-regulated in rat spinal cord tissues following I/R. IRF5 was a target gene of miR-22-3p and could be negatively regulated by miR-22-3p. Silencing IRF5 or over-expressing miR-22-3p relieved inflammation, elevated Tarlov score, and reduced the degree of severity of spinal cord I/R injury. Increased miR-22-3p facilitated M2 polarization of macrophages and inhibited inflammation in tissues by inhibiting IRF5, thereby attenuating spinal cord I/R injury. Taken together, these results demonstrate that increased miR-22-3p can inhibit the progression of spinal cord I/R injury by repressing IRF5 in macrophages, highlighting the discovery of a promising new target for spinal cord I/R injury treatment.

Intrathecal morphine versus transversus abdominis plane block for caesarean delivery: a systematic review and meta-analysis.

BACKGROUND: The number of caesarean deliveries has been increasing. Although intrathecal morphine (ITM) can relieve pain and is widely applied in caesarean deliveries, it is associated with many side effects. Transversus abdominis plane block (TAPB), a new analgesic technology, has also began playing a certain role after caesarean delivery, with fewer adverse effects. This study mainly compares the analgesic and adverse effects of ITM and TAPB in caesarean delivery. METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, and Web of Science, for randomised controlled trials (RCTs) published before 9 October, 2020 to compare the effects of ITM and TAPB. Primary outcome of the study was the pain score at rest 24 h after caesarean delivery, whereas the secondary outcomes were the pain score at movement 24 h after operation, postoperative nausea and vomiting (PONV), itching, and morphine consumption. For the outcome assessment, we conducted a sensitivity analysis. RESULT: Six RCTs involving 563 patients and meeting the study inclusion criteria were included in this study. Results indicated no significant difference in the pain score between ITM and TAPB at 24 h of rest or movement. The sensitivity analysis results indicated that the resting pain score (95% CI = - 1.27 to - 0.28; P = 0.002) and 24-h moving pain score (95% CI = - 1.8 to - 0.07; P = 0.03) of the ITM group were lower than those of the TAPB group. The consumption of morphine in the ITM group was lower than in the TAPB group (95% CI = 1.92 to 4.87; P < 0.00001); however, in terms of adverse reactions, the incidence of pruritus (95% CI = 1.17 to 8.26; P = 0.02) and PONV (95% CI = 1.92 to 4.87, P < 0.00001) in the ITM group was higher than in the TAPB group. CONCLUSION: Parturients in the ITM and TAPB groups exhibited similar analgesic effects. However, in the sensitivity analysis performed by eliminating the studies causing heterogeneity, the ITM group was found to have superior analgesic effects compared with the TAPB group, with less morphine consumption. Differently, the TAPB group displayed less side effects such as PONV. Therefore, TAPB is still a valuable analgesia option for patients who cannot use ITM for analgesia after caesarean delivery or those having a high risk of PONV. TRIAL REGISTRATION: Registration number: Registered on Prospero with the registration number of CRD42020210135 .

PRR34-AS1 overexpression promotes protection of propofol pretreatment against ischemia/reperfusion injury in a mouse model after total knee arthroplasty via blockade of the JAK1-dependent JAK-STAT signaling pathway.

Long noncoding RNAs have been documented to be protective against ischemia/reperfusion (I/R) injury. However, few research works have focused on the protective effects of PRR34-AS1 on I/R injury after total knee arthroplasty (TKA). The objective of the present study was to investigate the possible effect of PRR34-AS1 on I/R injury after TKA. A mouse model with I/R injury after TKA was established. The interaction between PRR34-AS1 and Janus kinase 1 (JAK1) was examined and thoroughly investigated. Next, the effects of PRR34-AS1 on the expression of apoptosis-related proteins, JAS-signal transducer and activator of transcription (STAT) signaling pathways, and inflammation-related genes, chondrocyte proliferation, and apoptosis were analyzed after gain- and loss-of-function experiments. Attenuated symptoms were observed in mice pretreated with propofol, which was evidenced by decreased positive expression rate of JAK1 protein and superoxide dismutase content along with increased malondialdehyde content and IL-10 levels. PRR34-AS1 was poorly expressed in mice with I/R injury after TKA. JAK1 was a target of PRR34-AS1. Upregulated PRR34-AS1 diminished expression of JAK1, STAT1, JAK2, and STAT3 as well as cell apoptosis, while enhancing cell proliferation in vitro. Furthermore, JAK1 silencing could reverse the suppressed cell proliferation and enhanced cell apoptosis of chondrocytes imposed by silencing PRR34-AS1. Upregulation of PRR34-AS1 can potentially relieve I/R injury after TKA in mice pretreated with propofol through inhibition of the JAS-STAT signaling pathway by targeting JAK1.

Effect of ketamine combined with lidocaine in pediatric anesthesia.

BACKGROUND: We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. METHODS: This case-control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High-performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. RESULTS: Intra- and post-operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine-lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine-lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine-lidocaine complex, elimination half-life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. CONCLUSIONS: Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half-life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.

[Influence of capsaicin sensitive C fibers denervation on lung ischemia-reperfusion injury].

OBJECTIVE: To investigate the role of Capsaicin sensitive C fibers (CapsCF) denervation in lung ischemia-reperfusion (IR) injury and the possible mechanism related to oxidative stress. METHODS: Thirty two male New Zealand rabbits were randomized into four groups: IR group (IR), sham group (S), capsaicin pretreated IR group (CIR), and capsaicin pretreated sham group (CS). The rabbits in CIR and CS groups were pretreated with capsaicin (100 mg/kg) to induce functional ablation of CapsCF, and then subjected to lung ischemia and reperfusion. The rabbits in IR group were not treated with capsaicin before lung ischemia and reperfusion. Thereafter, blood samples and lung tissue samples were obtained for blood gas and biochemical analyses, including the measurements of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT). The lung wet/dry weight ratio and histopathological changes were also assessed. RESULTS: Compared to S and CS group, partial pressure of oxygen (PO2) values in IR and CIR groups significantly decreased (P < 0.05). In contrast, the alveolar-arterial oxygen gradient (A-aDO2), lung wet/dry weight ratio increased in IR and CIR groups (P < 0.05). Capsaicin pretreatment in CIR group increased lung wet/dry weight ratio and lung pathologic lesions, along with higher level of MDA and lower activity of SOD and CAT (P < 0.05, vs. IR). CONCLUSION: Denervation of CapsCF aggravated lung ischemia-reperfusion injury of rabbits, which seems to be closely related to the excerbation of oxidative stress.

Ct-based diagnosis of sarcopenia as a prognostic factor for postoperative mortality after elective open-heart surgery in older patients: a cohort-based systematic review and meta-analysis.

Background: Cardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis. Methods: We conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Results: A total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke. Conclusion: Sarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

[Effect of calcitonin gene-related peptide receptor on expression of NF-kappa b in rat lung after ischemia reperfusion injury].

OBJECTIVE: To study the effect of calcitonin gene-related peptide (CGRP) receptor on the expression of nuclear factor-kappa b (NF-kappa b) in rat lung after ischemia reperfusion injury. METHODS: Thirty-two adult male Sprague Dawley rats were divided into four groups (8 per group) as follows: sham group (sham thoracotomy), IR group (occlusion of the left pulmonary hilus for 0.5 h followed by reperfusion for 4 h), another two groups were pretreated with CGRP or CGRP8-37 (a CGRP receptor antagonist). Arterial blood was collected at the end of reperfusion to test blood gas, arterial oxygen pressure (PaO2) and alveolar arterial oxygen difference (A-aDO2). Lung tissue was collected to measure the expression level of NF-kappa b mRNA by using RT-PCR. Light microscopic changes of lung tissue were also examined. RESULTS: Compared with sham group, rats in the IR group had poorer gas exchange (lower PaO2, higher A-aDO2), upregulation of NF-kappa b mRNA expression (P < 0.05) and more severe histological injury. Pretreatment with CGRP improved gas exchange function, significantly decreased NF-kappa b mRNA expression (P < 0.05 versus IR and CGRP837 groups). Administration of CGRP also attenuated IR-induced pathological lesions. The pretreatment of CGRP8-37 showed the opposite results to those of CGRP. CONCLUSION: CGRP receptor plays an important protective role in lung IR injury, which is closely related to the downregulation of NF-kappa b mRNA.

Effect of sarcopenia in predicting postoperative mortality in emergency laparotomy: a systematic review and meta-analysis.

BACKGROUND: While emergency laparotomy has been associated with high rates of postoperative mortality and adverse events, preoperative systematic evaluation of patients may improve perioperative outcomes. However, due to the critical condition of the patient and the limited operation time, it is challenging to conduct a comprehensive evaluation. In recent years, sarcopenia is considered a health problem associated with an increased incidence of poor prognosis. This study aimed to investigate the effect of sarcopenia on 30-day mortality and postoperative adverse events in patients undergoing emergency laparotomy. METHODS: We systematically searched databases including PubMed, Embase, and Cochrane for all studies comparing emergency laparotomy in patients with and without sarcopenia up to March 1, 2022. The primary outcome was of 30-day postoperative mortality. Secondary outcomes were the length of hospital stay, the incidence of adverse events, number of postoperative intensive care unit (ICU) admissions, and ICU length of stay. Study and outcome-specific risk of bias were assessed using the Quality in Prognosis Studies (QUIPS) tool. We rated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). RESULT: A total of 11 eligible studies were included in this study. The results showed that patients with sarcopenia had a higher risk of death 30 days after surgery (OR = 2.42, 95% CI = 1.93-3.05, P < 0.00001). More patients were admitted to ICU after surgery (OR = 1.58, 95% CI = 1.11-2.25, P = 0.01). Both the ICU length of stay (MD = 0.55, 95% CI = 0.05-1.06, P = 0.03) and hospital length of stay (MD = 2.33, 95% CI = 1.33-3.32, P < 0.00001) were longer in the sarcopenia group. The incidence of postoperative complications was also significantly higher in patients with sarcopenia (OR = 1.78, 95% CI = 1.41-2.26, P < 0.00001). CONCLUSION: In emergency laparotomy, sarcopenia was associated with increased 30-day postoperative mortality. Both the lengths of stay in the ICU and the total length of hospital stay were significantly higher than those in non-sarcopenic patients. Therefore, we concluded that sarcopenia can be used as a tool to identify preoperative high-risk patients, which can be considered to develop new postoperative risk prediction models. Registration number Registered on Prospero with the registration number of CRD42022300132.

Corrigendum: Combined Scutellarin and C18H17NO6 Imperils the Survival of Glioma: Partly Associated With the Repression of PSEN1/PI3K-AKT Signaling Axis.

[This corrects the article DOI: 10.3389/fonc.2021.663262.].

[Apoptosis inhibition of capsaicin on myocardial ischemia-reperfusion injury in rats].

OBJECTIVE: To determine apoptosis inhibition effect of capsaicin on myocardial ischemia-reperfusion injury in rats and its underlying mechanisms. METHODS: The rat model of myocardial ischemia-reperfusion injury was established by ligating the left anterior descending coronary artery for 45 min and then loosing the ligation (reperfusion) for 120 min. Twenty healthy male rats were randomly divided into sham group, control group (I/R), capsaicin group (CAP+I/R), capsazepine group (CAPZ+CAP+I/R), and S-3144 group (S-3144+CAP+I/R). All drugs were delivered bolusly into left ventricle (LV)via right carotid artery at 10 min and 5 min before ischemia. Rats in I/R group and sham group only received vehicle injection. Myocardial protection was assessed by measurements of heart rate (HR) and left ventricular developed pressure (LVDP). The pathologic changes of myocardial tissue in each group were observed under light microscopy. TUNEL-positive nuclei were tested by immunofluorescent method. RESULTS: At 120 min after reperfusion, there were significant increases of HR and LVDP in CAP+I/R group when compared with control group, capsazepine group, and S-3144 group (P < 0.05). The apoptotic index in the sham group was lower than that in the groups with ischemia/reperfusion injury (P < 0.05). Among the groups with ischemia/reperfusion injury, CAP+I/R group had the lowest apoptotic index (P < 0.05). CONCLUSION: CAP could generate cardioprotection associated with cardiomyocyte apoptosis inhibition in vivo, likely by stimulating TRPV1 and further activating NK1 receptor.

The role of immune cells in the course of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the central nervous system. The pathological manifestations mainly consist of α-synuclein accumulation, degeneration and death of dopaminergic neurons, and insufficient dopamine secretion. There are many pathophysiological mechanisms leading to these pathological changes. The role of autoimmunity in Parkinson's disease is one of the academic hotspots in recent years. Many types of immune cells actively participate in the pathogenesis of Parkinson's disease, such as dendritic cells, microglia, T lymphocytes, B lymphocytes and natural killer (NK) cells, which lead to abnormal immune response in Parkinson's disease patients. Therefore, this paper focuses on reviewing the research progress of immune cells in Parkinson's disease.

MiR-132-3p Modulates MEKK3-Dependent NF-κB and p38/JNK Signaling Pathways to Alleviate Spinal Cord Ischemia-Reperfusion Injury by Hindering M1 Polarization of Macrophages.

Spinal cord ischemia-reperfusion (SCIR) injury is a serious complication of open surgical and endovascular aortic procedures. MicroRNA-132-3p (miR-132-3p) has been reported to be involved in the progression of various diseases, but its role in SCIR injury is unclear. Thus, we aimed in this study to investigate the mechanism of miR-132-3p in SCIR injury and explore its pathway as a therapeutic target for SCIR injury. We first constructed a SCIR injury rat model and documented motor function in the model. Reverse transcription quantitative polymerase chain reaction (RT-qPC)R and Western blot analysis were used to detect the expression of miR-132-3p and mitogen-activated protein kinase kinase kinase 3 (MEKK3) in SCIR injury rats. The interaction between miR-132-3p and MEKK3 was identified by dual-luciferase reporter gene assay. Then, the effects of miR-132-3p and MEKK3 on macrophage M1 polarization were evaluated in vitro and in vivo by altering their expression in macrophages of SCIR injury rats, with treatments altering the nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)/p38 signaling pathways using SP600125, SB203580, or PDTC. The SCIR injury rats had a high Tarlov score and low miR-132-3p expression along with high MEKK3 expression. miR-132-3p could directly bind to MEKK3, and that macrophage M1 polarization and inflammation could be inhibited by overexpression of miR-132-3p through downregulating MEKK3 and inactivating the NF-κB and p38/JNK signaling pathways. Besides, increased miR-132-3p expression could decrease the injured rat Tarlov score. Overall, our study demonstrated that miR-132-3p can suppress M1 polarization of macrophages and alleviate SCIR injury by blocking the MEKK3-dependent activation of the NF-κB and p38/JNK signaling pathway. Thus, miR-132-3p and its downstream pathways may be useful targets to alleviate the symptoms of SCIR injury.

Manual Removal versus Spontaneous Delivery of the Placenta at Cesarean Section: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Several randomized clinical trials (RCTs) investigated the effects of the manual placental removal on hemorrhage or other hemorrhage-related complications compared with the spontaneous placental removal during cesarean section (CS), while the results remained controversial and were inconsistent. The purpose of this meta-analysis was to quantify the pooled effects of the methods of placental removal on hemorrhage during CS. PATIENTS AND METHODS: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Heterogeneity was tested by I 2 statistics and Q-statistic. The random-effects model or fixed-effects model were used to calculate the pooled effect for the included studies according to heterogeneity. And the term of standardized mean difference (SMD) with 95% confidence intervals (CI) was pooled and estimated the effects across all studies. RESULTS: A total of nine RCTs were included in this meta-analysis. Compared with spontaneous group, manual placental removal increased the amount of hemorrhage (SMD = 0.53, 95% CI [0.12, 0.94]; Z = 2.54, P = 0.011) and increased the risk of endometritis (OR = 1.84, 95% CI [1.31, 2.58]; Z = 3.52, P < 0.0001). In contrast, there was no significant difference concerning the operating time (SMD = -0.30, 95% CI [-0.85, 0.24]; Z = 1.09, P = 0.276), the length of hospital stays (SMD = 0.11, 95% CI [-0.08, 0.30]; Z = 1.11, P = 0.265), and blood transfusion requirement (OR = 1.36, 95% CI [0.91, 2.04]; Z = 1.52, P = 0.129), respectively. CONCLUSION: Comparing with spontaneous placental removal, manual placental removal appeared to be less positive effect during CS. Because of the limitations of this meta-analysis, more high-quality RCTs are needed to confirm our findings.

Combined Scutellarin and C18H17NO6 Imperils the Survival of Glioma: Partly Associated With the Repression of PSEN1/PI3K-AKT Signaling Axis.

Glioma, the most common intracranial tumor, harbors great harm. Since the treatment for it has reached the bottleneck stage, the development of new drugs becomes a trend. Therefore, we focus on the effect of scutellarin (SCU) and its combination with C18H17NO6 (abbreviated as combination) on glioma and its possible mechanism in this study. Firstly, SCU and C18H17NO6 both suppressed the proliferation of U251 and LN229 cells in a dose-dependent manner, and C18H17NO6 augmented the inhibition effect of SCU on U251 and LN229 cells in vitro. Moreover, there was an interactive effect between them. Secondly, SCU and C18H17NO6 decreased U251 cells in G2 phase and LN229 cells in G2 and S phases but increased U251 cells in S phase, respectively. Meanwhile, the combination could further reduce U251 cells in G2 phase and LN229 cells in G2 and S phases. Thirdly, SCU and C18H17NO6 both induced the apoptosis of U251 and LN229. The combination further increased the apoptosis rate of both cells compared with the two drugs alone. Furthermore, SCU and C18H17NO6 both inhibited the lateral and vertical migration of both cells, which was further repressed by the combination. More importantly, the effect of SCU and the combination was better than positive control-temozolomide, and the toxicity was low. Additionally, SCU and C18H17NO6 could suppress the growth of glioma in vivo, and the effect of the combination was better. Finally, SCU and the combination upregulated the presenilin 1 (PSEN1) level but inactivated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling in vitro and in vivo. Accordingly, we concluded that scutellarin and its combination with C18H17NO6 suppressed the proliferation/growth and migration and induced the apoptosis of glioma, in which the mechanism might be associated with the repression of PSEN1/PI3K-AKT signaling axis.

Coronary angiography or not after cardiac arrest without ST segment elevation: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to review the available evidence and evaluate the necessity of immediate coronary angiography (CAG) to obtain positive outcomes for out-of-hospital cardiac arrest (OHCA) patients without ST segment elevation. DATA SOURCES: Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases. STUDY SELECTION: We included observational and case-control studies of outcomes among individuals without ST segment elevation experiencing OHCA who had immediate, delayed, or no CAG. DATA EXTRACTION: We extracted study details, as well as patient characteristics and outcomes. DATA SYNTHESIS: Six studies (n = 2665) investigating mortality until discharge demonstrated a significant increase in survival benefit with early CAG (odds ratio [OR] = 1.78; 95%CI = 1.51-2.11; I = 81%; P < .0001). Seven studies (n = 2909) showed a significant preservation of neurological functions with early CAG at discharge (OR = 1.66; 95%CI = 1.37-2.02; P < .00001). Four studies (n = 1357) investigating survival outcomes with middle-term follow-up revealed no significant benefit with early CAG (OR = 1.21; 95%CI = 0.93-1.57; I = 66%; P = .15). CONCLUSIONS: Our meta-analysis demonstrates that there may be significant benefits in performing immediate CAG on patients who experience OHCA without ST segment elevation.

The Effects of Safflower Yellow on Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Randomized, Controlled Clinical Trial.

OBJECTIVES: To evaluate the efficacy of safflower yellow in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: In a prospective, randomized, controlled trial, 127 patients who met the inclusion criteria were enrolled and were randomly divided into two groups. The control group included 64 patients treated according to the global strategy for diagnosis, management, and prevention of COPD (www.goldcopd.org, updated 2011). The intervention group included 63 patients who received intravenous infusions of safflower yellow (100 mg of safflower yellow dissolved in 250 ml 0.9% saline) once daily for 14 consecutive days in addition to standard diagnosis and treatment. The difference in the average length of the hospital stay between the two groups of patients was determined. The follow-up period was 28 days; the differences in symptoms, clinical indicators, and 28-day mortality in the two groups were compared. Statistical analysis was conducted using SPSS 22.0 software to determine whether there were statistically significant differences (P <0.05) between groups. RESULTS: There were no statistically significant differences between the intervention group and the control group in changes in secondary indicators. There were no statistically significant differences in the 28-day mortality or in the survival curves of the two groups (P=0.496 and P=0.075, respectively). Safflower yellow treatment of AECOPD may relieve the patient's clinical symptoms, such as dyspnoea, shorten the average length of hospital stay (P=0.006, respectively), and decrease the duration of mechanical ventilation. CONCLUSION: Safflower yellow in the treatment of AECOPD has a degree of clinical value. This trial is registered under the identifier ChiCTR-IPR-17014176.

microRNA-128 enhances neuroprotective effects of dexmedetomidine on neonatal mice with hypoxic-ischemic brain damage by targeting WNT1.

OBJECTIVE: Hypoxic-ischemic brain damage (HIBD) is a major cause of acute mortality and chronic neurological morbidity in infants and children. Dexmedetomidine (DEX) is an effective choice in HIBD treatment. Recent findings have revealed that microRNA-128 (miR-128) is implicated in cerebral ischemia reperfusion. Hence, this study aimed to investigate the role of miR-128 in HIBD. METHODS: HIBD models of neonatal mice were established. HIBD mice were treated with DEX, and injected with agomir (ago)-miR-128 or antagomir (anti)-miR-128 into the lateral ventricles to explore the influence of miR-128 on the neuroprotective effects of DEX on HIBD. Subsequently, the mice body weight, left/right (L/R) brain weight ratio, left-brain water content as well as learning and memory abilities were measured. Furthermore, the pathological changes of brain tissues and apoptosis rate of nerve cells were determined. The potential relationship between miR-128 and WNT1 was analyzed. RESULTS: Over-expression of miR-128 caused an increase in mouse body weight, L/R brain weight ratio, and learning and memory abilities, while led to a decline in left-brain water content, brain tissue injury and apoptosis rate of nerve cells in DEX-treated HIBD mice. WNT1 was targeted and negatively regulated by miR-128. Silencing of WNT1 exerted the same effect as miR-128 on enhancing the neuroprotective effect of DEX on HIBD mice. CONCLUSION: Collectively, miR-128 enhanced neuroprotective effect of DEX on HIBD neonatal mice by inhibiting WNT1.

Long non-coding RNA MALAT1 sponges microRNA-429 to regulate apoptosis of hippocampal neurons in hypoxic-ischemic brain damage by regulating WNT1.

Hypoxic-ischemic brain damage (HIBD) is a common neurological disorder. Emerging reports reveal that long non-coding RNAs and microRNAs (miRs) are implicated in the progress of HIBD. In this study we tried to ascertain whether lncRNA MALAT1, with the involvement of miR-429 and WNT1, affects HIBD. Initially, a HIBD mouse model was established. Then, we treated HIBD mice with dexmedetomidine (DEX) and then up- or down-regulated the expression of MALAT1, miR-429 and WNT1 in HIBD mice and neurons. Meanwhile, brain injury and hippocampal neuronal apoptosis were evaluated. Moreover, the interaction among MALAT1, miR-429 and WNT1 in HIBD was investigated. MALAT1 and WNT1 were high-expressed in brain tissues of HIBD mice while miR-429 was low-expressed in brain tissues from HIBD mice. Interestingly, MALAT1 silencing was observed to enhance the cerebral protection of DEX against HIBD. In addition, it was confirmed that MALAT1 sponged miR-429 downregulating expression of miR-429, thereby promoting apoptosis of hippocampal neurons. This effect was achieved through up-regulating the level of WNT1. Taken together, this study demonstrates that silencing of MALAT1 enhances the cerebral protection of DEX against HIBD by suppressing WNT1 expression through miR-429.