Clinical Application and Research Progress of Remimazolam for Pediatric Patients.

Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.

Top 100 most-cited articles on tau protein: a bibliometric analysis and evidence mapping.

Background: Tau, a microtubule-associated protein extensively distributed within the central nervous system (CNS), exhibits close associations with various neurodegenerative disorders. Here, we aimed to conduct a qualitative and quantitative bibliometric study of the top 100 most-cited publications on tau protein and reveal the current research hotspots and future perspectives. Methods: The relevant literature was retrieved from the Web of Science Core Collection. CiteSpace (v6.2.R4) and VOSviewer (1.6.19) were adopted for bibliometric analysis with statistical and visual analysis. Results: Citations per article ranged from 615 to 3,123, with a median number of 765.5 times. "Neuroscience" emerged as the most extensively researched subject in this field. The USA has emerged as the leading country, with a publication record (n = 65), total citations (n = 66,543), strong centrality (0.29), and extensive international collaborations. Harvard University (n = 11) and the University of California, San Francisco (n = 11) were the top two institutions in terms of publications. Neuron dominated with 13 articles in the 37 high-quality journals. M. Goedert from the MRC Laboratory of Molecular Biology was the most productive (n = 9) and top co-cited (n = 179) author. The most frequently studied keywords were Alzheimer's disease (n = 38). Future research is anticipated to intensify its focus on the pathogenesis of various tau-related diseases, emphasizing the phosphorylation and structural alterations of tau protein, particularly in Alzheimer's disease. Conclusion: The pathogenesis of various tau-related diseases, including the phosphorylation and structural alterations of the tau protein, will be the primary focus of future research, with particular emphasis on Alzheimer's disease as a central area of investigation.

Preoperative Ultrasound-Guided Internal Branch Block of Superior Laryngeal Nerve Reduces Postoperative Sore Throat Caused by Double Lumen Endotracheal Intubation: A Randomized Trial.

BACKGROUND: Postoperative sore throat (POST) is one of the more common side effects of tracheal intubation patients under general anesthesia (GA) after extubation using double-lumen endobronchial tubes (DLTs). The internal branches of the superior laryngeal nerve (SLN) block (iSLNB) have been reported to anesthetize the larynx for airway manipulation (such as awake tracheal intubation) and pain treatment efficiently. We hypothesized that ultrasound-guided iSLNB (US-guided iSLNB) combined with GA would ameliorate the incidence and severity of POST and hoarseness. METHODS: Patients (n = 82) undergoing thoracoscopic resection of pulmonary nodules/lobes/segments with one-lung ventilation (OLV) under GA were randomized into 2 groups depending on whether performed with iSLNB (S group, n = 41) or not (C group, n = 41) under GA. Patients in the S group received US-guided iSLNB bilaterally before surgery. POST and hoarseness were assessed at 2, 6, and 24 hours after surgery. The primary outcome of this study was the incidence of POST at 6 hours after surgery between groups. RESULTS: The overall accumulated incidence of POST was lower in the S goup than in the C group (9/41 vs 20/41; 95% CI, 0.30 [0.11-0.77]; P = .011). The incidence and severity of POST was lower in the S group than in the C group at 2 hours (9/41 vs 20/41; 95% CI, 0.30 [0.11-0.77]; P = .008 and P = .004) and 6 hours after (7/41 vs 17/41; 95% CI, 0.29 [0.10-0.81]; P = .012 and P = .015) surgery. The incidence and severity of POST at 24 hours after surgery was nonsignificant. However, the incidence and severity of hoarseness was comparable between the 2 groups at 2, 6, and 24 hours after surgery. CONCLUSIONS: Preoperative US-guided iSLNB could significantly ameliorate the incidence and severity of POST induced by double-lumen bronchial catheter intubation.

Dexmedetomidine as an Adjuvant in Peripheral Nerve Block.

Peripheral nerve block technology is important to balanced anesthesia technology. It can effectively reduce opioid usage. It is the key to enhance clinical rehabilitation as an important part of the multimodal analgesia scheme. The emergence of ultrasound technology has accelerated peripheral nerve block technology development. It can directly observe the nerve shape, surrounding tissue, and diffusion path of drugs. It can also reduce the dosage of local anesthetics by improving positioning accuracy while enhancing the block's efficacy. Dexmedetomidine is a highly selective drug α2-adrenergic receptor agonist. Dexmedetomidine has the characteristics of sedation, analgesia, anti-anxiety, inhibition of sympathetic activity, mild respiratory inhibition, and stable hemodynamics. Numerous studies have revealed that dexmedetomidine in peripheral nerve blocks can shorten the onset time of anesthesia and prolong the time of sensory and motor nerve blocks. Although dexmedetomidine was approved by the European Drug Administration for sedation and analgesia in 2017, it has not yet been approved by the US Food and Drug Administration (FDA). It is used as a non-label drug as an adjuvant. Therefore, the risk-benefit ratio must be evaluated when using these drugs as adjuvants. This review explains the pharmacology and mechanism of dexmedetomidine, the effect of dexmedetomidine on various peripheral nerve block as an adjuvant, and compare it with other types of adjuvants. We summarized and reviewed the application progress of dexmedetomidine as an adjuvant in nerve block and look forward to its future research direction.

Knockdown of lncRNA BDNF-AS alleviates isoflurane-induced neuro-inflammation and cognitive dysfunction through modulating miR-214-3p.

INTRODUCTION: As one of the most commonly used anesthetics, isoflurane has been demonstrated to possess a variety of protective effects. However, its' neurological impaired effect should be considered during clinical application. Roles of lncRNA BDNF-AS (BDNF-AS) and miR-214-3p in isoflurane-injured microglia and rats were investigated in this study, aiming to disclose the mechanism of isoflurane damage and to provide candidate therapeutic targets. MATERIAL AND METHODS: Isoflurane-induced microglia cells and rat models were established with 1.5% isoflurane. Inflammation and oxidative stress of microglia cells were evaluated with a level of pro-inflammation cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and nitrite. Cognitive and learning function of rats were assessed with Morris water maze task. Expressions of BDNF-AS and miR-214-3p and their function in the isoflurane-induced microglia cells and rats were estimated with PCR and corresponding transfection. RESULTS: Isoflurane induced significant neuro-inflammation and oxidative stress in the microglia cells. The increased BDNF-AS and the decreased miR-214-3p were noted, and BDNF-AS was found to negatively regulate miR-214-3p in the isoflurane-induced microglia cells. Isoflurane caused cognitive dysfunction in rats, and resulted in a significant inflammatory response. The knockdown of BDNF-AS significantly alleviated the neurological impairment induced by isoflurane, which was reversed by silencing miR-214-3p. CONCLUSIONS: In isoflurane-induced neuro-inflammation and cognitive dysfunction, BDNF-AS showed a significant protective effect on the neurological impairment induced by isoflurane through modulating miR-214-3p.

Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.

Cognitive disorders are mental health disorders that can affect cognitive ability. Surgery and anesthesia have been proposed to increase the incidence of cognitive dysfunction, including declines in memory, learning, attention and executive function. Tau protein is a microtubule-associated protein located in the axons of neurons and is important for microtubule assembly and stability; its biological function is mainly regulated by phosphorylation. Phosphorylated tau protein has been associated with cognitive dysfunction mediated by disrupting the stability of the microtubule structure. There is an increasing consensus that anesthetic drugs can cause cognitive impairment. Herein, we reviewed the latest literature and compared the relationship between tau protein and cognitive impairment caused by different anesthetics. Our results substantiated that tau protein phosphorylation is essential in cognitive dysfunction caused by anesthetic drugs, and the possible mechanism can be summarized as "anesthetic drugs-kinase/phosphatase-p-Tau-cognitive impairment".

Protective role of trametenolic acid B against sevoflurane-induced cognitive impairments by its different regulatory modalities of mir-329-3p in neurons and microglia.

BACKGROUND: Postoperative cognitive dysfunction induced by anesthetics commonly occurs in elderly patients. This study aimed to evaluate the protective role of trametenolic acid B (TAB) in sevoflurane-induced cognitive impairments, and explore the underlying mechanisms. METHODS: Animal and cell experiments were performed in rats, differentiated PC12 and HAPI cells by exposing to 2% sevoflurane for 5 h. Different concentration (20, 40 and 80 µg/mL) of TAB was administrated in rats and cells. The cognitive function of rats was evaluated using the Morris water maze test and fear conditioning test. The cell proliferation and apoptosis were investigated using a CCK-8 assay and the flow cytometry. Pro-inflammatory cytokines in microglia were measured using ELISA kits. A miRNA microarray assay was conducted to screen differentially expressed miRNAs by TAB in both PC12 and HAPI cells. The luciferase reporter assay and western blot assay were used to assess the E2F1/CCNA2 and NF-κB pathways. RESULTS: TAB significantly alleviated sevoflurane-induced cognitive impairments in rats, improved PC12 cell viability, and inhibited the neuroinflammation of HAPI cells. miR-329-3p was downregulated in PC12 cells but upregulated in HAPI cells by TAB treatment, which mediated the effects of TAB on neurotoxicity and neuroinflammation. E2F1 and NF-κB P65 were two targets of miR-329-3p, and the E2F1/CCNA2 and NF-κB pathways were inhibited by miR-329-3p in PC12 and HAPI cells, respectively. CONCLUSIONS: All the results provide evidence for the protective role of TAB against sevoflurane-induced cognitive impairments, which was achieved by alleviating neurotoxicity and neuroinflammation through differentially regulating miR-329-3p in neurons and microglia.

METTL3 suppresses neuropathic pain via modulating N6-methyladenosine-dependent primary miR-150 processing.

Methyltransferase-like 3 (METTL3)-modulated N6-methyladenosine (m6A) was recently identified as an important epigenetic regulation type during RNA processing and contributes to multiple pathological processes. Neuropathic pain (NP) is induced by a lesion of the somatosensory nervous system, and the detailed pathways by which METTL3/m6A regulated to modulate gene dysregulation and enable NP have remained unclear. Therefore, this study investigated the function of METTL3-mediated m6A methylation on miRNA maturation, and investigated how this regulation contributes to NP progression. A rat model characterized with typical NP was established by a spared nerve-injury (SNI) method. By analyzing the expression levels of METTL3 and m6A methylation, we found that METTL3, along with m6A methylation, was dramatically downregulated in NP rats in contrast to the sham ones. Functionally, enhanced METTL3 promoted the m6A methylation in total RNAs and inhibited NP progression, whereas silencing METTL3 suppressed m6A methylation and increased NP severity. Mechanistically, METTL3 accelerated miR-150 maturation via mediating m6A methylation of primiR-150 at locus 498, cooperating with the "m6A reader" YTHDF2. Meanwhile, miR-150 could directly target brain-derived neurotrophic factor (BDNF) mRNA, and the METTL3/miR-150/BDNF regulatory pathway was finally established. Clinically, we proved that serum METTL3 mRNA was also downregulated in Shingles patients with NP, suggesting its diagnostic potential. In conclusion, we demonstrated an essential function of METTL3-regulated N6-methyladenosine during NP progression via modulating primiR-150 maturation. Serum METTL3 could effectively differentiate NP patients from healthy people, and is useful for dynamic monitoring of diseases after treatment. Therefore, the METTL3/miR-150/BDNF pathway may be a promising therapeutic target for NP patients.

Renoprotective Effect of Intraoperative Dexmedetomidine in Renal Transplantation.

BACKGROUND: Renal dysfunction after kidney transplantation may be influenced by many reasons. This study was designed to evaluate whether the administration of dexmedetomidine (Dex) could ameliorate renal function and prognosis after kidney transplantation. METHODS: A total of 65 patients were divided into Dex group (n = 33) and Con group (Con, n = 32). Dex group intravenously received an initial loading dose of 0.6 µg/kg Dex for 15 min before anaesthesia induction, followed by a rate of 0.4 µg/kg/h until 30 min after kidney reperfusion. By contrast, Con group received saline. The concentration of urinary kidney injury molecule-1 (KIM-1), serum creatinine (Cr), blood urea, urine output, ß2 microglobulin (ß2-MG), Cystatin C (CysC), and estimated glomerular filtration rate (eGFR) was recorded and compared between two groups during the course of the hospitalization or follow-up. Mean arterial pressure (MAP) and heart rate (HR), vasoactive drugs, and anaesthetics were recorded during the operation. Pain degree was evaluated using a visual analogue scale (VAS) after operation. Delayed graft function (DGF), graft loss, length of hospital stay, and mortality were compared between groups. RESULTS: The concentration of KIM-1 in Dex group was lower than Con group at 2 h (P = 0.018), 24 h (P = 0.013), 48 h (P < 0.01), and 72 h (P < 0.01) after reperfusion. MAP of Dex group after tracheal intubation (P = 0.012) and incision (P = 0.018) and HR after intubation (P = 0.021) were lower than that of Con group. The dosage of sufentanil during operation in Dex group was less than Con group (P = 0.039). Patients that used atropine in Dex group were more than Con group (P = 0.027). Patients who received Dex presented with lower VAS scores at 6 h (P = 0.01) and 12 h (P = 0.002) after operation. Concentration of serum Cr and blood urea had no significant differences between groups before operation and on postoperative day 1 to 6. Urine output was recorded for 6 days after operation and had no differences between groups. Also, no differences were identified between two groups in urea, Cr, ß2-MG, CysC, and eGFR in the first 3 months after operation. Incidence of DGF after operation was detected no difference between groups, while length of hospital stay in Dex group was less than Con group (P = 0.012). CONCLUSION: Dex can decrease kidney injury marker level, attenuate perioperative stress, relieve the dosage of sufentanil and postoperative pain, and reduce length of hospital stay. However, Dex is not associated with changes in prognosis in the first 3 months after transplantation.

Long non-coding RNA maternally expressed 3 (MEG3) regulates isoflurane-induced cognitive dysfunction by targeting miR-7-5p.

This study aimed to investigate the role and mechanism of long non-coding RNA maternally expressed gene 3 (MEG3) in cognitive dysfunction induced by isoflurane (ISO). Morrier water maze analysis was performed to evaluate the cognitive function of rats. Modified modified neurological severity score (mNSS) scores were assessed for neurological damage. The levels of MEG3 in hippocampal tissues of rats and hippocampal neuron cell lines HT22 were examined by reverse transcription-quantitative polymerase chain reaction (qRT-PCR). Moreover, the cell viability and apoptosis were assessed by the Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Indicators of inflammation and oxidative stress were determined using enzyme-linked immunosorbent assay (ELISA) and commercial assay kits. Relationship between MEG3 and microRNA (miR)-7-5p was verified by the dual-luciferase reporter gene assay. MEG3 was increased in hippocampal tissues and HT22 after ISO treatment (p < 0.05). MEG3 downregulation alleviated the increase in neurological severity score and cognitive dysfunction caused by ISO treatment (p < 0.05). In vitro, MEG3 downregulation alleviates the decrease in cell activity and increased apoptosis induced by ISO. What's more, MEG3 reduction eliminated activation of neuroinflammation and oxidative stress promoted by ISO treatment in rats and HT22 (p < 0.05). MEG3 was confirmed to specifically bind to miR-7-5p. Inhibition of miR-7-5p eliminated the alleviating effects of MEG3 downregulation on cognitive dysfunction caused by ISO treatment. Decreased MEG3 alleviates cognitive dysfunction caused by ISO by targeting miR-7-5p and play a neuroprotective effect. We present a strategy for MEG3 as a potential target for brain protection during anesthesia.

Neuroprotective Effect of HOTAIR Silencing on Isoflurane-Induced Cognitive Dysfunction via Sponging microRNA-129-5p and Inhibiting Neuroinflammation.

INTRODUCTION: This article purposed to detect the function of the HOTAIR and HOTAIR/microRNA-129-5p (miR-129-5p) axis on the isoflurane (ISO)-injured cells and rat, and propounded a novel perspective in exploring the molecular pathogenesis of ISO damage. METHODS: The expression of HOTAIR and miR-129-5p was tested by quantitative real-time PCR. The viable cells were identified using MMT, and the apoptotic cells were provided by flow cytometry. The concentration of proinflammatory indicators was revealed by enzyme-linked immunosorbent assay kits. The function of HOTAIR on oxidative stress was detected by commercial kits. A luciferase assay was performed to confirm the relationship between miR-129-5p and HOTAIR. The Morris water maze test was conducted to elucidate the cognition of SD rats. RESULTS: The expression of HOTAIR was enhanced and the expression of miR-129-5p was lessened in the ISO-evoked SD rats and HT22 cells. The interference of HOTAIR reversed the injury of ISO on cell viability, apoptosis, inflammation, and oxidative stress. Besides, HOTAIR might be a target ceRNA of miR-129-5p. MiR-129-5p abrogated the function of silenced HOTAIR on cell viability, cell apoptosis, inflammation, and oxidative stress. Moreover, in vivo, the intervention of HOTAIR reversed the influence of ISO on cognition and oxidative stress by binding miR-129-5p. DISCUSSION/CONCLUSION: Lowly expressed HOTAIR contributed to the recovery of the ISO-injured HT22 cell model from the abnormal viability, apoptosis, inflammation, and oxidative stress by regulating miR-129-5p. miR-129-5p mediated the function of HOTAIR on cognition and oxidative balance in the ISO-managed SD rat model.

Sevoflurane Promotes Neurodegeneration Through Inflammasome Formation in APP/PS1 Mice.

Sevoflurane (SEVO) is a highly fluorinated methyl isopropyl ether used as an inhalational anesthetic for general anesthesia. Previous studies have shown that SEVO may induce impaired memory and recognition ability and may be associated with neurodegenerative disease, e.g., Alzheimer's disease (AD). However, the underlying mechanism remains unknown. Here, we used a mouse AD model, APP/PS1, to study the effects of SEVO on neurodegeneration occurring in AD. We found that SEVO exposure significantly impaired the spatial reference memory, sensorimotor, and cognitive function of the mice. Mechanistically, we found that SEVO induced formation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and its downstream caspase 1-mediated production of IL-1ß and IL-18, which subsequently deactivated brain-derived neurotrophic factor (BDNF) to promote neurodegeneration. Together, these data suggest that NLRP3 inflammasome is essential for SEVO-induced AD.

Effect of Different Concentrations of Esmolol on Perioperative Hemodynamics and Analgesia in Patients Undergoing Colectomy: A Prospective, Randomized Controlled Study.

PURPOSE: The aim of this study was to investigate the efficacy of esmolol on intraoperative hemodynamic and perioperative analgesic management. METHODS: Totally, 125 patients undergoing colectomy were randomly divided into three groups. Group S (saline group) was administered 0.75 mL/kg/h of normal saline for 5 min before anesthesia induction and maintenance of 0.25 mL/kg/h; Group E1 and Group E2 were administered 0.5 mg/kg and 1.0 mg/kg esmolol for 5 min before anesthesia induction, and maintained of 0.5 mg/kg/h and 2.0 mg/kg/h, respectively. Several parameters including indexes of hemodynamics variation (primary outcome), intra- and postoperative analgesic usage, and pain score were measured. RESULTS: Group E1 and Group E2 had significantly lower intubation response than Group S (P = 0.007, P = 0.001), and extubation response of Group E2 was significantly lower than Group S (P = 0.007). The opioid consumption in Group E1 and Group E2 was significantly lower than in Group S intraoperatively (P = 0.020 and 0.007). The incidence of postoperative adverse reactions among the three groups was not statistically significant (P = 0.368 and 0.772). CONCLUSION: Esmolol 0.5 mg/kg and 1.0 mg/kg infusion before intubation both can effectively inhibit the intubation response, while only maintenance with 2.0 mg/kg/h of esmolol can reduce the incidence of extubation response. At the same time, esmolol can decrease intraoperative opioid requirement without increasing the risk of adverse reactions. TRIAL REGISTRATION: ChiCTR1900024538 and the date of registration was July 15, 2019 at http://www.chictr.org.cn.

Role of NR2B/ERK signaling in the neuroprotective effect of dexmedetomidine against sevoflurane induced neurological dysfunction in the developing rat brain.

Dexmedetomidine (DEX) is a potent α­2 adrenergic receptor agonist and has been widely applied in clinic. The present study explored the protective effect of DEX on sevoflurane­induced learning and cognitive impairment and examined its underlying mechanism. Sprague­Dawley rat pups were exposed to 0.85% sevoflurane for 6 h and injected with DEX in different doses. The Morris water maze test was performed to evaluate the learning and memory function of rats. Western blot was used for the measurement of protein levels. The water maze results indicated that sevoflurane treatment increased the escape latency but reduced the time spent in the original quadrant of rats. The protein levels of NR2B, phosphorylated ERK were significantly influenced by sevoflurane. Ifenprodil administration alleviated sevoflurane­induced neurological impairment. DEX treatment reversed the effect of sevoflurane on both escape latency and time in original quadrant in a dose manner, and pretreatment with DEX had the most dramatic effect. DEX regulated the NR2B/ERK signaling in sevoflurane treated rats. NR2B/ERK signaling is involved in sevoflurane induced neurological impairment. DEX may protect against sevoflurane induced neurological dysfunction in the developing rat brain via regulating the NR2B/ERK signaling.

Erector Spinae Plane Block for Perioperative Pain Control and Short-term Outcomes in Lumbar Laminoplasty: A Randomized Clinical Trial.

BACKGROUND: Spine surgery causes severe pain and can be associated with significant opioid utilization; however, the evidence for opioid-sparing analgesic techniques such as erector spinae plane (ESP) block from controlled studies is limited. We aimed to investigate the analgesic effects of ESP block in lumbar laminoplasty. METHODS: In this prospective, double-blind, controlled single-center trial, 62 consecutive elective lumbar laminoplasty patients were randomized into either a control group (Group G, N=32) or a treatment group (Group E, N=30). Group G received general anesthesia and multimodal analgesia, similar to group E, while Group E received additional bilateral ESP block after induction of general anesthesia. The primary outcome was postoperative pain scores for the first 48 h after surgery, and the secondary outcomes analyzed included intraoperative anesthetic usage, perioperative analgesic consumption, return of bowel function and satisfaction for acute pain management indicated by overall benefit of analgesia score (OBAS). RESULTS: Significant differences in pain scores over time were found between the two groups (P=0.010), with Group E patients having significantly lower pain scores than Group G during the first six hours (P=0.000). The opioid consumption in Group G was significantly higher than in Group E both intraoperatively (P=0.000) and postoperatively (P=0.0005). Group E patients had lower intraoperative sevoflurane requirement, improved satisfaction with pain management, and earlier return of bowel function than Group G patients. CONCLUSION: ESP block is effective in reducing postoperative pain scores and lowering opioid utilization (both intraoperatively and postoperatively), resulting in improved patient satisfaction for pain management in lumbar laminoplasty.

Long Non-coding RNA LINC01119 Promotes Neuropathic Pain by Stabilizing BDNF Transcript.

Neuropathic pain (NP) is caused by primary injury or dysfunction of the peripheral and the central nervous system. Long non-coding RNAs were critical regulators involved in nervous system diseases, however, the precise regulatory mechanism remains unclear. This study aims to uncover the essential role of LINC01119 in NP progression and further clarify the underlying regulatory mechanism at post-transcriptional level. LINC01119 was significantly upregulated in rats of spare nerve injury (SNI) group compared to sham group. Functionally, silencing of LINC01119 significantly alleviated the neuropathic pain-induced hypersensitivity and reduced the increase in IL-6, IL-1ß, and TNF-α caused by SNI. Mechanistically, Brain-derived neurotrophic factor (BDNF) was identified as the functional target of LINC01119. Besides, an RNA binding protein, ELAVL1 could directly interact with LINC01119, and this formed LINC01119- ELAVL1 complex binds to BDNF mRNA, strengthening its RNA stability and increasing the expression level of BDNF at both transcript and protein levels. Clinically, serum LINC01119 was verified as a promising diagnostic biomarker for NP patients. LINC01119 induces NP progression via binding with ELAVL1 and increasing BDNF mRNA stability and expression level. Therefore, LINC01119 may serve as a promising diagnostic marker and therapeutic target for NP treatment.

Isoflurane induces liver injury by modulating the expression of miR-125a-5p.

BACKGROUND: Isoflurane can cause hepatotoxicity, and microRNAs (miRNAs) are involved in the regulation of liver injury. Therefore, this study aimed to explore the effect of miR-125a-5p on isoflurane-induced liver injury. BASIC PROCEDURES: Sprague-Dawley (SD) male rats and BRL-3A cells were exposed to isoflurane to construct animal and cell models. Serum alanine transaminase (ALT) and aspartate transaminase (AST) levels of rats were detected. RT-qPCR was performed for the measurement of miR-125a-5p levels. Cell proliferation and apoptosis were also detected. MAIN FINDINGS: After isoflurane treatment, serum ALT and AST levels of rats increased in a time-dependent manner, and the differences reached significant levels from 3 days after isoflurane treatment. MiR-125a-5p levels increased significantly in the liver tissues of isoflurane-treated rats. MiR-125a-5p downregulation significantly attenuated isoflurane-induced increasing trend of serum ALT and AST levels in rats. In BRL-3A cells, isoflurane treatment significantly inhibited cell proliferation and promoted cell apoptosis, which was reversed by miR-125a-5p downregulation. PRINCIPAL CONCLUSIONS: Isoflurane exposure significantly elevates the level of miR-125a-5p in the liver tissues of rats. Downregulation of miR-125a-5p may protect against isoflurane-induced liver injury through regulating liver cell proliferation and apoptosis. Dysregulation of miR-125a-5p might be a possible mechanism of isoflurane-induced liver injury.

Neuroprotective effect of miR-212-5p on isoflurane-induced cognitive dysfunction by inhibiting neuroinflammation.

BACKGROUND: Isoflurane is a commonly used inhalation anesthetic in the clinic, which can induce cognitive dysfunction and neuroinflammation. miR-212-5p has been demonstrated to be involved in the neuronal system and play vital roles in memory formation. Its function in the learning and memory impairment and neuroinflammation induced by isoflurane was investigated in this study. METHODS: Cognitive dysfunction rat models were established by 3% isoflurane inhalation. The neurological function was evaluated by the modified Neurological Severity Scale. The learning and memory ability of rats was assessed by the Morris water maze test. The expression level of miR-212-5p was analyzed by RT-qPCR, and the protein levels of proinflammatory cytokines were detected by ELISA. RESULTS: Isoflurane induced cognitive dysfunction in rats with the neurological scores and the escape latency increased, and time spent in the target quadrant decreased. The protein levels of IL-1ß, IL-6, and TNF-α were increased in isoflurane treated rats. miR-212-5p was downregulated in cognitive impairment rats. The upregulation of miR-212-5p by the agomir injection decreased the neurological scores of rats and increased the learning and memory ability of impaired rats. Moreover, the neuroinflammation was inhibited by the overexpression of miR-212-5p. CONCLUSION: miR-212-5p showed a neuroprotective effect in isoflurane-induced cognitive dysfunction rats by inhibiting neuroinflammation.

Assessment of risk factors for postoperative cognitive dysfunction after coronary artery bypass surgery: a single-center retrospective cohort study.

AIM: To find out risk factors for postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG), and to provide basis for clinical prevention of POCD. A total of 88 patients who underwent CABG were surveyed with Telephone Questionnaire (TICS-M) for their cognitive impairment after 3, 7, 21, 90, 180 days post-surgery. The occurrence of POCD was diagnosed by Neuropsychological Battery which included Vocabular Learning Test (VLT), Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Symbol Digit Modalities Test (SDMT). The preoperative, intraoperative and postoperative risk factors were assessed by the χ2 or t test. Multivariate analysis was used to study the correlation between the risk factors and the occurrence of POCD. Age, aortic plaque, carotid artery stenosis, cerebrovascular disease, anesthesia time, the rate of decline in intraoperative hemoglobin concentration (ΔHb) and systemic inflammatory response syndrome (SIRS) score on postoperative day 2 had statistically significant (P<0.05) influence on the occurrence of POCD. Aortic plaque, carotid artery stenosis, anesthesia time and SIRS score (odds ratio (OR) value > 1, P<0.05) are the risk factors for POCD. The incidence of day-21 and -180 POCD was approximately 26.1 and 22.7%, respectively.