The long non-coding RNA NEAT1 contributes to aberrant STAT3 signaling in pancreatic cancer and is regulated by a metalloprotease-disintegrin ADAM8/miR-181a-5p axis.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and several studies demonstrate that STAT3 has critical roles throughout the course of PDAC pathogenesis. METHODS: TCGA, microarray, and immunohistochemistry data from a PDAC cohort were used for clinical analyses. Panc89 cells with ADAM8 knockout, re-expression of ADAM8 mutants, and Panc1 cells overexpressing ADAM8 were generated. Gene expression analyses of ADAM8, STAT3, long non-coding (lnc) RNA NEAT1, miR-181a-5p and ICAM1 were performed by quantitative PCR. Subcellular fractionation quantified NEAT1 expression in cytoplasm and nucleus of PDAC cell lines. Cell proliferation, scratch, and invasion assays were performed to detect growth rate, migration and invasion capabilities of cells. Gain and loss of function experiments were carried out to investigate the biological effects of lncRNA NEAT1 and miR-181a-5p on PDAC cells and downstream genes. Dual-luciferase reporter gene assay determined interaction and binding sites of miR-181a-5p in lncRNA NEAT1. Pull down assays, RNA binding protein immunoprecipitation (RIP), and ubiquitination assays explored the molecular interaction between lncRNA NEAT1 and STAT3. RESULTS: High ADAM8 expression causes aberrant STAT3 signaling in PDAC cells and is positively correlated with NEAT1 expression. NEAT1 binding to STAT3 was confirmed and prevents STAT3 degradation in the proteasome as increased degradation of STAT3 was observed in ADAM8 knockout cells and cells treated with bortezomib. Furthermore, miRNA-181a-5p regulates NEAT1 expression by direct binding to the NEAT1 promoter. CONCLUSION: ADAM8 regulates intracellular STAT3 levels via miR-181a-5p and NEAT1 in pancreatic cancer.

UM171 suppresses breast cancer progression by inducing KLF2.

PURPOSE: Breast cancer is the most frequent cancer in women with significant death rate. Morbidity is associated with drug resistance and metastasis. Development of novel drugs is unmet need. The aim of this study is to show potent anti-neoplastic activity of the UM171 compound on breast cancer cells and its mechanism of action. METHODS: The inhibitory effect of UM171 on several breast cancer (BC) cell lines was examined using MTT and colony-forming assays. Cell cycle and apoptosis assays were utilized to determine the effect of UM171 on BC cell proliferation and survival. Wound healing scratch and transwell migration assays were used to examine the migration of BC cell lines in culture. Xenograft of mouse model with 4T1 cells was used to determine inhibitory effect of UM171 in vivo. Q-RT-PCR and western blotting were used to determine the expression level of genes effected by UM171. Lentivirus-mediated shRNAs were used to knockdown the expression of KLF2 in BC cells. RESULTS: UM171 was previously identified as a potent agonist of human hematopoietic stem cell renewal and inhibitor of leukemia. In this study, UM171 was shown to inhibit the growth of multiple breast cancer cell lines in culture. UM171-mediated growth inhibition was associated with the induction of apoptosis, G2/M cell cycle arrest, lower colony-forming capacity, and reduced motility. In a xenotransplantation model of mouse triple-negative breast cancer 4T1 cells injected into syngeneic BALB/c mice, UM171 strongly inhibited tumor growth at a level comparable to control paclitaxel. UM171 increased the expression of the three PIM genes (PIM1-3) in breast cancer cells. Moreover, UM171 strongly induced the expression of the tumor suppressor gene KLF2 and cell cycle inhibitor P21CIP1. Accordingly, knockdown of KLF2 using lentivirus-mediated shRNA significantly attenuated the growth suppressor activity of UM171. As PIM1-3 act as oncogenes and are involved in breast cancer progression, induction of these kinases likely impedes the inhibitory effect of KLF2 induction by UM171. Accordingly, combination of UM171 with a PAN-PIM inhibitor LGH447 significantly reduced tumor growth in culture. CONCLUSION: These results suggested that UM171 inhibited breast cancer progression in part through activation of KLF2 and P21. Combination of UM171 with a PAN-PIM inhibitor offer a novel therapy for aggressive forms of breast cancer.

Apamin, an SK2 Inhibitor, Attenuated Neonatal Sevoflurane Exposures Caused Cognitive Deficits in Mice through the Regulation of Hippocampal Neuroinflammation.

Cognitive dysfunction induced by anesthesia in the infant is a crucial clinical issue that is still being debated and the focus of concern for the parents. However, the mechanism of cognitive decline caused by anesthesia and the corresponding treatment methods remain unclear. Postnatal day 7 (PND7) C57BL/6 mice included in the study were randomly divided into a control group (Control), a group with repeated exposure to sevoflurane (Sevo), and an Apamin intervention group (Sevo + Apamin). Apamin (0.5 µL at the concentration of 100 nmol/L) was injected into the bilateral hippocampus of mice. qRT-PCR, enzyme-linked immunosorbent assay (ELISA), and western blotting assay were used to evaluate the protein levels in the hippocampus. Object location memory (OLM) and novel object recognition (NOR) tasks, as well as elevated plus maze and contextual and cued fear conditioning tasks were used to evaluate the cognitive function of mice. Apamin mitigated sevoflurane-induced cognitive impairment of mice, sevoflurane-induced neuronal injury, and sevoflurane-induced activation of microglial in the hippocampus of the mice. Apamin inhibited M1-type polarization but promoted M2-type polarization of microglia after neonatal sevoflurane exposures in the hippocampus. In conclusion, Apamin attenuates neonatal sevoflurane exposures that cause cognitive deficits in mice through regulating hippocampal neuroinflammation.

The Efficacy of Ultrasound-Guided Superior Laryngeal Nerve Block as an Adjuvant to General Anesthesia during Suspension Laryngoscopy Vocal Cord Polypectomy.

Background: In the current study, we assessed the effect of the ultrasound-guided internal branch of the upper laryngeal nerve (USG-guided iSLN) block combined with general anesthesia on perioperative sore throat (POST), cough, hoarseness of voice, intraoperative hemodynamic changes, and the quality of early recovery for the patients undergoing suspension laryngoscopy vocal cord polypectomy (SLVCP). Methods: This was a randomized controlled trail. Eighty patients, aged from 18 to 70 years old, ASA I ∼ II, scheduled for polypectomy of the vocal cord by using a laryngoscope, were randomized into 2 groups (n = 40 each) using a random number table. Patients in group C received general anesthesia (GA), whereas those in group S received USG-guided iSLN block bilaterally (37.5 mg of 0.375% ropivacaine, 5 ml each side) combined with GA. The primary outcome was the quality of patients' recovery using the Quality of Recovery Questionnaire (QoR-9). The secondary outcomes were postoperative cough, sore throat, hoarseness of voice, and hemodynamic changes in both groups at corresponding time points. The adverse reactions such as postoperative chocking, or aspiration, and dyspnea was recorded as well. Results: The QoR-9 scores of patients in group C were lower than those of group S at time points of D1∼D2 (P < 0.05). Patients in group S had a significantly lower incidence of perioperative cough than those in group C in the early postoperative period (1 hour after extubation) (P < 0.05), the scores of sore throat were lower in group S than those in group C (P < 0.05), the incidence of postoperative hoarseness was increased in group S than that in group C at the time points of 30 min, 2 h, and 4 h after extubation (P < 0.05); however, the incidence of postoperative hoarseness was decreased in group S than that in group C at the time point of 24 h after extubation (P < 0.05). MAP and HR of group S was lower than those of group C at time points of T1∼T4 (P < 0.05). No serious adverse events were observed in both groups. Conclusion: The study found that the application of ultrasound guided superior laryngeal nerve block combined with general anesthesia for the patients undergoing SLVCP could effectively promote the quality of early recovery. Clinical trial registration: This trial is registered with NCT05309174. The date of registration: March 12th 2021.Trial registry name: The Study of Bilateral Upper Laryngeal Nerve Block for Supporting the Removal of Vocal Cord Polyps Under Laryngoscopy.

Propofol mediates pancreatic cancer cell activity through the repression of ADAM8 via SP1.

Propofol is a commonly used anesthetic with controversial effects on cancer cells. A growing number of studies have demonstrated that low concentrations of propofol are associated with tumor suppression and when used as an intravenous anesthesia improved recurrence­free survival rates for many cancers, but deeper insights into its underlying mechanism are needed. The study detailed herein focused upon the effect of propofol on pancreatic cancer cells and the mechanism by which propofol reduces A disintegrin and metalloproteinase 8 (ADAM8) expression. The ability of propofol to impact the proliferation, migration and cell cycle of pancreatic cancer cell lines was assessed in vitro. This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of specificity protein 1 (SP1) on ADAM8 following propofol treatment to be further explored. Ultimately, this study was able to show that propofol significantly inhibited the proliferation, migration and invasion of pancreatic cancer cells and decreased the percentage of cells in S­phase. Propofol treatment was also shown to repress ADAM8 and SP1 expression, but was unable to affect ADAM8 expression following knockdown of SP1. Moreover, a direct physical interaction between SP1 and ADAM8 was verified using co­immunoprecipitation and dual­luciferase reporter assays. Cumulatively, these results suggest that propofol represses pathological biological behaviors associated with pancreatic cancer cells through the suppression of SP1, which in turn results in lower ADAM8 mRNA expression and protein levels.

Neonatal exposure to sevoflurane caused learning and memory impairment via dysregulating SK2 channel endocytosis.

Numerous studies have demonstrated that anesthetics' exposure to neonates imposes toxicity on the developing brain but the underlying mechanisms need to be further elucidated. Our present study aimed to explore the role of small conductance Ca2+-activated potassium channel type2 in memory and learning dysfunction caused by exposing neonates to sevoflurane. Postnatal day 7 Sprague-Dawley rats and hemagglutinin-tagged small conductance Ca2+-activated potassium channel type2 channel transfected COS-7 cells were exposed to sevoflurane and the trafficking of small conductance Ca2+-activated potassium channel type2 channels was analyzed; furthermore, memory and learning ability was analyzed by the Morris water maze test on postnatal day30-35 (juvenile period). Our results showed that sevoflurane exposure inhibited small conductance Ca2+-activated potassium channel type2 channel endocytosis in both hippocampi of postnatal day 7 rats and hemagglutinin-tagged small conductance Ca2+-activated potassium channel type2 channel transfected COS-7 cells and the memory and learning ability was impaired in the juvenile period after sevoflurane exposure to neonatal rats. Herein, our results demonstrated that exposing neonates to sevoflurane caused memory and learning impairment via dysregulating small conductance Ca2+-activated potassium channel type2 channels endocytosis.

NK6 Homeobox 2 Regulated Gastrokin-2 Suppresses Gastric Cancer Cell Proliferation and Invasion via Akt Signaling Pathway.

This study aims to explore the role of Gastrokin-2 (GKN2) in gastric cancer and its function in the progression and metastasis of gastric cancer. The expression of GKN2 in the patient samples was examined by qRT-PCR and western blot. The transcription factor NK6 Homeobox 2 (NKX6-2), which binds to the GKN2 promoter, was predicted by cBioportal and JSPAR. Binding between NKX6-2 and the GKN2 promoter was analyzed by dual-luciferase assay. MTT assay and transwell assay were used to detect changes in gastric cancer cell viability and migration after GKN2 overexpression, which was achieved by transfection of GKN2 overexpression vector. Akt signaling pathway markers were assessed by western blot. GKN2 is downregulated in gastric cancer and low GKN2 expression is correlated to poor survival, metastasis, and higher clinical stages. NKX6-2 binds the promoter region of GKN2 and regulate its expression. GKN2 overexpression inhibits the proliferation, migration, and invasion of gastric cancer cells, which was mediated by Akt signaling pathway. NKX6-2 regulated GKN2 inhibits the proliferation and invasion of gastric cancer cells by inhibiting Akt signaling pathway. GKN2 can be used as a potential diagnostic and therapeutic target for patients with clinical gastric cancer.

Propofol affects the growth and metastasis of pancreatic cancer via ADAM8.

BACKGROUND: Anesthesia is a major component of surgery and recently considered an important regulator of cell phenotypes. Here we aimed to investigate propofol, an anesthesia drug, in suppressing pancreatic cancer (PDAC), focusing on A disintegrin and metalloprotease 8, (ADAM8) as a molecular mediator. METHODS: Quantitative real-time PCR and western blot were used to assess the change of ADAM8 expression in Panc1 PDAC cells treated with 5 or 10 µg/mL propofol, using cells treated with BB-94 inhibitor as controls. ADAM8 activity was measured through quantifying fluorescence release induced by PEPDAB013 decomposition. MTT assay, scratch wound assay and Matrigel invasion assay were used to investigate the proliferation, migration and invasion of the cells. Western blot and immunohistochemical analysis were used to quantify integrin ß1, ERK1/2, MMP2 and MMP9 expression. RESULTS: Propofol and BB-94 reduced ADAM8 expression, cell proliferation and migration of Panc1 cells. Tumor growth was inhibited by propofol and BB-94, concomitant with downregulation of integrin ß1, ERK1/2, MMP2 and MMP9. ADAM8 is downregulated by propofol, leading to inhibition of pancreatic cancer proliferation and migration. CONCLUSION: Pancreatic tumor growth is also inhibited by propofol and BB-94, which is attributed to suppression of ERK/MMPs signaling.

The effect of TEAS on the quality of early recovery in patients undergoing gynecological laparoscopic surgery: a prospective, randomized, placebo-controlled trial.

INTRODUCTION: In current study we assessed the effect of transcutaneous electrical acupoint stimulation (TEAS) on the quality of early recovery in patients undergoing gynecological laparoscopic surgery. METHODS: Sixty patients undergoing gynecological laparoscopic surgery were randomly assigned to TEAS (TEAS group) or control group (Con group). TEAS consisted of 30 min of stimulation (12-15 mA, 2/100 Hz) at the acupoints of Baihui (GV20), Yingtang (EX-HN-3), Zusanli (ST36) and Neiguan (PC6) before anesthesia. The patients in the Con group had the electrodes applied, but received no stimulation. Quality of recovery was assessed using a 40-item questionnaire as a measure of quality of recovery (QoR-40; maximum score 200) scoring system performed on preoperative day 1 (T0), postoperative day 1 (T1) and postoperative day 2 (T2); 100-mm visual analogue scale (VAS) scores at rest, mini-mental state examination (MMSE) scores, the incidence of nausea and vomiting, postoperative pain medications, and antiemetics were also recorded. RESULTS: QoR-40 and MMSE scores of T0 showed no difference between two groups (QoR-40: 197.50 ± 2.57 vs. 195.83 ± 5.17), (MMSE: 26.83 ± 2.74 vs. 27.53 ± 2.88). Compared with the Con group, QoR-40 and MMSE scores of T1 and T2 were higher in the TEAS group (P < 0.05) (QoR-40: T1, 166.07 ± 8.44 vs. 175.33 ± 9.66; T2, 187.73 ± 5.47 vs. 191.40 ± 5.74), (MMSE: T1, 24.60 ± 2.35 vs. 26.10 ± 2.78; T2, 26.53 ± 2.94 vs. 27.83 ± 2.73). VAS scores of T1 and T2 were lower (P < 0.05) in the TEAS group (T1, 4.73 ± 1.53 vs. 3.70 ± 1.41; T2, 2.30 ± 0.95 vs. 1.83 ± 0.88); the incidence of postoperative nausea and vomiting (PONV), remedial antiemetics and remedial analgesia was lower in the TEAS group (P < 0.05) (PONV: 56.7% vs. 23.3%; incidence of remedial antiemetics: 53.3% vs. 23.3%; incidence of remedial analgesia: 80% vs. 43.3%). CONCLUSION: The use of TEAS significantly promoted the quality of early recovery, improved MMSE scores and reduced the incidence of pain, nausea and vomiting in patients undergoing gynecological laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02619578. Registered on 2 December 2015. Trial registry name: https://clinicaltrials.gov.

Effect of sevoflurane treatment on microglia activation, NF-kB and MAPK activities.

Microglia activation has been implicated in neurodegenerative disease. Sevoflurane is fluorinated methyl isopropyl ether with anti-inflammatory activity. In this study, we evaluated the potential effects of sevoflurane on lipopolysaccharides (LPS)-induced microglia activation. We treated primary microglia cells with sevoflurane prior to LPS treatment and tested the microglia migration, the productions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-6 and interleukin-8. We also explored the effects of sevoflurane on NF-κB and p38 MAPK activation. Finally, we examined the effect of sevoflurane on cytokines production in rat brain. Sevoflurane significantly reduced LPS-induced microglial migration. Sevoflurane significantly decreased the production of pro-inflammatory cytokines both in vitro and in vivo. Sevoflurane attenuated activations of NF-κB and MAPK signaling pathways. Sevoflurane treatment decreased microglia activation by suppressing NF-kB and MAPK signaling pathways.

Effect of transcutaneous electrical acupuncture point stimulation on expression of p-JNK in the dorsal root ganglion in a rat model of myofascial pain syndrome.

BACKGROUND: Acupuncture has been used to treat myofascial pain syndrome (MPS) for 2000 years in China, but its mechanisms are still not entirely clear. In the present study, we explored the effects of transcutaneous electrical acupuncture point stimulation (TEAS) at an Ashi acupuncture point on expression of phosphorylated c-Jun N-terminal kinase (p-JNK) in the dorsal root ganglion (DRG) using a rat model of MPS. METHODS: 32 rats were divided into four groups: normal, MPS, MPS+TEAS and MPS+sham- TEAS. MPS was produced by a blunt strike to the left vastus medialis combined with eccentric exercise for 8 weeks. Rats in the MPS+TEAS group received TEAS (6-9 mA, 2 Hz, 30 min) treatment at the Ashi acupuncture point for 2 weeks; rats in the MPS+sham -TEAS group had the same electrodes applied but received no stimulation. Paw withdrawal thermal latency (PWTL) was studied at baseline and on days 3, 7, 11 and 15 after treatment. Haematoxylin and eosin staining was used to examine for morphological changes in the left vastus medialis muscles; expression of p-JNK in the L3-L5 DRG was determined by immunofluorescence staining and western blotting after treatment. RESULTS: Compared with the normal group, PWTL decreased significantly (P<0.01) and the expression of p-JNK in the DRG increased in the MPS and MPS-sham-TEAS groups (P<0.01); compared with the MPS group, PWTL was increased significantly (P<0.01) and expression of p-JNK in the DRG was decreased in the MPS+TEAS group. However, when compared with the normal group, PWTL did not recover to baseline and expression of p-JNK was still higher. CONCLUSION: TEAS treatment may produce an analgesic effect, probably by inhibiting the expression of p-JNK in the DRG of rats with MPS.

Propofol inhibits pancreatic cancer progress under hypoxia via ADAM8.

BACKGROUND: To investigate the potential anti-tumoral properties of propofol in pancreatic cancer and elucidate the underlying mechanisms. METHODS: The relative expression of ADAM metallopeptidase domain 8 (ADAM8) in response to hypoxia in Panc1 cells was analyzed by western blotting. The enzymatic activity was determined by fluorescence release from PEPDAB013 decomposition. Cell growth was measured via cell counting and cell viability was measured using CCK-8 kit. Cell migrative capacity was evaluated by transwell and adhesion assay. The relative abundance of angiogenesis-related markers including platelet-derived growth factor AA, angiogenin, endothelin-1 and vascular endothelial growth factor were determined by real-time polymerase chain reaction and western blotting. The anti-tumoral activity of propofol was investigated with Panc1-derived xenograft mice model. RESULTS: ADAM8 was significantly induced by hypoxia and efficiently inhibited by co-treatment with propofol. Propofol suppressed proliferation and compromised viability of Panc1 cells. In addition, the migrative capacity was greatly inhibited by propofol dosage. Comprehensive profiling of angiogenesis-related markers demonstrated that propofol remarkably suppressed neovascularization response in Panc1 cells under hypoxia. We further uncovered that propofol administration via subcutaneous injection delayed xenograft tumor progression. CONCLUSION: Propofol specifically inhibited ADAM8 expression and activation in response to hypoxia in pancreatic cancer, and held great value for therapeutic effects.

Propofol inhibits pancreatic cancer proliferation and metastasis by up-regulating miR-328 and down-regulating ADAM8.

Propofol is commonly used for anaesthesia during surgery, and accumulating evidence has demonstrated that propofol is associated with tumour suppression. For example, propofol down-regulates the expression of vascular endothelial growth factor to inhibit pancreatic cancer malignancy. However, deeper insights into its underlying mechanism are needed. In this study, we treated pancreatic cell lines Panc1 and Bxpc3 with or without propofol. Cell proliferation, migration and invasion were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and transwell assays. Real-time polymerase chain reaction was used to measure RNA expression levels. Luciferase assay was performed to determine the transcriptional activity of microRNAs (miRNAs). We found that propofol significantly reduced the proliferation, migration and invasion of pancreatic cancer cells compared to untreated cells. By testing the changes in miRNAs after propofol treatment, propofol was shown to strikingly enhance the expression of miR-328. Luciferase assays demonstrated that propofol repressed the transcriptional activity of miR-328, while a disintegrin and metalloproteinase 8 (ADAM8) was a direct target of miR-328. Knockdown of miR-328 or ADAM8 led to significantly decreased cell growth and viability. Our results implicate that propofol inhibits pancreatic cancer growth and metastasis by enhancing miR-328 which targets ADAM8.

Sevoflurane anesthesia impairs metabotropic glutamate receptor-dependent long-term depression and cognitive functions in senile mice.

AIM: Postoperative cognitive dysfunction is often observed in older patients. Previous reports described the link between postoperative cognitive dysfunction and general anesthetics, such as sevoflurane, but the exact mechanism remains unclear. We therefore sought to characterize the effects of sevoflurane on hippocampal-dependent cognitive functions, as well as hippocampal plasticity, and to delineate the underlying mechanisms. METHODS: Behavioral assays including the novel object recognition test and the Morris water maze test were carried out to assess the cognitive performance of control and sevoflurane-exposed mice. Electrophysiological recordings were carried out to evaluate the sevoflurane-induced changes of synaptic plasticity in the hippocampus. Furthermore, western blot assay was utilized to quantitatively assess the altered protein expression resulting from sevoflurane exposure. RESULTS: Sevoflurane anesthesia impaired cognitive functions, as well as metabotropic glutamate receptor-dependent long-term depression, through elevated surface expression of small conductance calcium-activated potassium type 2 channels. Blockage of calcium-activated potassium type 2 channels reversed the sevoflurane-induced deficits at both cellular and behavioral levels. CONCLUSIONS: Sevoflurane anesthesia impaired metabotropic glutamate receptor-dependent long-term depression and thereby affected cognitive functions in old mice. Inhibitory modulators of calcium-activated potassium type 2 channels might prevent cognitive decline elicited by sevoflurane. Geriatr Gerontol Int 2019; 19: 357-362.

Neonatal exposure to sevoflurane caused cognitive deficits by dysregulating SK2 channels and GluA2-lacking AMPA receptors in juvenile rat hippocampus.

Anesthetics exposure to neonates leads to impairment of hippocampal synaptic plasticity and cognitive functions later in life. This phenomenon complies with the concept of metaplasticity: a priming stimulation can affect induction of synaptic plasticity mins or days later. We aimed to understand whether small conductance Ca2+-activated potassium channel type2 (SK2) and subunit composition of AMPA receptors are altered and contribute to sevoflurane-induced metaplasticity. To fulfill this goal, we exposed neonatal rats (postnatal day 7) to 2% sevoflurane for 2 h (sevoflurane rats) and examined synaptic plasticity in the hippocampus and cognitive function in juvenile rats (postnatal day 30-35). We observed that the juvenile sevoflurane rats showed elevation in the threshold for LTP induction, facilitation of LTD induction, and cognitive dysfunctions. Meanwhile, these rats also exhibited increased surface expression of SK2 and enhanced synaptic recruitment of GluA2-lacking AMPA receptors, which possess stronger inward rectification. Blocking SK2 eliminated inward rectification of AMPA receptors in juvenile sevoflurane rats. Interestingly, blocking either SK2 channels or GluA2-lacking AMPA receptors normalized LTP, LTD, and spatial memory in juvenile sevoflurane rats. Our data indicate that neonatal sevoflurane anesthesia have negative impact on cognitive function extended to juvenile rats probably through increasing surface expression of SK2 and synaptic recruitment of GluA2-lacking AMPA receptors. This study provides a new sight for sevoflurane induced metaplasticity.

Cardioprotection of Electroacupuncture for Enhanced Recovery after Surgery on Patients Undergoing Heart Valve Replacement with Cardiopulmonary Bypass: A Randomized Control Clinical Trial.

We attempted to investigate cardioprotection of electroacupuncture (EA) for enhanced recovery after surgery on patients undergoing heart valve replacement with cardiopulmonary bypass. Forty-four patients with acquired heart valve replacement were randomly allocated to the EA group or the control group. Patients in the EA group received EA stimulus at bilateral Neiguan (PC6), Ximen (PC4), Shenting (GV24), and Baihui (GV20) acupoints twenty minutes before anesthesia induction to the end of surgery. The primary end point was cardioprotection effect of electroacupuncture postoperatively and the secondary endpoints were quality of recovery and cognitive functioning postoperatively. The present study demonstrated that electroacupuncture reduced the occurrence of complications and played a role of cardioprotective effect on patients after heart valve replacement surgery with cardiopulmonary bypass, and it benefits patients more comfortable and contributes to recovery after surgery. This trial is registered with ChiCTR-IOC-16009123.

Effect of transcutaneous electrical acupuncture point stimulation at different frequencies in a rat model of neuropathic pain.

BACKGROUND: Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats. METHODS: CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague-Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the CCI+TEAS-H group received high frequency stimulation (6-9 mA, 100 Hz) at GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation (6-9 mA, 2 Hz) at the same points. Rats in the control group had the same electrodes applied but received no stimulation. All three groups were subjected to behavioural studies after treatment. Expression of µ opioid receptors (MORs) in the L3-L5 dorsal root ganglion (DRG) was determined by immunofluorescence staining and Western blotting after treatment. RESULTS: Compared with the untreated CCI group, both mechanical allodynia and thermal hypergesia were significantly attenuated, and MOR expression in the DRG was significantly increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In contrast, no significant differences were observed between the CCI and CCI+TEAS-H groups. CONCLUSIONS: The use of low frequency TEAS significantly mitigated neuropathic pain in this rat model, and its analgesic effect is likely mediated by upregulation of MOR expression in the DRG.

Preventing Emergence Agitation Using Ancillary Drugs with Sevoflurane for Pediatric Anesthesia: A Network Meta-Analysis.

Using sevoflurane for pediatric anesthesia plays a pivotal role in surgeries. Emergence agitation (EA) is a major adverse event accompanied with pediatric anesthesia. Other anesthetic adjuvants can be combined with sevoflurane in clinical practices for different purposes. However, it is uncertain that such a practice may have substantial influence on the risk of EA. We conducted a literature search in online databases, including PubMed, Embase, Cochrane Library, and Clinical Trials. Key data were extracted from eligible randomized control trials (RCTs). Both pairwise and network meta-analysis (NMA) were conducted for synthesizing data from eligible studies. The relative risk of EA was assessed using the odds ratios (ORs) and their corresponding 95 % confidence intervals (CI) or credible intervals (CrI). Ranking scheme based on the surface under the cumulative ranking curve (SUCRA) values was produced. Several key assumptions of NMA such as heterogeneity, degree of consistence, and publication bias were validated by different statistical or graphical approaches. Evidence from 67 randomized control trials was synthesized. The relative risk of EA associated with eight anesthetic adjuvants was analyzed, including ketamine, propofol, dexmedetomidine, clonidine, midazolam, fentanyl, remifentanil, and sufentanil. Patients with the following anesthetic adjuvants appeared to have significantly reduced risk of EA in relation to those with placebo: dexmedetomidine (OR = 0.18, 95 % CrI 0.12-0.25), fentanyl (OR = 0.19, 95 % CrI 0.12-0.30), sufentanil (OR = 0.20, 95 % CrI 0.08-0.50), ketamine (OR = 0.21, 95 % CrI 0.13-0.34), clonidine (OR = 0.25, 95 % CrI 0.14-0.46), propofol (OR = 0.32, 95 % CrI 0.18-0.56), midazolam (OR = 0.46, 95 % CrI 0.27-0.77), and remifentanil (OR = 0.29, 95 % CrI 0.13-0.68). The SUCRA values for each anesthetic adjuvant were: dexmedetomidine (73.65 %), fentanyl (68.04 %), sufentanil (60.81 %), ketamine (59.99 %), clonidine (47.74 %), remifentanil (40.15 %), propofol (33.23 %), midazolam (16.33 %), and placebo (0.06 %). Incorporating anesthetic adjuvants particularly dexmedetomidine into sevoflurane appeared to be significantly associated with a decreased risk of EA in pediatric anesthesia.

The effect of parturient height on the median effective dose of intrathecally administered ropivacaine.

BACKGROUND: Pain during cesarean delivery is one of the more common reasons for a successful medicolegal claim. However, creating an extensive block area can result in hypotension, so determining the precise dose of local anesthetic is critical. OBJECTIVES: Investigate effects of parturient height on the median effective dose (ED50) of intrathecally-administered ropivacaine. DESIGN: Prospective cross-sectional analytic study. SETTING: Anesthesiology department in a provinicial hospital in China. METHODS: Parturients undergoing cesarean delivery under combined spinal and epidural anesthesia were stratified according to height as follows: 150 cm to 155 cm, 156 cm to 160 cm, 161 cm to 165 cm and 166 cm to 170 cm. The spinal component of the anesthetic was established by bolus administration of up-and-down doses of 0.75% plain ropivacaine as determined by the Dixon method. The initial dose of ropivacaine was 5.79 mg and the testing interval dose change was set at 0.75 mg. The block height for the first cold feeling at T5 was considered satisfactory anesthesia. MAIN OUTCOME MEASURES: ED50 values and vasopressor requirements, nausea, vomiting and shivering. RESULTS: In 120 parturients, the ED50 for satisfactory block height using intrathecal ropivacaine was 5.92 mg (95% confidence interval[CI] 5.02-6.86 mg) patients of 150 to 155 cm in height; 6.52 mg (95% CI 5.45-7.65 mg) in 156 cm to 160 cm; 7.49 mg (95%CI 6.83-8.25 mg) in 161 cm to 165 cm; 8.35 mg (95%CI 7.55-9.23 mg) in 166 to 170 cm. The ED50 of ropivacaine increased with increasing height of the subject. There were no significant differences in incidence of hypotension, vasopressor requirements, nausea, vomiting and shivering. CONCLUSION: The ED50 of intrathecal ropivacaine using sensitivity to cold sensation increased with parturient height, indicating that dose may be determined in part by height. LIMITATION: The ED95 rather than the ED50 for spinal anesthesia is more useful clinically. We did not control for the effect of weight on the dose of local anesthetic. Factors such as baricity, volume, concentration injected, temperature of the solution, and viscosity can affect intrathecal spread of the local anesthetics and block quality.

EGb761 Ameliorates Neuropathic Pain by Scavenging Reactive Oxygen Species.

BACKGROUND: Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Until recently, researchers have found that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during neuropathic pain. METHODS: In this study, we investigated the antinociceptive efficacy of Ginkgo biloba extract (EGb761) in chronic constriction injury (CCI) model of neuropathic pain of rats. To explore the underlying mechanisms, the effects of EGb761 on the excitability of dorsal root ganglion (DRG) neurons and activation of JNK in DRG were explored. RESULTS: We showed that systemic administration of EGb761 inhibited the behavioral responses of neuropathic pain and found that EGb761 treatment could inhibit the H2O2-induced depolarization in the acutely dissociated DRG neurons. In addition, we found that EGb761 treatment could inhibit the expression of p-JNK in DRG. CONCLUSION: Taken together, our results suggest that administration of EGb761 can ameliorate neuropathic pain, and further indicate that JNK, which is activated by both exogenous and endogenous ROS, might be the mechanism underlying the effects of EGb761 on CCI neuropathic pain.