Randomized clinical trial of continuous transversus thoracis muscle plane block for patients undergoing open heart valve replacement surgery.

The optimal analgesia regimen after open cardiac surgery is unclear. The aim of this study was to investigate the beneficial effects of continuous transversus thoracis muscle plane (TTMP) blocks initiated before surgery on open cardiac surgery outcomes. A group of 110 patients were randomly allocated to either receive bilateral continuous TTMP blocks (TTP group) or no nerve block (SAL group). The primary endpoint was post-operative pain at 4, 8, 16, 24, 48 and 72 h after extubation at rest and exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen axetil administration), time to extubation, incidence of reintubation, length of stay in the ICU, incidence of post-operative nausea and vomiting (PONV), time until return of bowel function, time to mobilization, urinary catheter removal and length of hospital stay. The length of stay in the ICU and length of hospital stay were significantly longer in the SAL group than in the TTP group. NRS scores at rest and exercise were significantly lower in the TTP group than in the SAL group at all time points. The TTP group required significantly less intraoperative and post-operative sufentanil and post-operative dynastat consumption than the SAL group. Time to extubation, time to first flatus, time until mobilization and time until urinary catheter removal were significantly earlier in the TTP group than in the SAL group. The incidence of PONV was significantly lower in the TTP group. Bilateral continuous TTMP blocks provide effective analgesia and accelerate recovery in patients undergoing open heart valve replacement surgery.

Role and targeting of the AGC kinase family in pulmonary fibrosis (Review).

Pulmonary fibrosis (PF) is a progressive and irreversible pulmonary disease with a high mortality rate and limited treatment options. The cAMP-dependent protein kinase A, cGMP-dependent protein kinase G and phospholipid-dependent protein kinase C, collectively known as AGC kinases, are evolutionarily conserved protein kinases that are widely distributed among eukaryotes. AGC kinases serve a crucial role in a variety of cellular functions and pathological processes, including cancer, diabetes, inflammation and viral infections, where they have been implicated the pathogenesis of PF. The present review summarizes the evidence for the involvement of specific AGC kinases in the pathogenesis of PF, and provides a theoretical basis for the development of targeted AGC kinase small molecule inhibitors or targeted drugs, offering more effective treatment options and strategies for patients with PF.

MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy.

Alterations in autophagy are involved in pulmonary hypoxia/reoxygenation (H/R)-induced injury. Here, we intended to explain the function of microRNA-141-3p (miR-141-3p) in regulating autophagy under the H/R condition. Rat pulmonary microvascular endothelial cells (PMVECs) were applied for H/R cell model establishment, followed by tracing of autophagy formation. SIRT1 plays a critical role in controlling the lifespan of yeast, flies, and mice. Interaction between SIRT1 and Beclin-1, an indicator protein for autophagy, and between miR-141-3p and SIRT1 was assayed with their roles in PMVEC injury. Autophagy of PMVECs was activated after hypoxia treatment and further activated after H/R treatment. The binding of miR-141-3p and SIRT1 was verified. In H/R-treated PMVECs, the binding of miR-141-3p and SIRT1 was reduced. Furthermore, SIRT1 acted as a deacetylase to stabilize the Beclin-1 protein, promoting autophagy and PMVEC injury. H/R rat models were established, and in vivo, experiments further confirmed that miR-141-3p regulated autophagy and lung injury in H/R rats through SIRT1/Beclin-1 axis. The current study highlighted that reduced miR-141-3p in H/R-treated PMVECs promoted deacetylation of Beclin-1 by SIRT1, thus causing PMVEC injury.

Remimazolam Dosing for Gastroscopy: A Randomized Noninferiority Trial.

BACKGROUND: Remimazolam, an ultra-short-acting benzodiazepine, may provide adequate sedation for endoscopy while causing less cardiovascular or respiratory disturbance than propofol. Although fixed-dose administration is suggested, body weight affects the volume of the central chamber and thus affects the sedation depth that can be achieved by the first dose. This study aimed to compare the efficacy and safety of different doses of remimazolam and propofol by body weight for sedation during gastroscopy. METHODS: This multicenter, randomized, single-blind, parallel-controlled noninferiority trial recruited patients from five centers between March 2021 and July 2022. A total of 1,883 patients scheduled to undergo gastroscopy were randomized to groups receiving 0.15 mg/kg remimazolam, 0.2 mg/kg remimazolam, or 1.5 mg/kg propofol. The noninferiority margin was set to 5%. The primary outcome was the success rate of sedation. Adverse events were recorded to evaluate safety. RESULTS: The sedation success rate of the 0.2 mg/kg remimazolam group was not inferior to that of the 1.5 mg/kg propofol group (98.7% vs. 99.4%; risk difference, -0.64%; 97.5% CI, -2.2 to 0.7%, meeting criteria for noninferiority). However, the sedation success rate of the 0.15 mg/kg remimazolam group was 88.5%, and that of the 1.5 mg/kg propofol group was 99.4% (risk difference, -10.8%; 97.5% CI, -14.0% to -8.0%), demonstrating inferiority. Simultaneously, the overall adverse events rate of remimazolam was lower than that of propofol, and the incidence of bradycardia, hypotension, subclinical respiratory depression, and hypoxia in the remimazolam groups was significantly lower than that in the propofol group. CONCLUSIONS: This trial established the noninferior sedation success rate of remimazolam (0.2 mg/kg but not 0.15 mg/kg) compared with propofol (1.5 mg/kg), with a superior safety profile.

Lidocaine induces neurotoxicity in spinal cord neurons in Goto-Kakizaki rats via AMPK-mediated mitophagy.

OBJECTIVE: Lidocaine has been reported to induce neurotoxicity, which is further enhanced by high glucose levels. This study is aimed to explore the underlying mechanisms of lidocaine neurotoxicity in spinal cord neurons of diabetes. METHODS: Take thirty specific pathogen-free (SPF) healthy Sprague-Dawley (SD) rats and thirty Goto-Kakizaki (GK) rats, aged 12 weeks, weighing 180-200 g. The spinal cord neurons of rats were isolated and cultured in vitro. Cell Counting Kit-8 was used to detect cell proliferation to determine the appropriate concentration and duration of lidocaine. Mitochondrial function was assessed using ATP content, cellular oxygen consumption rate, mitochondrial membrane potential, ROS production, and mitochondrial ultrastructure. Western blot was applied to detect the expression of autophagy- and mitophagy-related molecules PINK1, p-AMPK, LC-3II/LC3-I ratio and mTORC1. Immunofluorescent staining was used to detect the expression of PINK1 and LC3. RESULTS: Lidocaine decreased cell viability of spinal cord neurons in concentration- and time-dependent manners. And lidocaine treatment aggravated mitochondrial dysfunction in GK rats. Furthermore, mitophagy was activated in diabetes, and lidocaine exposure up-regulated mitophagy. AMPK activator MK8722 aggravated mitochondrial damage, increased the expression of PINK1, p-AMPK, LC-3II/LC3-I ratio, and decreased the expression of mTORC1, while AMPK inhibitor Compound C and autophagy inhibitor Bafilomycin A1 reduced mitochondrial damage and decreased the expression of PINK1, p-AMPK, LC-3II/LC3-I ratio, and increased the expression of mTORC1. CONCLUSIONS: Lidocaine induced neurotoxicity of spinal cord neurons in GK rats via AMPK-mediated mitophagy.

Role of Extracellular microRNAs in Sepsis-Induced Acute Lung Injury.

Acute lung injury (ALI) is a life-threatening pathological disease characterized by the damage of pulmonary endothelial cells and epithelial cell barriers by uncontrolled inflammation. During sepsis-induced ALI, multiple cells cooperate and communicate with each other to respond to the stimulation of inflammatory factors. However, the underlying mechanisms of action have not been fully identified, and the modes of communication therein are also being investigated. Extracellular vesicles (EVs) are a heterogeneous population of spherical membrane structures released by almost all types of cells, containing various cellular components. EVs are primary transport vehicles for microRNAs (miRNAs), which play essential roles in physiological and pathological processes in ALI. EV miRNAs from different sources participated in regulating the biological function of pulmonary epithelial cells, endothelial cells, and phagocytes by transferring miRNA through EVs during ALI induced by sepsis, which has great potential diagnostic and therapeutic values. This study aims to summarize the role and mechanism of extracellular vesicle miRNAs from different cells in the regulation of sepsis-induced ALI. It provides ideas for further exploring the role of extracellular miRNA secreted by different cells in the ALI induced by sepsis, to make up for the deficiency of current understanding, and to explore the more optimal scheme for diagnosis and treatment of ALI.

Effect of transverse thoracic muscle plane block on postoperative cognitive dysfunction after open cardiac surgery: A randomized clinical trial.

The transversus thoracis muscle plane (TTMP) block provides effective analgesia in cardiac surgery patients. The aim of this study was to assess whether bilateral TTMP blocks can reduce the incidence of postoperative cognitive dysfunction (POCD) in patients undergoing cardiac valve replacement. A group of 103 patients were randomly divided into the TTM group (n = 52) and the PLA (placebo) group (n = 51). The primary endpoint was the incidence of POCD at 1 week after surgery. Secondary outcome measures included a reduction of intraoperative mean arterial pressure (MAP) >20% from baseline, intraoperative and postoperative sufentanil consumption, length of stay in the ICU, incidence of postoperative nausea and vomiting (PONV), time to first faeces, postoperative pain at 24 h after surgery, time to extubation and the length of hospital stay. Interleukin (IL)-6, TNF-α, S-100ß, insulin, glucose and insulin resistance were measured at before induction of anaesthesia, 1, 3and 7 days after surgery. The MoCA scores were significantly lower and the incidence of POCD decreased significantly in TTM group compared with PLA group at 7 days after surgery. Perioperative sufentanil consumption, the incidence of PONV and intraoperative MAP reduction >20% from baseline, length of stay in the ICU, postoperative pain at 24 h after surgery, time to extubation and the length of hospital stay were significantly decreased in the TTM group. Postoperatively, IL-6, TNF-α, S-100ß, HOMA-IR, insulin, glucose levels increased and the TTM group had a lower degree than the PLA group at 1, 3 and 7 days after surgery. In summary, bilateral TTMP blocks could improve postoperative cognitive function in patients undergoing cardiac valve replacement.

Sevoflurane protects against intracerebral hemorrhage via microRNA-133b/FOXO4/BCL2 axis.

The application of Sevoflurane (Sev) in neurological diseases has been documented. We herein clarified the role of Sev in intracerebral hemorrhage (ICH). Through bioinformatics analysis, ICH-related microRNA (miRNA) was collected with microRNA-133b (miR-133b) chosen for the study subject. Then, the related downstream gene Forkhead box O4 (FOXO4) was identified. For in vivo assays, an ICH mouse model was established by autologous blood injection. For in vitro assays, hippocampal neurons were extracted from mouse brain tissues, and erythrocyte lysates were employed to simulate in vitro hemorrhage. Interaction between miR-133b and FOXO4 as well as between FOXO4 and BCL2 were assayed. We found decreased miR-133b in the brain tissue of ICH mice and erythrocyte lysate-treated hippocampal neurons. Sev treatment attenuated ICH and hippocampal neuronal apoptosis in mice by upregulating miR-133b. miR-133b targeted FOXO4 expression, and inhibition of FOXO4 attenuated hippocampal neuronal apoptosis by increasing BCL2 expression. Sev attenuated ICH in mice by increasing BCL2 expression through regulation of miR-133b-mediated FOXO4 expression. The findings highlighted the protective effect of Sev on ICH mice through the regulation of miR-133b-mediated FOXO4 expression.

miR-182-5p Delivered by Plasma Exosomes Promotes Sevoflurane-Induced Neuroinflammation and Cognitive Dysfunction in Aged Rats with Postoperative Cognitive Dysfunction by Targeting Brain-Derived Neurotrophic Factor and Activating NF-κB Pathway.

The objective of this study was to discuss the possible mechanism and effect of miR-182-5p delivered by plasma exosomes on sevoflurane-induced neuroinflammation and cognitive disorder in aged rats with postoperative cognitive dysfunction (POCD). Firstly, aged POCD rat models were constructed by sevoflurane anesthesia and superior mesenteric artery occlusion. Subsequently, exosomes and miR-182-5p were inhibited by injection of GW4869 and miR-182-5p-sponge, respectively. Then, exosomes were extracted from the plasma of rats in each group, followed by the determination of the morphology and diameters of exosomes as well as the expression of exosome markers CD63 and CD81 by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Besides, the Morris water maze (MWM) and fear conditioning test were used to evaluate the learning and memory ability of rats; Western blot to detect the expression levels of neurotrophic factors (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) as well as NF-κB pathway-related proteins (p65 and p-p65) in rat hippocampal tissues or PC-12 cells; qRT-PCR to assess the expression levels of miR-182-5p and BDNF in rat plasma, plasma exosomes, hippocampal tissues, and PC-12 cells; ELISA to evaluate the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß in rat hippocampal tissues; and dual-luciferase reporter assay to verify the targeting relationship between miR-182-5p and BDNF. After examination, the results were obtained as follows. miR-182-5p expression was up-regulated in POCD rats and could be delivered by plasma exosomes. Inhibition of plasma exosomes or miR-182-5p could significantly ameliorate learning and memory disorders; decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß; increase the expression of BDNF and NGF; and inhibit the activity of NF-κB signaling pathway in POCD rat hippocampus. In addition, miR-182-5p could also target and inhibit BDNF. All in all, miR-182-5p delivered by plasma exosomes promotes sevoflurane-induced neuroinflammation and cognitive dysfunction in aged POCD rats by targeting BDNF and activating the NF-κB pathway.

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity. Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients. Design, Setting, and Participants: This multicenter, parallel-group, noninferiority randomized clinical trial (Etomidate vs Propofol for In-hospital Complications [EPIC]) was conducted between August 15, 2017, and November 20, 2020, at 22 tertiary hospitals in China. Participants were aged 65 to 80 years and were scheduled for elective abdominal surgery. Patients and outcome assessors were blinded to group allocation. Data analysis followed a modified intention-to-treat principle. Interventions: Patients were randomized 1:1 to receive either etomidate or propofol for general anesthesia by target-controlled infusion. Main Outcomes and Measures: Primary outcome was a composite of major in-hospital postoperative complications (with a noninferiority margin of 3%). Secondary outcomes included intraoperative hemodynamic measurements; postoperative adrenocortical hormone levels; self-reported postoperative pain, nausea, and vomiting; and mortality at postoperative months 6 and 12. Results: A total of 1944 participants were randomized, of whom 1917 (98.6%) completed the trial. Patients were randomized to the etomidate group (n = 967; mean [SD] age, 70.3 [4.0] years; 578 men [59.8%]) or propofol group (n = 950; mean [SD] age, 70.6 [4.2] years; 533 men [56.1%]). The primary end point occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion (risk difference [RD], 0.6%; 95% CI, -1.6% to 2.7%; P = .66). In the etomidate group, mean (SD) cortisol levels were lower at the end of surgery (4.8 [2.7] µg/dL vs 6.1 [3.4] µg/dL; P < .001), and mean (SD) aldosterone levels were lower at the end of surgery (0.13 [0.05] ng/dL vs 0.15 [0.07] ng/dL; P = .02) and on postoperative day 1 (0.14 [0.04] ng/dL vs 0.16 [0.06] ng/dL; P = .001) compared with the propofol group. No difference in mortality was observed between the etomidate and propofol groups at postoperative month 6 (2.2% vs 3.0%; RD, -0.8%; 95% CI, -2.2% to 0.7%) and 12 (3.3% vs 3.9%; RD, -0.6%; 95% CI, -2.3% to 1.0%). More patients had pneumonia in the etomidate group than in the propofol group (2.0% vs 0.3%; RD, 1.7%; 95% CI, 0.7% to 2.8%; P = .001). Results were consistent in the per-protocol population. Conclusions and Relevance: Results of this trial showed that, compared with propofol, etomidate anesthesia did not increase overall major in-hospital morbidity after abdominal surgery in older patients, although it induced transient adrenocortical suppression. Trial Registration: ClinicalTrials.gov Identifier: NCT02910206.

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate TRX-Induced PHN in Mice.

Varicella zoster virus-induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by TRX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were decreased in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate TRX-induced PHN in mice.

Perioperative Pain Management With Bilateral Pecto-intercostal Fascial Block in Pediatric Patients Undergoing Open Cardiac Surgery.

Purposes: Pediatric open cardiac surgical patients usually suffer from acute pain after operation. The current work aimed to explore the impact of bilateral PIFB in children suffering from open cardiac surgery. Methods: This work randomized altogether 110 child patients as bilateral PIFB (PIF) and non-nerve block (SAL) groups. This work adopted post-operative pain at exercise and rest statuses as the primary endpoint, whereas time-to-drain removal/extubation/initial defecation, intraoperative/post-operative fentanyl use, and length of ICU and hospital stay as the secondary endpoints. Results: MOPS were significantly higher at 24-h post-operatively at coughing and rest statuses in SAL group compared with PIF group. Meanwhile, PIF group exhibited markedly lower intraoperative/post-operative fentanyl use amounts, as well as markedly reduced time-to-extubation/initial flatus, and length of ICU/hospital stay. Conclusion: Bilateral PIFB in pediatric open cardiac surgical patients provide effective analgesia and lower the length of hospital stay.

Sensory Assessment and Block Duration of Deep Parasternal Intercostal Plane Block in Patients Undergoing Cardiac Surgery: A Prospective Observational Study.

INTRODUCTION: There has been increasing interest in using deep parasternal intercostal plane (PIP) block as a supplement to multimodal analgesia regimens in cardiac surgery. The aim of this study was to observe cutaneous sensory block distribution and its duration for deep PIP blocks in patients undergoing open cardiac surgery. METHODS: This observational, prospective clinical study consisted of 113 participants. All patients received bilateral ultrasound-guided deep PIP block with 40 ml 0.33% ropivacaine. The primary study outcome was cutaneous sensory block distribution of deep PIP blocks in patients undergoing open cardiac surgery. Secondary outcome included block duration in all participants. The area of cutaneous sensory block was tested by using a cold stimulus (ice cube) 30 min after the end of deep PIP block administration. Cutaneous sensory testing was performed once every hour after extubation until the return of normal sensation. RESULTS: Thirty minutes after bilateral deep PIP block administration, the successful block rate of dermatomes T4 to T6 was almost 100%. However, T2 (percentage of left T2 block: 64.6%; percentage of right T2 block: 42.5%) and T3 (percentage of left T3 block: 88.5%; percentage of right T3 block: 87.6%) had a lower percentage of success. A few patients had blocked dermatomes at T1 or T7 (percentage of left T1 block: 7.08%; percentage of right T1 block: 2.65%; percentage of left T7 block: 6.19%; percentage of right T7 block: 10.6%). The mean effective duration of the deep PIP block was 17 h. CONCLUSION: Bilateral deep PIP blocks can produce a widespread cutaneous sensory blockade with variable dermatomal distribution in the mid-sternum for a considerable effective duration. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100047755).

Comparison of Ultrasound-Guided Caudal Epidural Blocks and Spinal Anesthesia for Anorectal Surgery: A Randomized Controlled Trial.

INTRODUCTION: The aim of this study is to observe the effect of spinal anesthesia (SA) and ultrasound-guided caudal epidural blocks (CEB) on perioperative satisfaction in patients undergoing anorectal surgery. METHODS: A group of 106 patients were randomly allocated to receive either SA (the SA group) or CEB (the CEB group), and 11 patients were excluded. Finally, 95 patients were left, with 48 in the SA group and 47 in the CEB group for data analysis. The primary endpoint was patient satisfaction with the quality of their anesthetic technique. The secondary outcome measures included postoperative pain at 2, 4, 8, 16, 24, and 48 h after surgery at rest, time to first analgesic request, analgesia requirements, incidence of phantom limb syndrome (PLS), time until return of bowel function, time to ambulation, incidence of postoperative nausea and vomiting (PONV), intraoperative mean arterial pressure (MAP) reduction > 20% from baseline, and surgeon satisfaction. RESULTS: A significantly lower proportion of patients in the SA group was highly satisfied with the quality of their anesthetic technique compared with the CEB group (20.8% versus 68.1%). NRS scores at rest were significantly lower at 4, 8, 16, and 24 h after surgery in the CEB group compared with the SA group. The time to first analgesic request was significantly earlier for patients in the SA group compared with patients in the CEB group. Analgesia requirements, the incidence of PLS, the incidence of PONV, and intraoperative MAP reduction > 20% from baseline were significantly decreased in the CEB group. There were no significant differences between the groups in time until return of bowel function, surgeon satisfaction, or time to ambulation. CONCLUSIONS: Ultrasound-guided caudal epidural blocks have higher patient satisfaction compared with spinal anesthesia. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR 2000041026) on 06/12/2020.

Clinical significance of methyl-CpG binding protein 2 in postherpetic neuralgia: an observational study / Importancia clínica de la proteína 2 de unión a metil-CpG (MECP2) en la neuralgia posherpética: un estudio observacional

Abstract The present study was aimed to investigate the clinical significance of methyl-CpG binding protein 2 (MECP2) in patients with postherpetic neuralgia (PHN). This prospective case control study enrolled 319 cases of PHN patients from April 2017~December 2019. The patients' sleep quality and quality of life were evaluated using the Pittsburgh sleep quality score and the SF- 36 scale, respectively. The serum levels of MECP2, CRP, IL -6 and TNF-α were tested using enzyme linked immunosorbent assay (ELISA). The pain condition of the patients was evaluated using the visual analogue scale (VAS). The levels of MECP2 were significantly increased in PHN patients compared with the patients without PHN. Serum MECP2 levels were the highest in patients with severe pain, and were the lowest in patients with mild pain. Similarly, the frequency of severe pain in patients with low expression of MECP2 was significantly lower than the patients with higher MECP2 expression. Besides, serum levels of inflammatory factors CRP, IL -6 and TNF-α were markedly increased in PHN patients, which were also increased with the increase of the severity of pain. CRP, IL -6 and TNF-α were positively correlated with serum levels of MECP2 in PHN patients. Before the study, patients with lower MECP2 levels showed a significantly higher SF-36 score and lower Pittsburgh and VAS scores than patients with higher levels of MECP2. However, after one month, no significant difference was found between the patients. ROC curve showed MECP2 had the potential as a diagnostic biomarker for PHN. In conclusion, higher serum MECP2 levels are associated with a more severe pain condition and increased release of inflammatory factors.

Resumen El objetivo de este estudio fue investigar la importancia clínica de la MECP2 en pacientes con neuralgia posherpética (NPH). Este estudio observacional prospectivo incluyó 319 pacientes con NPH entre abril de 2017 y diciembre de 2019. La calidad del sueño y la calidad de vida de los pacientes se evaluaron con la escala de calidad del sueño de Pittsburgh y la escala SF - 36, respectivamente. Los niveles séricos de MECP2, PCR, IL -6 y TNF-α fueron determinados por ELISA. Se utilizó la escala visual analógica (EVA) para evaluar la intensidad del dolor. Los niveles de MECP2 en pacientes con NPH aumentaron significativamente en comparación con los pacientes sin NPH. El nivel sérico de MECP2 fue más alto en pacientes con dolor grave y el más bajo en pacientes con dolor leve. Además, la incidencia de dolor grave en pacientes con baja expresión de MECP2 fue significativamente menor que en pacientes con alta expresión de MECP2. Además, los niveles séricos de PCR, IL -6 y TNF-α aumentaron significativamente en pacientes con NPH, y se incrementaron con el aumento del grado de dolor. Los niveles séricos de PCR, IL -6 y TNF-α en pacientes con NPH se correlacionaron positivamente con los niveles séricos de MECP2. Antes del estudio, los pacientes con niveles más bajos de MECP2 tenían puntuaciones significativamente más altas de SF - 36, y puntuaciones más bajas de Pittsburgh y EVA que los pacientes con niveles más altos de MECP2. Sin embargo, no se encontraron diferencias significativas entre los pacientes un mes después. Las curvas ROC mostraron que la MECP2 podría ser un biomarcador de diagnóstico para la NPH. En general, los niveles séricos más altos de la MECP2 se asociaron con condiciones de dolor más graves y un aumento de la liberación de factores inflamatorios.

Continuous Pecto-Intercostal Fascial Block Provides Effective Analgesia in Patients Undergoing Open Cardiac Surgery: A Randomized Controlled Trial.

BACKGROUND: The optimal analgesia regimen after open cardiac surgery has been unclear. The aim of this study was to investigate the beneficial effects of continuous pecto-intercostal fascial blocks (PIFB) initiated before surgery on outcomes after open cardiac surgery. METHODS: A group of 116 patients were randomly allocated to receive either bilateral continuous PIFB (PIF group) or the same block with saline (SAL group). The primary endpoint was postoperative pain at 4, 8, 16, 24, 48, and 72 hours after extubation at rest and during exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen consumption), time to extubation, length of stay in the intensive care unit, incidence of postoperative nausea and vomiting, time until return of bowel function, time to mobilization, time to urinary catheter removal, and the length of hospital stay. RESULTS: The length of stay in the intensive care unit (29 ± 7 hours vs 13 ± 4 hours, P < 0.01) and length of hospital stay (8.9 ± 0.9 days vs 6.5 ± 1.1 days, P < 0.01) were significantly longer in the SAL group than in the PIF group. Resting pain scores (2 hours after extubation: 1.1 vs 3.3, P < 0.01; 4 hours after extubation: 1.0 vs 3.5, P < 0.01; 8 hours after extubation: 1.2 vs 3.7, P < 0.01; 16 hours after extubation: 1.3 vs 3.7, P < 0.01; 24 hours after extubation: 1.4 vs 2.8, P < 0.01; 48 hours after extubation: 0.9 vs 2.2, P < 0.01; 72 hours after extubation: 0.8 vs 2.1, P < 0.01) and dynamic pain scores (2 hours after extubation: 1.4 vs 3.7, P < 0.01; 4 hours after extubation: 1.3 vs 3.8, P < 0.01; 8 hours after extubation: 1.4 vs 3.5, P < 0.01; 16 hours after extubation: 1.2 vs 3.4, P < 0.01; 24 hours after extubation: 1.1 vs 3.1, P < 0.01; 48 hours after extubation: 1.0 vs 2.9, P < 0.01; 72 hours after extubation: 0.9 vs 2.8, P < 0.01) were significantly lower in the PIF group than in the SAL group at all time points. The PIF group required significantly less intraoperative sufentanil consumption (123 ± 32 µg vs 63 ± 16 µg, P < 0.01), postoperative sufentanil consumption (102 ± 22 µg vs 52 ± 17 µg, P < 0.01), and postoperative flurbiprofen consumption (350 ± 100 mg vs 100 ± 100 mg, P < 0.01) than the SAL groups. Time to extubation (8.9 ± 2.4 hours vs 3.2 ± 1.3 hours, P < 0.01), time to first flatus (43 ± 6 hours vs 30 ± 7 hours, P < 0.01), time until mobilization (35 ± 5 hours vs 24 ± 7 hours, P < 0.01), and time until urinary catheter removal (47 ± 9 hours vs 31 ± 4 hours, P < 0.01) were significantly earlier in the PIF group than in the SAL group. The incidence of postoperative nausea and vomiting was significantly lower in the PIF group (9.1% vs 27.3%, P < 0.01). CONCLUSION: Bilateral continuous PIFB reduced the length of hospital stay and provided effective postoperative pain relief for 3 days.

Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1.

Endothelial inflammation is a crucial event in the initiation of atherosclerosis. Here, we identify Ataxin-10 protein as a novel negative modulator of endothelial activation by suppressing IRF-1 transcription activity. The protein level of Ataxin-10 is relatively higher in human vascular endothelial cells, which can be significantly suppressed by TNF-α in both HUVECs and HLMECs. Overexpression of Ataxin-10 markedly inhibited the mRNA expressions of VCAM-1 and several cytokines including MCP-1, CXCL-1, CCL-5, and TNF-α; thus, it can also suppress monocyte adhesion to endothelial cells. Accordingly, Ataxin-10 silencing promoted endothelial inflammation. However, Ataxin-10 did not affect the MAPK/NF-κB signaling pathway stimulated by TNF-α in HUVECs. Using the yeast two-hybrid assay, we found that Ataxin-10 can directly bind to interferon regulatory factor-1 (IRF-1). Upon TNF-α stimulation, Ataxin-10 promoted the cytoplasmic localization of IRF-1, which inhibited the transcription of VCAM-1. Moreover, knockdown of IRF-1 can eliminate the effect of Ataxin-10 on the expression of VCAM-1 in HUVECs induced by TNF-α. Taken together, these results indicate that Ataxin-10 inhibits endothelial cell activation and may serve as a promising therapeutic target for some vascular inflammatory-related diseases such as atherosclerosis.

Mechanism of Catechol-O-methyltransferase Regulating Orofacial Pain Induced by Tooth Movement.

OBJECTIVE: To explore the mechanism of catechol-O-methyltransferase (COMT) in tooth movement pain. METHODS: The experimental groups were randomly allocated into the healthy control, sham operation, model, model+shCOMT experimental, model+shCOMT control, and model+COMT antagonist groups. A tooth movement pain model was established. The pain stimulation and behavior test were performed. The duration of grooming behavior was determined. The appropriate experimental force and duration for application were selected. COMT shRNA vector was constructed and packaged as adenovirus. The shCOMT adenovirus was injected into the left infraorbital foramen. Seven days later, the trigeminal ganglia of all treatment groups were obtained. The COMT and IL-17 expressions were detected by western blot. The appropriate COMT antagonist concentration was selected. The pathological results of each group were detected by HE staining. The tooth movement distance was determined. The COMT gene expression was detected by FISH. The COMT and IL-17 expressions in the right trigeminal ganglion tissue of each group were detected by western blot. RESULTS: The 60 g force and 14-day duration required the lowest stimulus intensity, the duration of grooming behavior was the longest, and the effect on COMT and IL-17 was the most significant. In the model group, formation of digestive cavity was seen in the trigeminal ganglion tissue, with infiltration of inflammatory cells, upregulation of the COMT and IL-17 expressions, and significant increase in the tooth movement distance. Compared with the model group, the shCOMT experimental group and the COMT antagonist group significantly improved the trigeminal ganglion tissue injury, significantly decreased the tooth movement distance, and significantly inhibited the COMT and IL-17 expressions. CONCLUSION: The efficiency of tooth movement can be influenced by interfering the COMT-related gene expression. This proves that the COMT system can regulate the orthodontic tooth movement pain.