Dexmedetomidine inhibited arrhythmia susceptibility to adrenergic stress in RyR2R2474S mice through regulating the coupling of membrane potential and intracellular calcium.

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. METHODS: Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. RESULTS: DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. CONCLUSION: DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.

Dexmedetomidine and Perioperative Arrhythmias.

The highly selective α2-adrenoceptor agonist dexmedetomidine is a commonly used sedative drug for patients undergoing anesthesia and intensive care treatment. Several studies have indicated that dexmedetomidine may have a potential role in preventing and treating perioperative tachyarrhythmias. However, the specific effect and mechanism of action of dexmedetomidine in this context remain unclear. Dexmedetomidine is known to regulate the electrophysiologic function of the myocardium by inhibiting the function of the sinus node and atrioventricular node, as well as affecting myocardial repolarization. This paper aims to provide a theoretical basis for the prevention and treatment of perioperative arrhythmias by summarizing the effects of dexmedetomidine on myocardial electrophysiologic function and its impact on different types of arrhythmias.

The safety and efficacy of remimazolam tosylate combined with propofol in upper gastrointestinal endoscopy: A multicenter, randomized clinical trial.

INTRODUCTION: Hypotension is the most common adverse event under propofol-mediated sedation and is possible to cause varying degrees of damage to patients. Whereas remimazolam has a poorer sedative effect than propofol. AIM: The aim of this study was to explore the advantages of the combination of remimazolam tosylate and propofol. METHODS: 304 patients were divided into the remimazolam tosylate group (RT group), the propofol group (P group), and the remimazolam tosylate plus propofol group(R+T group). The primary outcome was the incidence of hypotension. Secondary outcomes included the results of sedation and recovery. The safety results mainly include the incidence of Hypotension, adverse respiratory events, postoperative nausea and vomiting, hiccup, cough, body movement and bradycardia. RESULTS: The incidence of hypotension was 56.7% in the P group, 12.6% in the RT group, and 31.3% in the R+P group, three groups of pairwise comparisons showed statistical differences, with P< 0.001. The incidence of body movement was significantly higher in the RT group (26.1%) than in the P group (10.3%) and the R+P group (12.5%), P = 0.004. The endoscopist satisfaction was higher in the P (3.87±0.44) and R+P (3.95±0.22)groups than in the RT(3.53±0.84) group. The incidence of adverse events, in descending order, was P group, RT group, and R+P group (93.8%vs.61.3%vs.42.7%). CONCLUSION: Co-administration had fewer adverse events than propofol monotherapy, also had a better sedative effect and higher endoscopist satisfaction than remimazolam monotherapy. TRIAL REGISTRATION: Clinical trial registration number: NCT05429086.

Can the Negative Cognitive Bias Be Predicted by Early Victimization of College Students? The Dual Role of Resilience.

Victimization could cause cognitive dysfunction like negative cognitive bias. While there are studies of contemporaneous consequences, there is insufficient research on whether and how early victimization will affect adult negative cognitive bias. This study examined the dual role of resilience (i.e., whether resilience would moderate the relationship between early victimization and negative cognitive bias, and/or whether resilience would mediate the same relationship). A total of 972 college students (40% were males, Mage = 19.25, SD = 1.17, range = 16-25) from three universities in Central China completed a series of anonymous questionnaires on early victimization, resilience, and negative cognitive bias. After controlling for demographic variables, the results indicated that early victimization was positively correlated with negative cognitive bias of college students. Moderation analysis indicated that resilience moderated the relationship between early victimization and negative cognitive bias. Mediation analysis revealed that resilience partially mediated the same relationship. Specifically, the effect of early victimization on negative cognitive bias was stronger for college students with high level of resilience than those with low level of resilience. Meanwhile, early victimization affected negative cognitive bias partially through resilience. The findings elucidate the dual role of resilience in the relationship between early victimization and negative cognitive bias. On the one hand, negative cognitive bias can be reduced by enhancing resilience among victims, on the other hand, the protective role of resilience may be weakened with the increase of victimization, reminding us to pay more attention to victims with high level of resilience.

Effects of ultrasound-guided erector spinae plane block on postoperative acute pain and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy: a prospective randomized, controlled trial.

OBJECTIVE: To investigate the effects of ultrasound-guided erector spinae plane block (ESPB) on acute and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy. METHODS: A total of 94 patients, who underwent elective unilateral video-assisted thoracoscopic lobotomy from August 2021 to December 2021 were randomly divided into general anesthesia group (group A, n = 46) and ESPB combined with general anesthesia group (group B, n = 48) by computer. Patient controlled intravenous analgesia(PCIA) was performed in both groups after operation. The numerical rating scale(NRS) of rest and cough pain at post anesthesia care unit(PACU), 2 h, 6 h, 12 h, 24 and 48 h after operation, frequency of PCIA in 24 h after operation, frequency of rescue analgesia, patient satisfaction, adverse reactions and complications were recorded in the two groups. Incidence of chronic pain at 3 months and 6 months after operation, the effect of daily life and rating of chronic pain management measures were recorded in the two groups. RESULTS: Compared with group A, rest and cough NRS score at 2 h, 6 h, 12 h, 24 and 48 h after surgery, frequency of PCIA use at 24 h after surgery, frequency of rescue analgesia were significantly decreased in group B (P < 0.05). There was no significant difference in NRS scores of rest and cough at PACU after operation between 2 groups after surgery at post anesthesia care unit (P > 0.05). There were no significant differences in the incidence of postoperative chronic pain between the 2 groups(P > 0.05);The effect of postoperative chronic pain on daily life and pain management measures in group B were significantly lower than those in group A(P < 0.05). Compared with group A, patients in group B had higher satisfaction degree, lower incidence of postoperative nausea and vomiting(PONV), and lower incidence of agitation during anesthesia recovery (P < 0.05). There were no pneumothorax, hematoma and toxicity of local anesthetic in the 2 groups. CONCLUSION: Ultrasound-guided erector spinae plane block can significantly reduce acute post-surgical pain, can not reduce the incidence of chronic post-surgical pain, but can significantly reduce the severity of chronic pain in patients underwent video-assisted thoracoscopic lobectomy. TRIAL REGISTRATION: ChiCTR2100050313,date of registration:26/08/2021.

Does Early Victimization of School Bullies Affect Core Self-Evaluations in Young Adulthood? A Moderated Mediation Model.

Early victimization is associated with a range of psychological adaptation problems in young adulthood, including core self-evaluations. However, little is known about the mechanisms underlying the association between early victimization and young adults' core self-evaluations. This study examined the mediating role of negative cognitive processing bias and the moderating role of resilience in the relationship. A total of 972 college students were recruited to complete measures of early victimization, negative cognitive processing bias, resilience, and core self-evaluations. The results showed that early victimization significantly and negatively predicted the core self-evaluations in young adulthood. The negative association between early victimization and core self-evaluations was completely mediated by negative cognitive processing bias. Resilience moderated the relationship between early victimization and negative cognitive bias, and the relationship between negative cognitive processing bias and core self-evaluations. Resilience has both risk-buffering and risk-enhancing effects. In light of these results, in order to help victims maintain good mental health, we should intervene in individual cognitive factors. Notably, while resilience is a protective factor in most cases, the benefits of resilience should not be overstated. So, we should not only cultivate students' resilience but also provide them with more support and resources and intervene in risk factors at the same time.

Optimization of programmed intermittent epidural bolus volume for different concentrations of ropivacaine in labor analgesia: a biased coin up-and-down sequential allocation trial.

BACKGROUND AND OBJECTIVES: To date, programmed intermittent epidural bolus (PIEB) has been widely used in obstetric analgesia, while no optimal PIEB regimen has been proposed. This study aimed to assess effective analgesia in 90% of women (EV90) with different concentrations of ropivacaine (0.075% and 0.1%) combined with 0.5 µg/mL sufentanil, at an interval of 40 min using the biased coin design-up-and-down method (BCD-UDM), and to explore whether there is a difference in EV90 with the increase of ropivacaine concentration. METHODS: In total, 103 primiparous women were assigned to two groups, including group A (n = 52) and group B (n = 51). Parturients in group A were treated with 0.075% ropivacaine and 0.5 µg/mL sufentanil, while those in group B were treated with 0.1% ropivacaine and 0.5 µg/mL sufentanil. Used the biased coin up-and-down sequential allocation method to determine the EV90. The secondary outcomes were sensory block level, motor block, and adverse events (hypotension, urinary retention, and pruritus). RESULTS: The results revealed that EV90 was 10 mL (95% confidence interval (CI):8.03-11.54) in group A, and EV90 was 9 mL (95% CI:7.49-10.51) in group B by the isotonic regression method. The highest level of the sensory block was T8, and the lowest was T12. No case of hypotension was recorded,and only 4 parturients complained of motor block. CONCLUSION: With an interval of 40 min, the optimal PIEB bolus volume of 0.075% ropivacaine and 0.5 µg/mL sufentanil was 10 mL, 0.1% ropivacaine and 0.5 µg/mL sufentanil was 9 mL. Moreover, the PIEB volume decreased along with the higher concentration of ropivacaine. TRIAL REGISTRATION: ChiCTR registration number: ChiCTR2000040917 . Registration date: December 15, 2020.

Plasmonic Coupling in Silver Nanoparticle Aggregates and Their Polymer Composite Films for Near-Infrared Photothermal Biofilm Eradication.

Plasmonic nanoparticles with near-IR (NIR) light absorption are highly attractive in biomedicine for minimally invasive photothermal treatments. However, these optical properties are typically exhibited by plasmonic nanostructures with complex, nonspherical geometries that may prohibit their broad commercialization and further integration into photothermal devices. Herein, we present the single-step aerosol self-assembly of plasmonic nanoaggregates that consisted of spherical silver nanoparticles with tunable extinction from visible to NIR wavelengths. This tunable extinction was achieved by the addition of SiO2 during the flame synthesis of the nanoparticles, which acted as a dielectric spacer between the spherical silver nanoparticles and was also computationally validated by simulating the extinction spectra of similar silver nanoaggregates. These plasmonic nanoaggregates were easily deposited on silicone polymeric surfaces and further encased with a top polymer layer, forming plasmonic photothermal nanocomposite films. The photothermal properties of the NIR nanocomposite films were utilized to eradicate the established biofilms of clinically relevant Escherichia coli and Staphylococcus aureus, with a relationship observed between the final surface temperature and biofilm eradication.

Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro.

BACKGROUND Studies in vivo have shown that dexmedetomidine (DEX) could protect the myocardium and modulate the coronary blood flow. This study aimed to investigate the direct and concentration-dependent effects of DEX on the tone of porcine coronary artery in vitro and the underlying mechanisms. MATERIAL AND METHODS Distal branches of the porcine anterior descending coronary arteries were dissected and cut into 3-5 mm rings. The tones of coronary rings in response to cumulative DEX were measured using the PowerLab system. Coronary rings were divided into three groups: 1) endothelium-intact coronary rings without drug pretreatment (control); 2) endothelium-intact coronary rings pretreated with either yohimbine, tetraethylamine (TEA) or NG-nitro-L-arginine methyl ester (L-NAME); and 3) endothelium-denuded coronary rings pretreated with either yohimbine or TEA. RESULTS DEX induced coronary ring relaxation at lower concentrations (10^-9 to 10^-7 M) followed by constriction at higher concentrations (10^-6 to 10^-5 M). The coronary constrictive effect of higher DEX (10^-5 M) was greater in the endothelium-denuded rings than in the endothelium-intact rings. Yohimbine reduced the coronary constrictive effect of DEX at higher concentrations (10^-6 to 10^-5 M). TEA and L-NAME significantly reduced the coronary relaxing effect of DEX at lower concentrations (10^-9 to 10^-7 M) in endothelium-intact rings. TEA attenuated the coronary relaxation induced by DEX in endothelium-denuded rings. CONCLUSIONS DEX exerts bidirectional effects on porcine coronary tone. The coronary relaxing effect of DEX at lower concentrations is likely associated with endothelium integrity, NO synthesis and BKCa channel activation, while the coronary constrictive effect of DEX at higher concentrations is mediated by a2 adrenoceptors in the coronary smooth muscle cells.

Impact of ketamine on learning and memory function, neuronal apoptosis and its potential association with miR-214 and PTEN in adolescent rats.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic and anti-depressive drug. Recent studies suggest that ketamine enhances neuronal apoptosis in developing rats. The goal of this study is to explore whether ketamine could result in learning and memory impairment and neurodegeneration in adolescent rats, and if so, whether the effects of ketamine are associated with miR-214 and PTEN expression. Fifty-day-old SD rats were randomly divided into three groups receiving ketamine at 30, or 80 mg/kg, i.p. or saline for seven consecutive days. Twenty-four hours after the last treatment, learning and memory function were tested by the Morris water maze. The rats were then decapitated, and the brains were isolated for detection of neuronal apoptosis and protein PTEN expression by TUNEL and immunohistochemistry respectively. Expression levels of the miR-214 and PTEN in the hippocampus were measured by qRT-PCR and western blot analysis respectively. Ketamine administered to the adolescent rats at a dose of 80 mg/kg rather than the lower dose of 30 mg/kg caused learning and memory impairment, increased the number of apoptotic cells in the hippocampal CA1 region, cerebral cortex and subcortical region, decreased the miR-214 levels and increased PTEN protein expression in hippocampus. The results suggest that ketamine at a dose of 80 mg/kg in the adolescent rats is able to induce the learning and memory impairment and neurodegeneration, in which the down-regulation of miR-214 and high expression of PTEN protein may be involved.

Socially regulated reproductive development: analysis of GnRH-1 and kisspeptin neuronal systems in cooperatively breeding naked mole-rats (Heterocephalus glaber).

In naked mole-rat (NMR) colonies, breeding is monopolized by the queen and her consorts. Subordinates experience gonadal development if separated from the queen. To elucidate the neuroendocrine factors underlying reproductive suppression/development in NMRs, we quantified plasma gonadal steroids and GnRH-1- and kisspeptin-immunoreactive (ir) neurons in subordinate adults and in those allowed to develop into breeders, with or without subsequent gonadectomy. In males and females, respectively, plasma testosterone and progesterone are higher in breeders than in subordinates. No such distinction occurs for plasma estradiol; its presence after gonadectomy and its positive correlation with adrenal estradiol suggest an adrenal source. Numbers of GnRH-1-ir cell bodies do not differ between gonad-intact breeders and subordinates within or between the sexes. As in phylogenetically related guinea pigs, kisspeptin-ir processes pervade the internal and external zones of the median eminence. Their distribution is consistent with actions on GnRH-1 neurons at perikaryal and/or terminal levels. In previously investigated species, numbers of kisspeptin-ir cell bodies vary from substantial to negligible according to sex and/or reproductive state. NMRs are exceptional: irrespective of sex, reproductive state, or presence of gonads, substantial numbers of kisspeptin-ir cell bodies are detected in the rostral periventricular region of the third ventricle (RP3V) and in the anterior periventricular (PVa), arcuate, and dorsomedial hypothalamic nuclei. Nevertheless, the greater number in the RP3V/PVa of female breeders compared with female subordinates or male breeders suggests that emergence from a hypogonadotrophic state in females may involve kisspeptin-related mechanisms similar to those underlying puberty or seasonal breeding in other species.

Propofol pretreatment increases antidepressant-like effects induced by acute administration of ketamine in rats receiving forced swimming test.

Animal and clinical studies have demonstrated that ketamine has quick, obvious and persistent antidepressant-like effect, but such side effects as cardiovascular system excitement and hallucinogenic activity have limited its clinical application. Intravenous anesthetic propofol can remarkably inhibit or eliminate ketamine's side effects including cardiovascular system excitement and hallucinogenic activity even in a sub-anesthesia dose. However, effect of propofol on rapid antidepressant-like action induced by ketamine still remains unclear. The present study aimed to investigate effect of pretreatment with propofol on the ketamine-induced rapid antidepressant-like action in rats receiving forced swimming test. Open field test and forced swimming test were used to investigate behavior changes of rats receiving different medication. Expression of brain derived neurotrophic factors (BDNF) and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) pGluR1-Ser845 in hippocampus was measured with sandwich-ELISA and Western Blot, respectively. Results demonstrated that rats receiving propofol alone showed neither antidepressant-like effects nor increased BDNF content; pretreatment with propofol could increase the ketamine-induced antidepressant-like effects and the expression of AMPA pGluR1-Ser845 in hippocampus, but could not further reinforce the increased BDNF content induced by ketamine in hippocampus; after AMPA receptor was antagonized, the strengthening effect of propofol on ketamine-induced antidepressant-like action significantly decreased. The results indicated that propofol in a sub-anesthetic dose could increase the ketamine-induced antidepressant-like effect.