Drp1 regulates transcription of ribosomal protein genes in embryonic hearts.

Mitochondrial dysfunction causes severe congenital cardiac abnormalities and prenatal/neonatal lethality. The lack of sufficient knowledge regarding how mitochondrial abnormalities affect cardiogenesis poses a major barrier for the development of clinical applications that target mitochondrial deficiency-induced inborn cardiomyopathies. Mitochondrial morphology, which is regulated by fission and fusion, plays a key role in determining mitochondrial activity. Dnm1l encodes a dynamin-related GTPase, Drp1, which is required for mitochondrial fission. To investigate the role of Drp1 in cardiogenesis during the embryonic metabolic shift period, we specifically inactivated Dnm1l in second heart field-derived structures. Mutant cardiomyocytes in the right ventricle (RV) displayed severe defects in mitochondrial morphology, ultrastructure and activity. These defects caused increased cell death, decreased cell survival, disorganized cardiomyocytes and embryonic lethality. By characterizing this model, we reveal an AMPK-SIRT7-GABPB axis that relays the reduced cellular energy level to decrease transcription of ribosomal protein genes in cardiomyocytes. We therefore provide the first genetic evidence in mouse that Drp1 is essential for RV development. Our research provides further mechanistic insight into how mitochondrial dysfunction causes pathological molecular and cellular alterations during cardiogenesis.

Efficacy of erector spinae plane block for postoperative analgesia lumbar surgery: a systematic review and meta-analysis.

OBJECTIVES: The erector spinae plane (ESP) block is a newly defined regional anesthesia technique first described in 2016. The aim of this meta-analysis is to assess the efficacy of ESP block in improving analgesia following lumbar surgery. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) that compared the analgesic efficacy of the ESP block with non-block care for lumbar surgery from inception 3 August 2021. The primary outcomes were postoperative opioid consumption and pain scores during the first 24 h. Postoperative pain was measured as pain at rest and on movement at postoperative 0, 4, 8, 12, and 24 h expressed on a visual analog scale (VAS), where 0 = no pain and 10 = the most severe pain. RESULTS: 11 studies involving 775 patients were included in our analysis. The use of ESP block significantly decreased 24-h opioid consumption (WMD, -8.70; 95% CI, -10.48 to -6.93; I2 = 97.5%; P < 0.001) compared with the non-block. Moreover, ESP block reduced pain scores at postoperative time-points up to 24 h. ESP block also prolonged the time to first analgesic request (WMD = 6.93; 95% CI: 3.44 to 10.43, I2 = 99.8%; P < 0.001). There was less PONV with ESP block versus non-block group (RR, 0.354; 95% CI, 0.23 to 0.56; I2 = 25.2%; P < 0.001), but no difference in pruritus. CONCLUSIONS: ESP block provides less opioid consumption and PONV, lower pain scores, and longer time to first analgesic request in patients undergoing lumbar surgery compared to general anesthesia alone.

SEMA6D regulates perinatal cardiomyocyte proliferation and maturation in mice.

Cardiomyocytes undergo dramatic changes during the fetal to neonatal transition stage to adapt to the new environment. The molecular and genetic mechanisms regulating these changes remain elusive. In this study, we showed Sema6D as a novel signaling molecule regulating perinatal cardiomyocyte proliferation and maturation. SEMA6D is a member of the Semaphorin family of signaling molecules. To reveal its function during cardiogenesis, we specifically inactivated Sema6D in embryonic cardiomyocytes using a conditional gene deletion approach. All mutant animals showed hypoplastic myocardial walls in neonatal hearts due to reduced cell proliferation. We further revealed that expression of MYCN and its downstream cell cycle regulators is impaired in late fetal hearts in which Sema6D is deleted, suggesting that SEMA6D acts through MYCN to regulate cardiomyocyte proliferation. In early postnatal mutant hearts, expression of adult forms of sarcomeric proteins is increased, while expression of embryonic forms is decreased. These data collectively suggest that SEMA6D is required to maintain late fetal/early neonatal cardiomyocytes at a proliferative and less mature status. Deletion of Sema6D in cardiomyocytes led to reduced proliferation and accelerated maturation. We further examined the consequence of these defects through echocardiographic analysis. Embryonic heart deletion of Sema6D significantly impaired the cardiac contraction of male adult hearts, while having a minor effect on female mutant hearts, suggesting that the effect of Sema6D-deletion in adult hearts is sex dependent.

Overactivation of the sodium-calcium exchanger and transient receptor potential in anesthesia-induced malignant hyperthermia.

Malignant hyperthermia is a pharmacogenetic disorder, which is an uncommon but frequently fatal intricacy of inhalation anesthesia in man. It causes a quick rise in body temperature to highly irreversible levels, which causes death in around three of four cases. The trigger anesthetics cause an anomalous, continued ascent in myoplasmic calcium levels. Possible mechanisms by which continuous release of sodium, calcium from skeletal muscle plasma membrane and sarcoplasmic reticulum stores respectively can produce the profound hyperthermia are discussed.

Eu-doped carbon quantum dot as a selective probe for visualizing and monitoring sulfite in biological systems.

The detection of SO3 2- in complex environments and its visualization at the cellular level are critical for understanding its role in biological processes. In this study, we developed an Eu-doped long-wavelength fluorescent carbon quantum dot (CD2) and investigated the detection mechanism, interference effects and cellular imaging applications of the fluorescent probe CD2. The results show that the addition of SO3 2- induces an electronic rearrangement that restores CD2 to its original structure, leading to a rapid increase in fluorescence intensity. Selectivity experiments showed that CD2 has excellent selectivity to SO3 2-, with minimal interference from common anions. In addition, CD2 shows good biocompatibility for cellular imaging applications, as evidenced by the high cell viability observed in HeLa cells. Using confocal microscopy, we detected a significant enhancement of red fluorescence in HeLa cells after addition of exogenous SO3 2-, demonstrating the potential of CD2 as a probe for monitoring cellular SO3 2- levels. These findings highlight the promise of CD2 as a selective SO3 2- detection probe in complex environments and its utility in cellular imaging studies. Further studies are necessary to fully exploit the potential of CD2 in various biological and biomedical applications.

Perioperative dexmedetomidine reduces emergence agitation without increasing the oculocardiac reflex in children: A systematic review and meta-analysis.

BACKGROUND: Intravenous dexmedetomidine (DEX) has been used to prevent emergence agitation (EA) in children. The aim of this meta-analysis was to evaluate whether DEX decreases EA incidence without augmenting oculocardiac reflex (OCR) in pediatric patients undergoing strabismus surgery. METHODS: We searched PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wan Fang, and the Cochrane Library to collect the randomized controlled trials (RCTs) investigating the effects of intraoperative DEX in children undergoing strabismus surgery from inception to October 2019. Postoperative Pediatric Agitation and Emergence Delirium (PAED) score, postoperative EA, extubation or laryngeal mask airway (LMA) removal time, postanesthetic care unit (PACU) stay time, OCR, and postoperative vomiting (POV) were evaluated. RESULTS: 11 RCTs including 801 patients were included in this study. Compared with control group, intravenous DEX significantly reduced postoperative PAED score (WMD, 3.05; 95% CI: -3.82 to -2.27, P = .017) and incidences of postoperative EA 69% (RR, 0.31; 95% CI: 0.17 to 0.55, P < .00) and POV (RR, 0.28; 95% CI: 0.13 to 0.61, P = .001). Furthermore, the use of DEX significantly delayed extubation or LMA removal time (WMD, 2.11; 95% CI: 0.25 to 3.97, P < .001). No significant difference was found in the incidence of ORC and PACU stay time. CONCLUSION: Intravenous DEX reduced the incidences of EA without increasing OCR in pediatric patients undergoing strabismus surgery. Meanwhile, DEX infusion decreased the incidence of POV in children.

Clinical analgesic efficacy of pectoral nerve block in patients undergoing breast cancer surgery: A systematic review and meta-analysis.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women, and more than half of breast surgery patients experience severe acute postoperative pain. This meta-analysis is designed to examine the clinical analgesic efficacy of Pecs block in patients undergoing breast cancer surgery. METHODS: An electronic literature search of the Library of PubMed, EMBASE, Cochrane Library, and Web of Science databases was conducted to collect randomized controlled trials (RCTs) from inception to November 2018. These RCTs compared the effect of Pecs block in combination with general anesthesia (GA) to GA alone in mastectomy surgery. Pain scores, intraoperative and postoperative opioid consumption, time to first request for analgesia, and incidence of postoperative nausea and vomiting were analyzed. RESULTS: Thirteen RCTs with 940 patients were included in our analysis. The use of Pecs block significantly reduced pain scores in the postanesthesia care unit (weighted mean difference [WMD] = -1.90; 95% confidence interval [CI], -2.90 to -0.91; P < .001) and at 24 hours after surgery (WMD = -1.01; 95% CI, -1.64 to -0.38; P < .001). Moreover, Pecs block decreased postoperative opioid consumption in the postanesthesia care unit (WMD = -1.93; 95% CI, -3.51 to -0.34; P = .017) and at 24 hours (WMD = -11.88; 95% CI, -15.50 to -8.26; P < .001). Pecs block also reduced intraoperative opioid consumption (WMD = -85.52; 95% CI, -121.47 to -49.56; P < .001) and prolonged the time to first analgesic request (WMD = 296.69; 95% CI, 139.91-453.48; P < .001). There were no statistically significant differences in postoperative nausea and vomiting and block-related complications. CONCLUSIONS: Adding Pecs block to GA procedure results in lower pain scores, less opioid consumption and longer time to first analgesic request in patients undergoing breast cancer surgery compared to GA procedure alone.

Effect of 5-µg Dose of Dexmedetomidine in Combination With Intrathecal Bupivacaine on Spinal Anesthesia: A Systematic Review and Meta-analysis.

PURPOSE: Intrathecal dexmedetomidine (DEX) has been used to improve the quality and duration of spinal anesthesia. The aim of this meta-analysis is to evaluate whether intrathecal DEX could prolong the duration of sensory and motor block during spinal anesthesia. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials that investigated the facilitatory effects of intrathecal administration of DEX compared with those of a placebo on spinal anesthesia from inception to April 2019. Sensory and motor block durations, sensory and motor block onset times, time to first analgesic request, and DEX-related adverse effects were evaluated. Results were combined using fixed-effects or random effects modeling when appropriate. FINDINGS: A total of 1478 patients from 25 clinical studies were included in the analysis. Compared with placebo, intrathecal DEX significantly prolonged the durations of both sensory block (weighted mean difference [WMD] = 134.42 min; 95% CI, 109.71-159.13 min; P < 0.001) and motor block (WMD = 114.27 min; 95% CI, 93.18-135.35 min; P < 0.001). It also hastened the onset of sensory block (WMD = -0.80 min; 95% CI, -1.21 to -0.40; P < 0.001) and motor block (WMD = -1.03 min; 95% CI, -1.51 to -0.56 min; P < 0.001). Furthermore, it delayed the time to first analgesic request (WMD = 216.90 min; 95% CI, 178.90-254.90 min; P < 0.001) and reduced the incidence of shivering (risk ratio [RR] = 0.39; 95% CI, 0.27-0.55; P < 0.001). DEX was associated with increased risk of transient bradycardia (RR = 1.59; 95% CI, 1.07-2.37; P = 0.022) and hypotension (RR = 1.40; 95% CI, 1.04-1.89; P = 0.026) but did not increase the incidence of postoperative nausea and vomiting (RR = 0.87; 95% CI, 0.62-1.24; P = 0.45). IMPLICATIONS: Intrathecal DEX can prolong the duration of sensory block, the duration of motor block, and the time to first analgesic request associated with spinal anesthesia.

The effectiveness of air-free warming systems on perioperative hypothermia in total hip and knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Perioperative hypothermia is a common and serious complication during surgery. Different warming systems are used to prevent perioperative hypothermia. However, there have been no previous meta-analyses of the effectiveness of air-free warming systems on perioperative hypothermia in patients undergoing joint arthroplasty. METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases to collect randomized controlled trials (RCTs) from inception to August 2018. These RCTs compared the effects of air-free warming with forced-air (FA) warming system in patients undergoing joint arthroplasty. Postoperative temperature, core temperature during surgery, thermal comfort, blood loss and incidence of shivering and hypothermia were analyzed. RESULTS: A total of 287 patients from 6 clinical studies were included in the analysis. In summary, there was no significant difference in the postoperative temperature (WMD -0.043, 95% CI -0.32 to 0.23, P = .758) between the air-free warming and FA warming groups. No statistical difference (WMD 0.058, 95% CI -0.10 to 0.22, P = .475) was found in core temperatures at 0 minutes during surgery between the air-free warming and FA warming groups. Furthermore, there was no statistical difference in thermal comfort, blood loss or incidence of shivering and hypothermia between the air-free warming and FA warming groups. CONCLUSIONS: Air-free warming system was as effective as FA warming system in patients undergoing joint arthroplasty.

Dexmedetomidine as an Adjuvant to Local Anesthetics in Transversus Abdominis Plane Block: A Systematic Review and Meta-analysis.

OBJECTIVES: The objective of this meta-analysis was to evaluate the analgesic effects of dexmedetomidine (DEX) in transversus abdominis plane (TAP) blocks for abdominal surgery. METHODS: Electronic databases, including PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wan Fang, and the Cochrane Library, were conducted to collect the randomized controlled trials (RCTs) from inception to March 2018. RCTs investigating the impact of adding DEX to local anesthetics for TAP blocks were included in this analysis. Pain scores (at rest and movement), opioid consumption, the duration of the TAP block and the common adverse effects were analyzed. RESULTS: Twenty published trials including 1212 patients met the inclusion criteria. The addition of DEX significantly reduced pain scores 8 hours postoperatively at rest (WMD, -0.78; 95% CI, -1.27 to -0.30; P=0.001), 4 hours postoperatively on movement (WMD, -1.13; 95% CI, -1.65 to -0.60; P<0.001), and opioid consumption (WMD, -13.71; 95% CI, -17.83 to -9.60; P<0.001) when compared with control group. Furthermore, perineural DEX significantly prolonged the duration of the TAP block (WMD, 3.33; 95% CI, 2.85 to 3.82; P<0.001). It did not affect the incidence of postoperative nausea and vomiting, hypotension, bradycardia, somnolence, or pruritus. CONCLUSIONS: DEX is a potential anesthetic adjuvant that can facilitate better postoperative analgesia, reduce postoperative analgesic requirements, and prolong the local anesthetic effect when administered in TAP blocks.

Warming infusion improves perioperative outcomes of elderly patients who underwent bilateral hip replacement.

BACKGROUND: This prospective, randomized, and controlled study was performed to determine the benefits of prewarmed infusion in elderly patients who underwent bilateral hip replacement. METHODS: Between September 2015 and April 2016, elderly patients who underwent bilateral hips replacement that met the inclusion and exclusion criteria were included in this study. After inclusion, patients were randomized into one of the study groups: in the control group, patients received an infusion of fluid kept at room temperature (22-23°C); in the warming infusion group, patients received an infusion of fluid warmed using an infusion fluid heating apparatus (35°C). Postoperative outcomes, including recovery time, length of hospital stay, visual analogue scale (VAS) score, and postoperative complications rate of patients from both groups, were compared. RESULTS: A total of 64 patients were included in our study (71.2 ±â€Š7.6 years, 53.1% males), with 32 patients in the control group and 32 patients in warming infusion group. No significant difference was found in terms of demographic data and intraoperative blood transfusion rate between 2 groups (P > 0.05). Patients receiving a prewarmed infusion had a significantly shorter time to spontaneous breath, eye opening, consciousness recovery, and extubation than the control group (P < 0.05). In addition, significant differences were found in Steward score and VAS score between 2 groups (P < 0.05). Moreover, warming infusion group also showed an obviously decreased incidence of shivering and postoperative cognitive dysfunction (P < 0.05). CONCLUSION: A prewarmed infusion could reduce the incidence of perioperative hypothermia and improve outcomes in the elderly during bilateral hip replacement.