Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord.

ABSTRACT: Glial cells play crucial roles in regulating physiological and pathological functions, including sensation, the response to infection and acute injury, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system, and satellite glial cells and Schwann cells in the peripheral nervous system. Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models, few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord. Here, we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these findings with those from mice. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were each divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into five, four, and five distinct transcriptomic subclusters, respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice. Additionally, we detected sex differences in gene expression in human spinal cord glial cells. Specifically, in all astrocyte subtypes, the levels of NEAT1 and CHI3L1 were higher in males than in females, whereas the levels of CST3 were lower in males than in females. In all microglial subtypes, all differentially expressed genes were located on the sex chromosomes. In addition to sex-specific gene differences, the levels of MT-ND4, MT2A, MT-ATP6, MT-CO3, MT-ND2, MT-ND3, and MT-CO2 in all spinal cord oligodendrocyte subtypes were higher in females than in males. Collectively, the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cord-related illnesses, including chronic pain, amyotrophic lateral sclerosis, and multiple sclerosis.

Serum proteomics study on cognitive impairment after cardiac valve replacement surgery: a prospective observational study.

Objective: The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we conducted a prospective observational study to observe serum proteomics differences in PND patients after cardiac valve replacement surgery. Methods: Two hundred and twenty-six patients who underwent cardiac valve surgery were included. They were categorized based on scoring into non-PND group (group non-P) and PND group (group P'). The risk factors associated with PND were analyzed. These patients were further divided into group C and group P by propensity score matching (PSM) to investigate the serum proteome related to the PND by serum proteomics. Results: The postoperative 6-week incidence of PND was 16.8%. Risk factors for PND include age, chronic illness, sufentanil dosage, and time of cardiopulmonary bypass (CPB). Proteomics identified 31 down-regulated proteins and six up-regulated proteins. Finally, GSTO1, IDH1, CAT, and PFN1 were found to be associated with PND. Conclusion: The occurrence of PND can impact some oxidative stress proteins. This study provided data for future studies about PND to general anaesthesia and surgeries.

Distinct Neural Mechanisms Between Anesthesia Induction and Emergence: A Narrative Review.

Anesthesia induction and emergence are critical periods for perioperative safety in the clinic. Traditionally, the emergence from general anesthesia has been recognized as a simple inverse process of induction resulting from the elimination of general anesthetics from the central nervous system. However, accumulated evidence has indicated that anesthesia induction and emergence are not mirror-image processes because of the occurrence of hysteresis/neural inertia in both animals and humans. An increasing number of studies have highlighted the critical role of orexinergic neurons and their involved circuits in the selective regulation of emergence but not the induction of general anesthesia. Moreover, additional brain regions have also been implicated in distinct neural mechanisms for anesthesia induction and emergence, which extends the concept that anesthetic induction and emergence are not antiparallel processes. Here, we reviewed the current literature and summarized the evidence regarding the differential mechanism of neural modulation in anesthesia induction and emergence, which will facilitate the understanding of the underlying neural mechanism for emergence from general anesthesia.

Effects of flipped classroom teaching in anaesthesiology residents: a protocol for systematic review and meta-analysis.

INTRODUCTION: The flipped classroom teaching model is widely used in medical education and is indicated to be better than traditional lecture approaches in many medical specialties. Emerging studies have evaluated the effects of the flipped classroom teaching model on anaesthesiology residents. This protocol aims to perform a systematic review and meta-analysis to determine whether the flipped classroom teaching model is superior to traditional teaching methods for anaesthesiology residents. METHODS AND ANALYSIS: Seven databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure, Wanfang Data and the VIP database, will be systematically searched from their inception to 1 June 2024. Randomised controlled trials that compared the effects of flipped classrooms versus traditional teaching methods in anaesthesiology residents will be included. The primary outcome will be the theoretical knowledge score. The secondary outcomes will include skill scores and the proportion of anaesthesiology residents who preferred the flipped classroom model. RevMan V.5.4 software will be used to perform the statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will assess the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval is not applicable to this protocol. The results of this study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42024497935.

Optimal approach for ultrasound-guided transversus abdominis plane (TAP) blocks for abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.

Comparison of the effects of ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Ultrasound-guided quadratus lumborum block and erector spinae plane block are widely used for postoperative analgesia in adult patients undergoing abdominal surgeries. This protocol aims to compare the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries. METHODS AND ANALYSIS: Four databases, including PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), will be searched. Randomised controlled trials that compared the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in adult patients will be identified. The primary outcomes are time to the first analgesic request and postoperative analgesic consumption over 24 hours. Secondary outcomes will include postoperative pain scores and the incidence of side effects. RevMan V.5.3 software will be used for data processing and statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will be used to assess the evidence quality of outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Results of this present study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023445802.

Spatial transcriptomics and single-nucleus RNA sequencing reveal a transcriptomic atlas of adult human spinal cord.

Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and neural diseases, the underlying organization of neuronal clusters and their spatial location remain elusive. Recently, several studies have attempted to define the neuronal types and functional heterogeneity in the spinal cord using single-cell or single-nucleus RNA sequencing in animal models or developing humans. However, molecular evidence of cellular heterogeneity in the adult human spinal cord is limited. Here, we classified spinal cord neurons into 21 subclusters and determined their distribution from nine human donors using single-nucleus RNA sequencing and spatial transcriptomics. Moreover, we compared the human findings with previously published single-nucleus data of the adult mouse spinal cord, which revealed an overall similarity in the neuronal composition of the spinal cord between the two species while simultaneously highlighting some degree of heterogeneity. Additionally, we examined the sex differences in the spinal neuronal subclusters. Several genes, such as SCN10A and HCN1, showed sex differences in motor neurons. Finally, we classified human dorsal root ganglia (DRG) neurons using spatial transcriptomics and explored the putative interactions between DRG and spinal cord neuronal subclusters. In summary, these results illustrate the complexity and diversity of spinal neurons in humans and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.

Optimal concentration of ropivacaine for peripheral nerve blocks in adult patients: a protocol for systematic review and meta-analysis.

INTRODUCTION: Ropivacaine is the most widely used local anaesthetic for peripheral nerve blocks (PNBs). The effects of various concentrations of ropivacaine in PNB have been investigated and compared by many randomised controlled trials (RCTs). This protocol aims to identify the optimal concentration of ropivacaine for PNB in adult patients. METHODS AND ANALYSIS: PubMed, EMBASE, the Cochrane library and Web of Science will be searched from their inception to 10 July 2023. RCTs that compare the analgesic effects of different concentrations of ropivacaine for PNB will be included. Retrospective studies, meta-analyses, reviews, case reports, letters, conference abstracts and paediatric studies will be excluded. The duration of analgesia will be named as the primary outcome. Secondary outcomes will include the onset time of motor and sensory blockade, postoperative pain scores, analgesic requirements over 24 hours and the incidence of adverse effects. The study selection, data extraction and quality assessment will be performed by two independent reviewers. Data processing and analysis will be performed by RevMan 5.4. The quality of the evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not applicable. The results of this study will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023406362.

Optimal concentration of ropivacaine for brachial plexus blocks in adult patients undergoing upper limb surgeries: a systematic review and meta-analysis.

Aim of the Study: Brachial plexus block (BPB) is widely used for patients undergoing upper limb surgeries. Ropivacaine is the most commonly used local anesthetic for BPB. This study aimed to identify the optimal ropivacaine concentration for BPB in adult patients undergoing upper limb surgeries. Materials and Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify randomized controlled trials (RCTs) that compared the effects of different concentrations of ropivacaine for BPB in adult patients undergoing upper limb surgeries. The primary outcomes were the onset time of sensory and motor block. RevMan 5.4 software was used for analysis. The GRADE approach was used to assess evidence quality. Results: Nine studies involving 504 patients were included. Compared to 0.5% ropivacaine, 0.75% ropivacaine shortened the onset time of sensory (WMD, -2.54; 95% CI; -4.84 to -0.24; <0.0001, moderate quality of evidence) and motor blockade (WMD, -2.46; 95% CI, -4.26 to -0.66; p = 0.01; moderate quality of evidence). However, 0.5% and 0.75% ropivacaine provided similar duration time of sensory (WMD, -0.07; 95% CI, -0.88 to 0.74; p = 0.81; high quality of evidence) and motor blockade (WMD, -0.24; 95% CI, -1.12 to 0.65; p = 0.55; high quality of evidence), as well as time to first request for oral analgesia (WMD, -1.57; 95% CI, -3.14 to 0.01; p = 0.5; moderate quality of evidence). Conclusion: Moderate-quality evidence suggested that, in terms of the onset time of sensory and motor blockade, 0.75% ropivacaine is a preferred concentration for BPB in upper limb surgeries. Systematic Review Registration: identifier CRD42023392145.

Metabolomics analysis in rat hearts with ischemia/reperfusion injury after diazoxide postconditioning.

Background: Diazoxide is a selective mitochondrial-sensitive potassium channel opening agent that has a definite effect on reducing myocardial ischemia/reperfusion injury (MIRI). However, the exact effects of diazoxide postconditioning on the myocardial metabolome remain unclear, which might contribute to the cardioprotective effects of diazoxide postconditioning. Methods: Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, diazoxide (DZ) group and 5-hydroxydecanoic acid + diazoxide (5-HD + DZ) group. The heart rate (HR), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum left ventricular pressure (+dp/dtmax) were recorded. The mitochondrial Flameng scores were analysed according to the ultrastructure of the ventricular myocardial tissue in the electron microscopy images. Rat hearts of each group were used to investigate the possible metabolic changes relevant to MIRI and diazoxide postconditioning. Results: The cardiac function indices in the Nor group were better than those in the other groups at the end point of reperfusion, and the HR, LVDP and +dp/dtmax of the Nor group at T2 were significantly higher than those of the other groups. Diazoxide postconditioning significantly improved cardiac function after ischaemic injury, and the HR, LVDP and +dp/dtmax of the DZ group at T2 were significantly higher than those of the I/R group, which could be abolished by 5-HD. The HR, LVDP and +dp/dtmax of the 5-HD + DZ group at T2 were significantly lower than those of the DZ group. The myocardial tissue in the Nor group was mostly intact, while it exhibited considerable damage in the I/R group. The ultrastructural integrity of the myocardium in the DZ group was higher than that in the I/R and 5-HD + DZ groups. The mitochondrial Flameng score in the Nor group was lower than that in the I/R, DZ and 5-HD + DZ groups. The mitochondrial Flameng score in the DZ group was lower than that in the I/R and 5-HD + DZ groups. Five metabolites, namely, L-glutamic acid, L-threonine, citric acid, succinate, and nicotinic acid, were suggested to be associated with the protective effects of diazoxide postconditioning on MIRI. Conclusion: Diazoxide postconditioning may improve MIRI via certain metabolic changes. This study provides resource data for future studies on metabolism relevant to diazoxide postconditioning and MIRI.

A missed diagnosis of sputum crust with fiberoptic bronchoscope causing extubation failure: a case report.

BACKGROUND: Fiberoptic bronchoscopy (FOB) and bronchoscopic biopsy are the established methods for diagnosing and treating sputum crust. However, sputum crust in concealed locations can sometimes be missed or undiagnosed, even with bronchoscopy. CASE PRESENTATION: We present the case of a 44-year-old female patient who experienced initial extubation failure and postoperative pulmonary complications (PPCs) due to the missed diagnosis of sputum crust by FOB and low-resolution bedside chest X-ray. The FOB examination showed no apparent abnormalities prior to the first extubation, and the patient underwent tracheal extubation 2 h after aortic valve replacement (AVR). However, she was reintubated 13 h after the first extubation due to a persistent irritating cough and severe hypoxemia, and a bedside chest radiograph revealed pneumonia and atelectasis. Upon performing a repeat FOB examination prior to the second extubation, we serendipitously discovered the presence of sputum crust at the end of the endotracheal tube. Subsequently, we found that the sputum crust was mainly located on the tracheal wall between the subglottis and the end of the endotracheal tube during the "Tracheobronchial Sputum Crust Removal" procedure, and most of the crust was obscured by the retained endotracheal tube. The patient was discharged on the 20th day following therapeutic FOB. CONCLUSION: FOB examination may miss specific areas in endotracheal intubation (ETI) patients, particularly the tracheal wall between the subglottis and distal end of the tracheal catheter, where sputum crust can be concealed. When diagnostic examinations with FOB are inconclusive, high-resolution chest CT can be helpful in identifying hidden sputum crust.

Role of sodium leak channel (NALCN) in sensation and pain: an overview.

The sodium leak channel (NALCN) is widely expressed in the central nervous system and plays a pivotal role in regulating the resting membrane potential (RMP) by mediating the Na+ leak current. NALCN was first reported in 1999, and since then, increasing evidence has provided insights into the structure and functions of NALCN. As an essential component of neuronal background currents, NALCN has been shown to be involved in many important physiological functions, particularly in the respiratory rhythm, as NALCN mutant mice have a severely disrupted respiratory rhythm and die within 24 h of birth. Many patients with NALCN mutations also develop serious clinical syndromes, such as severe hypotonia, speech impairment, and cognitive delay. Recently, emerging studies have clarified the human NALCN structure and revealed additional properties and functions of NALCN. For instance, accumulating evidence highlights that the NALCN is involved in normal sensation and pain. Here, we review the current literature and summarize the role of the NALCN in sensation and pain.

Percutaneous fully endoscopic surgical management of the ruptured epidural catheter: Rescue of the novice anesthesiologist from his dilemma.

Background: Epidural nerve block and analgesia are basic anesthetic techniques for anesthesia. Epidural catheter rupture and partial retention are adverse events and rare complications of epidural catheterization technique. The probability of occurrence when applied by novice doctors is high. Removal of the residual catheter by conventional surgery causes more trauma and bleeding, slows recovery, and may causes medical disputes. We hypothesized that percutaneous spinal endoscopy a safe and effective remediation technique. This study was to analyze the efficacy and safety of removing the residual dural catheter by a percutaneous full-endoscopic technique(PFET) and discuss the clinical technique and precautions. Methods: This was a retrospective analysis of 7 patients with ruptured epidural catheters treated in our department from October 2015 to October 2019 using the PFET to remove the remaining epidural catheter. The operation time, intraoperative bleeding volume, surgical complications, and neurological symptoms before and after surgery were recorded. The Self-Rating Anxiety Scale (SAS) was used to assess the anxiety level of the anesthesiologist and the patient before and after the catheter removal operation, and the postoperative low back pain VAS score was recorded. Results: The remaining epidural catheter was successfully removed from all 7 patients. The operation time was 54.14 ± 14.45 (32-78) minutes, and the intraoperative blood loss was 9.134 ± 3.078 (5-15) ml. There were no cases of dural damage, cerebrospinal fluid leakage, sensorimotor dysfunction of the lower limbs, or bowel dysfunction. The anxiety symptoms of the patient and the anesthesiologist disappeared after removal of the residual epidural catheter. The patients' postoperative back pain VAS score was 0 to 2 points. Conclusion: PFET is a safe and effective minimally invasive technique for removing residual epidural catheters. It causes less trauma and less bleeding, allows a faster recovery. It does not affect the recovery of patients from other surgical operations and reduces both medical risks and medical costs. At the same time, it avoids or reduces the occurrence of medical disputes and eliminates the pressure on novice anesthesiologists regarding similar adverse events.

Activation of locus coeruleus-spinal cord noradrenergic neurons alleviates neuropathic pain in mice via reducing neuroinflammation from astrocytes and microglia in spinal dorsal horn.

BACKGROUND: The noradrenergic neurons of locus coeruleus (LC) project to the spinal dorsal horn (SDH), and release norepinephrine (NE) to inhibit pain transmission. However, its effect on pathological pain and the cellular mechanism in the SDH remains unclear. This study aimed to explore the analgesic effects and the anti-neuroinflammation mechanism of LC-spinal cord noradrenergic pathway (LC:SC) in neuropathic pain (NP) mice with sciatic chronic constriction injury. METHODS: The Designer Receptors Exclusively Activated by Designer Drugs (DREADD) was used to selectively activate LC:SC. Noradrenergic neuron-specific retro-adeno-associated virus was injected to the spinal cord. Pain threshold, LC and wide dynamic range (WDR) neuron firing, neuroinflammation (microglia and astrocyte activation, cytokine expression), and α2AR expression in SDH were evaluated. RESULTS: Activation of LC:SC with DREADD increased the mechanical and thermal nociceptive thresholds and reduced the WDR neuron firing. LC:SC activation (daily, 7 days) downregulated TNF-α and IL-1ß expression, upregulated IL-4 and IL-10 expression in SDH, and inhibited microglia and astrocytes activation in NP mice. Immunofluorescence double staining confirmed that LC:SC activation decreased the expression of cytokines in microglia of the SDH. In addition, the effects of LC:SC activation could be reversed by intrathecal injection of yohimbine. Immunofluorescence of SDH showed that NE receptor α2B-AR was highly expressed in microglia in CCI mice. CONCLUSION: These findings indicate that selective activation of LC:SC alleviates NP in mice by increasing the release of NE and reducing neuroinflammation of astrocytes and microglia in SDH.

Whole-exome sequencing reveals genetic variations in humans with differential sensitivity to sevoflurane：A prospective observational study.

BACKGROUND: The anesthesia sensitivity is heterogeneous both in animals and humans, while the underlying molecular mechanism has not yet been determined. Here, for the first time, we conducted a prospective observational study to test whether genetic variations contribute to the differential sensitivity to sevoflurane in humans. METHODS: Five hundred patients who underwent abdominal surgeries were included. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain Bispectral index (BIS) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. These patients were further divided into high sensitivity group (mean - SD, H group) and low sensitivity group (mean + SD, L group) to investigate the genetic variants related to the differential sensitivity to sevoflurane by whole-exome sequencing (WES) and genome-wide association study (GWAS) in karyocyte from peripheral blood. RESULTS: The mean ETsevo of these 500 patients was 1.60% ± 0.34%. After pairing, 55 patients from H group and 59 patients from L group were selected for WES (ETsevo of H group: 1.06% ± 0.13% vs. ETsevo of L group: 2.17% ± 0.16%, P < 0.001), respectively. Finally, FAT atypical cadherin 2 (FAT2, SNP rs174272, rs174271, and rs174261), acireductone dioxygenase 1 (ADI1, SNP rs117278), NEDD4 E3 ubiquitin protein ligase (NEDD4, SNP rs70048, rs70049, and rs70056), and FAD dependent oxidoreductase domain containing 2 (FOXRED2, SNP rs144281) were found to be associated with sevoflurane sensitivity. CONCLUSIONS: Genetic variations may contribute to the differential sensitivity to sevoflurane among humans.

Clinical characteristics and remission of nine cases with coronavirus disease 2019 infection in Zunyi, Southwest of China: A retrospective study.

The outbreak of coronavirus disease 2019 (COVID-19) has become a rock-ribbed public pandemic and caused substantial health concerns worldwide. In addition to therapeutic strategies, the epidemiologic features and clinical characteristics of patients responded to COVID-19 infection are of equal importance. The study aims to systematically evaluate the clinical presentations and remission of cases with COVID-19 infection in Zunyi, Southwest of China, and to determine the similarities and variations for further clinical classification and comprehensive treatment. Herein, we conducted a retrospective study upon 9 patients in Zunyi, southwest of China, including 1 mild (LPA), 5 severe (SPA) and 3 critical (CPA) types of COVID-19 infection. In details, the demographic data, historical epidemiology, previous medical history, clinical symptoms and complications, laboratory examination, chest imaging, treatment and outcomes of the patients were throughout explored. The non-normal distribution of the data was conducted by utilizing the SPSS software, and significant statistical differences were identified when P < .05. By retrospective analysis of the 9 cases, we found there were multifaceted similarities and differences among them in clinical representation. The patients collectively showed negative for nucleic acid test (NAT) and favorable prognosis after receiving comprehensive therapy such as hormonotherapy, hemopruification, and antiviral administration as well as respiratory support. On the basis of the information, we systematically dissected the clinical features and outcomes of the enrolled patients with COVID-19 and the accompanied multiple syndromes, which would serve as new references for clinical classification and comprehensive treatment. Analysis of clinical characteristics and therapeutic effect of 9 cases of novel coronavirus pneumonia (COVID-19), ChiCTR2000031930. Registered April 15, 2020 (retrospective registration).

The optimal dose of intravenous dexamethasone in peripheral nerve blocks: A protocol for systematic review and meta-analysis.

BACKGROUND: Although intravenous dexamethasone prolongs the duration of analgesia for peripheral nerve blocks (PNB), the optimal dose of dexamethasone is not yet determined. This protocol aims to compare the analgesic effects of different doses of intravenous dexamethasone on PNB. METHODS: We will search PubMed, EMBASE, the Cochrane Central register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials that compared the effects of different doses of intravenous dexamethasone for PNB. The duration of analgesia will be defined as the primary outcome. Secondary outcomes will include pain scores, analgesics consumption >48 hours, and the incidence of adverse effects. RevMan 5.3 software will be used for data analysis. RESULTS: This study will explore the optimal dose of intravenous dexamethasone for the prolongation of analgesia in PNB. CONCLUSION: The results of this study will provide evidence for the dose selection of intravenous dexamethasone in PNB.

Metabolomics and Whole-Exome Sequencing in Patients with Differential Sensitivity to Sevoflurane: A Protocol for a Prospective Observational Trial.

Introduction: Different sensitivity to volatile anesthetics in Drosophila, nematodes and mice is related to mutation of energy metabolism genes. In clinical practice, we find that the end-tidal sevoflurane concentration (ETsevo) differs among patients at the same depth of anesthesia, indicating that the sensitivity to sevoflurane varies among patients. However, the underlying mechanism remains unclear. The sensitivity of an anesthetic is associated with the postoperative outcomes of patients and the mechanism of action of volatile anesthetics. We therefore propose this protocol to determine whether differences in metabolite profile and genetic variations contribute to patients' sensitivity to volatile anesthetics. Methods and Analysis: This is a single-centre, prospective observational study. 720 patients undergoing abdominal surgery were included. General anesthesia was induced with inhaled sevoflurane, a bolus of sufentanil (0.2-0.4 µg/kg) and cis-atracurium (0.2-0.3 mg/kg). The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain a BIS (bispectral index) value between 40-60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery (steady state) was calculated for each patient. Patients were further divided into a high-sensitivity group (mean ETsevo - SD) and a low-sensitivity group (mean ETsevo + SD) to investigate the sensitivity to sevoflurane. Cases were paired from the high-sensitivity group (group H) and low-sensitivity group (group L) according to age, sex, body mass index (BMI), ASA physical status classification, vital signs, BIS, ephedrine use, sufentanildose, and cis-atracurium dose at anesthesia induction and steady state. Differences in metabolite levels, single nucleotide polymorphisms (SNPs) and protein-coding gene sequence variations between group H and group L will be determined through plasma metabolomics, whole-exome sequencing (WES), genome-wide association study (GWAS), and bioinformatics analyses. These results will be analysed to determine the reasons for the differential sensitivity to sevoflurane in humans. Ethics and Dissemination: This prospective observational study protocol has received ethical approval from the Ethical Committee of West China Hospital of Sichuan University on May 19, 2017 (Approval No. 78). Informed consent will be obtained before patient enrolment. The results will be submitted to international peer-review journals. Trial Registration Number: ChiCTR1800014327.

Effects of Tranexamic Acid on Bleeding in Pediatric Surgeries: A Systematic Review and Meta-Analysis.

Background: Major pediatric surgeries can cause severe intraoperative blood loss. This meta-analysis aims to evaluate the efficacy of tranexamic acid (TXA) in pediatric surgeries. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library from the conception to March 31, 2021 to identify eligible randomized controlled trials (RCTs) that evaluated the efficacy of TXA in pediatric surgeries. Two reviewers choosed studies, evaluated quality, extracted data, and assessed the risk of bias independently. Mean difference (MD) was calculated as the summary statistic for continuous data. We used a random-effects model to measure mean effects. Data were generated from the corresponding 95% confidence interval (CI) using RevMan 5.3 software. Primary outcomes included intraoperative and postoperative blood loss, red blood cell (RBC) transfusion as well as fresh frozen plasma (FFP) transfusion. Results: Fifteen studies enrolling 1,332 patients were included in this study. The pooled outcomes demonstrated that TXA was associated with a decreased intraoperative (MD = -1.57 mL/kg, 95% CI, -2.54 to -0.60, P = 0.002) and postoperative (MD = -7.85 mL/kg, 95% CI, -10.52 to -5.19, P < 0.001) blood loss, a decreased intraoperative (MD = -7.08 mL/kg, 95% CI, -8.01 to -6.16, P < 0.001) and postoperative (MD = -5.30 mL/kg, 95% CI, -6.89 to -3.70, P < 0.001) RBC transfusion, as well as a decreased intraoperative (MD = -2.74 mL/kg, 95% CI, -4.54 to -0.94, P = 0.003) and postoperative (MD = -6.09 mL/kg, 95% CI, -8.26 to -3.91, P < 0.001) FFP transfusion in pediatric surgeries. However, no significant difference was noted between two groups in duration of surgery (MD = -12.51 min, 95% CI -36.65 to 11.63, P = 0.31). Outcomes of intraoperative and postoperative blood loss and the duration of surgery in included studies were not pooled due to the high heterogeneity. Conclusion: This meta-analysis demonstrated that TXA was beneficial for bleeding in pediatric surgeries.

Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study.

BACKGROUND: Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes. METHODS: Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean - SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure. RESULTS: The mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure. CONCLUSIONS: Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries. TRIAL REGISTRATION: www.chictr.org.cn . identifier: ChiCTR1800014327 .