Causal role of immune cells in inflammatory bowel disease: A Mendelian randomization study.

Inflammatory bowel disease (IBD) is characterized by an inflammatory response closely related to the immune system, but the relationship between inflammation and IBD remains unclear. We performed a comprehensive 2-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and IBD. Using publicly available genetic data, we explored the relationship between 731 immune cell characteristics and IBD risk. Inverse-variance weighting was the primary analytical method. To test the robustness of the results, we used the weighted median-based, MR-Egger, simple mode, and mode-based methods. Finally, we performed a reverse MR analysis to assess the possibility of reverse causality. We identified suggestive associations between 2 immune cell traits and IBD risk (P = 4.18 × 10-5 for human leukocyte antigen-DR on CD14+ monocytes, OR: 0.902; 95% CI: 0.859-0.947; for CD39+ CD4+ T cells, P = 6.24 × 10-5; OR: 1.042; 95% CI: 1.021-1.063). Sensitivity analysis results of these immune cell traits were consistent. In reverse MR analysis, we found no statistically significant association between IBD and these 2 cell traits. Our study demonstrates the close connection between immune cells and IBD using MR, providing guidance for future clinical and basic research.

A Study on Prognosis of Diffuse Glioma Based on Clinical Factors and Magnetic Resonance Imaging Radiomics.

PURPOSE: To construct an optimal prognostic model to assess the prognosis of patients with diffuse glioma. MATERIALS AND METHODS: Preoperative magnetic resonance imaging and clinical data were retrospectively collected from 266 patients (training cohort : validation cohort = 7:3) with pathologically confirmed diffuse gliomas. A radiomics prognostic model (R-model) based on the radiomics features was constructed. A prognostic model based on clinical factors (C-model) and a fusion model (F-model) were also constructed. Based on the optimal model of three models, the nomogram was constructed. Finally, a "Prognosis Calculator for Diffuse Glioma" was constructed based on the nomogram. RESULTS: The c-index of the R-, C-, and F-models in the validation cohort was 0.742, 0.796, and 0.814, respectively. In the validation cohort, the 1-year AUC of the R-, C-, and F-models was 0.749, 0.806, and 0.836, respectively; the 3-year AUC was 0.896, 0.966, and 0.963, respectively. In the training cohort, validation cohort, all cohorts, and different grades of glioma cohorts, F-model (optimal model) could identify low- and high-risk groups well. The "Prognosis Calculator for Diffuse Glioma" was available at https://github.com/HDCurry/prognosis. CONCLUSIONS: Among the three models, the F-model (radiomics combined with clinical factors) had optimal predictive efficacy and could more accurately assess the prognosis of diffuse glioma. The "Prognosis Calculator for Diffuse Glioma" constructed based on this model could assist clinicians in more easily and accurately assessing the prognosis of patients with diffuse glioma, thus enabling them to make more reasonable treatment strategies.

Genetic Code Expansion in Pseudomonas putida KT2440.

Emerging microorganism Pseudomonas putida KT2440 is utilized for the synthesis of biobased chemicals from renewable feedstocks and for bioremediation. However, the methods for analyzing, engineering, and regulating the biosynthetic enzymes and protein complexes in this organism remain underdeveloped.Such attempts can be advanced by the genetic code expansion-enabled incorporation of noncanonical amino acids (ncAAs) into proteins, which also enables further controls over the strain's biological processes. Here, we give a step-by-step account of the incorporation of two ncAAs into any protein of interest (POI) in response to a UAG stop codon by two commonly used orthogonal archaeal tRNA synthetase and tRNA pairs. Using superfolder green fluorescent protein (sfGFP) as an example, this method lays down a solid foundation for future work to study and enhance the biological functions of KT2440.

Quadratus lumborum block vs. transversus abdominis plane block for postoperative pain control in patients with nephrectomy: A systematic review and network meta-analysis.

STUDY OBJECTIVE: This systematic review and network meta-analysis aimed to compare the analgesic efficacy of transversus abdominis plane block (TAPB) and quadratus lumborum block (QLB) on nephrectomy. DESIGN: Systematic review and network meta-analysis. PATIENTS: Patients undergoing nephrectomy. INTERVENTIONS: TAPB and QLB for postoperative analgesia. MEASUREMENTS: The primary outcome was 24 h morphine-equivalent consumptions after surgery. Secondary outcomes included postoperative pain scores, postoperative opioid consumption, postoperative rescue analgesia, postoperative nausea and vomiting (PONV), length of hospital stay after surgery, and patient satisfaction. MAIN RESULTS: Fourteen studies involving 883 patients were included. Seven studies compared TAPB to control, six studies compared QLB to control, and one study compared TAPB to QLB. For direct meta-analysis of the post-surgical 24 h morphine-equivalent consumption, QLB was lower than control (mean difference [95%CI]: -18.16 [-28.96, -7.37]; I2 = 88%; p = 0.001), while there was no difference between TAPB and control (mean difference [95%CI]: -8.34 [-17.84, 1.17]; I2 = 88%; p = 0.09). Network meta-analysis showed similar findings that QLB was ranked as the best anesthetic technique for reducing postoperative 24 h opioid consumption (p-score = 0.854). Moreover, in direct meta-analysis, as compared to control, the time of first postoperative rescue analgesia was prolonged after QLB (mean difference [95%CI]: 165.00 [128.99, 201.01]; p < 0.00001), but not TAPB (mean difference [95%CI]: 296.82 [-91.92, 685.55]; p = 0.13). Meanwhile, QLB can effectively reduce opioid usages at intraoperative period, as well as at postoperative 6 h and 48 h, while TAPB can only reduce opioid consumption at 6 h after surgery. As compared to control, both TAPB and QLB exhibited the reduction in PONV and pain scores at post-surgical some timepoints. Also, QLB (mean difference [95%CI]: -0.29 [-0.49, -0.08]; p = 0.006) but not TAPB (mean difference [95%CI]: 0.60 [-0.25, 1.45]; p = 0.17) exhibited the shorter postoperative length of hospital stay than control. CONCLUSIONS: QLB is more likely to be effective in reducing postoperative opioid use than TAPB, whereas both of them are superior to control with regard to the reduction in postoperative pain intensity and PONV. TRIAL REGISTRATION: PROSPERO identifier: CRD42022358464.

Corrigendum: Association between nutritional status, physical fitness and executive functions in preadolescents: a person-centered approach.

[This corrects the article DOI: 10.3389/fped.2022.966510.].

Electrochemically selective ammonium recovery from wastewater via coupling hydrogen bonding and charge storage.

Electrochemical ammonium (NH4+) storage (EAS) has been established as an efficient technology for NH4+ recovery from wastewater. However, there are scientific difficulties unsolved regarding low storage capacity and selectivity, restricting its extensive engineering applications. In this work, electrochemically selective NH4+ recovery from wastewater was achieved by coupling hydrogen bonding and charge storage with self-assembled bi-layer composite electrode (GO/V2O5). The NH4+ storage was as high as 234.7 mg N g-1 (> 102 times higher than conventional activated carbon). Three chains of proof were furnished to elucidate the intrinsic mechanisms for such superior performance. Density functional theory (DFT) showed that an excellent electron-donating ability for NH4+ (0.08) and decrease of diffusion barrier (22.3 %) facilitated NH4+ diffusion onto electrode interface. Physio- and electro-chemical results indicated that an increase of interlamellar spacing (14.3 %) and electrochemical active surface area (ECSA, 388.9 %) after the introduction of GO were responsible for providing greater channels and sites toward NH4+ insertion. Both non-ionic chemical-bonding (V5+=O‧‧‧H, hydrogen-bonding) and charge storage were contributed to the higher capacity and selectivity for NH4+. This work offers underlying guideline for exploitation a storage manner for NH4+ recovery from wastewater.

New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: a Chinese population-based cohort study.

BACKGROUND AND AIMS: Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope. METHODS AND RESULTS: This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline. CONCLUSION: Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.

Construction of ecological security pattern in Ningbo based on remote sensing ecological index and graph theory knowledge.

Constructing ecological security pattern and identifying ecological important areas are the focus of current research on regional ecological security. With Ningbo City as a case study area, we identified ecological sources by remote sensing ecological index, the ecological corridors and pinch point by circuit theory model, and the minimum spanning tree and cuts by graph theory algorithm. The results showed that there were 203 ecological sources in Ningbo, and that the main type of land cover was forest, including a small amount of paddy fields and flooded vegetation. There were 368 ecological corridors with a total length of 573.42 km, being dense in the southwest and sparse in the northeast. There were 91 ecological pinch points, which mainly distributed between coastal areas and closely related ecological sources. According to current situation, we put forward the optimization strategy with 187 primary corridors, 181 secondary corridors, 50 ecological restoration priority areas and 59 long-term ecological restoration areas. The optimization strategy combined with graph theory and circuit theory model would provide a refe-rence for the constructing of ecological security pattern.

GPCR activation and GRK2 assembly by a biased intracellular agonist.

Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands1-6. The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gαq and the arrestin-biased ligand SBI-5537. The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gαq protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling.

Relationship among positive self-esteem, physical literacy, and physical activity in college students: a study of a mediation model.

Background: In light of the substantial decline in physical activity during college years, this study aims to examine the relationship between positive self-esteem, physical literacy, and physical activity in order to investigate the mechanisms for improving physical activity in college students and to provide a foundation for future interventions. Methods: A cross-sectional study design was employed in this study. A total of 5,184 Participants, aged between 17 and 21 years (M = 18.97, SD = 1.10), completed the Positive Version of Rosenberg Self-esteem Scales, Perceived Physical Literacy Instruments, and the International Physical Activity Questionnaires. A mediation model was utilized to explore the associations among the three concepts. Results: The three regression models were as follows: Physical literacy = 18.03 + 0.98 *Self-esteem, Physical activity = 43.23 + 0.16 *Self-esteem, and Physical activity = 28.18 + 0.11 *Physical literacy. Positive self-esteem, physical literacy, and physical activity were significantly linked with each other. Physical literacy mediated 26.93% of the effect, indicating a partial mediator in the relationship between positive self-esteem and physical activity. Conclusion: The mediating effect of physical literacy on the relationship between positive self-esteem and physical activity was identified. Our findings support the development of positive self-esteem and physical literacy in college physical education curricula as part of an overall program to address students' physical inactivity at school and in the future. This study provides a new intervention perspective for improving physical inactivity in college students.

Genetic Code Expansion in Mammalian Cells Through Quadruplet Codon Decoding.

Genetic code expansion enables the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins both in vitro and in vivo. In addition to a widely applied nonsense suppression strategy, the use of quadruplet codons could further expand the genetic code. A general approach to genetically incorporate ncAAs in response to quadruplet codons is achieved by utilizing an engineered aminoacyl-tRNA synthetase (aaRS) together with a tRNA variant containing an expanded anticodon loop. Here we provide a protocol to decode quadruplet UAGA codon with a ncAA in mammalian cells. We also describe microscopy imaging and flow cytometry analysis of ncAA mutagenesis in response to quadruplet codons.

Neural representation of perceived race mediates the opposite relationship between subcomponents of self-construals and racial outgroup punishment.

Outgroup aggression characterizes intergroup conflicts in human societies. Previous research on relationships between cultural traits and outgroup aggression behavior showed inconsistent results, leaving open questions regarding whether cultural traits predict individual differences in outgroup aggression and related neural underpinnings. We conducted 2 studies to address this issue by collecting self-construal scores, EEG signals in response to Asian and White faces with painful or neutral expressions, and decisions to apply electric shocks to other-race individuals in a context of interracial conflict. We found that interdependent self-construals were well explained by 2 subcomponents, including esteem for group (EG) and relational interdependence (RI), which are related to focus on group collectives and harmonious relationships, respectively. Moreover, EG was positively associated with the decisions to punish racial outgroup targets, whereas RI was negatively related to the decisions. These opposite relationships were mediated by neural representations of perceived race at 120-160 ms after face onset. Our findings highlight the multifaceted nature of interdependent self-construal and the key role of neural representations of race in mediating the relationships of different subcomponents of cultural traits with racial outgroup punishment decisions in a context of interracial conflict.

The clinical potential of optogenetic interrogation of pathogenesis.

BACKGROUND: Opsin-based optogenetics has emerged as a powerful biomedical tool using light to control protein conformation. Such capacity has been initially demonstrated to control ion flow across the cell membrane, enabling precise control of action potential in excitable cells such as neurons or muscle cells. Further advancement in optogenetics incorporates a greater variety of photoactivatable proteins and results in flexible control of biological processes, such as gene expression and signal transduction, with commonly employed light sources such as LEDs or lasers in optical microscopy. Blessed by the precise genetic targeting specificity and superior spatiotemporal resolution, optogenetics offers new biological insights into physiological and pathological mechanisms underlying health and diseases. Recently, its clinical potential has started to be capitalized, particularly for blindness treatment, due to the convenient light delivery into the eye. AIMS AND METHODS: This work summarizes the progress of current clinical trials and provides a brief overview of basic structures and photophysics of commonly used photoactivable proteins. We highlight recent achievements such as optogenetic control of the chimeric antigen receptor, CRISPR-Cas system, gene expression, and organelle dynamics. We discuss conceptual innovation and technical challenges faced by current optogenetic research. CONCLUSION: In doing so, we provide a framework that showcases ever-growing applications of optogenetics in biomedical research and may inform novel precise medicine strategies based on this enabling technology.

STING controls opioid-induced itch and chronic itch via spinal tank-binding kinase 1-dependent type I interferon response in mice.

BACKGROUND: Patients receiving epidural or intrathecal opioids administration for neuraxial analgesia frequently suffer from an irritating itch. STING (stimulator of interferon genes), an innate immune modulator, is strongly implicated in pain pathogenesis via neuron-immune modulation. Given that pain and itch share some common neurocircuits, we evaluate the therapeutic potential of STING agonists in opioid-induced itch and chronic itch. METHODS: Opioids (morphine, fentanyl and sufentanil) were intrathecally injected to induce acute itch. Chronic itch was induced by dry skin and contact dermatitis. Opioids analgesic effect, itch-induced scratching behavior, spinal expression of STING, phosphorylation of TBK1 (tank-binding kinase 1), IRF3 (interferon regulatory factor-3) and ERK (extracellular signal-regulated kinase), as well as production of IFN-α and IFN-ß were examined. STING agonists (DMXAA and ADU-S100), TBK1 inhibitor, recombinant IFN-α and IFN-ß elucidated the mechanism and treatment of itch. Whole-brain functional connectivity was evaluated using resting-state fMRI. RESULTS: We report the primary expression of STING protein by the spinal dorsal horn neurons. Intraperitoneal injection of DMXAA dose-dependently reduces morphine-induced scratch bouts, without impairing morphine antinociception. Simultaneously, DMXAA alleviates fentanyl- and sufentanil-induced itching-like behavior, and chronic scratching behavior caused by dry skin and contact dermatitis. Furthermore, DMXAA drastically increases spinal phosphorylation of TBK1 and IRF3 following morphine exposure, dry skin and contact dermatitis. DMXAA-induced anti-pruritus effects and spinal productions of IFN-α and IFN-ß are compensated by intrathecal delivery of the TBK1 inhibitor. Also, ADU-S100, recombinant IFN-α and IFN-ß exhibits remarkable attenuation in scratching behaviors after morphine injection and dermatitis. Recombinant IFN-α inhibits morphine-induced spinal phosphorylation of ERK. Finally, DMXAA prevents dermatitis-induced the increase of cerebral functional connectivity between regions of interests such as primary somatosensory cortex, piriform cortex, retrosplenial cortex, colliculus and ventral thalamus. CONCLUSIONS: STING activation confers protection against opioid-induced itch and chronic itch through spinal up-regulation of TBK1-IRF3-type I interferon cascades in mice, suggesting that STING agonists are promising candidates in translational development for pruritus relief.

Maleic hydrazide prompting growth and delaying senescence of mother frond in S. Polyrriza 7498.

The effect and function mechanism of maleic hydrazide on the growth of mature leaves is unclear. Duckweed is widely used as a model plant to study the effect of compounds on plant growth. The observation of section and ultrastructure of the fronds, the comparation of SOD enzyme activity and related-gene transcriptional expression level showed that 75 µg/mL maleic hydrazide could prompt the growth of the mother fronds in S. Polyrriza 7498. The half-mother fronds (without meristematic tissue, cut from the mother fronds) with little meristematic tissue could repair themselves and delay their senescence by 75 µg/mL MH. The mother fronds turned more greener with 50 µg/mL MH and exogenous 0.1 µmol/L 6-BA (a kind of cytokinin) treatment, as well as with the increasing of fresh and dry weight in S. Polyrriza 7498. RNA-Seq data found that the happy growth of the mother fronds caused by MH, was probably resulted from up-regulating the expression of gene related to the synthesis and signaling transduction of cytokinin in S. Polyrriza 7498. Which are responsible for the maintaining membrane system integrate and transport protein function. The work gives lights to the study of function mechanism of MH prompting mature leaves growth and delaying mature leaves senescence in plant. And it provides a strategy to increase biomass with the application of low concentration MH and 6-BA in the same time in agriculture.

Structural basis of peptide recognition and activation of endothelin receptors.

Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETAR) and B (ETBR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETAR and ETBR bound to ET-1 and ETBR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes.

Are women more empathetic than men? Questionnaire and EEG estimations of sex/gender differences in empathic ability.

The debate regarding whether women are more empathetic than men has broad scientific, social and clinical implications. However, previous independent questionnaires and brain imaging studies that tested different samples reported inconsistent results regarding sex/gender differences in empathic ability. We conducted three studies to investigate sex/gender differences in empathic ability using large-sample questionnaires and electroencephalography (EEG) measures. We showed that the estimation of empathic ability using the Interpersonal Reactivity Index questionnaire showed higher rating scores in women than in men in all studies. However, our EEG measures of empathy, indexed by both phase-locked and non-phased-locked neural responses to others' painful (vs neutral) facial expressions, support a null hypothesis of the sex/gender difference in empathic ability. In addition, we showed evidence that priming social expectations of women and men's ability to share and care about others' feelings eliminated the sex/gender difference in questionnaire measures of empathic ability. Our large-sample EEG results challenge the notion of women's superiority in empathy that is built based on subjective questionnaire measures that are sensitive to social desirability. Our findings indicate that whether the notion of women's superiority in empathic ability reflects a biological/social difference between women and men or a gender-role stereotype remains an open question.

Dual signal amplified electrochemical aptasensor based on PEI-functionalized GO and ROP for highly sensitive detection of cTnI.

Cardiac troponin I (cTnI) is considered as the gold standard for the diagnosis of acute myocardial infarction (AMI) because of its excellent specificity and sensitivity. Herein, a novel aptasensor based on the dual signal amplification strategy of Polyethyleneimine functionalized Graphene oxide (GO) and ring-opening polymerization (ROP) for the first time was successfully constructed to achieve high sensitivity detection of cTnI. Briefly, cTnI-aptamer 1 (Apt1) was immobilized on the surface of gold electrode by self-assembly of Au-S bonds to specifically capture cTnI. After specific recognition of cTnI, Apt2 coated PEI-functionalized GO composites acted as macroinitiators for the subsequent ROP reaction. Next, α-amino acid-N-carboxylic acid anhydride ferrocene derivatives (NCA-Fc), the monomer for ROP reaction, was added to the electrode surface. The combined application of PEI-functionalized GO and NCA-Fc better achieves the high sensitivity and signal amplification of the aptasensor. Under optimal conditions, the aptasensor exhibited a wide linear range of 10 fg mL-1 to 10 ng mL-1 and the limit of detection was 3.78 fg mL-1. Moreover, this method displayed the advantages of good selectivity, simple operation and excellent stability. Meanwhile, the aptasensor had good accuracy and applicability even in real serum samples analysis, demonstrating its considerable application potential in biomedical assays.

A randomized controlled trial evaluating the effects of transversus abdominis plane block with compound lidocaine hydrochloride injection on postoperative pain and opioid consumption and gastrointestinal motility in patients undergoing gynecological laparotomy.

Introduction: Incorporation of transversus abdominis plane (TAP) block into multimodal analgesia has been emphasized in Enhanced Recovery protocols (ERPs). However, benefit is limited in clinical practice. A potential explanation is the short duration of analgesia of standard local anesthetics. Herein, this randomized, double-blind, controlled trial evaluated whether TAPB with long-acting compound lidocaine hydrochloride injection reduces postoperative pain. Methods: 164 patients undergoing elective gynecological laparotomy under sevoflurane anesthesia randomly received ultrasound-guided TAP block with either saline, or ropivacaine, or compound lidocaine before anesthesia induction. The postoperative pain intensity (primary outcome) was evaluated by pain 11-point numerical rating scale. We also recorded sufentanil consumptions, time to first flatus, side-effects and hospital stay after surgery. Results: We reported that pain scores at rest at postoperative 3h in group 0.375% ropivacaine was lower than that in group saline [mean 2.4 (SD 1.2) vs. 3.0 (1.0), p = 0.036]. Compared with saline, 0.4% and 0.6% compound lidocaine caused lower pain scores at rest at postoperative 12h [2.8 (0.9) vs. 2.1 (0.9) and 2.0 (0.9), p = 0.016 and p = 0.006]. Sufentanil usage for the first postoperative 48h was lower in group 0.6% compound lidocaine than group saline [24.2 (5.4) vs. 45.6 (7.5) µg, p < 0.001]. Time to first flatus and hospital stay after surgery was shortest and the incidence of postoperative nausea was lowest in patients receiving 0.6% compound lidocaine. Conclusion: TAP block with 0.6% compound lidocaine hydrochloride injection attenuates postoperative pain, reduces opioid consumption, accelerates gastrointestinal function recovery, and shortens length of hospital stay in patients after gynecological laparotomy. Trial registration: ClinicalTrials.gov, identifier: NCT04938882.

Nalmefene vs. dexmedetomidine for prevention of postoperative hyperalgesia in patients undergoing laparoscopic gynecological surgery with remifentanil infusion: A randomized double-blind controlled trial.

Intraoperative remifentanil infusion may paradoxically induce post-surgical hyperalgesia. Dexmedetomidine reportedly reduces opioid-induced hyperalgesia. Nalmefene selectively reverses several side-effects of opioids without impairing analgesia. Herein, this randomized, double-blind controlled trial investigated whether nalmefene, dexmedetomidine, and both drugs combined prevent remifentanil-induced hyperalgesia. One hundred and fifty patients undergoing elective laparoscopic gynecological surgery under desflurane anesthesia randomly received either intraoperative sufentanil 0.20 µg kg-1 (Group S), or remifentanil 0.20 µg kg-1 min-1 (Group R), or remifentanil and pre-anesthesia nalmefene 0.20 µg kg-1 (Group N), or remifentanil and pre-anesthesia dexmedetomidine 0.50 µg kg-1 (Group D), or remifentanil and the combination of dexmedetomidine 0.25 µg kg-1 and nalmefene 0.10 µg kg-1 (Group DN). The threshold of postoperative mechanical hyperalgesia (primary outcome) was measured with von Frey filaments. We also recorded pain intensity, analgesic consumptions, hyperalgesic area, and side-effects for 24 h postoperatively. Compared with Group S, remifentanil reduced hyperalgesic threshold on the forearm [mean 89.4 (SD 13.7) vs. 62.2 (10.7) g, p < 0.001] at postoperative 24 h. Pain threshold on the forearm at postoperative 24 h was significantly lower in Group R than in Groups N, D and DN [62.2 (10.7) vs. 71.1 (12.3), 72.4 (12.9) and 78.0 (13.8) g]. Compared with Group R, Postoperative pain intensity, analgesic consumption and hyperalgesic area were lower likewise in Groups D and DN. However, the incidence of intraoperative bradycardia was lower and post-anesthesia recovery time was shorter in Group DN than Group D. Preoperative therapy of dexmedetomidine and nalmefene combined attenuates postoperative hyperalgesia in patients undergoing laparoscopic gynecological surgery under desflurane-remifentanil anesthesia.