Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis.

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.

The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior.

The synaptic insertion or removal of AMPA receptors (AMPAR) plays critical roles in the regulation of synaptic activity reflected in the expression of long-term potentiation (LTP) and long-term depression (LTD). The cellular events underlying this important process in learning and memory are still being revealed. Here we describe and characterize the AAA+ ATPase Thorase, which regulates the expression of surface AMPAR. In an ATPase-dependent manner Thorase mediates the internalization of AMPAR by disassembling the AMPAR-GRIP1 complex. Following genetic deletion of Thorase, the internalization of AMPAR is substantially reduced, leading to increased amplitudes of miniature excitatory postsynaptic currents, enhancement of LTP, and elimination of LTD. These molecular events are expressed as deficits in learning and memory in Thorase null mice. This study identifies an AAA+ ATPase that plays a critical role in regulating the surface expression of AMPAR and thereby regulates synaptic plasticity and learning and memory.

Immunological nanomaterials to combat cancer metastasis.

Metastasis causes greater than 90% of cancer-associated deaths, presenting huge challenges for detection and efficient treatment of cancer due to its high heterogeneity and widespread dissemination to various organs. Therefore, it is imperative to combat cancer metastasis, which is the key to achieving complete cancer eradication. Immunotherapy as a systemic approach has shown promising potential to combat metastasis. However, current clinical immunotherapies are not effective for all patients or all types of cancer metastases owing to insufficient immune responses. In recent years, immunological nanomaterials with intrinsic immunogenicity or immunomodulatory agents with efficient loading have been shown to enhance immune responses to eliminate metastasis. In this review, we would like to summarize various types of immunological nanomaterials against metastasis. Moreover, this review will summarize a series of immunological nanomaterial-mediated immunotherapy strategies to combat metastasis, including immunogenic cell death, regulation of chemokines and cytokines, improving the immunosuppressive tumour microenvironment, activation of the STING pathway, enhancing cytotoxic natural killer cell activity, enhancing antigen presentation of dendritic cells, and enhancing chimeric antigen receptor T cell therapy. Furthermore, the synergistic anti-metastasis strategies based on the combinational use of immunotherapy and other therapeutic modalities will also be introduced. In addition, the nanomaterial-mediated imaging techniques (e.g., optical imaging, magnetic resonance imaging, computed tomography, photoacoustic imaging, surface-enhanced Raman scattering, radionuclide imaging, etc.) for detecting metastasis and monitoring anti-metastasis efficacy are also summarized. Finally, the current challenges and future prospects of immunological nanomaterial-based anti-metastasis are also elucidated with the intention to accelerate its clinical translation.

Integrated analysis of the DNA methylome and RNA transcriptome during the development of skeletal muscle in Duroc pigs.

BACKGROUND: Skeletal muscle development plays a crucial role in yield and quality of pork; however, this process is influenced by various factors. In this study, we employed whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing to comprehensively investigate the longissimus dorsi muscle (LDM), aiming to identify key genes that impact the growth and development of Duroc pigs with different average daily gains (ADGs). RESULTS: Eight pigs were selected and divided into two groups based on ADGs: H (774.89 g) group and L (658.77 g) group. Each pair of the H and L groups were half-siblings. The results of methylation sequencing revealed 2631 differentially methylated genes (DMGs) involved in metabolic processes, signalling, insulin secretion, and other biological activities. Furthermore, a joint analysis was conducted on these DMGs and the differentially expressed genes (DEGs) obtained from transcriptome sequencing of the same individual. This analysis identified 316 differentially methylated and differentially expressed genes (DMEGs), including 18 DMEGs in promoter regions and 294 DMEGs in gene body regions. Finally, LPAR1 and MEF2C were selected as candidate genes associated with muscle development. Bisulfite sequencing PCR (BSP) and quantitative real-time PCR (qRT-PCR) revealed that the promoter region of LPAR1 exhibited significantly lower methylation levels (P < 0.05) and greater expression levels (P < 0.05) in the H group than in the L group. Additionally, hypermethylation was observed in the gene body region of MEF2C, as was a low expression level, in the H group (P < 0.05). CONCLUSIONS: These results suggest that the differences in the ADGs of Duroc pigs fed the same diet may be influenced by the methylation levels and expression levels of genes related to skeletal muscle development.

Recent insights into the effect of endoplasmic reticulum stress in the pathophysiology of intestinal ischaemia‒reperfusion injury.

Intestinal ischaemia‒reperfusion (I/R) injury is a surgical emergency. This condition is associated with a high mortality rate. At present, there are limited number of efficient therapeutic measures for this injury, and the prognosis is poor. Therefore, the pathophysiological mechanisms of intestinal I/R injury must be elucidated to develop a rapid and specific diagnostic and treatment protocol. Numerous studies have indicated the involvement of endoplasmic reticulum (ER) stress in the development of intestinal I/R injury. Specifically, the levels of unfolded and misfolded proteins in the ER lumen are increased due to unfolded protein response. However, persistent ER stress promotes apoptosis of intestinal mucosal epithelial cells through three signalling pathways in the ER, impairing intestinal mucosal barrier function and leading to the dysfunction of intestinal tissues and distant organ compartments. This review summarises the mechanisms of ER stress in intestinal I/R injury, diagnostic indicators, and related treatment strategies with the objective of providing novel insights into future therapies for this condition.

Cerebrospinal fluid markers of neuroinflammation and coagulation in severe cerebral edema and chronic hydrocephalus after subarachnoid hemorrhage: a prospective study.

BACKGROUND: Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH. METHODS: Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH. RESULTS: Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1ß, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function. CONCLUSIONS: Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction.

SfREPAT38, a pathogen response gene (REPAT), is involved in immune response of Spodoptera frugiperda larvae through mediating Toll signalling pathway.

REPAT (response to pathogen) is an immune-associated gene family that plays important roles in insect immune response to pathogens. Although nine REPAT genes have been identified in Spodoptera frugiperda (Lepidoptera: Noctuidae) currently, their functions and mechanisms in the immune response to pathogens still remain unclear. Therefore, SfREPAT38, a pathogen response gene (REPAT) of S. frugiperda, was characterised and its function was analysed. The results showed that SfREPAT38 contains a signal peptide and a transcription activator MBF2 (multi-protein bridging factor 2) domain. Quantitative real-time polymerase chain reaction analysis showed that SfREPAT38 was highly expressed in the sixth-instar larvae (L6) and was the highest in expression in the midgut of L6. We found that the expression of SfREPAT38 could be activated by challenge with four microbial pathogens (Bacillus thuringiensis, Metarhizium anisopliae, Spodoptera exigua nuclearpolyhedrosis and Escherichia coli), except 12 h after E. coli infection. Furthermore, the SfREPAT38 expression levels significantly decreased at 24, 48 and 72 h after SfREPAT38 dsRNA injection or feeding. Feeding with SfREPAT38 dsRNA significantly decreased the weight gain of S. frugiperda, and continuous feeding led to the death of S. frugiperda larvae from the fourth day. Moreover, SfREPAT38 dsRNA injection resulted in a significant decrease of weight gain on the fifth day. Silencing SfREPAT38 gene down-regulated the expression levels of immune genes belonging to the Toll pathway, including SPZ, Myd88, DIF, Cactus, Pell and Toll18W. After treatment with SfREPAT38 dsRNA, S. frugiperda became extremely sensitive to the B. thuringiensis infection, and the survival rate dramatically increased, with 100% mortality by the eighth day. The weight of S. frugiperda larvae was also significantly lower than that of the control groups from the second day onwards. In addition, the genes involved in the Toll signalling pathway and a few antibacterial peptide related genes were down-regulated after treatment. These results showed that SfREPAT38 is involved in the immune response of S. frugiperda larvae through mediating Toll signalling pathway.

lncRNA BANCR promotes the colorectal cancer metastasis through accelerating exosomes-mediated M2 macrophage polarization via regulating RhoA/ROCK signaling.

Cancer cells-derived exosomal lncRNAs could modulate the tumorigenesis of colorectal cancer (CRC) via modulating macrophage M2 polarization. However, the clarified mechanism and function of lncRNA BANCR in CRC remains unclear. Exosomes were identified by TEM, NTA, western blot and fluorescent staining. M2 macrophages were identified by CD206 and CD163 expressions using by flow cytometry and RT-qPCR. In addition, the relation between IGF2BP2 and BANCR or RhoA were explored by RIP assay. The malignant behaviors of CRC cells were examined by CCK-8, EdU and transwell assays. Histopathological changes in mice were observed by H&E staining. Silencing of BANCR notably inhibited the proliferation, migration and invasion of CRC cells. SW620 and HCT-15 cells-derived exosomal BANCR positively regulated the macrophage M2 polarization. In addition, exosomal BANCR remarkably enhanced the promoting roles mediated by M2 macrophages on proliferation and invasion in CRC cells. Meanwhile, exosomal BANCR promoted the M2 macrophage polarization via activation of RhoA/Rock pathway by recruiting IGF2BP2. Inhibition of RhoA/Rock pathway reversed exosomal BANCR-mediated macrophages M2 polarization and CRC malignant behaviors in SW620 and HCT-15 cells. Exosomal lncRNA BANCR derived from SW620 and HCT-15 cells promoted the metastasis of CRC via inducing the polarization of M2 macrophages. Thus, BANCR might be a new target for the treatment of CRC.

Dietary cholesterol intervention could alleviate the intestinal injury of Oreochromis niloticus induced by plant-based diet via the intestinal barriers.

This study aims to explore the effects of supplementing cholesterol in plant-based feed on intestinal barriers (including physical barrier, chemical barrier, immune barrier, biological barrier) of GIFT strain tilapia (Oreochromis niloticus). Four isonitrogenous and isolipidic diets were prepared as follows: plant-based protein diet (Con group) containing corn protein powder, soybean meal, cottonseed meal, and rapeseed meal, with the addition of cholesterol at a level of 0.6 % (C0.6 % group), 1.2 % (C1.2 % group), and 1.8 % (C1.8 % group), respectively. A total of 360 fish (mean initial weight of (6.08 ± 0.12) g) were divided into 12 tanks with 30 fish per tank, each treatment was set with three tanks and the feeding period lasted 9 weeks. Histological analysis revealed that both the C0.6 % and C1.2 % groups exhibited a more organized intestinal structure, with significantly increased muscle layer thickness compared to the Con group (P < 0.05). Furthermore, in the C1.2 % group, there was a significant up-regulation of tight junction-related genes (claudin-14, occludin, zo-1) compared to the Con group (P < 0.05). 5-ethynyl-2'-deoxyuridine staining results also demonstrated a notable enhancement in intestinal cell proliferation within the C1.2 % group (P < 0.05). Regarding the intestinal chemical barrier, trypsin and lipase activities were significantly elevated in the C1.2 % group (P < 0.05), while hepcidin gene expression was considerably down-regulated in this group but up-regulated in the C1.8 % group (P < 0.05). In terms of the intestinal immune barrier, inflammation-related gene expression levels (tnf-α, il-1ß, caspase 9, ire1, perk, atf6) were markedly reduced in the C1.2 % group (P < 0.05). Regarding the intestinal biological barrier, the composition of the intestinal microbiota indicated that compared to the Con group, both the 0.6 % and 1.2 % groups showed a significant increase in Shannon index (P < 0.05). Additionally, there was a significant increase in the abundance of Firmicutes and Clostridium in the C1.2 % group (P < 0.05). In summary, supplementation of 1.2 % cholesterol in the plant-based diet exhibits the potential to enhance intestinal tight junction function and improve the composition of intestinal microbiota, thereby significantly promoting tilapia's intestinal health.

Effects of dietary succinic acid supplementation on growth performance, digestive ability, intestinal development and immunity of large yellow croaker (Larimichthys crocea) larvae.

The application of artificial micro-diet is an effective way to improve and standardize the quality of aquatic animal larvae. However, the widespread adoption of micro-diet faces a bottleneck due to the limited utilization capacity of the larvae. A 30-day feeding experiment was carried out to investigate the effect of dietary succinic acid (SA) on the growth performance, digestive ability, intestinal development, and immunity of large yellow croaker larvae (initial body weight 11.33 ± 0.57 mg). Four isonitrogenous and isolipidic diets were formulated, incorporating 0.00%, 0.01%, 0.02% and 0.03% SA separately. The results showed that a diet with 0.02% SA significantly increased both the final body weight and the specific growth rate of the larvae. Regarding digestive ability, 0.01% SA supplementation significantly enhanced trypsin activity in both intestinal and pancreatic segments. In addition, 0.01% SA supplementation notably improved amylase activity in the intestinal segment, while diets with 0.01%-0.02% SA significantly improved lipase activity in the pancreatic segment. In terms of intestinal development, 0.01% SA supplementation remarkably boosted the activities of alkaline-phosphatase and leucine-aminopeptidase on brush border membrane in intestine. Furthermore, 0.03% SA supplementation significantly increased the expression of occludin. In terms of immunity, larvae fed diets with 0.01%-0.02% SA exhibited significantly higher lysozyme activity compared to the control group. Supplementation with 0.01% SA also significantly increased both iNOS activity and NO content. In summary, the findings of this study suggested that adding 0.02% SA can improve the growth performance of large yellow croaker larvae by improving digestive enzymes activities, promoting intestinal development, and enhancing nonspecific immunity.

Topological phases, local magnetic moments, and spin polarization triggered by C558-line defects in armchair graphene nanoribbons.

The topological and magnetic properties induced by topological defects in graphene have attracted attention. Here, we study a novel topological defect structure for graphene nanoribbons interspersed with C558-line defects along the armchair boundary, which possesses topological properties and is tritopic. Using strain engineering to regulate the magnitude of hopping at defects, the position of the energy level can be easily changed to achieve a topological phase transition. We also discuss the local magnetic moment and the ferromagnetic ground state in the context of line defects. This leads to spin polarization of the whole system. Finally, when C558 graphene nanoribbons are controlled by a nonlocal exchange magnetic field, spin-polarized quantum conductivity occurs near the Fermi level. Consequently, spin filtering can be achieved by varying the incident energy of the electrons. Our results provide new insights into realizing topological and spin electronics in low-dimensional quantum devices.

Effects of V and Gd doping on novel positive colossal electroresistance and quantum transport in PbPdO2 thin films with (002) preferred orientation.

In this work, PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 thin films with (002) preferred orientation were prepared using a pulsed laser deposition technique. The temperature dependence of resistivities ρI(T) was investigated under various applied DC currents. Colossal electroresistance (CER) effects were found in PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2. It was found that the positive CER values of PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 reach 3816% and 154% for I = 1.00 µA at 10 K, respectively. In addition, the ρI(T) cycle curves of PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 thin films showed a critical temperature similar to that of PbPdO2 (Tc = 260 K). Particularly, charge transfer between O1- and O2- was confirmed by in situ XPS. Additionally, based on first-principles calculations and internal electric field models, the CER and magnetic sources in PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 can be well explained. Finally, it was found that thin film samples doped with V and G ions exhibit weak localization (WL) and weak anti-localization (WAL) quantum transport properties. Ion doping leads to a transition from WAL to WL. The study results indicate that PbPdO2, one of the few oxide topological insulators, can exhibit novel quantum transport behavior after ion doping.

A synergetic promotion of surface stability for high-voltage LiCoO2 by multi-element surface doping: a first-principles study.

The utilization of high-voltage LiCoO2 is an effective approach to break through the bottleneck of practical energy density in lithium ion batteries. However, the structural and interfacial degradations at the deeply delithiated state as well as the associated safety concerns impede the application of high-voltage LiCoO2. Herein, we present a synergetic strategy for promoting the surface stability of LiCoO2 at high voltage by Ti-Mg-Al co-doping and systematically study the effects of the dopants on the surface stability, electronic structure and Li+ diffusion properties of the LiCoO2 (104) surface using first-principles calculations. It is found that Ti, Mg and Al dopants can be facilely introduced into the Co sites of the LiCoO2 (104) surface. Furthermore, the co-doping could significantly stabilize the surface oxygen of LiCoO2 at a high delithiation state. Particularly, by aggregating Ti-Mg-Al co-dopant distribution in the surface layer, surface oxygen loss is dramatically suppressed. In addition, analysis of the electronic structure indicates that Ti-Mg-Al co-doping can enhance the electronic conductivity of the LiCoO2 (104) surface and greatly inhibit the charge deficiency of the superficial lattice O atoms at a highly delithiated state. In spite of a negligible improvement in the surface Li+ diffusion kinetics, the Ti-Mg-Al surface-modified LiCoO2 is expected to exhibit improved electrochemical performance at high voltage due to its superior surface stability. Our results suggest that aggregating Ti, Mg and Al co-dopant distribution in the surface layer is a promising modulation strategy to synergistically promote the surface oxygen stability of LiCoO2 at high voltages.

Safety and effectiveness of opioid-free anaesthesia in thoracoscopic surgery: a preliminary retrospective cohort study.

BACKGROUND: This study aimed to observe the effect of opioid-free anaesthesia (OFA) on intraoperative haemodynamic,postoperative analgesia and postoperative nausea and vomiting (PONV) in thoracoscopic surgery in order to provide more evidence for evaluating the safety and effectiveness of OFA technology. METHODS: This was a single-centre retrospective observational study.Adult patients who underwent thoracoscopic surgery with the preoperative thoracic paravertebral block between January 2017 and June 2020 were included.A cohort of 101 thoracoscopic surgery patients who received the OFA technique were matched with 101 thoracoscopic surgery patients who received standard opioid-containing anaesthesia(SOA). Heart rate (HR) and mean arterial blood pressure (MAP) were measured before anaesthesia induction, immediately after endotracheal intubation, at the beginning of surgery, and 10, 20, and 30 min after surgery began.The total amount of intraoperative infusion, frequency of vasoactive drugs use, morphine ingested via the patient-controlled intravenous analgesia (PCIA) 24 h post-surgery,visual analogue scale (VAS) scores at rest and activity on the first day post-surgery, and frequency of nausea and vomiting within 24 h post-surgery were analysed. RESULTS: There was no significant difference in intraoperative HR between the two groups (F = 0.889, P = 0.347); however, there was significant difference in intraoperative MAP (F = 16.709, P < 0.001), which was lower in SOA patients than in OFA patients. The frequency of vasoactive drug use and amount of infusion was less in OFA patients (P = 0.001). The consumption of morphine used by the PCIA 24 h post-surgery was significantly lower in OFA patients (OFA, 1.8 [0, 4.8] mg vs. SOA, 3.6 [0.6, 23] mg, P < 0.001). There was no significant difference in VAS scores at rest (P = 0.745) or during activity (P = 0.792) on the first day post-surgery. There was also no statistically significant difference in nausea and vomiting within 24 h post-surgery (P = 0.651). CONCLUSIONS: This case-control study demonstrated that compared with SOA, OFA can effectively maintain the stability of intraoperative MAP, reduce the incidence of hypotension. Although OFA reduced morphine consumption via the PCIA pump 24 h post-surgery, postoperative pain scores and nausea and vomiting within 24 h post-surgery were similar between the groups.But this study was only a preliminary study and needed to confirm in a larger, more robust trial.

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial.

BACKGROUND: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. METHODS: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h- 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. RESULTS: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. CONCLUSION: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg- 1. h- 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

Safety and efficacy of a novel dexmedetomidine nasal spray for pre-anesthetic sedation in children: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. OBJECTIVE: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. METHODS: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. RESULTS: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity. CONCLUSIONS: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile.

Influence of blood loss on cerebral oxygen saturation in paediatric patients undergoing surgery for scoliosis correction: A retrospective observational study.

AIM: Surgery for congenital scoliosis correction in children is often associated with considerable blood loss. Decrease in regional oxygen saturation (rScO2) can reflect insufficient cerebral perfusion and predict neurological complications. This retrospective observational study explored the relationship between blood loss during this surgery and a decrease in rScO2 in children. METHODS: The following clinical data of children aged 3-14 years who underwent elective posterior scoliosis correction between March 2019 and July 2021 were collected: age, sex, height, weight, baseline rScO2, basal mean invasive arterial pressure (MAP), preoperative Cobb angle, number of surgical segments, preoperative and postoperative haemoglobin level, percentage of lowest rScO2 below the baseline value that lasted 3 min or more during the operation (decline of rScO2 from baseline, D-rScO2%), intraoperative average invasive MAP, end-tidal carbon dioxide pressure, fluid infusion rate of crystalloids and colloids, operation time, and percentage of total blood loss/patient's blood volume (TBL/PBV). RESULTS: A total of 105 children were included in the study. Massive haemorrhage (TBL/PBV ≥50%) was reported in 53.3% of patients, who had significantly higher D-rScO2 (%) (t = -5.264, P < 0.001) than those who had non-massive haemorrhage (TBL/PBV <50%). Multiple regression analysis revealed that TBL/PBV (ß = 0.04, 95% CI: 0.018-0.062, P < 0.05) was significantly associated with D-rScO2%. CONCLUSIONS: Intraoperative massive blood loss in children significantly increased D-rScO2%. Monitoring should be improved, and timely blood supplementation should be performed to ensure maintenance of the blood and oxygen supply to vital organs, improve the safety of anaesthesia, and avoid neurological complications.

Bilateral ultrasound-guided erector spinae plane block for postoperative analgesia in paediatric idiopathic scoliosis patients undergoing posterior spine fusion surgery: a randomized controlled trial.

PURPOSE: Major spinal surgery causes severe pain. We examined the ability of erector spinae plane block (ESPB) to alleviate pain after posterior spinal fusion (PSF) in paediatric scoliosis patients. METHODS: Seventy-two patients who underwent PSF were randomized into a preoperative ultrasound-guided ESPB group or a no-block control group. The composite primary outcome was the area under the curve (AUC) of the numerical rating scale (NRS) score in the first 24 h after surgery and the number of parent-controlled intravenous analgesia (PCIA) boluses administered 24 h after surgery. The secondary outcomes included the NRS score, opioid consumption, rescue analgesia, adverse events, and quality of recovery. RESULTS: The AUC-NRS at rest was 62 (13) in the ESPB group and 89 (13) in the control group (P < 0.001). There were 15 (5) 24-h PCIA boluses administered in the ESPB group and 30 (7) in the control group (P < 0.001). Compared with those in the control group, the NRS scores at rest were lower in the ESPB group at 0, 3, 6, and 9 h postoperatively, and the NRS scores during movement were lower in the ESPB group at 0, 3, 6, 9 and 12 h postoperatively. The ESPB group showed a lower need for PCIA than did the control group at 0-6, 6-12, 12-18 and 1-24 h postoperatively. In the ESPB group, fewer patients required rescue analgesics, and patients exhibited a higher quality of recovery. CONCLUSION: Preoperative ESPB improves postoperative analgesia in paediatric scoliosis patients who underwent PSF. TRIAL REGISTRATION NUMBER: ChiCTR2300074505. DATE OF REGISTRATION: August 8, 2023.

Pediatric anesthesia in China.

In China, healthcare has lagged relative to its economic boom during the past 40 years. While the top tier hospitals offer pediatric perioperative care like high-income countries, lower-tier hospitals deliver lesser services of variable quality and safety related to equipment, supplies, clinician education, and availability. The national residency training program and the pediatric anesthesia fellowship program was established in 2013 and 2018 respectively. Increasing clinician workload from patient demand and a lack of consistency in quality and capability between rural and urban areas remain challenging.

Complete Shrinking of Mixed Growth Hormone and Prolactin-Secreting Pituitary Adenoma With Bromocriptine Therapy Alone.

A 40-year-old man presented with acromegaly, reduction of visual acuity and visual field, and elevated blood sugar. Imaging examinations demonstrated a large sellar adenoma with suprasellar extension that compresses the optic chiasma upward, spreads downward to the sphenoid sinus, and invades the cavernous sinus bilaterally. Random prolactin and growth hormone were beyond the scope of normal. The patient achieved complete shrinking of the adenoma by taking bromocriptine orally. For some kinds of giant mixed growth hormone-prolactin adenomas, surgical treatment is not necessary, and drug treatment can also achieve good results.