Neonatal Exposure to Polystyrene Nanoplastics Impairs Microglia-Mediated Synaptic Pruning and Causes Social Behavioral Defects in Adulthood.

The increasing prevalence and persistence of nanoplastics (NPs) have become critical environmental concerns. These particles have the potential to enter the food chain and accumulate in living organisms, which exerts their adverse effects on human health. The release of nanoparticles from feeding bottles raises concerns about potential health issues, especially for newborns exposed to NPs at the neonatal stage. In this study, we examined the impacts of neonatal exposure to polystyrene nanoplastics (PS-NPs) on neurodevelopment. Our study demonstrates that exposure to PS-NPs in newborn mice impairs microglial autophagic function and energy metabolism, leading to the disruption of microglia-mediated synaptic pruning during early neurodevelopment. These mice subsequently develop social behavioral defects in adulthood, suggesting the long-lasting effects of neonatal PS-NP exposure on brain development and behavior. Together, these data provide insights into the mechanism by which PS-NPs affect early neurodevelopment, thus emphasizing the crucial need to address plastic pollution globally.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial.

INTRODUCTION: Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown. METHODS AND ANALYSIS: This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition. DISCUSSION: This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions. CLINICAL TRIAL REGISTRATION: https://beta. CLINICALTRIALS: gov/study/NCT05635877 , NCT05635877.

Transcriptome profiling provides insights into leaf color changes in two Acer palmatum genotypes.

BACKGROUND: Ornamental trees with seasonally-dependent leaf color, such as Acer palmatum, have gained worldwide popularity. Leaf color is a main determinant of the ornamental and economic value of A. palmatum. However, the molecular mechanisms responsible for leaf color changes remain unclear. RESULTS: We chose A. palmatum cultivars with yellow ('Jinling Huangfeng') and red ('Jinling Danfeng') leaves as the ideal material for studying the complex metabolic networks responsible for variations in leaf coloration. The 24 libraries obtained from four different time points in the growth of 'Jinling Huangfeng' and 'Jinling Danfeng' was subjected to Illumina high-throughput sequencing. We observed that the difference in cyanidin and delphinidin content is the primary reason behind the varying coloration of the leaves. Transcriptomic analyses revealed 225,684 unigenes, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes (DEGs) confirmed that they were involved in 'anthocyanin biosynthesis.' Eighteen structural genes involved in anthocyanin biosynthesis were thought to be related to anthocyanin accumulation, whereas 46 MYBs, 33 basic helix-loop-helixs (bHLHs), and 29 WD40s were presumed to be involved in regulating anthocyanin biosynthesis. Based on weighted gene co-expression network analysis (WGCNA), three candidate genes (ApRHOMBOID, ApMAPK, and ApUNE10) were screened in the significant association module with a correlation coefficient (r2) of 0.86. CONCLUSION: In this study, the leaf color changes of two A. palmatum genotypes were analyzed. These findings provide novel insights into variations in leaf coloration and suggest pathways for targeted genetic improvements in A. palmatum.

Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation.

BACKGROUND: Ventilator-induced lung injury (VILI) is caused by stretch stimulation and other factors related to mechanical ventilation (MV). NOD-like receptor protein 3 (NLRP3), an important innate immune component, is strongly associated with VILI. This study aimed to investigate the effect and mechanisms of aerobic exercise (EX) on VILI. METHODS: To test the effects of the PKC inhibitor bisindolylmaleimide I on PKC and NLRP3, male C57BL/6 mice (7 weeks old, 19 ~ 23 g) were randomly divided into four groups: control group(C), bisindolylmaleimide I-pretreated group(B), MV group, and bisindolylmaleimide I-pretreated + MV (B + MV) group. The mice were pretreated with bisindolylmaleimide I through intraperitoneal injection (0.02 mg/kg) 1 h before MV. MV was performed at a high tidal volume (30 ml/kg). To explore the ameliorative effect of EX on VILI, the mice were randomly divided into C group, MV group, EX group and EX + MV group and subjected to either MV or 5 weeks of EX training. After ventilation, haematoxylin-eosin (HE) staining and wet/dry weight ratio was used to assess lung pathophysiological changes. PKCɑ, P-PKCɑ, ASC, procaspase-1, caspase-1, pro-IL-1ß, IL-1ß, NLRP3 and occludin (tight junction protein) expression in lung tissues was determined by Western blotting. The level of IL-6 in alveolar lavage fluid was determined by ELISA. RESULTS: NLRP3, P-PKCɑ, and PKCɑ levels were inceased in MV group, but bisindolylmaleimide I treatment reversed these changes. Inhibition of PKC production prevented NLRP3 activation. Moreover, MV increased ASC, procaspase-1, caspase-1, pro-IL-1ß, and IL1ß levels and decreased occludin levels, but EX alleviated these changes. HE staining and lung injury scoring confirmed an absence of obvious lung injury in C group and EX group. Lung injury was most severe in MV group but was improved in EX + MV group. Overall, these findings suggest that MV activates the NLRP3 inflammasome by activating PKCɑ and inducing occludin degradation, while Exercise attenuates NLRP3 inflammasome and PKCɑ activation. Besides, exercise improves cyclic stretch-induced degradation of occludin. CONCLUSION: PKC activation can increase the level of NLRP3, which can lead to lung injury. Exercise can reduce lung injury by inhibiting PKCɑ and NLRP3 activation. Exercise maybe a potential measure for clinical prevention of VILI.

Protective role of p120-catenin on mitochondria by inhibiting NLRP3 in ventilator-induced lung injury.

Mitochondria supply energy to maintain the integrity of cell junctions. NLRP3, as the core component of the inflammatory response, is crucial in mechanical stretching. Mechanical stretching could activate NLRP3 and induce mitochondrial dysfunction. The relationship between p120 and mitochondria in ventilator-induced lung injury (VILI) has not been elucidated. MLE-12 cells and wild-type male C57BL/6 mice were pre-treated with MCC950 (specific and highly efficient inhibitor of NLRP3) or a p120 siRNA-liposome complex. Then, the cells were subjected to 20% cyclic stretching, and the mice were subjected to mechanical ventilation at a high tidal volume. Cell lysates and lung tissues were obtained to detect the expression of NLRP3, p120, TLR4 pathway components, IL-6 and IL-1ß, to determine the functions and structures of mitochondria, and the wet/dry ratio of the lung, and to perform pathological staining and an Evans blue dye assay. Mechanical stretching could increase the levels of NLRP3, ROS and damaged mitochondria, while these changes could be reversed by MCC950. Moreover, p120 prevented the activation of NLRP3 and regulated NLRP3 by inhibiting the TLR4 pathway and ROS production. Additionally, p120 played a vital role in protecting mitochondrial structures and functions after mechanical stretching. Taken together, these findings suggest that p120 depletion during mechanical stretching aggravates mitochondrial dysfunction by activating NLRP3, which indicates that p120 has a protective role on mitochondria in VILI by inhibiting NLRP3 activation.

Analysis of Long Noncoding RNA Expression Profile in Human Pulmonary Microvascular Endothelial Cells Exposed to Lipopolysaccharide.

BACKGROUND/AIMS: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a continuum of life-threatening lung changes. Pulmonary vascular injury is one of the most important initial causes of ALI and ARDS. However, the functions of long noncoding RNAs (lncRNAs) in pulmonary endothelial injury remain largely unknown. The aim of the present study was to determine the lncRNA expression profile of human pulmonary microvascular endothelial cells (HPMECs) exposed to lipopolysaccharide (LPS) and explore the potential functions of differentially expressed lncRNAs. METHODS: Microarray analysis was used to identify differentially expressed lncRNAs and mRNAs. Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, lncRNA-mRNA coexpression network and transcription factor (TF)-lncRNA network analyses, were performed to predict the functions of significantly differentially expressed lncRNAs and mRNAs. Realtime polymerase chain reaction (PCR) was used to determine the expression of selected lncRNAs and mRNAs. RESULTS: In this study, we found that 213 lncRNAs and 212 mRNAs were significantly differentially expressed in HPMECs exposed to LPS (fold change > 2.0, p < 0.05). Furthermore, we found that mRNAs co-expressed with lncRNAs were significantly enriched in the TNF signaling pathway, the NF-κB signaling pathway, cell adhesion molecules (CAMs), cytokine-cytokine receptor interactions, and extracellular matrix (ECM)-receptor interactions. The expression levels of all but one of the selected lncRNAs and mRNAs detected by real-time PCR were similar to those detected by microarray analysis. CONCLUSION: Our data indicate that lncRNAs play an important role in LPS-induced pulmonary endothelial inflammation and barrier dysfunction and may be potential preventive and therapeutic targets for ALI and ARDS.

Stromal-Interacting Molecule 1 (Stim1)/Orai1 Modulates Endothelial Permeability in Ventilator-Induced Lung Injury.

BACKGROUND Increased endothelial permeability is involved in ventilator-induced lung injury (VILI). Stim1/Orai1 mediates store-operated Ca2+ activation, which modulates endothelial permeability. However, the underlying mechanisms of the Stim1/Orai1 pathway in VILI are poorly understood. MATERIAL AND METHODS Wistar rats were exposed to low tidal volume (7 mL/kg) or high tidal volume (40mL/kg) ventilation. Human Lung Microvascular Endothelial Cells (HULEC) were subjected to 8% or 18% cyclic stretching (CS). BTP2 pretreatment was performed. Lung wet/dry weight ratio, histological changes of lung injury, and bronchoalveolar lavage fluid (BALF) protein were measured. Endothelial permeability and intracellular calcium concentration were evaluated in HULECs. Protein expression was determined by Western blotting. RESULTS High tidal volume mechanical ventilation-induced lung injury (such as severe congestion and hemorrhage) and BTP2 pretreatment protected lungs from injury. The expression of Stim1, Orai1, and PKCα, lung wet/dry weight ratio, and BALF protein level significantly increased in the high tidal volume group compared to the control group and low tidal volume group. Importantly, BTP2 pretreatment alleviated the above-mentioned effects. Compared with exposure to 8% CS, the protein levels of Stim1, Orai1, and PKCα in HULECs significantly increased after exposure to 18% CS for 4 h, whereas BTP2 pretreatment significantly inhibited the increase (P<0.05). BTP2 pretreatment also suppressed increase of endothelial permeability and the intracellular calcium induced by 18% CS (P<0.05). CONCLUSIONS When exposed to high tidal volume or large-magnitude CS, Stim1 and Orai1 expression are upregulated, which further activates calcium-sensitive PKCα and results in calcium overload, endothelial hyperpermeability, and, finally, lung injury.

Role of the PKCα-c-Src tyrosine kinase pathway in the mediation of p120-catenin degradation in ventilator-induced lung injury.

BACKGROUND AND OBJECTIVE: Ventilator-induced lung injury (VILI) is commonly associated with respiratory barrier dysfunction; however, the mechanisms have not been fully elucidated. This study aimed to determine the order and components of the signalling pathway that mediates the degradation of adherin junction of p120-catenin in VILI. METHODS: For the in vivo study, C57BL/6 mice were pre-treated with inhibitors for 60 min prior to 4 h of mechanical ventilation. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells were pre-treated with inhibitors for 60 min or small interfering RNA (siRNA) for 48 h prior to cyclic stretch at 20% for 4 h. The protein levels of protein kinase Cα (PKCα), activated c-Src and p120-catenin were determined via western blot analysis. Lung injury was determined via HE staining, immunofluorescence, wet/dry ratio and lung injury scores. RESULTS: High tidal volume mechanical ventilation and 20% cyclic stretch resulted in the degradation of p120-catenin. Inhibitors of PKCα blocked c-Src kinase activation and p120-catenin degradation in VILI. Inhibitors of c-Src kinase or PP2 or siRNA blocked p120-catenin degradation but not PKCα activation. CONCLUSION: The current findings demonstrates that PKCα and c-Src kinase participate in VILI. PKCα activation phosphorylates c-Src kinase and further decreases p120-catenin in VILI.

Protective role of p120-catenin in maintaining the integrity of adherens and tight junctions in ventilator-induced lung injury.

BACKGROUND: Ventilator-induced lung injury (VILI) is one of the most common complications for patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Although p120 is an important protein in the regulation of cell junctions, further mechanisms should be explored for prevention and treatment of VILI. METHODS: Mouse lung epithelial cells (MLE-12), which were transfected with p120 small interfering (si)RNA, p120 cDNA, wild-type E-cadherin juxtamembrane domain or a K83R mutant juxtamembrane domain (K83R-JMD), were subjected to 20% cyclic stretches for 2 or 4 h. Furthermore, MLE-12 cells and mice, which were pretreated with the c-Src inhibitor PP2 or RhoA inhibitor Y27632, underwent 20% cyclic stretches or mechanical stretching, respectively. Moreover, wild-type C57BL/6 mice were transfected with p120 siRNA-liposome complexes before mechanical ventilation. Cell lysates and lung tissues were then analyzed to detect lung injury. RESULTS: cyclic stretches of 20% actived c-Src, which induced degradation of E-cadherin, p120 and occludin. However, loss of p120 increased the degradation and endocytosis of E-cadherin. Immunoprecipitation and Immunofluorescence results showed a decrease in the association between p120 and E-cadherin, while gap formation increased in p120 siRNA and K83R-JMD groups after 20% cyclic stretches. Loss of p120 also reduced the occludin level and decreased the association of occludin and ZO-1 by enhancing RhoA activity. However, the altered levels of occludin and E-cadherin were reversed by PP2 or Y27632 treatments compared with the cyclic stretch group. Consistently, the expression, redistribution and disassociation of junction proteins were all restored in the p120 overexpression group after 20% cyclic stretches. Moreover, the role of p120 in VILI was confirmed by increased wet/dry weigh ratio and enhanced production of cytokines (tumor necrosis factor-α and interleukin-six) in p120-depleted mice under mechanical ventilation. CONCLUSIONS: p120 protected against VILI by regulating both adherens and tight junctions. p120 inhibited E-cadherin endocytosis by increasing the association between p120 and juxtamembrane domain of E-cadherin. Furthermore, p120 reduced the degradation of occludin by inhibiting RhoA activity. These findings illustrated further mechanisms of p120 in the prevention of VILI, especially for patients with ALI or ARDS.

Nefopam for the prevention of perioperative shivering: a meta-analysis of randomized controlled trials.

BACKGROUND: Shivering is a frequent complication following surgery and anaesthesia. A large variety of studies have been reported that nefopam may be efficacious for the prevention and treatment of perioperative shivering. Regrettably, there is still no conclusion of the efficacy and safety of nefopam for the prevention of perioperative shivering. The aim of this analysis is to evaluate the efficacy of nefopam for the prevention of perioperative shivering in patients undergoing different types of anaesthesia compared with placebo group and other active interventions. METHODS: PubMed, EMBASE, Cochrane Central Register of Control Trials were systematically searched for potentially relevant trials. Trial quality and extracted data were evaluated by two authors independently. Dichotomous data on the absence of shivering was extracted and analysed by using relative risk (RR) with 95% confidence interval (CI). Continuous outcome was abstracted and analysed by using weighted mean difference (WMD) with 95% confidence interval (CI). Outcome data was analysed by using random effect model or fixed effect model in accordance with heterogeneity. RESULTS: Compared with placebo, prophylactic administration of nefopam significantly reduced the risk of perioperative shivering not only in the patients under general anaesthesia but also neuraxial anaesthesia (RR 0.08; 95% CI 0.05-0.13). As compared with clonidine, nefopam was more efficacious in the prevention of perioperative shivering (RR 0.34; 95% CI 0.17-0.70). Nefopam has no influence on the extubation time (WMD 0.92; 95% CI -0.15-1.99). CONCLUSION: Our analysis has demonstrated that nefopam is associated with the decrease of risk of perioperative shivering following anaesthesia without influencing the extubation time.

Effect of apoptosis in neural stem cells treated with sevoflurane.

BACKGROUND: At present, sevoflurane inhalation anesthesia used on infants is well-known. But long-time exposure to inhalation anesthetic could cause neurologic disorder, especially nerve degeneration in infant and developing brain. The central nervous system degeneration of infants could affect the memory and cognitive function. γ-Aminobutyric acid (GABA) is a known inhibitory neurotransmitter in central nervous system. Inhalation anesthetic sevoflurane may activate GABAA receptor to inhibit central nervous system, leading to apoptosis of neural degeneration, cognitive dysfunction in the critical period of brain development. METHODS: Neural stem cells were derived from Wistar embryos, cultured in vitro. Third generation of neural stem cells were randomly divided into four groups according to cultured suspension: Sevoflurane group (Group S), GABAA receptor antagonists, Bicuculline group (Group B), Sevoflurane + GABAA receptor antagonists, Bicuculline group (Group S + B), dimethyl sulphoxide (DMSO) group (Group D). Group B and Group D did not receive sevoflurane preconditioning. Group S and Group S + B were pretreated with 1 minimum alveolar concentration (MAC) sevoflurane for 0 h, 3 h, 6 h, and 12 h. Group S + B and Group B were pretreated with bicuculline (10 uM). Group D was treated with DMSO (10 uL/mL). After treatments above, all groups were cultured for 48 h. Then we measured the cells viability by Cell Counting Kit (CCK-8) assay, cytotoxicity by Lactate Dehydrogenase (LDH) assay, apoptosis ratio with Annexin V/propidium iodide (PI) staining by flow cytometry, and the expression of GABAAR, anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax and Caspase-3 by western blotting. RESULTS: After exposing to sevoflurane for 0 h, 3 h, 6 h, and 12 h with 1MAC, we found that cell viability obviously decreased and cytotoxicity increased in time-dependent way. And Annexin V/PI staining indicated increased apoptosis ratio by flow cytometry. The protein level of GABAA receptor, pro-apoptotic protein Bax and apoptosis protein Caspase-3 increased; while anti-apoptotic protein Bcl-2 decreased. And bicuculline could reverse all detrimental results caused by sevoflurane. CONCLUSION: Sevoflurane can inhibit the central nervous system by activating GABAA, resulting in apoptosis of neural stem cells, thus leading to the NSCs degeneration.

Activation of c-Src tyrosine kinase mediated the degradation of occludin in ventilator-induced lung injury.

BACKGROUND: Ventilator-induced lung injury (VILI) is characterized by increased alveolar permeability, pulmonary edema. The tyrosine kinase, c-Src, is involved in VILI but its role has not been fully elucidated. This study examined the relationship between c-Src activation and occludin levels in VILI both in vitro and in vivo. METHODS: For the in vivo study, Wistar rats were randomly divided into five groups: control (group C); normal tidal volume (group M); normal tidal volume + c-Src inhibitor (PP2) (group M + P); high tidal volume (group H); and high tidal volume + c-Src inhibitor (PP2) (group H + P). Rats in all groups but group C underwent mechanical ventilation for 4 h. For the in vitro study, MLE-12 cells pretreated with PP2 and siRNA underwent cyclic stretching at 8% or 20% for 0, 1, 2 and 4 h. The expressions of occludin, c-Src, and p-c-Src were analyzed by western blotting, hematoxylin and eosin (HE) staining, and immunofluorescence. RESULTS: For the in vivo study, rats in group H showed decreased occludin expression and activated c-Src compared with group C. HE staining and lung injury score showed more severe lung injury and alveolar edema in group H compared with group M and group C. Group H + P had less pulmonary edema induced by the high tidal volume ventilation. For the in vitro study, occludin expression decreased and c-Src activation increased as indicated by the phosphorylation of c-Src over time. Consistently, PP2 could restore occludin levels. CONCLUSIONS: Mechanical ventilation can activate c-Src by phosphorylation and increase the degradation of occludin. c-Src inhibitor can ameliorate barrier function and lung injury by up-regulating occludin.

Upregulation of the tight junction protein occludin: effects on ventilation-induced lung injury and mechanisms of action.

BACKGROUND: Occludin, a tight junction protein, plays an important role in maintaining the integrity of the lung epithelial barrier; however, its role in ventilation-induced lung injury has not been explored. Here, we measured the expression of occludin with different tidal volumes. Our study indicated that the level of occludin was significantly decreased and alveolar permeability was increased owing to acute lung injury. METHODS: Thirty healthy Wistar rats (15 female, 15 male) weighing 250-300 g, were randomly divided into 5 groups (n = 6 in each group): a control group (group C), a low tidal volume group (group L), a low tidal volume + protein kinase C(PKC) inhibitor group (group L + P), a high tidal volume group (group H) and a high tidal volume + PKC inhibitor group (group H + P). Tracheas of rats in the control group underwent incision without any special treatment. The other four groups were mechanically ventilated for 4 h. The rats in groups L + P and H + P were treated with a PKC inhibitor (bisindolylmaleimide I, 0.12 mg/kg) by intramuscular injection 1 h before anesthesia. Rats were sacrificed after mechanical ventilation. Specimens of lung tissues were harvested. Lung pathological changes were observed using an optical microscope, and lung wet/dry weight ratio was measured. The occludin protein level was assayed by immunohistochemistry and Western blotting. RESULTS: HE staining and immunohistochemistry results showed that occludin was mainly located in alveolar epithelial cells and some alveolar endothelial cells. The lung injury and alveolar edema were more serious in high tidal volume groups than in low tidal volume groups. Occludin expression was reduced and PKC activation was increased in rats in the high tidal volume groups compared with rats in the low tidal volume groups. Rats that were pretreated with the PKC inhibitor had less pulmonary edema induced by the high tidal volume ventilation. CONCLUSION: Mechanical ventilation can activate the PKC signaling pathway and tight junction proteins participate in this pathway. Up-regulation of occludin can reduce ventilation-induced lung injury.

Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy.

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 µg, followed by a continuous infusion of 2.25 µg/h. The patient self-administration of sufentanil was 0.75 µg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma ß-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P<0.05). The total dose of sufentanil was 115±6.0 µg in EAS group, significantly lower than that in control (134.3±5.9 µg) and sham (133.5±7.0 µg) groups. Similarly, the rescue dose of dezocine was the least in EAS group (P<0.05) among the three groups. Plasma ß-EP levels in EAS group at T3 (176.90±45.73) and T4 (162.96±35.00 pg/mL) were significantly higher than those in control (132.33±36.75 and 128.79±41.24 pg/mL) and sham (136.56±45.80 and 129.85±36.14 pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3 (41±5 and 40±5 pg/mL respectively) were significantly lower than those in control (64±5 and 62±7 pg/mL) and sham (66±6 and 62±6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66±40.85) and T3 (154.66±52.49 ng/mL) were significantly lower than those in control (168.33±56.94 and 225.28±82.03) and sham (164.54±47.53 and 217.74±76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and ß-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points (P>0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous ß-EP and inhibition of inflammatory mediators (5-HT and PGE2).

The novel HLA-A*11:01:124 allele was identified in a Chinese individual.

The HLA-A*11:01:124 allele differs from HLA-A*11:01:01 by one nucleotide substitution, (C > T) position 459 in exon 3.

Anesthesia strategies for elderly patients with craniocerebral injury due to foreign-body penetration in the plateau region: a case report.

Background: The administration of anesthesia for elderly individuals who are critically ill, suffering from severe craniocerebral injuries, and living in plateau regions presents a rare, intricate, and high-risk challenge. This case study outlines the specific anesthesia management protocols necessary for plateau-dwelling patients with significant craniocerebral damage undergoing prolonged invasive procedures. Case report: A 76-year-old male patient had a 26-year history of foreign-body penetration of the skull and had experienced local purulent discharge and pain for the previous 20 days. The diagnoses included right hypoplasia, a foreign body in the skull with an infection, hypokalemia, hypoproteinemia, pulmonary fibrous foci, and bilateral pleural effusion. For almost 6 months, the patient suffered from recurring headaches, blurred vision, and sluggish bodily movement. The patient had a poor diet, poor sleep quality, normal urination, and no noticeable weight loss since the onset of the illness. The right anterior ear had a 2 cm skin abscess with yellow pus and a black metal foreign body tip. The left eyelid was red and swollen, and the left conjunctiva was hyperemic; the right eyelid showed no abnormalities, and both pupils were wide and round, with light and adjustment reflexes and no cyanosis on the lips. Skull development was normal. No dry or moist rales were audible in either lung. The heart rhythm was regular, and the heart rate was 50 bpm. Chest CT revealed left lung calcification foci, bilateral pleural effusion, and fiber foci in the lower lobes of both lungs. Conclusion: Furthermore, the patient in question was of advanced age and had a complex medical history, including prolonged exposure to high altitudes and previous instances of severe craniocerebral trauma, among other uncommon pathophysiological characteristics. In particular, the patient also underwent surgical interventions at both high and low altitudes, adding to the complexity of their case. To ensure patient safety, close multidisciplinary collaboration, the development of a precise surgical plan, and the implementation of a suitable perioperative anesthetic management strategy are imperative.