Association between ABO blood groups and postoperative pain in children after adenotonsillectomy: a prospective cohort study.

BACKGROUND: It has been known that ABO blood groups are linked to the phenotypes of certain diseases; however, and the relationship between ABO blood groups and postoperative pain have not been extensively studied, especially in children. This study was to investigate whether there would be an association between the four major ABO blood groups and postoperative pain, as indicated by the differences in pain scores and rescue fentanyl requirements among blood groups in children after adenotonsillectomy. METHODS: A total of 124 children, aged 3-7 years, ASA I or II, and undergoing elective adenotonsillectomy were enrolled in the study. Postoperative pain was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and the rescue fentanyl requirement in post anesthesia care unit (PACU) was analyzed. Pediatric Anesthesia Emergence Delirium (PAED) score and the duration of PACU were recorded. The postoperative nausea and vomiting (PONV) within 24 h were documented. RESULTS: Among four blood type groups, no significant differences were observed regarding surgery time, and the gaps of fentanyl given at the anesthesia induction and the first rescue fentanyl injection in PACU. However, patients from AB and B blood groups had significantly higher pain score at initial CHEOPS assessment and consequently, higher consumption of rescue fentanyl during PACU stay. A significantly higher percentage of patients had received > 1 µg/kg rescue fentanyl. Higher PAED scores were also observed in AB and B blood groups. CONCLUSION: Paediatric patients with AB and B blood type had higher postoperative CHEOPS pain score and required significantly more fentanyl for pain control than those with A and O blood type after T&A. The initial scores of PAED in patients with AB and B blood type were also higher than that in patients with A and O blood type.

FERM domain containing kindlin 1 knockdown attenuates inflammation induced by intracerebral hemorrhage in rats via NLR family pyrin domain containing 3/nuclear factor kappa B pathway.

Intracerebral hemorrhage (ICH) is an incurable neurological disease. Microglia activation and its related inflammation contribute to ICH-associated brain damage. FERM domain containing kindlin 1 (FERMT1) is an integrin-binding protein that participates in microglia-associated inflammation, but its role in ICH is unclear. An ICH model was constructed by injecting 50 µl of autologous blood into the bregma of rats. FERMT1 siRNA was injected into the right ventricle of the rat for knockdown of FERMT1. A significant striatal hematoma was observed in ICH rats. FERMT1 knockdown reduced the water content of brain tissue, alleviated brain hematoma and improved behavioral function in ICH rats. FERMT1 knockdown reduced microglia activity, inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome activity and decreased the expression of inflammatory factors including IL-1ß and IL-18 in the peri-hematoma tissues. BV2 microglial cells were transfected with FERMT1 siRNA and incubated with 60 µM Hemin for 24 h. Activation of NLRP3 inflammasome induced by hemin were reduced in microglia when FERMT1 was knocked down, leading to decreased production of inflammatory factors IL-1ß and IL-18. In addition, knockdown of FERMT1 prevented the activation of nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. Our findings suggested that down-regulation of FERMT1 attenuated microglial inflammation and brain damage induced by ICH via NLRP3/NF-κB pathway. FERMT1 is a key regulator of inflammatory damage in rats after ICH.

[Effect of expression of c-jun N-terminal kinase on neuron autophagy following diffuse brain injury in rats].

OBJECTIVE: To study the effect and potential mechanism of expression of c-jun N-terminal kinase (JNK) signal pathway on neuron autophagy after diffuse brain injury (DBI). METHODS: Male Sprague Dawley rats (n = 216) were randomly divided into four groups: DBI group (n = 54), SP600125 intervene group (n = 54), DMSO group (n = 54) and sham operation group (n = 54). DBI rat model was established according to the description of Marmarou DBI. At different time points (1, 6, 12, 24, 48 and 72 h) after operation, the histopathologic changes of neurons in cortex were observed by HE staining method; The expression of p-JNK, p-P53, DRAM and Beclin-1 were detected by Western blot and immunohistochemistry. RESULTS: The results showed that under light microscope degenerated and necrotic neurons were observed to be scattered in cortex at 6 h after operation in DBI group, but these changes were low in SP600125 intervene group. Compared with SP600125 intervene group, the expression of p-JNK in DBI group were enhanced obviously at 6, 12 and 24 h (F = 17.902, P < 0.05); the expression of p-P53 in DBI group were enhanced obviously at 12, 24, 48 and 72 h (F = 7.107, P < 0.05); the expression of DRAM in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 15.455, P < 0.05); the expression of Beclin-1 in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 11.517, P < 0.05). Compared with DBI group, the expression of p-JNK, p-P53, DRAM and Beclin-1 in DMSO group were similar at 1, 6, 12, 24, 48 and 72 h (F = 1.509, P > 0.05). CONCLUSIONS: The present results indicate that SP600125 can dramatically improve trauma brain injury from autophagy after DBI and the molecular mechanism is related to the modulation of JNK signal pathway following DBI, while it measures the neuron autophagy by means of intervening JNK signal pathway.

ER stress mediated­autophagy contributes to neurological dysfunction in traumatic brain injury via the ATF6 UPR signaling pathway.

A major public health problem, traumatic brain injury (TBI) can cause severe neurological impairment. Although autophagy is closely associated with the pathogenesis of TBI, the role of autophagy in neurological deficits is unclear. The purpose of the present study was to investigate the molecular mechanisms of endoplasmic reticulum (ER) stress­induced autophagy and its detrimental effects on neurological outcomes following TBI. A rat model of TBI was established by controlled cortical impact. ER stress activation, autophagy induction and autophagic flux dysfunction were examined in the damaged hippocampus post­TBI. Pharmacological inhibition of ER stress significantly blocked post­traumatic autophagy activation, as evidenced by decreased conversion of microtubule­associated protein 1 light chain 3 (LC3)­I to LC3­II and Beclin­1 expression levels in the hippocampus region. Short hairpin RNA­mediated activating transcription factor 6 knockdown significantly prevented ER stress­mediated autophagy stimulation via targeting essential autophagic genes, including autophagy related (ATG)3, ATG9 and ATG12. Furthermore, neurological scores, foot fault test and Morris water maze were used to evaluate the neurological functions of TBI rats. The results revealed that the blockage of ER stress or autophagy attenuated TBI­induced traumatic damage and functional outcomes. In conclusion, these findings provided new insights into the molecular mechanisms of ER stress­induced autophagy and demonstrated its potential role in neurological deficiency following TBI.

Effect of c-Jun NH2-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats.

BACKGROUND: Activation of c-Jun NH(2)-terminal kinase (JNK) has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury (TBI). However, the underlying molecular pathway remains unclear. Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI. METHODS: A total of 186 male Sprague-Dawley (SD) rats (300 - 350 g) were used in this study. By randomized block method rats were randomly divided into four groups: sham-operated (n = 46), TBI (n = 60), TBI + dimethyl sulfoxide (DMSO) (n = 40), and TBI + SP600125 (n = 40). JNK was treated with SP600125, a specific JNK inhibitor. JNK, p-P53, Beclin-1, damage-regulated autophagy modulator (DRAM) and p-bcl-2 were evaluated by Western blotting analysis. The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry, and the expression of Beclin-1-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation. Multiple-group comparisons were conducted using analysis of variance (ANOVA). P values of less than 0.05 were considered statistically significant. RESULTS: It was observed that the expression of JNK, p-P53, Beclin-1, DRAM and p-bcl-2 was increasing after TBI, and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons. But these were significantly inhibited in SP600125 group compared with sham group and TBI + SP600125 group (P < 0.05). The expression of Beclin-1-Bcl-2/Bcl-xL complexes was reduced after TBI. CONCLUSION: JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.