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Gardenia jasminoides Ellis is rich in geniposide, which can be transformed into the anti-oxidant and anti-inflammatory agent genipin. Genipin exhibits greater efficacy than geniposide, but it is unstable and difficult to preserve. In this study, a mouse model for sepsis was established by cecal ligation and puncture, and then we explored the effects and mechanism of Lactobacillus casei strain Shirota (LcS) on the enhancement of the ability of geniposide to reduce sepsis and decrease inflammatory and oxidative levels in mice by the regulation of sirtuin type 1 (SIRT1). The mice were evaluated and analyzed by the open field test, Morris water maze test, flow cytometry, kit assay, qPCR, and western blot. The LcS + geniposide increased the survival rate in mice with sepsis, and increased the total travel distance, number of times the mice stood up, amount of time the mice spent grooming their fur, duration in the target quadrant, and crossing area number. The testing of mouse nerve cells showed that LcS + geniposide reduced the rate of nerve cell apoptosis caused by sepsis. LcS + geniposide also decreased the amount of inflammatory-related indicators of TNF-α, IL-6, and IL-1ß, and the oxidation-related levels of malondialdehyde (MDA) in the hippocampi of septic mice, and it increased the oxidase activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, LcS + geniposide increased the SOD1, SOD2, and CAT mRNA expression in the hippocampi of mice with sepsis and decreased the expression of TNF-α, IL-1ß, NF-κB, and p53 mRNA. LcS+geniposide also increased the SIRT1 protein expression and decreased the Ac-FOXO1, Ac-NF-κB, and Ac-p53 protein expression in the hippocampi of mice with sepsis. We also observed that LcS + geniposide decreased the inflammatory and oxidative damage in the mice with sepsis. The effect of LcS + geniposide was similar to that of the drug dexamethasone and stronger than the effect of geniposide utilized alone. LcS also enhanced the ability of geniposide to activate SIRT1 and decrease the inflammation and oxidative stress in the septic mice, and it achieved an effect same with that obtained by the use of the drug dexamethasone.

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Osteoarthritis (OA) is one of the most common degenerative joint diseases in aging people. The activation of chondrocytes and their dysregulation are closely related to the pathogenesis of OA. GPR55 is an unique orphan G-receptor which binds to cannabinoids. In this study, we explored the role of GPR55 in advanced glycation end productions (AGEs)- induced chondrocytes activation in cultured cells. We showed that AGEs dose dependently induced GPR55 expression in ATDC5 chondrocytes. The blockage of GPR55 by its newly discovered antagonist-CID16020046 mitigated AGEs- induced increase in cellular ROS and decrease in antioxidant NRF2. Moreover, CID16020046 showed a dose-response suppressive effect on AGEs- induced expression of the major inflammatory mediators, including COX-2 and iNOS, and the production of NO and PGE2. CID16020046 also dose responsively inhibited AGEs- induced key effectors of cartilage degradation such as MMP-3 and MMP-13. In consequence, CID16020046 showed robust inhibition on AGEs- induced type II collagen degradation. Mechanistically, our data demonstrated that CID16020046 mediated GPR55 blockage ameliorated AGEs- induced NF-κB activation as revealed by its inhibition on IκBα, nuclear p65 translocation and NF-κB promoter activity. Collectively, our study demonstrates that GPR55 signaling mediates AGEs- induced chondrocyte activation, and the targeted blockage of GPR55 pathway could be therapeutic choice in the treatment of osteoarthritis.

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To investigate the antiepileptic and neuroprotective effects of dexmedetomidine (Dex) in pilocarpine- (Pilo-) induced status epilepticus (SE) juvenile rats, rats were randomly assigned to the following six groups (n = 20): normal, normal+Dex, SE, SE+Cap, SE+Dex, and SE+Dex+Cap. The rats were treated with either diazepam (i.p., an antiepileptic drug) or Dex after the onset of SE. The Morris water maze was used to assess rat cognitive behavior. Flow cytometry was used to detect the concentrations of Ca2+, mitochondrial membrane potential, and reactive oxygen species. Transmission electron microscopy was performed to evaluate specimens of brain tissue. The levels of caspase 3 and TRPV1 were examined by western blot and immunohistochemistry (IHC). Treatment with Dex significantly decreased the escape latency of the SE rats (P < 0.05). Capsaicin, a TRPV1 agonist, delivery aggravated the performance of SE rats. Pathological changes in SE rat were attenuated by Dex and deteriorated by capsaicin. Swollen mitochondria and abnormal endoplasmic reticulum were found in SE rats and were then aggravated by capsaicin and reversed by Dex. Moreover, our data showed that Dex significantly restrained calcium overload, ROS production, and mitochondrial membrane potential loss, all of which were induced by Pilo and capsaicin (P < 0.05). Dex decreased the apoptotic rate in the Model SE group (P < 0.05) and TRPV1 and caspase 3 expression in the Dex treatment group (P < 0.05). Interestingly, all these effects of Dex were partially counteracted by the TRPV1 agonist, capsaicin (P < 0.05). Our study showed that Dex exerted a neuroprotective effect in Pilo-induced SE rats by inhibiting TRPV1 expression and provided information for therapy to SE patients.

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OBJECTIVES: The purpose of this study was to examine modifiable factors and their impact on perioperative blood transfusion for pediatric patients with major abdominal procedures. METHODS: This is a retrospective review of 1,506 patients who underwent major abdominal surgical procedures in a tertiary medical center from January 2008 to June 2018. Clinical data about blood administration including triggers and targets for intra- or postoperative transfusion were collected and analyzed. The inappropriate transfusion (transfusion > 8.0 g/dL of hemoglobin [Hb] trigger) and overtrans-fusion criteria (target transfusion > 10.0 g/dL or > 2 g/dL of target minus trigger level) were applied to examine the intraoperative factors with the intraoperative transfusion practice. Perioperative morbidity was further assessed based on the inappropriate transfusion and overtransfusion status. RESULTS: Intraoperative transfusion was used in 468 (31.1%) of the 1,506 patients included in the study. Among them, 212 (45.3%) intraoperative transfusion episodes were classified as inappropriate, and 135 cases (28.8%) were confirmed as overtransfusion. On univariate analysis, inappropriate transfusions were observed more commonly among patients with younger age (p < 0.001) and who underwent hepatic resection (p < 0.001) or intestinal resection (p < 0.001). Overtransfusion was also associated with elevated trigger of 8.0 g/dL Hb (p = 0.006) and younger age (p = 0.003). No perioperative complications were associated with inappropriate transfusions and overtransfusion under multivariate analysis. CONCLUSIONS: Overtransfusion was common in hepatic resection and younger age, but to definitely prove this hypothesis, a prospective randomized trial needs to be performed.

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INTRODUCTION: Intraoperative fluid administration is important for postoperative recovery and might be associated with postoperative complications. MATERIALS AND METHODS: This retrospective review included 471 patients who underwent Roux-en-Y hepaticojejunostomy. Patients were separated into two groups based on whether they received low (<15.27 mL/kg/h) or high (>15.27 mL/kg/h) volumes of corrected crystalloid fluids. Propensity score matching was performed to adjust for any potential selection bios for the two groups. In 192 matched patients, clinical outcomes, including postoperative complications and length of hospital stay, were compared. RESULTS: Higher use of diuresis (p = 0.027) was found in the high fluid group. Receiving low volumes of crystalloids was associated with postoperative gastrointestinal functional recovery, reflected by the first defecation (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.31-1.07; p = 0.047) and first bowel movement (OR, 0.56; 95% CI, 0.38-0.98; p = 0.013). However, the occurrence of renal complications did not show significant differences between the groups. A lower postoperative complication rate (OR, 0.54; 95% CI, 0.42-0.94; p = 0.016) was noted in patients with low crystalloids compared with high crystalloids. The total length of hospital stay was longer in patients with high crystalloid fluid (9.21 ± 3.24 days) than patients with low volumes (7.83 ± 2.58 days; p = 0.012). CONCLUSION: Low crystalloid fluid administration was associated with favorable postoperative outcomes.

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Cardiopulmonary bypass (CPB) is the most general technique applied in congenital heart disease (CHD). However, standard CPB poses a specific pathologic condition for patients during surgery: exposure to reoxygenation. When surgery is performed on cyanotic infants, standard CPB is usually initiated at a high concentration of oxygen without consideration of cytotoxic effects. Controlled reoxygenation is defined as using normoxic CPB with a pump primed to the PO2 (oxygen tension in the blood), which is matched to the patient's preoperative saturation. The aim of this study was to determine whether controlled reoxygenation could avoid standard reoxygenation injury and also to clarify the molecular signaling pathways during hypoxia. We successfully reproduced the abnormal brain observed in mice with chronic hypoxia during early postnatal development - equivalent to the third trimester in human. Mice were treated with standard reoxygenation and controlled reoxygenation after hypoxia for 24 h. We then assessed the brain tissue of these mice. In standard reoxygenation-treated hypoxia mice, the caspase-3-dependent neuronal apoptosis was enhanced by increasing concentration of oxygen. Interestingly, controlled reoxygenation inhibited neuron and glial cell apoptosis through suppressing cleavage of caspase-3 and PARP. We also found that controlled reoxygenation suppressed LCN2 expression and inflammatory cytokine (including TNF-α, IL-6, and CXCL10) production, in which the JAK2/STAT3 signaling pathway might participate. In conclusion, our findings propose the novel therapeutic potential of controlled reoxygenation on CPB during CHD.

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A diagnostic accuracy study was adopted to evaluate the ability of Cerebral edema monitor by comparing the index test results with those of the reference standard. The serum levels of astrocyte S100 protein and neuron-specific enolase (NSE) were determined. Changes in the cerebral electrical impedance coefficient (CEIC) was detected with the BORN-BE monitor. The left- and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB group significantly increased from the beginning to the end of the operation (P < .05). Furthermore, left and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB-B group were significantly higher than those of the CPB-A group (P < .05). Detection rates of cerebral edema in the CPB-B group at the 24 h post-operative time point were significantly higher than those in the CPB-A group (P < .05). The degree of brain damage is positively correlated with the CPB and aortic cross-clamping. CEIC is a sensitive index reflecting brain damage during CPB in infants.

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BACKGROUND Status epilepticus (SE) is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment and early neuroprotection. Dexmedetomidine (DEX) is mainly used for its sedative, analgesic, anxiolytic, and neuroprotective effects with light respiratory depression. The purpose of this study was to comprehensively analyze the metabolic events associated with anticonvulsion and neuroprotection of DEX on pilocarpine-induced status epilepticus rats by LC-MS/MS-based on metabolomics methods combined with histopathology. MATERIAL AND METHODS In this research, rats were divided into 3 groups: a normal group, an SE group, and an SE+DEX group. Hippocampus of rats from each group were collected for further LC-MS/MS-based metabolomic analysis. We collected brains for HE staining and Nissl staining. Multivariate analysis and KEGG enrichment analysis were performed. RESULTS Results of metabolic profiles of the hippocampus tissues of rats proved that dexmedetomidine relieved rats suffering from the status epilepticus by restoring the damaged neuromodulatory metabolism and neurotransmitters, reducing the disturbance in energy, improving oxidative stress, and alleviating nucleic acid metabolism and amino acid in pilocarpine-induced status epilepticus rats. CONCLUSIONS This integral metabolomics research provides an extremely effective method to access the therapeutic effects of DEX. This research will further development of new treats for status epilepticus and provide new insights into the anticonvulsive and neuroprotective effects of DEX on status epilepticus.

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BACKGROUND This meta-analysis was conducted to evaluate the analgesics effect and safety of dexmedetomidine (DEX) combined with bupivacaine (BU) on caudal epidural block. MATERIAL AND METHODS Published studies were identified using the PubMed, EMBASE, Web of Science, and the Cochrane Library from inception until October 2017. Relative risk (RR), the standardized mean difference (SMD), and the corresponding 95% confidence interval (CI) were calculated using the STATA 12.0. RESULTS Ten randomized controlled trials (RCTs) were selected for this meta-analysis, involving a total of 691 patients. There was a longer duration of postoperative analgesia in children receiving DEX (SMD=3.19, 95% CI: 2.16-4.22, P<0.001). Furthermore, there was a lower number of patients requiring rescue analgesics in the (BU) + (DEX) group (6 hours: RR=0.09, 95% CI: 0.05-0.17, P<0.001; 12 hours: RR=0.50, 95% CI: 0.32-0.79, P=0.003; 24 hours: RR=0.66, 95% CI: 0.51-0.85, P=0.002). Finally, the occurrence of adverse events, between BU and DEX + BU group, was not statistically significant (RR=0.96, 95% CI: 0.58-1.58, P>0.05). CONCLUSIONS DEX seems to be a promising adjuvant to BU increase duration of caudal analgesia without an increase in side effects in children. However, the result may be influenced by clinical heterogeneity. More large-scale, multicenter, approaching, double-blinded RCTs are required to confirm our results.

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BACKGROUND AND AIM: Trigger thumb is a common hand disability in children and is primarily treated with open surgery. A conscious median nerve block can usually meet the requirements for trigger thumb-releasing surgery in adults; however, its effectiveness in children requires further clarification. The present study aims to demonstrate whether ultrasound-guided lower forearm median nerve blockade is a viable option for children undergoing open surgery for trigger thumb. METHODS: A prospective randomized study was designed to compare median nerve blocks guided by ultrasonography with those guided by anatomic landmarks. Following induction of general anesthesia, the children received a median nerve block performed either by ultrasound-guided block of the lower forearm (group U) or landmark-based blocking at the proximal wrist crease level (group T) with a 0.2% ropivacaine injection. The success rates were compared between groups as the primary endpoint; additional sufentanil and propofol administration, anesthesia recovery time, and other secondary endpoints were also compared. RESULTS: A total of 100 children (age 1-3 years) with ASA status I who were scheduled for open surgery for trigger thumb were included in this study (n = 50 per group). Thirty-seven children in group T and 50 children in group U underwent successful blocks. The rate of unsuccessful blockade was significantly lower in group U than group T (0% and 26%, respectively), and rate of additional sufentanil and propofol administration was also lower in group U than in group T. CONCLUSION: Ultrasound-guided lower forearm median nerve block can provide more effective analgesia, a higher success rate, and lower general and local anesthetic dosages than the anatomic landmark-based blocking method in children undergoing open surgery for trigger thumb.

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