Continuous intravenous infusion of remifentanil improves the experience of parturient undergoing repeated cesarean section under epidural anesthesia, a prospective, randomized study.

BACKGROUND: Unsatisfactory analgesia would occur frequently during repeated cesarean section under epidural anesthesia. The aim of this study is to observe the effects of intravenous remifentanil on maternal comfort, maternal and neonatal safety during repeated cesarean section under epidural anesthesia. METHODS: A total of 80 parturients undergoing repeated cesarean section were involved in the study. The patients were randomly divided into the intravenous remifentanil- assisted epidural group (group R) and epidural group (group E), respectively (n = 40). In group R, the remifentanil was continuously intravenously infused as an adjuvant to epidural anesthesia. In group E, 0.75% ropivacaine epidural or intravenous ketamine was administered as needed. Parturient baseline characteristics, vital signs, VAS scores, and comfort scores during surgery were recorded. Adverse effects were also recorded. RESULTS: A total of 80 patients were enrolled in the current study and the final analyses included 39 patients in group R and 38 patients in group E. No differences in patients' baseline characteristics were found between the two groups (p > 0.05). Compared with group E, the comfort score was significantly higher in group R (9.1 ± 1.0 vs. 7.5 ± 1.3, p <  0.001), whereas the maximum VAS score was significantly lower in group R (1.8 ± 1.2 vs. 4.1 ± 1.0, p <  0.001). Maternal and neonatal adverse effects did not differ between the two groups during surgery (p > 0.05). CONCLUSIONS: Continuous intravenous infusion of low-dose remifentanil can significantly improve the experience of parturients undergoing repeated cesarean section under epidural anesthesia, without noticeable maternal or neonatal adverse effects. TRIAL REGISTRATION: This study was pre-registered at http://www.chictr.org.cn/index.aspx (ChiCTR1800018423) on 17/09/2018.

A Novel Tumor-Suppressor, CDH18, Inhibits Glioma Cell Invasiveness Via UQCRC2 and Correlates with the Prognosis of Glioma Patients.

BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.

Mild volume acute normovolemic hemodilution is associated with lower intraoperative transfusion and postoperative pulmonary infection in patients undergoing cardiac surgery -- a retrospective, propensity matching study.

BACKGROUND: Perioperative allogenic transfusion is required in almost 50% of patients undergoing cardiac surgery and is associated with higher risk of mortality and morbidity (Xue et al., Lancet 387:1905, 2016; Ferraris et al., Ann Thorac Surg 91:944-82, 2011). Acute normovolemic hemodilution (ANH) is recommended as a potential strategy during cardiac surgery, but the blood conservation effect and the degree of ANH was still controversial. There is also an increasing concern about the improved outcomes associated with ANH. Therefore, a better understanding of the effect of mild volume ANH during cardiac surgery is urgently needed. METHODS: This retrospective study included 2058 patients who underwent cardiac surgery between 2010 and 2015. The study population was split into two groups (with and without mild volume ANH). Propensity score adjustment analysis was applied. We reported the association between the use of mild volume ANH and perioperative outcomes. RESULTS: A total of 1289 patients were identified. ANH was performed in 358 patients, and the remaining 931 patients did not receive any ANH. Five hundred of the total patients (38.8%) received perioperative RBC transfusions, 10% (129/1289) of patients received platelet, and 56.4% (727/1289) of patients received fresh frozen plasma transfusions. Mild volume ANH administration was significantly associated with decreased intraoperative RBC transfuse rate (8.5% vs. 14.4%; p = 0.013), number of RBC units (p = 0.019), and decreased postoperative pulmonary infection (6.8 vs. 11.3%; p = 0.036) during cardiac surgery. However, there was no significant difference regarding intraoperative fresh frozen plasma (FFP) and platelet concentrate transfusions, as well as postoperative and total perioperative allogeneic transfusions. Furthermore, there was no significant difference regarding postoperative outcomes including mortality, prolonged wound healing, stroke, atrial fibrillation, reoperation for postoperative bleeding and acute kidney injury. There was also no difference in postoperative ventilation time, length of ICU and hospital stay. CONCLUSION: Based on the 5-year experience of mild volume ANH in cardiac surgeries with CPB in our large retrospective cohort, mild volume ANH was associated with decreased intraoperative RBC transfusion and postoperative pulmonary infection in Chinese patients undergoing cardiac surgery. However, there was no significant difference regarding postoperative and total perioperative allogeneic transfusions.

Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway.

Myocardial ischemia/reperfusion (I/R) injury in diabetes is associated with oxidative stress, endothelial nitric oxide synthase (eNOS) dysfunction, and mitochondrial collapse, whereas luteolin is known to protect the cardiovascular system against diabetes and I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in diabetic rats by affecting eNOS and the mitochondrial permeability transition pore (mPTP). After diabetic rats were produced by streptozotocin treatment (65 mg/kg) for 3 weeks, luteolin (100 mg·kg·d) or L-NAME (25 mg·kg·d) was administered intragastrically for 2 weeks. Hearts were then isolated and subjected to 30 minutes of global ischemia followed by 120 minutes of reperfusion. Pretreatment with luteolin significantly improved left ventricular function and coronary flow throughout reperfusion, increased cardiac tissue viability and manganese superoxide dismutase (MnSOD) activity, and reduced coronary lactate dehydrogenase release, and the myocardial malonaldehyde level in diabetic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by L-NAME. Luteolin also significantly upregulated eNOS expression in diabetic rat hearts after I/R. Ca-induced mPTP opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated diabetic rats, and this effect was attenuated by L-NAME. These findings indicate that luteolin protects the diabetic heart against I/R injury by upregulating the myocardial eNOS pathway, and downstream effects include the enhancement of MnSOD and inhibition of mPTP.

CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.

Peripheral nerve injury induces the cleavage of CX3CL1 from the membrane of neurons, where the soluble CX3CL1 subsequently plays an important role in the transmission of nociceptive signals between neurons and microglia. Here we investigated whether CX3CL1 regulates microglia activation through the phosphorylation of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord of rats with spinal nerve ligation (SNL). ERK5 and microglia were activated in the spinal cord after SNL. The knockdown of ERK5 by intrathecal injection of antisense oligonucleotides suppressed the hyperalgesia and nuclear impact of nuclear factor-κB induced by SNL. The blockage of CX3CR1, the receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL. In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. Our study suggests that CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.

[Sevoflurane preconditioning produces delayed cardioprotection effect through up-regulation of inducible nitric oxide synthase in rats].

OBJECTIVE: To investigate whether inhaled sevoflurane is capable of producing delayed cardioprotection effect in rats and its underlying mechanisms. METHODS: Male Sprague-Dawley rats inhaled 1.0 minimum alveolar concentration (MAC) sevoflurane, 1.5 MAC sevoflurane,or O(2) for 1 h. After 24 h and 48 h the left coronary artery of rats was occluded for 30 min,followed by 120 min of reperfusion. Hemodynamics was continuously recorded and myocardial infarct size was determined by Evans blue and triphenyltetrazolium chloride staining. The expression of nitric oxide synthase (NOS) was assessed by immunoblotting. RESULTS: 1.0 MAC sevoflurane and 1.5 MAC sevoflurane improved cardiac pump function after reperfusion and reduced myocardial infarct size with the increased iNOS expression (P<0.05). However,the expression of eNOS and p-eNOS was not affected (P>0.05). A selective iNOS inhibitor 1400 W abolished the cardioprotection effect induced by inhalation of 1.0 MAC sevoflurane for 24 h. CONCLUSION: Sevoflurane produces delayed cardioprotection through the up-regulation of iNOS expression.

YTHDF2 promotes temozolomide resistance in glioblastoma by activation of the Akt and NF-κB signalling pathways via inhibiting EPHB3 and TNFAIP3.

Objectives: Temozolomide (TMZ) resistance is a key factor that restricts the therapeutic effect of glioblastoma (GBM). YTH-domain family member 2 (YTHDF2) is highly expressed in GBM tissues, while the mechanism of YTHDF2 in TMZ resistance in GBM remains not fully elucidated. Methods: The YTHDF2 expression in TMZ-resistant tissues and cells was detected. Kaplan-Meier analysis was employed to evaluate the prognostic value of YTHDF2 in GBM. Effect of YTHDF2 in TMZ resistance in GBM was explored via corresponding experiments. RNA sequence, FISH in conjugation with fluorescent immunostaining, RNA immunoprecipitation, dual-luciferase reporter gene and immunofluorescence were applied to investigate the mechanism of YTHDF2 that boosted TMZ resistance in GBM. Results: YTHDF2 was up-regulated in TMZ-resistant tissues and cells, and patients with high expression of YTHDF2 showed lower survival rate than the patients with low expression of YTHDF2. The elevated YTHDF2 expression boosted TMZ resistance in GBM cells, and the decreased YTHDF2 expression enhanced TMZ sensitivity in TMZ-resistant GBM cells. Mechanically, YTHDF2 bound to the N6-methyladenosine (m6A) sites in the 3'UTR of EPHB3 and TNFAIP3 to decrease the mRNA stability. YTHDF2 activated the PI3K/Akt and NF-κB signals through inhibiting expression of EPHB3 and TNFAIP3, and the inhibition of the two pathways attenuated YTHDF2-mediated TMZ resistance. Conclusion: YTHDF2 enhanced TMZ resistance in GBM by activation of the PI3K/Akt and NF-κB signalling pathways via inhibition of EPHB3 and TNFAIP3.

[Sevoflurane postconditioning attenuates myocardial apoptosis in isolated rat hearts via a modulation of Bcl-2 family proteins].

OBJECTIVE: To explore the effects of sevoflurane postconditioning on ischemic/reperfused myocardial apoptosis. METHODS: Isolated perfused rat hearts were randomly assigned into 3 groups: sham-operation (sham), ischemia/reperfusion (I/R) and sevoflurane postconditioning (SPC). Except for the sham group, the hearts were subjected to 40 min global myocardial ischemia and 120 min reperfusion. Left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximum increase rate of LVDP (+dp/dt), maximum decrease rate of LVDP (-dp/dt), heart rate (HR) and coronary flow (CF) were measured at baseline, R (reperfusion) 30 min, R60 min, R90 min and R120 min. Creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at 5 min and 10 min post-reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion. The expressions of Bcl-2 and Bax were determined by Western blot. RESULTS: The values of LVSP, LVDP, ± dp/dt and CF were higher while that of LVEDP was lower in the SPC group than the I/R group at all time points of reperfusion (P < 0.05). The releases of CK and LDH and infarct size were significantly reduced in the SPC group versus the I/R group (22.2% ± 2.8% vs I/R: 44.9% ± 6.6%, P < 0.05). The expression of Bcl-2 increased significantly while that of Bax decreased in the SPC group verus the I/R group. CONCLUSION: Sevoflurane postconditioning may improve myocardial functions, reduce infarct size and attenuate myocardial apoptosis. And the modulated expression of apoptotic proteins plays an important role in sevoflurane-induced myocardial protection.

The impact of simulation-based triage education on nursing students' self-reported clinical reasoning ability: A quasi-experimental study.

Few studies have comprehensively examined the effectiveness of simulation-based triage education on clinical reasoning of nursing students. This study evaluated the impact of a simulation-based triage exercise on nursing students' self-reported clinical reasoning ability. Three cohorts of third-year nursing students were divided into intervention group a (IG a, n = 62), intervention group b (IG b, n = 57), and a control group (CG, n = 53). Students in IG a and IG b participated in a simulation-based triage education consisting of 2 h of multiple patient triage simulations and an hour of structured debriefing. The CG participated in a traditional didactic triage course consisting of a 3-h lecture. Self-reported clinical reasoning ability in pre and post-triage education was measured by the Nurses Clinical Reasoning Scale. There was no significant difference in mean clinical reasoning ability scores between the three groups in pre-test (p > 0.05). Clinical reasoning ability scores in post-test among students in IG a and IG b were significantly higher than those in CG (p < 0.001). Nursing students exposed to a simulation-based triage education had more improvement in self-reported clinical reasoning ability as compared with students who participated in a lecture-based triage education program.

Admission delay is associated with worse surgical outcomes for elderly hip fracture patients: A retrospective observational study.

BACKGROUND: The influence of surgical delay on mortality and morbidity has been studied extensively among elderly hip fracture patients. However, most studies only focus on the timing of surgery when patients have already been hospitalized, without considering pre-admission waiting time. Therefore, the present study aims to explore the influence of admission delay on surgical outcomes. METHODS: In this retrospective study, we recorded admission timing and interval from admission to surgery for included patient. Other covariates were also collected to control confounding. The primary outcome was 1-year mortality. The secondary outcomes were 1-month mortality, 3-month mortality, ICU admission and postoperative pneumonia. We mainly used multivariate logistic regression to determine the effect of admission timing on postoperative outcomes. An additional survival analysis was also performed to assess the impact of admission delay on survival status in the first year after operation. RESULTS: The proportion of patients hospitalized on day 0, day 1, day 2 after injury was 25.4%, 54.7% and 66.3%, respectively. And 12.6% patients visited hospital one week later after injury. Mean time from admission to surgery was 5.2 days (standard deviation 2.8 days). Hospitalization at one week after injury was a risk factor for 1-year mortality (OR 1.762, 95% CI 1.026-3.379, P=0.041). CONCLUSION: Admission delay of more than one week is significantly associated with higher 1-year mortality. As a supplement to the current guidelines which emphasizes early surgery after admission, we also advocate early admission once patients get injured.

Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function.

Luteolin has been reported to attenuate ischemia/reperfusion (I/R) injury in the diabetic heart through endothelial nitric oxide synthase- (eNOS-) related antioxidative response. Though the nuclear factor erythroid 2-related factor 2 (Nrf2) is regarded as a key endogenous factor to reduce diabetic oxidative stress, whether luteolin reduces cardiac I/R injury in the diabetic heart via enhancing Nrf2 function needs to be clarified. We hypothesized that pretreatment with luteolin could alleviate cardiac I/R injury in the diabetic heart by affecting the eNOS/Nrf2 signaling pathway. The diabetic rat was produced by a single injection of streptozotocin (65 mg/kg, i.p.) for 6 weeks, and then, luteolin (100 mg/kg/day, i.g.), eNOS inhibitor L-NAME, or Nrf2 inhibitor brusatol was administered for the succedent 2 weeks. After that, the isolated rat heart was exposed to 30 min of global ischemia and 120 min of reperfusion to establish I/R injury. Luteolin markedly ameliorated cardiac function and myocardial viability; upregulated expressions of heme oxygenase-1, superoxide dismutase, glutathione peroxidase, and catalase; and reduced myocardial lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R heart. All these ameliorating effects of luteolin were significantly reversed by L-NAME or brusatol. Luteolin also markedly reduced S-nitrosylation of Kelch-like ECH-associated protein 1 (Keap1) and upregulated Nrf2 and its transcriptional activity. This effect of luteolin on Keap1/Nrf2 signaling was attenuated by L-NAME. These data reveal that luteolin protects the diabetic heart against I/R injury by enhancing eNOS-mediated S-nitrosylation of Keap1, with subsequent upregulation of Nrf2 and the Nrf2-related antioxidative signaling pathway.

Prognostic values of preoperative albumin to globulin ratio for predicting clinical outcome in patients with high-grade gliomas.

BACKGROUND: Gliomas was the most common primary central nervous system tumors which have an increased morbidity in recent years. And the clinical prognosis of high-grade gliomas (HGG, WHO grade III to IV) was most with an average survival rate of only dozens of months. Many researchers concluded that the level of preoperative albumin-to-globulin ratio (AGR) could predict the clinical outcome of patients with solid malignant tumors. METHODS: Two hundred and thirty-two cases of patients who were diagnosed HGG by pathology were enrolled in the study. The relevant data of the cohort included sex, age, preoperative Karnofsky performance score (KPS), extent of resection, albumin count and globulin count, isocitrate dehydrogenase (IDH) and survival time were collected. The survival rate was obtained by using the Kaplan-Meier method. The cut-off value of AGR was determined by X-tile software. Univariate survival analysis was performed by the log-rank method. Proportional hazards model (Cox model) was performed for multivariate analysis. RESULTS: The optimal cut-off value of AGR was 1.32. Results showed that the preoperative AGR was correlated with clinical prognosis of patients with HGG, and the survival time of the patients with high AGR (AGR >1.32) was significantly longer. Moreover, the prognosis of patients with high AGR was better in IDH wild-type HGG. CONCLUSIONS: Preoperative AGR might predict the clinical prognosis of patients with HGG.

Preliminary application of mxed reality in neurosurgery: Development and evaluation of a new intraoperative procedure.

During neurological surgery, neurosurgeons have to transform the two-dimensional (2D) sectional images into three-dimensional (3D) structures at the cognitive level. The complexity of the intracranial structures increases the difficulty and risk of neurosurgery. Mixed reality (MR) applications reduce the obstacles in the transformation from 2D images to 3D visualization of anatomical structures of central nervous system. In this study, the holographic image was established by MR using computed tomography (CT), computed tomography angiography (CTA) and magnetic resonance imaging (MRI) data of patients. The surgeon's field of vision was superimposed with the 3D model of the patient's intracranial structure displayed on the mixed reality head-mounted display (MR-HMD). The neurosurgeons practiced and evaluated the feasibility of this technique in neurosurgical cases. We developed the segmentation image masks and texture mapping including brain tissue, intracranial vessels, nerves, tumors, and their relative positions by MR technologies. The results showed that the three-dimensional imaging is in a stable state in the operating room with no significant flutter and blur. And the neurosurgeon's feedback on the comfort of the equipment and the practicality of the technology was satisfactory. In conclusion, MR technology can holographically construct a 3D digital model of patient's lesions and improve the anatomical perception of neurosurgeons during craniotomy. The feasibility of the MR-HMD application in neurosurgery is confirmed.

Preoperative Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio are Associated with the Prognosis of Group 3 and Group 4 Medulloblastoma.

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P < 0.001) and PLR (platelet-to-lymphocyte ratio, PFS, P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors.

Prognostic value of preoperative hematological markers combined with molecular pathology in patients with diffuse gliomas.

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore.

BACKGROUND: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. METHODS: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 micromol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 micromol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). RESULTS: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48+/-2.70)% vs (48.47+/-6.03)%, P<0.05; PPC vs CTRL: (35.60+/-2.10)% vs (48.47+/-6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48+/-2.70)% vs (35.60+/-2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. CONCLUSION: Postconditioning of sevoflurane and propofol has cardioprotective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.

Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling.

Myocardial ischemia/reperfusion (I/R) injury in hypercholesterolemia is associated with oxidative stress, while luteolin is known to reduce oxidative stress by activating Akt/nuclear factor erythroid-2-related factor 2 (Nrf2) signaling and alleviate cardiac I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in hypercholesterolemic rats by activating Akt/Nrf2 signaling. Hypercholesterolemic rats were produced by 2% cholesterol diet for 8 weeks. Luteolin (100 mg/kg/day, i.g.) or LY294002 was administered for the last 2 weeks. The hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. Pretreatment with luteolin significantly improved left ventricular function throughout reperfusion, increased cardiac tissue viability, reduced coronary lactate dehydrogenase release and the myocardial malondialdehyde level, upregulated p-Akt and p-GSK3ß expressions, inhibited nuclear translocation of Fyn, and activated Nrf2 function in hypercholesterolemic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by LY294002. Ca2+-induced mitochondrial permeability transition pore (mPTP) opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated hypercholesterolemic rats, which were attenuated by LY294002. These results indicate that luteolin protects the hypercholesterolemic heart against I/R injury due to upregulation of Akt-mediated Nrf2 antioxidative function and inhibition of mPTP.

IDH mutations but not TERTp mutations are associated with seizures in lower-grade gliomas.

Glioma is the most common malignant tumor in the central nervous system (CNS). Lower-grade gliomas (LGG) refer to Grade II and III gliomas. In LGG patients, seizure often appears as an initial symptom and play an important role in clinical performance and quality of life of the patients. To date, the relationship between the onset of seizures and the molecular pathology in gliomas is still poorly investigated. In this study, we investigate the potential relationship between isocitrate dehydrogenase (IDH)/telomerase reverse transcriptase promoter (TERTp) mutations and preoperative seizures in patients with LGG. 289 adult LGG patients were enrolled in this study. Data of clinical characteristics and molecular pathology were acquired. Sanger sequencing was used to detect IDH/TERTp mutations. Chi-square test was performed to determine if the IDH/TERTp mutations were associated with seizures and seizure types. In 289 LGG patients, preoperative seizures accounted for 25.3% (73/289), IDH mutations accounted for 34.3%(99/289), and TERTp mutations accounted for 44.3% (128/289). The correlation analysis demonstrated that IDH mutation is a significant factor influencing the occurrence of tumor-related epilepsy (P <.001, chi-square test). On the other hand, the statistical analysis revealed no significant correlation between TERTp mutations and seizure in LGG patients (P = .102, chi-square test). The tumor-related epilepsy rates vary among different subgroups according to IDH/TERTp mutations. However, there is no definite correlation between the IDH (P = 1.000, chi-square test)/TERTp (P = .613, chi-square test) mutations and the types of epileptic seizure. IDH mutations are more common in preoperative LGG patients with epileptic symptoms, suggesting that this mutation is positively correlated with seizures. However, there was no significant correlation between TERTp mutations and seizures. Different molecular pathologic types based on IDH/TERTp have different incidences of tumor-associated epilepsy in LGGs.

Effect of perioperative autologous versus allogeneic blood transfusion on the immune system in gastric cancer patients.

BACKGROUND: Allogeneic blood transfusion-induced immunomodulation (TRIM) and its adverse effect on the prognosis of patients treated surgically for cancer remain complex and controversial. However, the potential risk associated with allogeneic blood transfusion has heightened interest in the use of autologous blood transfusion. In the present study, the serum concentrations of neopterin, interferon-gamma (IFN-gamma), T lymphocyte subsets (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+)) and a possible association between these variables were investigated. The purpose was to further evaluate the effect of autologous versus allogeneic blood transfusion on immunological status in patients undergoing surgery for gastric cancer. METHODS: Sixty ASA I-II (American Society of Anesthesiologists) patients undergoing elective radical resection for stomach cancer were randomly allocated to receive either allogeneic blood transfusion (n=30) or autologous blood transfusion (n=30). Serum concentrations of the neopterin, IFN-gamma and T lymphocyte subsets in the recipients were measured before induction of anesthesia, after operation, and on the 5th postoperative day. RESULTS: Both two groups, serum neopterin, IFN-gamma, percentages of T-cell subsets (CD3(+), CD4(+)), and CD4(+)/CD8(+) ratio had significantly decreased after operation, but decreased more significantly in group H (receiving allogeneic blood transfusion) than those in group A (receiving autologous whole blood transfusion) (P<0.05). On the 5th postoperative day, serum neopterin, IFN-gamma, CD3(+), CD4(+) T-cells, and CD4(+)/CD8(+) ratio returned to the baseline values in group A. In contrast, the above remain decreasing in group H, where there were no significant relations between serum neopterin and IFN-gamma. CONCLUSION: Perioperative surgical trauma and stress have an immunosuppressive impact on gastric cancer patients. Allogeneic blood transfusion exacerbates the impaired immune response. Autologous blood transfusion might be significantly beneficial for immune-compromised patients in the perioperative period, clearly showing its superiority over allogeneic blood transfusion.

The Effect of Early Use of Supplemental Therapy on Preventing Postherpetic Neuralgia: A Systematic Review and Meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common and refractory complication of herpes zoster (HZ). Aggressive treatment of acute pain in HZ has the potential to prevent the development of PHN, but the preventive efficacy of supplemental therapy commonly used in clinical practice is controversial. OBJECTIVES: Our aim is to examine the efficacy of supplemental therapy in preventing PHN. STUDY DESIGN: A meta-analysis. SETTING: All of the selected studies are randomized controlled trials (RCTs). METHODS: A systematic and comprehensive database search was performed in CENTRAL (1976 to March 2016), MEDLINE (1977 to January 2016), and EMBASE (May 1980 to December 2016). According to the selection criteria, data of the included studies were extracted by 2 independent reviewers. RevMan 5.3 (The Nordic Cochrane Centre for The Cochrane Collaboration, Copenhagen, Denmark) was used to perform this meta-analysis. RESULTS: Nine trials, with a total of 1,757 participants (888 in the treatment group and 867 in the control group), were included in the final analysis. Of the 9 trials, 3 compared systemic adjunct therapies with the control, and 6 trials compared interventional procedures with the control. The early use of supplemental therapy was associated with a significantly less incidence of PHN in 3 months after acute rash presence (RR 0.53, 95%CI 0.34 to 0.81, P = 0.004). The systemic adjunct treatments subgroup was not found with any benefit (RR 0.76, 95%CI 0.46 to 1.26, P = 0.29). A significant decrease in visual analog scale (VAS) score was reported in all of the 9 trials when compared with baseline, but the decrease slopes of the pain scores between the treatment group and the control group were similar in 5 trials. The most common adverse events in systemic adjunct treatments group were dizziness, nausea, dyspepsia, and dry mouth. The interventional procedures group was associated with procedure-related complications such as mild hypotension, voice change, dysphagia, drowsiness, and headache. LIMITATIONS: There were only a few RCTs and most of them lacked adequate allocation concealment and blinding. Further, the English-only approach might have omitted trials published in non-English journals. Finally, some of the secondary outcomes of data were insufficient for meta-analysis, and future studies are warranted. CONCLUSION: This meta-analysis demonstrates that the early use of supplemental therapy can significantly reduce the incidence of PHN. The subgroup analysis shows that supplemental interventional procedures have a beneficial effect on preventing PHN, while supplemental systemic adjunct treatments do not. The early use of interventional procedures for acute pain may be a preferred choice for patients without contraindication, but evidence is moderate. More data from high-quality RCTs will be needed to confirm these results.Key words: Postherpetic neuralgia, systemic treatment, local anesthesia, analgesia, meta-analysis.