A New Player in Depression: MiRNAs as Modulators of Altered Synaptic Plasticity.

Depression is a psychiatric disorder that presents with a persistent depressed mood as the main clinical feature and is accompanied by cognitive impairment. Changes in neuroplasticity and neurogenesis greatly affect depression. Without genetic changes, epigenetic mechanisms have been shown to function by regulating gene expression during the body's adaptation to stress. Studies in recent years have shown that as important regulatory factors in epigenetic mechanisms, microRNAs (miRNAs) play important roles in the development and progression of depression through the regulation of protein expression. Herein, we review the mechanisms of miRNA-mediated neuroplasticity in depression and discus synaptic structural plasticity, synaptic functional plasticity, and neurogenesis. Furthermore, we found that miRNAs regulate neuroplasticity through several signalling pathways to affect cognitive functions. However, these pathways do not work independently. Therefore, we try to identify synergistic correlations between miRNAs and multiple signalling pathways to broaden the potential pathogenesis of depression. In addition, in the future, dual-function miRNAs (protection/injury) are promising candidate biomarkers for the diagnosis of depression, and their regulated genes can potentially be used as target genes for the treatment of depression.

[Complications and short-term outcomes of intraoperative electron radiotherapy (IOERT) in patients with periarticular soft-tissue sarcomas of the extremities].

OBJECTIVE: To analyze the complications and short-term outcomes of patients receiving intraoperative electron radiotherapy (IOERT) for locally advanced and recurrent periarticular soft tissue sarcomas of the extremities. METHODS: Twenty-one adult patients with locally advanced and/or recurrent periarticular soft tissue sarcomas of the extremities treated with IOERT were included in this study. Among them 14 patients had recurrent diseases after prior operation and 7 patients with locally advanced disease with primary treatment. The total dose of radiation ranged from 11 Gy to 21 Gy of 6 - 12 MeV beta ray given by intraoperative radiotherapy after complete tumor resection with negative margins. Five patients were given external beam radiotherapy (EBRT) with a total dose of 40 - 50 Gy, and 10 patients received chemotherapy. RESULTS: The median follow-up time was 15 months. Five patients (23.8%) had tumor relapse, including one patients with local recurrence, one patient with regional recurrence, two patients with distant metastasis and one patient with local recurrence and distant metastasis. The actuarial local control rate at 1 year was 95.2% (20/21), and at 2 years was 90.5% (19/21). Acute skin toxicity (RTOG) within 3 months after surgery included grade I in 6 patients and grade II in 3 patients. Two year late skin toxicity (RTOG/EORTC) included grade I in 4 patients and grade II in 2 patients. Fibrosis included grade I in 3 patients and grade II in 3 patients. Six patients had joint dysfunction (3 patients with grade I and 3 with grade II) and 6 patients had healing problems. One patient got ipsilateral schiatic neuritis 9 months after IOERT. No adverse events occurred during surgery. CONCLUSIONS: IOERT brings tolerable complications of acute and late toxicities and favorable local control rate. IOERT should be followed by postoperative radiotherapy or increase the intraoperative radiation dose for locally advanced and recurrent sarcomas to get a better local control. Otherwise, distant metastasis is one of the main reasons of treatment failure, so chemotherapy should be added to the treatment regimen.

[Effects of intraoperative application of radical scavenger edaravone in severe elderly cases].

OBJECTIVE: To observe the effects of intraoperative application of radical scavenger edaravone in severe elderly cases. METHODS: A total of 400 severe elderly patients scheduled for surgery were randomly assigned to receive edaravone 60 mg/40 ml (Group Y) or an equal volume of normal saline (Group C). The arterial blood samples were harvested at immediately after pricking, 1 hour after the beginning of surgery and before saturation to determine the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). The operative duration, fluid volume, blood loss, blood transfusion volume, urine output, intraoperative adverse events, mortality rate, total hospital stay, intensive care unit (ICU) stay, postoperative mechanical ventilation time and complications were recorded. Patients undergoing off-pump coronary artery bypass graft (OPCABG) were evaluated for troponin I (cTnI) and left ventricular ejection fraction (LVEF) before and after 24 hours of surgery. RESULTS: SOD was higher and MDA lower in Group Y than those in Group C at 1 hour intraoperation and before saturation [SOD: (87 ± 14) U/ml vs (78 ± 14) U/ml, (83 ± 13) U/ml vs (77 ± 14) U/ml, P < 0.01, < 0.05; MDA: (11 ± 5) nmol/L vs (14 ± 7) nmol/L, (11 ± 5) nmol/L vs (14 ± 6) nmol/L, P < 0.05, < 0.01]. There were more intraoperative hypotension cases requiring a continuous application of vasoactive drugs in Group C (37 cases vs 19 cases), total hospital stay [(21 ± 9) d vs (23 ± 9) d, P < 0.05] and ICU stay [(10 ± 7) d vs (13 ± 9) d, P < 0.05] were also longer. Postoperative cTnI and LVEF of Group Y significantly improved in OPCABG cases (all P < 0.05). CONCLUSION: The intraoperative application of edaravone in severe elderly patients may prevent MDA increase and SOD decrease and reduce free radical damage. Especially in OPCABG patients, cTnIand LVEF improve significantly.

Assessment of right ventricular function by pressure-volume loops in off-pump coronary artery bypass surgery.

BACKGROUND: Right ventricular function plays an important role in the hemodynamic derangement during off-pump coronary artery bypass (OPCAB) surgery. Pressure-volume loops have been shown to provide load-independent information of cardiac function. Therefore, the aim of this study was to investigate the feasibility of construction of right ventricular pressure-volume loops with pressure and volume data measured by a volumetric pulmonary artery catheter (PAC) and to evaluate right ventricular systolic and diastolic function by end-systolic elastance (E(ES)) and end-diastolic stiffness (E(ED)) in OPCAB surgery. METHODS: Twenty-eight patients who underwent OPCAB surgery were included. After anesthesia induction, a volumetric PAC was placed via the right internal jugular vein. Data were recorded at: anesthesia steady-state before skin incision (T1); 5 minutes after the stabilizer device was placed for anastomosis on the heart's anterior wall (T2), lateral wall (T3), posterior wall (T4), respectively; after sternal closure (T5). Three sets of data were collected at each time point: first, hemodynamic variables were measured; second, right ventricular E(ES) and E(ED) were calculated; third, right ventricular pressure-volume loops were constructed with pressure and volume data measured from end-diastole point, end-isovolumic systole point, peak-ejection point, end-systole point and end-isovolumic diastole point. RESULTS: Right ventricular pressure-volume loops generally shifted to the left during OPCAB surgery. Especially, the end-diastolic point shifted upward and to the left at T2-T5 compared with that at T1. Decrease in right ventricular ejection fraction, stroke volume index and end-diastolic volume index occurred (P < 0.05) at T4 compared with values at T1. Pulmonary vascular resistance index at T4 increased relatively compared with that at T2 and T3. The change of E(ES) was not statistically significant during operation. Right atrial pressure increased only during coronary anastomoses (T2-T4, P < 0.05), whereas E(ED) increased throughout OPCAB surgery (P < 0.05). CONCLUSIONS: Right ventricular pressure-volume loops can be constructed using a volumetric PAC. Right ventricular systolic dysfunction occurred during anastomoses on the heart's posterior wall not due to impaired myocardial contractility but as a result of reduced preload and a relative increase in afterload. Right ventricular diastolic function was impaired throughout OPCAB surgery.

Investigation and analysis of incidence of awareness in patients undergoing cardiac surgery in Beijing, China.

BACKGROUND: Awareness under general anesthesia is a serious complication which leads to psychiatric disorders. The incidence of awareness in patients undergoing cardiac surgery has been reported in as many as 1.5% - 23% in foreign countries. But so far, medical literature about awareness during cardiac surgery is still rare in China. Therefore, we investigated the incidence of awareness in patients undergoing different kinds of cardiac surgery, the phases when awareness occurred and the effect of cardiopulmonary bypass on the incidence of awareness in coronary artery bypass grafting in Beijing. METHODS: Patients' recall of awareness during cardiac surgery was assessed. One hundred patients undergoing coronary artery bypass grafting (CABG) in Chaoyang Hospital, Beijing, one hundred patients undergoing CABG and one hundred patients undergoing valve replacement or septal defect repair in Fuwai Hospital, Beijing, were interviewed 3-6 days after surgery. Every report about patients on recall of awareness was recorded. An independent research team, blinded to patients' surgery and anesthesia, assessed every report of awareness. RESULTS: The incidence of awareness of patients received CABG under cardiopulmonary bypass (CPB), off -pump CABG, septal repair or valve replacement under CPB was 4.7% (5 of 106 cases), 9.6% (9 of 94 cases) and 4% (4 of 100 cases), respectively. CPB did not greatly affect the incidence of awareness during the period of CABG (P > 0.05). The incidence of awareness of patients who received CABG under CPB did not increase significantly, in comparison with that of patients who received septal repair or valve replacement under CPB in Fuwai Hospital (P > 0.05). Awareness easily occurred before bypass grafting or CPB. CONCLUSIONS: Awareness mainly occurs before bypass grafting or CPB in cardiac surgery. Most cases with awareness have auditory perceptions. CPB is not a main factor which affects the incidence of awareness of CABG. Surgical types do not affect the incidence of awareness of patients under CPB.

[Effect of propofol on the activation of nuclear factor-kappa B and expression of inflammatory cytokines in cerebral cortex during transient focal cerebral ischemia-reperfusion: experiment with rats].

OBJECTIVE: To investigate the effect of propofol on the activation of nuclear factor-kappa B (NF-kappa B) and the expression of inflammatory cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) in cerebral cortex during transient focal cerebral ischemia-reperfusion, and to discuss the probable mechanism of its protective effect. METHODS: Ninety male Wistar rats were randomly divided into 3 equal groups: sham operation group undergoing sham operation; ischemia/reperfusion (I/R) group undergoing thread embolism of the left middle cerebral artery occlusion (MCAO) to cause focal ischemia for 2 hours and then undergoing reperfusion; and propofol group undergoing peritoneal injection of propofol 2 hours before the ischemia-reperfusion of MCAO. Then the rats in the 3 groups were re-divided into subgroups of 5 rats, totally 18 subgroups, to be decapitated 2, 3, 6, 12, 24, and 72 hours after reperfusion for the latter 2 groups, and their brains were taken out and fixed. Immunohistochemistry was used to detect the translocation of NF-kappaB in the neurons and the expression of IL-1, TNF-alpha, and ICAM-1 in the brain. Western blotting was used to detect the expression of NF-kappa B. The opposite non-ischemic cortexes were used as controls. RESULTS: Two to 24 hours after the reperfusion NF-kappaB was significantly translocated from the cytoplasm into the nucleus; however, NF-kappa B remained in the cytoplasm of bilateral cortexes in the sham operation groups, and the nonischemic cortexes in the I/R and protofol groups. The translocation of NF-kappa B from cytoplasm into nucleus was significantly inhibited in the ischemic cortex of the propofol group. The expression values of NF-kappa B in the nuclei of ischemic cortexes in the I/R group 2 to 24 hours after reperfusion were significantly higher than those in the sham operation group and the nonischemic cortexes of the I/R and propofol groups (all P < 0.01). The expression values of NF-kappa B in the ischemic cortex of the propofol group 2 to 24 hours after reperfusion was significantly lower than that of the I/R group (all P < 0.05). The expression values of IL-1, TNF-alpha, and ICAM-1 in the ischemic cortexes were significantly higher than that in the cortex of the sham operation group and those in the nonischemic cortexes of the I/R group and propofol group (P < 0.01 or P < 0.05) and the expression values of IL-1, TNF-alpha, and ICAM-1 in the propofol group were all significantly lower than those in the I/R group (all P < 0.05). CONCLUSION: Propofol inhibits the inflammatory reaction by inhibiting the NF-kappa B activation during focal ischemia-reperfusion which may be one of the mechanisms of its neuroprotective function.