Background: Although several studies have compared conscious sedation (CS) with general anesthesia (GA) in patients undergoing mechanical thrombectomy (MT), there has been no affirmative conclusion. We conducted this trial to assess whether CS is superior to GA for patients undergoing MT for acute ischemic stroke (AIS).Methods: Acute ischemic stroke patients with anterior circulation large vascular occlusion were randomized into two groups. The primary outcome was modified Rankin scale score (0-2) at 90 days after stroke. Secondary outcomes included intraprocedural hemodynamics, time metrics, successful recanalization, neurointerventionalist satisfaction score, National Institutes of Health Stroke Scale (NIHSS) score, and Alberta Stroke Program Early CT Score (ASPECTS) at 48 h post-intervention, mortality at discharge and 3 months after stroke, and complications.Results: Compared with the CS group, heart rate was significantly lower at T1-T8 in the GA group except at T4 (P < 0.05). Mean arterial pressure (MAP) and systolic blood pressure were significantly lower in the GA group at T4-T6 and T9 (P < 0.05). Pulse oxygen saturation was significantly higher at T2-T9 in the GA group (P < 0.05). There were no significant differences in time metrics, vasoactive drug use, occurrence of >20% fall in MAP, pre-recanalization time spent with >20% fall in MAP, neurointerventionalist satisfaction, successful recanalization rate, NIHSS, and ASPECTS scores at 48 h post-intervention, and mortality rate at discharge and 3 months after stroke (P > 0.05). The cerebral infarction rate at 30 days was greater in the CS group, but not significantly (P > 0.05). There were no differences in complication rates except for pneumonia (P > 0.05). Conversion rate from CS to GA was 9.52%. Conclusion:Anesthetic management with GA or CS during MT had no differential impact on the functional outcomes and mortality at discharge or 3 months after stroke in AIS patients, but CS led to more stable hemodynamics and lower incidence of pneumonia.

F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF FBW7 (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes. Although FBW7 is required for vascular development, its function in the endothelium remains to be investigated. In this study, we show that FBW7 is an important regulator of endothelial functions, including angiogenesis, leukocyte adhesion and the endothelial barrier integrity. Using RNA interference, we found that the depletion of FBW7 markedly impairs angiogenesis in vitro and in vivo. We identified the zinc finger transcription factor Krüppel-like factor 2 (KLF2) as a physiological target of FBW7 in endothelial cells. Knockdown of FBW7 expression resulted in the accumulation of endogenous KLF2 protein in endothelial cells. FBW7-mediated KLF2 destruction was shown to depend on the phosphorylation of KLF2 via glycogen synthase kinase-3 (GSK3) at two conserved phosphodegrons. Mutating these phosphodegron motifs abolished the FBW7-mediated degradation and ubiquitination of KLF2. The siRNAmediated knockdown of FBW7 showed that KLF2 is an essential target of FBW7 in the regulation of endothelial functions. Moreover, FBW7-mediated KLF2 degradation was shown to be critical for angiogenesis in teratomas and in zebrafish development. Taken together, our study suggests a role for FBW7 in the processes of endothelial cell migration, angiogenesis, inflammation and barrier integrity, and provides novel insights into the regulation of KLF2 stability in vivo.

Background:The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Results: Cnr2 activation down-regulates 5-lipoxygenase (Alox5) expression by suppressing the JNK/c-Jun activation. Conclusion: The Cnr2-JNK-Alox5 axis modulates leukocyte inflammatory migration. Significance: Linking two important regulators in leukocyte inflammatory migration and providing a potential therapeutic strategy for treating human inflammation-associated diseases.

Both dexmedetomidine and sufentanil modulate spinal analgesia by different mechanisms, and yet no human studies are available on their combination for analgesia during the first 72 hours after abdominal hysterectomy.This CONSORT-prospective, randomized, double-blinded, controlled trial sought to evaluate the safety and efficacy of the combination of dexmedetomidine and sufentanil in intravenous patient-controlled analgesia (PCA) for 72 hours after abdominal hysterectomy.Ninety women undergoing total abdominal hysterectomy were divided into 3 equal groups that received sufentanil (Group C; 0.02 μg/kg/h), sufentanil plus dexmedetomidine (Group D1; 0.02 μg/kg/h, each), or sufentanil (0.02 μg/kg/h) plus dexmedetomidine (0.05 μg/kg/h) (Group D2) for 72 hours after surgery in this double-blinded, randomized study. The primary outcome measure was the postoperative sufentanil consumption, whereas the secondary outcome measures were pain intensity (visual analogue scale), requirement of narcotic drugs during the operation, level of sedation, Bruggrmann comfort scale, and concerning adverse effects.The postoperative sufentanil consumption was significantly lower in Groups D1 and D2 than in Group C during the observation period (P < 0.05), but lower in Group D2 than in Group D1 at 24, 48, and 72 hours after surgery (P < 0.05). The heart rate after intubation and incision was lower in Groups D1 and D2 than in Group C (P < 0.05). On arrival at the recovery room, Groups D1 and D2 had lower mean blood pressure than Group C (P < 0.05). The intraoperative requirement of sevoflurane was 30% lesser in Groups D1 and D2 than in Group C. The sedation levels were greater in Groups D1 and D2 during the first hour (P < 0.05). Compared with Groups C and D1, Group D2 showed lower levels of the overall incidence of nausea and vomiting (P < 0.05).Among the tested PCA options, the addition of dexmedetomidine (0.05 μg/kg/h) and sufentanil (0.02 μg/kg/h) showed better analgesic effect and greater patient satisfaction without other clinically relevant side effects for patients undergoing hysterectomy during the first 72 hours after abdominal hysterectomy.

The aim of this study was to assess the effect of preoperative sleep quality on acute postoperative pain in breast cancer patients.The Pittsburgh Sleep Quality Index questionnaire (PSQI) was used to assess the overall sleep status of women scheduled for unilateral modified radical mastectomy in the past month. Based on the responses, patients were allocated to good sleep group or poor sleep group. Postoperatively, acute pain was assessed using the numerical rating score in the first 24 hours; in addition, the requirement of analgesics and the incidence of postoperative complications were recorded.A total of 108 breast surgery patients were enrolled. Based on the PSQI results, 55 (51%) patients were allocated to poor sleep group and 53 (49%) to good sleep group. Pain scores were similar in the 2 groups at the end of surgery (P = .589); however, poor sleep group reported higher postoperative pain scores than the good sleep group at 2 (P = .002), 6 (P < .001), 12 (P < .001), and 24 (P = .002) hours after surgery. The incidence of severe pain in the poor sleep group was higher than that in the good sleep group (27% vs 8%, P = .018), and the ratio of participants who required rescued analgesics was greater in the poor sleep group (52% vs 22%, P = .002). In addition, patients with poor sleep quality had more postoperative complications and longer hospital stay.In this study, breast cancer patients with poor preoperative sleep quality reported more severe postoperative pain, required more analgesics, experienced more complications, and had longer hospital stay.

Background: The anesthetic characteristics of ultrasound-guided bi-level erector spinae plane block (ESPB) plus dexmedetomidine (Dex) remain unclear. We compared the efficacy and safety of ultrasound-guided bi-level ESPB plus different doses of Dex in patients undergoing video-assisted thoracic surgery (VATS).Methods: One-hundred eight patients undergoing VATS were randomized into three groups: R group (n = 38, 15 ml of 0.375% ropivacaine with 0.1 mg/kg dexamethasone), RD1 group (n = 38, 15 ml of 0.375% ropivacaine plus 0.5 μg/kg DEX with 0.1 mg/kg dexamethasone) and RD2 group (n = 38, 15 ml of 0.375% ropivacaine plus 1.0 μg/kg DEX with 0.1 mg/kg dexamethasone). The primary outcome was the pain 12 h after surgery. Secondary outcomes included the Prince Henry Hospital Pain Score; hemodynamics; consumption of sufentanil; anesthetized dermatomal distribution; recovery time; rescue analgesia; satisfaction scores of patients and surgeon; quick recovery index; adverse effects; the prevalence of chronic pain and quality of recovery.Results: The visual analog scale (VAS) and the Prince Henry pain score were significantly lower in both the RD1 and RD2 groups during the first 24 h after surgery (P &lt; 0.05). Both VAS with coughing and the Prince Henry pain score were significantly lower in the RD2 group than in the RD1 group 8–24 h after surgery (P &lt; 0.05). Both heart rate and mean arterial pressure were significantly different from T2 to T6 in the RD1 and RD2 groups (P &lt; 0.05). The receipt of remifentanil, propofol, Dex, and recovery time was significantly reduced in the RD2 group (P &lt; 0.05). The requirement for sufentanil during the 8–72 h after surgery, less rescue medication, and total press times were significantly lower in the RD2 group (P &lt; 0.05). The time to the first dose of rescue ketorolac was significantly longer in the RD2 group (P &lt; 0.05). Further, anal exhaust, removal of chest tubes, and ambulation were significantly shorter in the RD2 group (P &lt; 0.05). The incidence of tachycardia, post-operative nausea and vomiting, and chronic pain was significantly reduced in the RD2 group, while the QoR-40 score was significantly higher in the RD2 group (P &lt; 0.05).Conclusions: Pre-operative bi-level, single-injection ESPB plus 1 μg/kg DEX provided superior pain relief and long-term post-operative recovery for patients undergoing VATS.Clinical Trial Registration:http://www.chictr.org.cn/searchproj.aspx.

Dysregulation of ribosome biogenesis causes human diseases, such as Diamond-Blackfan anemia, del (5q-) syndrome and bone marrow failure. However, the mechanisms of blood disorders in these diseases remain elusive. Through genetic mapping, molecular cloning and mechanism characterization of the zebrafish mutant cas002, we reveal a novel connection between ribosomal dysfunction and excessive autophagy in the regulation of hematopoietic stem/progenitor cells (HSPCs). cas002 carries a recessive lethal mutation in kri1l gene that encodes an essential component of rRNA small subunit processome. We show that Kri1l is required for normal ribosome biogenesis, expansion of definitive HSPCs and subsequent lineage differentiation. Through live imaging and biochemical studies, we find that loss of Kri1l causes the accumulation of misfolded proteins and excessive PERK activation-dependent autophagy in HSPCs. Blocking autophagy but not inhibiting apoptosis by Bcl2 overexpression can fully rescue hematopoietic defects, but not the lethality of kri1lcas002 embryos. Treatment with autophagy inhibitors (3-MA and Baf A1) or PERK inhibitor (GSK2656157), or knockdown of beclin1 or perk can markedly restore HSPC proliferation and definitive hematopoietic cell differentiation. These results may provide leads for effective therapeutics that benefit patients with anemia or bone marrow failure caused by ribosome disorders.

Smoking is one of the most common addictions in the world. Nicotine inhalation could increase the risk of cardiorespiratory diseases. However, the solution that improved postoperative analgesia for highly nicotine-dependent patients undergoing thoracic surgery has not been specifically addressed.This CONSORT-prospective, randomized, double-blinded, controlled trial investigated the efficacy of combination of dexmedetomidine and sufentanil for highly nicotine (Fagerstrom test of nicotine dependence ≥6)-dependent patients after thoracic surgery.One hundred seventy-four male patients who underwent thoracic surgery were screened between February 2014 and November 2014, and a total of forty-nine were excluded. One hundred thirty-two highly nicotine-dependent male patients who underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia were divided into 3 groups after surgery in this double-blind, randomized study: sufentanil (0.02 μg/kg/h, Group S), sufentanil plus dexmedetomidine (0.02 μg/kg/h each, Group D1), or sufentanil (0.02 μg/kg/h) plus dexmedetomidine (0.04 μg/kg/h) (Group D2). The patient-controlled analgesia (PCA) program was programmed to deliver a bolus dose of 2 ml, with background infusion of 2 ml/h and a lockout of 5 min, 4-hour limit of 40 ml, as our retrospective study. The primary outcome measure was the cumulative amount of self-administered sufentanil; the secondary outcome measures were pain intensity (numerical rating scale, NRS), level of sedation (LOS), Bruggrmann comfort scale (BCS), functional activity score (FAS), and concerning adverse effects.The amount of self-administered sufentanil were lower in group D2 compared with S and D1 groups during the 72 hours after surgery (P < 0.05), whereas the total dosage and dosage per body weight of sufentanil were significantly lower in D1 group than that of S group only at 4, 8, and 16 hours after surgery (P < 0.05). Compared with S group, the NRS scores at rest at 1, 4, and 8 hours after surgery and with coughing at 4, 8, 16, and 24 hours after surgery were significantly lower in D2 group (P < 0.05). However, compared with D1 group, the NRS scores both at rest and with coughing at 4 and 8 hours after surgery were significantly lower in D2 group (P < 0.05). The NRS scores both at rest and with coughing show that there were no significant differences between D1 group and S group at each time point after surgery (P > 0.05). LOS of group D2 was higher than S and D1 groups at 1 hour after surgery (P < 0.05), BCS of group D2 was higher than S and D1 groups at 4, 8, and 16 hours after surgery (P < 0.05), and FAS of group D2 was higher than S and D1 groups at 48 and 72 hours after surgery (P < 0.05). The number of rescue analgesia during 72 hours after surgery in D2 group was lower than S and D1 groups (P < 0.05). There were no significant differences among the 3 groups in terms of baseline clinical characteristics and postoperative adverse effects except for itching (P > 0.05).Among the tested patient-controlled a...