TBK1 Facilitates GLUT1-Dependent Glucose Consumption by suppressing mTORC1 Signaling in Colorectal Cancer Progression.

Intestinal inflammation is a vital precipitating factor of colorectal cancer (CRC), but the underlying mechanisms are still elusive. TANK-binding kinase 1 (TBK1) is a core enzyme downstream of several inflammatory signals. Recent studies brought the impacts of TBK1 in malignant disease to the forefront, we found aberrant TBK1 expression in CRC is correlated with CRC progression. TBK1 inhibition impaired CRC cell proliferation, migration, drug resistance and tumor growth. Bioinformatic analysis and experiments in vitro showed overexpressed TBK1 inhibited mTORC1 signaling activation in CRC along with elevated GLUT1 expression without inducing GLUT1 translation. TBK1 mediated mTORC1 inhibition induces intracellular autophagy, which in turn decreasing GLUT1 degradation. As a rescue, blocking of autophagosome and retromer respectively via autophagy-related gene 7 (ATG7) or TBC1 Domain Family Member 5 (TBC1D5) silence diminished the regulation of TBK1 to GLUT1. GLUT1 staining presented that TBK1 facilitated GLUT1 membrane translocation which subsequently enhanced glucose consumption. Inhibitor of TBK1 also decreased GLUT1 expression which potentiated drug-sensitivity of CRC cell. Collectively, TBK1 facilitates glucose consumption for supporting CRC progression via initiating mTORC1 inhibition induced autophagy which decreases GLUT1 degradation and increases GLUT1 membrane location. The adaptive signaling cascade between TBK1 and GLUT1 proposes a new strategy for CRC therapy.

Dexmedetomidine combined with ropivacaine in ultrasound-guided tranversus abdominis plane block improves postoperative analgesia and recovery following laparoscopic colectomy.

The present prospective, double blind, randomized clinical study was designed to evaluate whether dexmedetomidine (Dex) combined with ropivacaine for tranversus abdominis plane (TAP) block could improve analgesic quality and duration, and promote recovery following laparoscopic colectomy. Following induction of anesthesia, ultrasound-guided bilateral TAP block was performed in 60 patients scheduled for elective laparoscopic colectomy with either 20 ml of 0.375% ropivacaine plus 2 ml normal saline 0.9% (R group), or 20 ml of 0.375% ropivacaine plus 2 ml Dex (0.5 µg/kg) (RD group). Visual analogue scale (VAS) score for pain, sedation level, length of hospital stay (LOS), and bowel function recovery time and associated complications were recorded. Overall patient satisfaction with postoperative pain management was also assessed. The hemodynamic variables were not significantly different between the two groups during the surgery. However, the duration of analgesia was significantly longer in the RD group compared with the R group (P<0.05). VAS scores at 1, 2, 6 and 12 h following surgery were significantly decreased in the RD group compared with those in the R group (P<0.05). There was no significant difference in sedation level between the two groups. Notably, postoperative nausea and vomiting in the RD group was significantly decreased compared with those in the R group in the first 24 h (P<0.05). There were no serious adverse events in any group. Furthermore, 90.0 and 66.7% patients were satisfied with the postoperative pain management in the RD group and R group, respectively. The postoperative first bowel movement time was significantly shorter in the RD group compared with the R group (P<0.05). However, the LOS was not significantly different between the two groups. In conlusion, the addition of Dex to ropivacaine could significantly improve the analgesic quality and duration of TAP block, which in turn promotes recovery following laparoscopic colectomy.

Efficacy of dexmedetomidine in reducing post-operative pain and improving the quality of recovery in patients with burn wounds undergoing tangential excision skin grafting.

Burn-induced acute post-operative pain and the associated stress response may result in prolonged convalescence. The present study investigated the effects of dexmedetomidine (DEX) administration on post-operative pain and the quality of recovery following surgical treatment of moderate-to-severe burn injuries. A total of 60 adult patients undergoing tangential excision skin grafting were randomized into two groups. The DEX group (Group D) received an intravenous (i.v.) single-dose bolus injection of DEX 0.5 µg/kg >10 min prior to induction of anesthesia. Patient-controlled intravenous analgesia (PCIA) was provided to the patients from the end of the surgery, which consisted of 100 µg sufentanil plus 200 µg DEX. The control group (Group C) received an equal volume of normal saline as a pre-operative bolus and post-operative PCIA of 100 µg sufentanil infusion. The Visual Analogue Scale (VAS) score at rest and during movement, the cumulative dose of sufentanil and the 40-item quality of recovery questionnaire (QoR-40) score were assessed at various time-points after the surgery. During the first 24 h post-surgery, patients in Group D exhibited a lower VAS score at rest and during movement, a lower number of PCIA pump presses (29.17±1.91 vs. 34.13±2.73) and lower sufentanil consumption (62.58±0.96 vs. 65.27±1.26) compared with those in Group C (P<0.05). Furthermore, the QoR-40 recovery score of patients in Group D at 24 h post-surgery was higher compared with that in Group C (P<0.01). In conclusion, the present study indicated that a pre-operative bolus of DEX (0.5 µg/kg) followed by DEX plus sufentanil by PCIA subsequent to surgery improved the quality of analgesia and promoted the quality of recovery at 24 h following tangential excision skin grafting treatment of patients with moderate-to-severe burn injuries compared to PCIA of 100 µg sufentanil only. The present study was retrospectively registered with the trial registration no. ChiCTR1800016646 (date of registration, 14/06/2018).

Transversus abdominis plane block reduces remifentanil and propofol consumption, evaluated by closed-loop titration guided by bispectral index.

The present prospective, randomized, double-blind study aimed to determine the impact of transversus abdominis plane (TAP) block on propofol and remifentanil consumption, when administered by closed-loop titration guided by processed electroencephalography, i.e., bispectral index (BIS) values. Following institutional review board approval, 60 patients were scheduled for laparoscopic colectomy under general anesthesia. Patients were randomly assigned to receive bilateral TAP block with 20 ml 0.375% ropivacaine (TAP group) or 20 ml 0.9% saline [control (CON) group]. General anesthesia was maintained with propofol and remifentanil administration using closed-loop titration guided by BIS values. The primary outcome was perioperative propofol and remifentanil consumption. The secondary outcomes were hypertensive or hypotensive events requiring treatment, recovery time in PACU and time to first rescue analgesia following surgery. A total of 58 patients participated in the present study. At similar depths of anesthesia, as measured by BIS during the maintenance phase (45-55), patients who received TAP blocks required less propofol (4.2±1.3 vs. 5.5±1.6 mg/kg/h; P<0.001) and remifentanil (0.16±0.05 vs. 0.21±0.05 µg/kg/min; P<0.001). Time to extubation was significantly shorter in the TAP group (9.8±3.2 min) than in the CON group (14.2±4.9 min) (P<0.05). The requirement to treat hemodynamic change was also significantly lower (P<0.05). Pain score at 2 h after surgery was also significantly reduced in the TAP group compared with the CON group (P<0.05), whereas the time to first rescue analgesia was delayed in patients who received TAP block (P<0.05). Postoperative nausea and vomiting occurred at comparable rates in each group (P>0.05). In conclusion, TAP block combined with general anesthesia reduced propofol and remifentanil consumption, shortened time to tracheal extubation and promoted hemodynamic stability in laparoscopic colectomy.