The Inhibitory Effects of Propofol on Colorectal Cancer Progression through the NF-κB/HIF-1α Signaling Pathway.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is a neoplastic disease that gradually develops due to genetic variations and epigenetic changes. Surgical excision is the first-line treatment for CRC. Accumulating evidence has shown that total intravenous anesthesia has beneficial effects for CRC patients as it decreases the probability of tumor recurrence and metastasis. Propofol is one of the most frequently used intravenous anesthetics in clinical practice. However, it remains unknown whether it can reduce recurrence and metastasis after surgery in cancer patients. METHODS: CRC cell lines (HCT116 and SW480) were cultured in vitro, and different concentrations of propofol were added to the cell culture medium. The proliferation effect of propofol on CRC cell lines was evaluated by CCK-8 assay. The effect of propofol on the migration and invasion of CRC cells was evaluated by scratch healing and Transwell experiments. The inhibitory effects of propofol on NF-κB and HIF-1α expressions in CRC cell lines were determined by Western blotting and immunofluorescence assays to further clarify the regulatory effects of propofol on NF-κB and HIF-1α. RESULTS: Compared to the control, propofol significantly inhibited the proliferation, migration, and invasion abilities of CRC cells (HCT116 and SW480) (P < 0.0001). The expression levels of NF-κB and HIF-1α gradually decreased with increasing propofol concentration in both cell lines. After activation and inhibition of NF-κB, the expression of HIF-1α changed. Further studies showed that propofol inhibited LPS-activated NF-κB-induced expression of HIF-1α, similar to the NF-κB inhibitor Bay17083 (P < 0.0001). CONCLUSION: In vitro, propofol inhibited the proliferation, migration, and invasion of CRC cells (HCT116 and SW480) in a dose-dependent manner, possibly by participating in the regulation of the NF-κB/HIF-1α signaling pathway.

Urinary oxygen tension and its role in predicting acute kidney injury: A narrative review.

Acute kidney injury occurs frequently in the perioperative setting. The renal medulla often endures hypoxia or hypoperfusion and is susceptible to the imbalance between oxygen supply and demand due to the nature of renal blood flow distribution and metabolic rate in the kidney. The current available evidence demonstrated that the urine oxygen pressure is proportional to the variations of renal medullary tissue oxygen pressure. Thus, urine oxygenation can be a candidate for reflecting the change of oxygen in the renal medulla. In this review, we discuss the basic physiology of acute kidney injury, as well as techniques for monitoring urine oxygen tension, confounding factors affecting the reliable measurement of urine oxygen tension, and its clinical use, highlighting its potential role in early detection and prevention of acute kidney injury.

Effects of different depth of anesthesia on perioperative inflammatory reaction and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy.

BACKGROUND: To investigate the effect of different depth of anesthesia on inflammatory factors and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy for gastric cancer, in order to select an appropriate depth of anesthesia to improve the prognosis of patients undergoing surgery and improve the quality of life of patients. METHODS: A total of 80 elderly patients aged 65 and above who underwent laparoscopic radical gastrectomy in our hospital were by convenience sampling and randomly divided into two groups : 55 groups ( group H ) and 45 groups ( group L ), 40 cases in each group. The depth of anesthesia was maintained using a closed-loop target-controlled infusion system: the EEG bispectral index was set to 55 in the H group and 45 in the L group. Venous blood samples were collected 2 h (T2), 24 h (T3) and 72 h (T4) after the start of surgery. The intraoperative dosage of propofol and remifentanil, operation duration, postoperative PACU stay time, intraoperative consciousness occurrence, postoperative hospital stay and postoperative pulmonary inflammatory events were recorded. RESULTS: The patient characteristic of the two groups had no statistical difference and were comparable (P > 0.05). The intraoperative dosage of propofol in group H was lower than that in group L (P < 0.05). Compared with the L group, the plasma IL-6 and IL-10 concentrations in the H group were significantly increased at T2 (P < 0.05), and the plasma IL-10 concentration was significantly increased at T4 (P < 0.05). The plasma concentrations of IL-6 and IL-10 were higher in both groups at T2, T3 and T4 than at T1, while at T4, the concentration of TNF-α in group H was higher than at T1 (P < 0.05). CONCLUSION: When the BIS value of the depth of anesthesia is 45, the perioperative release of inflammatory factors in elderly patients with laparoscopic radical gastrectomy for gastric cancer is less than BIS 55, and does not affect the prognosis.

Provisional Decision-Making for Perioperative Blood Pressure Management: A Narrative Review.

Blood pressure (BP) is a basic determinant for organ blood flow supply. Insufficient blood supply will cause tissue hypoxia, provoke cellular oxidative stress, and to some extent lead to organ injury. Perioperative BP is labile and dynamic, and intraoperative hypotension is common. It is unclear whether there is a causal relationship between intraoperative hypotension and organ injury. However, hypotension surely compromises perfusion and causes harm to some extent. Because the harm threshold remains unknown, various guidelines for intraoperative BP management have been proposed. With the pending definitions from robust randomized trials, it is reasonable to consider observational analyses suggesting that mean arterial pressures below 65 mmHg sustained for more than 15 minutes are associated with myocardial and renal injury. Advances in machine learning and artificial intelligence may facilitate the management of hemodynamics globally, including fluid administration, rather than BP alone. The previous mounting studies concentrated on associations between BP targets and adverse complications, whereas few studies were concerned about how to treat and multiple factors for decision-making. Hence, in this narrative review, we discussed the way of BP measurement and current knowledge about baseline BP extracting for surgical patients, highlighted the decision-making process for BP management with a view to providing pragmatic guidance for BP treatment in the clinical settings, and evaluated the merits of an automated blood control system in predicting hypotension.

Application of Ultrasound-Guided Upper Trunk Brachial Plexus Block in Observation of Lower Shoulder Surgery.

This study aims to ensure the wide application of ultrasound-guided superior brachial plexus block in shoulder surgery, solve the application problem of ultrasound-guided superior brachial plexus block in shoulder surgery, make up for severe postoperative pain after shoulder arthroscopy, and improve the patient's recovery ability. In this paper, 90 patients with shoulder arthroscopy were divided into 3 groups: A, B, and C. In recent years, with the rapid development of medicine, ultrasound-guided brachial plexus upper trunk block has been widely used in shoulder surgery. Shoulder arthroscopy is more and more used in the diagnosis and treatment of shoulder diseases because of its advantages of minimally invasive, safe, and rapid recovery. Compared with the traditional operation, it is found that the shoulder arthroscopic operation reduces the incision trauma through the microscope, but the shoulder operation involves more muscles and ligaments, so the perioperative pain of shoulder arthroscopic operation is still serious.

The Effect of Oxycodone on Post-operative Pain and Inflammatory Cytokine Release in Elderly Patients Undergoing Laparoscopic Gastrectomy.

Background: To evaluate the effect of oxycodone on post-operative pain and inflammation in elderly patients undergoing laparoscopic gastrectomy. Methods: Sixty patients who were of both sexes, American Society of Anesthesiologists Physical Status (ASA-PS) Class I or II, over 65 years of age and undergoing an elective laparoscopic radical gastrectomy were randomly divided into two groups: an oxycodone group (Group O) including 20 males and 10 females and a sufentanil group (Group S) including 21 males and 9 females. The post-operative analgesia regimen was as follows: 40 mg of parecoxib sodium and 0.1 mg/kg of oxycodone was intravenously injected into Group O before the abdomen closure, while 40 mg of parecoxib sodium and 0.1 µg/kg of sufentanil was injected intravenously into Group S. Both groups were infiltrated with 20 ml of 1% ropivacaine at the end of the operation. The level of serum IL-6 and IL-10 were assayed immediately at the following timepoints: at the conclusion of surgery (T1), 1 h (T2), 6 h (T3), and 24 h (T4) after the completion of the surgery. The numerical rating scale (NRS), the Ramsay sedation score, analgesic-related adverse events, post-operative pulmonary inflammation events and the post-operative stay were recorded. Results: Compared with Group S, the serum IL-6 concentrations of Group O decreased at T3 and T4, while the serum IL-10 concentrations increased (P < 0.05). In Group O, the serum IL-6 concentrations at T3 and T4 were lower than those at T1 (P < 0.05). The incidence of post-operative nausea and vomiting (PONV) and pulmonary inflammation in Group O was lower than that in Group S (P < 0.05). At each time point, the NRS of visceral pain in Group O was lower than that in Group S. At 6 and 24 h after extubation, the NRS of incision pain in Group O was lower than that in Group S (P < 0.05). Conclusion: Oxycodone can regulate the level of inflammatory cytokines and reduce post-operative inflammatory response.

Effects of salbutamol on the kinetics of sevoflurane and the occurrence of early postoperative pulmonary complications in patients with mild-to-moderate chronic obstructive pulmonary disease: A randomized controlled study.

Bronchodilators dilate the bronchi and increase lung volumes, thereby improving respiratory physiology in patients with chronic obstructive pulmonary disease (COPD). However, their effects on sevoflurane kinetics remain unknown. We aimed to determine whether inhaled salbutamol affected the wash-in and wash-out kinetics of sevoflurane and the occurrence of early postoperative pulmonary complications (PPCs) in patients with COPD undergoing elective surgery. This randomized, placebo-controlled study included 63 consecutive patients with COPD allocated to the salbutamol (n = 30) and control groups (n = 33). The salbutamol group received salbutamol aerosol (2 puffs of ~200 µg) 30 min before anesthesia induction and 30 min before surgery completion. The control group received a placebo. Sevoflurane kinetics were determined by collecting end-tidal samples from the first breaths at 1, 2, 3, 4, 5, 7, 10, and 15 min before the surgery (wash-in) and after closing the vaporizer (wash-out). PPCs were recorded for 7 days. The salbutamol group had higher end-tidal to inhaled sevoflurane ratios (p<0.05, p<0.01) than the control group, from 3 to 10 min during the wash-in period, but no significant differences were observed during the wash-out period. The arterial partial pressure of oxygen to the fraction of inhaled oxygen was significantly higher in the salbutamol group at 30 (320.3±17.6 vs. 291.5±29.6 mmHg; p = 0.033) and 60 min (327.8±32.3 vs. 309.2±30.5 mmHg; p = 0.003). The dead space to tidal volume ratios at 30 (20.5±6.4% vs. 26.3±6.0%, p = 0.042) and 60 min (19.6±5.1% vs. 24.8±5.5%, p = 0.007) and the incidence of bronchospasm (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.23-0.67, p = 0.023) and respiratory infiltration (OR 0.52, 95% CI, 0.40-0.65, p = 0.017) were lower in the salbutamol group. In patients with COPD, salbutamol accelerates the wash-in rate of sevoflurane and decreases the occurrence of postoperative bronchospasm and pulmonary infiltration within the first 7 days.

Inflammatory cytokines in midbrain periaqueductal gray contribute to diabetic induced pain hypersensitivity through phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

BACKGROUND: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. METHODS: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. RESULTS: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1ß, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. CONCLUSIONS: Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

RETRACTED ARTICLE: Involvement of pro-inflammatory cytokines in diabetic neuropathic pain via central PI3K/Akt/mTOR signal pathway.

Retraction statementWe, the Editors and Publisher of Archives of Physiology and Biochemistry, have retracted the following article:Zongming Jiang, Zhonghua Chen, Yonghao Chen, Jing Jiao and Zhifeng WangInvolvement of pro-inflammatory cytokines in diabetic neuropathic pain via central PI3K/Akt/mTOR signal pathway, Archives of Physiology and Biochemistry, Published Online 2019 Aug 9:1-9. DOI: 10.1080/13813455.2019.1651869The article has been retracted following receipt of information from the corresponding author, Zhifeng Wang, on September 11, 2019, informing us that it was realised that inappropriate doses of rapamycin and the corresponding antagonist were used in this study, which may have led to artificial results and misleading interpretations and ultimately do not support the final conclusions drawn by the authors. The article is withdrawn from all print and electronic editions.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted."

Extraluminal bronchial blocker placement using both nostrils for lung isolation in a patient with limited mouth opening: A CARE-compliant case report.

RATIONALE: The establishment of lung isolation is often particularly challenging for the anesthesiologist in patients with difficult airway. Usually, orotracheal intubation with double lumen tube is the commonly used technique for achieving 1 lung anesthesia. Whereas, in patients with limited mouth opening and restricted cervical mobility, this technique becomes extremely difficult and hazardous. We report a case in which bronchial blocker placement was succeeded via both nostrils in a difficult airway due to restricted mouth opening. PATIENT CONCERNS: A 50-year-old, non-smoking female with a painless mass in the left upper lobe. She had a 10-year history of ankylosing spondylitis and squamous cell carcinoma of the floor of the mouth after 5 operations 4 years previously. DIAGNOSES: Left upper lobe adenocarcinoma, ankylosing spondylitis and oral squamous cell carcinoma. INTERVENTIONS: To achieve 1 lung anesthesia, both nostrils were used for extraluminal bronchial blocker placement. OUTCOMES: Initially, oral intubation was selected for establishing a patent airway but failed. Then switched to nasal canal for insertion, after several attempts, a conventional nasal intubation tube (internal diameter 6.0 mm) was placed via 1 nostril under topical anesthesia, with the aid of a flexible fiberoptic bronchoscope, and a bronchial blocker was advanced to the desired position via the other nostril. LESSONS: In difficult airway with limited mouth opening and restricted cervical mobility, multidisciplinary experts participated discussion is a prerequisite for contemplating a scientific plan. Preoperative computed tomography scan and 3-dimensional computed tomography reconstruction would be helpful in detecting the narrowest part of airway conduit and determining a safe, reliable, and feasible airway program.

Effect of Intravenous Oxycodone in Combination With Different Doses of Dexmedetomdine on Sleep Quality and Visceral Pain in Patients After Abdominal Surgery: A Randomized Study.

OBJECTIVE: Oxycodone or dexmedetomidine (DEX) alone are widely used in clinical practice. The aim of this study was to observe the effect of 2 oxycodone and DEX combinations on postoperative sleep quality. METHODS: This was a prospective and randomized clinical study. A total of 99 patients underwent laparoscopic-assisted operations on stomach and intestines with general anesthesia were enrolled and randomly divided into 3 groups according to postoperative analgesic protocol (n=33 each). The analgesic protocols were as follows after the surgery. In group C, 0.6 mg/kg oxycodone alone was diluted to 100 mL in 0.9% saline. In group D1 or D2, 0.6 mg/kg oxycodone combined with 2.4 µg/kg or 4.8 µg/kg DEX was diluted to 100 mL in 0.9% saline, respectively. The intravenous patient-controlled analgesia device was set up to deliver a continuous infusion of 3 mL/h and a bolus of 1 mL, with a 12-minute lockout interval. The primary outcome was the percentage of stage 2 nonrapid eye movement (stage N2) sleep. Polysomnography was performed the night before operation (PSG-night0), the first (PSG-night1) and second (PSG-night2) nights after surgery. RESULTS: A total of 97 patients were included in the final analysis. Compared with group C, N2 sleep were higher in groups D1 and D2 on PSG-night1 (54±9% and 53±10%, respectively) and PSG-night2 (55±7% and 56±8%, respectively) (P<0.001 for all comparisons). No differences were observed regarding N1 and N2 sleep between groups D1 and D2 on PSG-night1 and PSG-night2 (P>0.05). Group C had higher percentage of N1 sleep on PSG-night1 (37±5%) and PSG-night2 (33±3%) when compared with groups D1 and D2 (P<0.001 for the comparisons). Groups D1 and D2 required lower rates of rescue analgesia (5% and 4.7%, respectively; P=0.012) and effective pressing times (10.7±4.8 times and 9.9±2.6 times, respectively; P<0.05) when compared with group C, whereas no statistical significance was found between groups D1 and D2. Furthermore, there were no significant difference about resting visual analogue scales at 4, 6, and 12 hours postoperatively between groups D1 and D2. In comparison with the other 2 groups, group D2 had a higher occurrence of postoperative hypotension (24.2%) (P<0.05), though without significant sinus bradycardia. DISCUSSION: DEX combined with oxycodone can improve sleep quality and provide good visceral analgesia. However, larger doses of DEX does not further improve sleep but increases the risk of hypotension.

Optimal blood pressure decreases acute kidney injury after gastrointestinal surgery in elderly hypertensive patients: A randomized study: Optimal blood pressure reduces acute kidney injury.

STUDY OBJECTIVE: To determine the appropriate mean arterial pressure (MAP) control level for elderly patients with hypertension during the perioperative period. DESIGN: A prospective, randomized study. SETTING: Three teaching hospitals in China. PATIENTS: Six hundred seventy-eight elderly patients with chronic hypertension undergoing major gastrointestinal surgery. INTERVENTIONS: Patients were randomly allocated to three groups and the target MAP level was strictly controlled to one of three levels: level I (65-79mmHg), level II (80-95mmHg), or level III (96-110mmHg). MEASUREMENTS: The primary outcome was acute kidney injury (AKI) (50% or 0.3mg·dL-1increase in creatinine level) during the first 7 postoperative days. The secondary outcomes were perioperative adverse complications. Moreover, vasoactive agents were observed during surgery. MAIN RESULTS: The overall incidence of postoperative AKI was 10.9% (71/648). AKI occurred significantly less often in patients with level II MAP control (6.3%;13/206) than in patients with level I (13.5%; 31/230) and level III (12.9%; 27/210) (P<0.001) MAP control. Level II was associated with lower incidences of hospital-acquired pneumonia (6.7%; 14/206; P=0.014) and admission to the intensive care unit (ICU) (4.4%; 9/206; P=0.015) and with shorter length of stay in the ICU (P=0.025) when compared with level I and level III. Use of norepinephrine, phenylephrine, and nitroglycerin was significantly higher for patients with level III MAP control than for patients with level I and level II MAP control (P=0.001). CONCLUSIONS: For elderly hypertensive patients, controlling intraoperative MAP levels to 80 to 95mmHg can reduce postoperative AKI after major abdominal surgery.

Internal jugular vein versus subclavian vein as the percutaneous insertion site for totally implantable venous access devices: a meta-analysis of comparative studies.

BACKGROUND: A totally implantable venous access device (TIVAD) provides reliable, long-term vascular access and improves patients' quality of life. The wide use of TIVADs is associated with important complications. A meta-analysis was undertaken to compare the internal jugular vein (IJV) with the subclavian vein (SCV) as the percutaneous access site for TIVAD to determine whether IJV has any advantages. METHODS: All randomized controlled trials (RCTs) and cohort studies assessing the two access sites, IJV and SCV, were retrieved from PubMed, Web of Science, Embase, and OVID EMB Reviews from their inception to December 2015. Random-effects models were used in all analyses. The endpoints evaluated included TIVAD-related infections, catheter-related thrombotic complications, and major mechanical complications. RESULTS: Twelve studies including 3905 patients published between 2008 and 2015, were included. Our meta-analysis showed that incidences of TIVAD-related infections (odds ratio [OR] 0.71, 95 % confidence interval [CI] 0.48-1.04, P = 0.081) and catheter-related thrombotic complications (OR 0.76, 95 % CI 0.38-1.51, P = 0.433) were not significantly different between the two groups. However, compared with SCV, IJV was associated with reduced risks of total major mechanical complications (OR 0.38, 95 % CI 0.24-0.61, P < 0.001). More specifically, catheter dislocation (OR 0.43, 95 % CI 0.22-0.84, P = 0.013) and malfunction (OR 0.42, 95 % CI 0.28-0.62, P < 0.001) were more prevalent in the SCV than in the IJV group; however, the risk of catheter fracture (OR 0.47, 95 % CI 0.21-1.05, P = 0.065) were not significantly different between the two groups. Sensitivity analyses using fixed-effects models showed a decreased risk of catheter fracture in the IJV group. CONCLUSION: The IJV seems to be a safer alternative to the SCV with lower risks of total major mechanical complications, catheter dislocation, and malfunction. However, a large-scale and well-designed RCT comparing the complications of each access site is warranted before the IJV site can be unequivocally recommended as a first choice for percutaneous implantation of a TIVAD.

Blocking mammalian target of rapamycin alleviates bone cancer pain and morphine tolerance via µ-opioid receptor.

The current study was to examine the underlying mechanisms responsible for the role of mammalian target of rapamycin (mTOR) in regulating bone cancer-evoked pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats and this evoked significant mechanical and thermal hyperalgesia. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) as well as phosphatidylinositide 3-kinase (p-PI3K) pathways were amplified in the superficial dorsal horn of the spinal cord of bone cancer rats compared with control rats. Blocking spinal mTOR by using rapamycin significantly attenuated activities of PI3K signaling pathways as well as mechanical and thermal hyperalgesia. Additionally, rapamycin enhanced attenuations of protein kinase Cɛ (PKCɛ)/protein kinase A (PKA) induced by morphine and further extended analgesia of morphine via µ-opioid receptor (MOR). Our data for the first time revealed specific signaling pathways leading to bone cancer pain, including the activation of mTOR and PI3K and downstream PKCɛ/PKA, and resultant sensitization of MOR. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of bone cancer pain often observed in clinics.