Dexmedetomidine ameliorates x-ray-induced myocardial injury via alleviating cardiomyocyte apoptosis and autophagy.

BACKGROUND: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice. METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1). RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy. CONCLUSION: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.

Pre-treatment with morphine prevents lipopolysaccharide-induced acute respiratory distress syndrome in rats via activation of opioid receptors.

PURPOSE: Acute respiratory distress syndrome (ARDS), a severe medical condition, is among the major causes of death in critically ill patients. Morphine is used as a therapeutic agent against severe pain. The mechanisms of its reactions over ARDS are not fully understood. The aim of this study was to assess the mechanism of morphine in rats with ARDS. METHODS: Rats were injected with lipopolysaccharide to induce ARDS, and some rats were pre-treated with graded doses of morphine in the lateral ventricles to assess survival and non-infected mortality. Immunohistochemical and HE staining were performed to measure MPO and CD68 activity in the lungs and lung injury. ELISA was conducted to detect the inflammatory factor levels in the plasma and BALF. Co-labeling of µ-opioid receptor (MOR) and c-Fos was observed in the brain tissues. MOR-positive cells in brain tissues were evaluated using immunohistochemistry. The effect of MOR antagonists on ARDS was examined in rats by pre-injection of naloxone or methylnaltrexone. The expression of MyD88, TLR4, and NF-κB was lastly assessed. RESULTS: Dose-independent improvement was observed in respiratory capacity and lung injury in ARDS rats after morphine pre-injection, along with reduced inflammatory factors in the plasma and BALF. MOR-positive cells were elevated after morphine, which occurred within the ventral part of the gigantocellular reticular nucleus (GiV). Naloxone and methylnaltrexone blocked the effects of morphine via central and peripheral MOR. Morphine activated TLR pathway in a MyD88-dependent manner. CONCLUSION: Morphine activates MOR within the GiV and the TLR pathway to attenuate ARDS in rats.

Postoperative infusion of dexmedetomidine via intravenous patient-controlled analgesia for prevention of postoperative delirium in elderly patients undergoing surgery.

BACKGROUND: Postoperative delirium (POD) is a common clinical complication in elderly patients after surgery and predicts poor outcomes. AIM: We researched whether postoperative infusion of dexmedetomidine (DEX) had prophylactic effect on POD in elderly patients. METHODS: A total of 236 patients over the age of 60 years undergoing thoracoabdominal tumor surgery were enrolled in Zhejiang Cancer Hospital from November 2016 to October 2020. The patients were randomly assigned into DEX group (group D) and control group (Group C). DEX was provided via PCIA pump 1-3 days after surgery, which consisted of 3 ug/kg sufentanil and 3 ug/kg DEX in group D, and 3 ug/kg sufentanil without DEX in group C. The PCIA parameters were programmed as follows: total amount 150 ml, 2 ml bolus dose with a lock-out of 10 min and background infusion rate 2 ml/h. The primary endpoint was the incidence of POD, assessed twice daily within 7 days after surgery by Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). The secondary endpoint was postoperative hospitalization days, ICU stay time, adverse events and non-delirium complications. RESULTS: The incidence of POD in all patients was 7%. The incidence of POD in group C was significantly higher than that in group D (10.1% vs 3.4%, P = 0.042). There were no significant differences in length of hospital stay after operation, ICU stay time, the percentage of patients discharged within 7 days after surgery, non-delirium complications, and 30-day all-cause deaths between the two groups. The incidence of hypertension in group D was lower than that in group C (P = 0.003), and there were no differences in other adverse events. CONCLUSION: Patients aged over 60 years received DEX in addition to intravenous patient-controlled analgesia (PCIA) for major thoracoabdominal surgery experienced less delirium.

Incidence of oxygen desaturation using a high-flow nasal cannula versus a facemask during flexible bronchoscopy in patients at risk of hypoxemia: a randomised controlled trial.

BACKGROUND: Patients with obstructive sleep apnoea (OSA), male sex, obesity, older age or hypertension are prone to hypoxemia during flexible bronchoscopy. This study investigated whether using a high-flow nasal cannula (HFNC) could reduce the incidence of oxygen desaturation during bronchoscopy under deep sedation in patients at risk of hypoxemia. METHODS: A total of 176 patients at risk of hypoxemia who underwent flexible bronchoscopy under deep sedation were randomly assigned to two groups: the HFNC group (humidified oxygen was supplied via a high-flow nasal cannula at a rate of 60 L/min and a concentration of 100%, n = 87) and the facemask group (oxygen was supplied via a tight-fitting facemask at a rate of 6 L/min and a concentration of 100%, n = 89). RESULTS: Oxygen desaturation occurred in 4 (4.6%) patients in the HFNC group and 26 (29.2%) patients in the facemask group (P < 0.001). The facemask group required more jaw thrust manoeuvres than the HFNC group (43[48.3%] vs. 5[5.7%], P < 0.001). 8 patients (9.0%) in the facemask group and none in the HFNC group required bag-mask ventilation (P = 0.012). CONCLUSION: The use of an HFNC can reduce the incidence of oxygen desaturation and the requirement for airway intervention in patients at risk of hypoxemia during flexible bronchoscopy under deep sedation. TRIAL REGISTRATION: www.chiCTR.org.cn Identifier: ChiCTR2100044105. Registered 11/03/2021.

Effect of Deep Versus Moderate Neuromuscular Block on Pain After Laparoscopic Colorectal Surgery: A Randomized Clinical Trial.

BACKGROUND: Anesthesia with deep neuromuscular block for laparoscopic surgery may result in less postoperative pain with lower intra-abdominal pressure. However, results in the existing literature are controversial. OBJECTIVE: The study aimed to evaluate the effect of deep neuromuscular block on postoperative pain at rest and during coughing after laparoscopic colorectal surgery. DESIGN: The design is a parallel-group, randomized clinical trial. SETTINGS: The study was conducted at a tertiary care center. PATIENTS: Patients undergoing laparoscopic resection of colorectal tumors were included. INTERVENTIONS: Patients were randomly assigned to either a deep (posttetanic count 1 to 2) or moderate (train-of-four 1 to 2) neuromuscular group. MAIN OUTCOME MEASURES: The coprimary efficacy outcomes were numeric rating scale scores of the postoperative pain at rest and during coughing after surgery. RESULTS: Pain was lower in the deep neuromuscular block group at rest and during coughing at 1, 6, 24, and 48 hours after surgery (median difference of 2 points and 1 point at 1 h; p < 0.001 at each time point). The deep neuromuscular block group displayed a significantly lower number of bolus attempts by the patient (4 in the deep group vs 9 in the moderate group; p < 0.001) and boluses delivered (4 in the deep group vs 9 in the moderate group; p < 0.001) on postoperative day 1. The number of rescue analgesics was lower in the deep group on postoperative day 2 (p < 0.001). The deep neuromuscular block group showed a lower frequency of postoperative nausea and vomiting (p = 0.02) and lower intraoperative intra-abdominal pressure (p < 0.001). LIMITATIONS: This was a single-center study. CONCLUSIONS: Deep neuromuscular block resulted in better pain relief and lower opioid consumption and use of rescue analgesics after laparoscopic colorectal surgery. Deep neuromuscular block was associated with less postoperative nausea and vomiting and facilitated the use of lower intra-abdominal pressure in laparoscopic surgery. See Video Abstract at http://links.lww.com/DCR/B458. EFECTO DEL BLOQUEO NEUROMUSCULAR PROFUNDO VERSUS MODERADO EN EL DOLOR, DESPUS DE LA CIRUGA COLORRECTAL LAPAROSCPICA UN ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La anestesia con bloqueo neuromuscular profunda para cirugía laparoscópica, puede resultar con menor dolor postoperatorio y con menos presión intraabdominal. Sin embargo, los resultados en la literatura existente son controvertidos.OBJETIVO:El objetivo del estudio, fue evaluar el efecto del bloqueo neuromuscular profundo en dolor postoperatorio de reposo y con la tos, después de cirugía colorrectal laparoscópica.DISEÑO:Ensayo clínico aleatorizado de grupos paralelos.AJUSTE:El estudio se realizó en un centro de atención terciaria.PACIENTES:Se incluyeron pacientes sometidos a resección laparoscópica de tumores colorrectales.INTERVENCIONES:Los pacientes fueron aleatorizados a un grupo neuromuscular profundo (recuento posttetánico 1 a 2) o moderado (tren de cuatro 1 a 2).PRINCIPALES MEDIDAS DE RESULTADO:Los resultados coprimarios de eficacia, fueron las puntuaciones numéricas en la escala de calificación del dolor postoperatorio en reposo y durante la tos, después de la cirugía.RESULTADOS:El dolor fue menor en el grupo de bloqueo neuromuscular profundo en reposo y durante la tos, en 1, 6, 24, 48 horas después de la cirugía, (diferencia de mediana de 2 puntos y 1 punto respectivamente en 1 hora; p <0,001 en cada punto de tiempo). El grupo de bloqueo neuromuscular profundo, mostró un número significativamente menor de intentos de bolo por parte del paciente, (4 en el grupo profundo versus 9 del grupo moderado, p <0,001) y de bolos administrados (4 en el grupo profundo versus 9 en el grupo moderado, p <0,001) en el primer día postoperatorio. El número de analgésicos de rescate, fue menor en el grupo profundo en el segundo día postoperatorio (p <0,001). El grupo de bloqueo neuromuscular profundo, mostró una menor frecuencia de náuseas y vómitos postoperatorios (p = 0,02) y una menor presión intraoperatoria e intraabdominal (p <0,001).LIMITACIONES:Este estudio fue un estudio de un solo centro.CONCLUSIONES:El bloqueo neuromuscular profundo, resultó en mayor alivio del dolor y menor consumo de opioides y uso de analgésicos de rescate, después de la cirugía colorrectal laparoscópica. El bloqueo neuromuscular profundo, se asoció con menos náuseas y vómitos posoperatorios y facilitó el uso de una presión intraabdominal más baja, en la cirugía laparoscópica. Consulte Video Resumen en http://links.lww.com/DCR/B458.

Sedation and Analgesia for Liver Cancer Percutaneous Radiofrequency Ablation: Fentanyl and Oxycodone Comparison.

Background: Sedation and analgesia use in percutaneous radiofrequency ablation (RFPA) for liver cancer is a necessary part of the procedure; however, the optimal medicine for sedation and analgesia for PRFA remains controversial. The aim of this study was to compare the perioperative pain management, haemodynamic stability and side effects between oxycodone (OXY) and fentanyl (FEN) use in patients under dexmedetomidine sedation. Methods: Two hundred and five adults with an American Society of Anaesthesiologists physical status score of I to II were included in this study. Patients were assigned to the OXY (n=101) or FEN (n=104) group. Radiofrequency ablation was performed under spontaneous breathing and with painless anaesthesia administered intravenously. The outcomes included fluctuations in mean arterial pressure, heart rate, side effects and the perioperative numerical rating scale (NRS). Results: Radiofrequency ablation was successfully performed in 205 patients. No significant differences were observed in mean blood pressure fluctuations between the two groups despite the longer durations of ablation and total sedation time in the OXY group. The highest NRS score during the surgery and 1 hour and 2 hours after the surgery were significantly lower in the OXY group than in the FEN group. Heart rate fluctuations were significantly lower in the OXY group than in FEN group throughout the surgery. More patients in the FEN group displayed unwanted body movement and respiratory depression. Conclusions: Both oxycodone and fentanyl can be applied for liver cancer percutaneous radiofrequency ablation; however, oxycodone provides a better patient experience, lower postoperative pain, less respiratory depression and stable haemodynamic fluctuations.

Sufentanil Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury by Suppressing Inflammation.

BACKGROUND Inflammation is one of the most significant mechanisms of hepatic ischemia-reperfusion injury (IRI). Sufentanil has a protective effect against liver injury by reducing inflammatory response. In this study, we used a cellular hepatic ischemic/reoxygenated (IR) model to determine whether sufentanil preconditioning protects against hepatic IRI. MATERIAL AND METHODS The human normal liver cells line L-O2 was studied. The levels of glutamic oxaloacetic transaminase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), and superoxide dismutase (SOD) were measured using corresponding assay kits. The protein levels of total and phosphorylated ERK1/2, JNK, and p38, and the expression of p65 and COX2 genes, were measured by Western blotting. The levels of inflammatory factors were examined by ELISA. The Cell Counting Kit-8 (CCK-8) was used to determine if the viability of L-O2 cells was affected by sufentanil. The effects of sufentanil on IR-induced cell apoptosis were examined by flow cytometry. RESULTS IR-induced caused L-O2 cells to become rounded and to have a lower adhesive rate than normal cells. The levels of AST, LDH, and MDA were higher but the level of SOD was lower in the IR group than in the control group. The phosphorylated protein levels of ERK1/2, JNK, and p38, along with the expression of p65 and COX2, were upregulated in the IR group compared to the normal group. In addition, a variety of inflammatory factors were secreted in L-O2 cells after IR. The viability of L-O2 cells decreased and cell apoptosis increased significantly after IR treatment. All indexes of cell injury were reversed by sufentanil in a concentration-dependent manner. CONCLUSIONS Sufentanil stimulation triggers downregulation of inflammatory factors such as HIF-1alpha, TNF-alpha, IL-1ß, and IL-6, possibly through suppressing the p38/ERK/JNK/NF-kappaB-p65/COX2 pathways, and thereby reduces the damage to IR hepatic cells.

Antiangiogenic effects of oridonin.

BACKGROUND: Oridonin, the major terpene found in Rabdosia rubescens (Henmsl.) Hara, is widely used as a dietary supplement and therapeutic drug. Oridonin has been proven to possess good anti-tumour activity, but little is known about its effect on angiogenesis. The aim of this study was to investigate the antiangiogenic effects of oridonin in vivo and in vitro and prove that oridonin anti-tumour activity is based on suppressing angiogenesis. METHODS: In vitro, the antiangiogenesis effect was studied by proliferation, apoptosis, migration, invasion, and tube formation experiments on human umbilical vascular endothelial cells (HUVECs). In vivo, using the Tg (fli1: GFP) zebrafish model, the embryonic vasculogenesis and postnatal regeneration were evaluated. The vascular endothelial growth factor (VEGF) signalling pathway gene expressions were assessed by reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the inhibition effects on tumour growth and metastasis were observed using a xenograft zebrafish tumour model and xenograft nude mouse tumour model. Angiogenesis was assayed by immunostaining with cluster of differentiation 31. Importantly, the proteins were identified as being differentially expressed in an in vivo model by two-dimensional electrophoresis-mass spectrometry (2D-MS) and western blot (WB). RESULTS: The results indicated that oridonin inhibited HUVEC proliferation, migration, invasion, and tube formation and induced cell apoptosis. Oridonin inhibited zebrafish angiogenesis during embryonic development and tail fin regeneration. RT-PCR showed that oridonin decreased the VEGFA, VEGFR2, and VEGFR3 expressions in zebrafish, while the TP53 expression increased. Moreover, oridonin had strong effects on tumour growth and metastasis in vivo. 2D-MS identified a total of 50 proteins differentially expressed (17 up-expressed, 28 down-expressed). Lastly, WB showed that Claudin 1, Claudin 4, and Claudin 7 were closely related to tumour growth and metastasis. CONCLUSION: This study demonstrated that oridonin could inhibit tumour growth and metastasis, which mainly based on oridonin antiangiogenic effects. Claudin 1, Claudin 4, and Claudin 7 were the main contributors to the mechanism.

Epigenetic modulation of neuronal apoptosis and cognitive functions in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE), which associates with neuronal apoptosis and cognitive disorders, is a common complication of systemic sepsis. However, the mechanism involving its modulation remains to be elucidated. Recent studies showed that histone deacetylases (HDACs) were implicated in neurodegeneration and cognitive functions. The current study was designed to investigate whether septic brain is epigenetically modulated by HDACs, using cecal ligation and peroration (CLP) rats and primary hippocampal neuronal cultures. We found that hippocampal acetylated histone 3 (AcH3), acetylated histone 4 (AcH4), cytoplasmic HDAC4 and Bcl-XL were inhibited in septic brain. Hippocampal Bax and nuclear HDAC4 expressions were enhanced in CLP rats. Administration of HDACs inhibitor, trichostatin A (TSA) or suberoylanilide hydroxamic acid (SAHA) rescued the changes of Bcl-XL and Bax in vivo, and decreased apoptotic cells in vitro. In addition, HDAC4 shRNA transfection significantly enhanced AcH3, AcH4 and Bcl-XL, but suppressed Bax. Neuronal apoptosis was also reduced by transfection of HDAC4 shRNA. Furthermore, CLP rats exhibited significant spatial learning and memory deficits, which could be ameliorated by application of TSA or SAHA without influence on locomotive activity. These results reveal that epigenetic modulation is involved in septic brain, and the inhibition of HDACs may serve as a potential therapeutic approach for SAE treatment.

Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study.

BACKGROUND: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate. OBJECTIVE: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy. DESIGN: Prospective, randomized, and controlled study. METHODS: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively. RESULTS: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate. CONCLUSION: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy. REGISTRATION: NCT05298319 at ClinicalTrials.gov.

High-flow nasal cannula oxygenation during bronchoscopyMany patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that's causing trouble to find out what's wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there's a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren't sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levels­like slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.

Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway.

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer.

Sevoflurane enhances autophagy via Rac1 to attenuate lung ischaemia‒reperfusion injury.

Sevoflurane can attenuate lung ischaemia‒reperfusion injury (LIRI). However, the protective mechanism is unclear. In this study, we developed a LIRI model in vivo that animals (SD, n = 15) were subjected to the administration of 2.2 % sevoflurane 30 min before the onset of left pulmonary artery clamping for 45 min, which was then followed by 60 min of reperfusion treatment. Then, transcriptome sequencing was used to analyse lung tissues. Autophagy inhibition (3-MA) and Rac1-overexpression transfection plasmids were used in BEAS-2B cells, and BEAS-2B cells were subjected to hypoxia reoxygenation (H/R) and sevoflurane treatment. In both animal tissue and cells, inflammatory cytokines and apoptotic and autophagy molecules were measured by quantitative real-time PCR, western blotting and immunostaining. As a result, decreased arterial partial oxygen and damage to the histological structure of lung tissues were observed in LIRI model rats, and these effects were reversed by sevoflurane treatment. Activation of inflammation (elevated IL-1ß, IL-6, and TNF-α) and apoptosis (elevated cleaved caspase3/caspase3 and Bax, degraded expression of Bcl2) and inhibition of autophagy (elevated P62, degraded expression of Beclin1 and LC3-II/LC3I) in the model group were ameliorated by sevoflurane. Transcriptome sequencing indicated that the PI3K/Akt pathway regulated by Rac1 plays an important role in LIRI. Furthermore, overexpression of Rac1 in a cell line inhibited the protective effect of sevoflurane in LIRI. Autophagy inhibition (3-MA) also prevented the protective effect of sevoflurane on inflammation and apoptosis. As shown in the present study, sevoflurane enhances autophagy via Rac1/PI3K/AKT signalling to attenuate lung ischaemia‒reperfusion injury.

Ultrasound-Guided Anterior Quadratus Lumborum Block at Lateral Supra-Arcuate Ligament vs Thoracic Epidural Analgesia after Open Liver Surgery: A Randomized, Controlled, Noninferiority Trial.

BACKGROUND: Thoracic epidural analgesia (TEA) has demonstrated great analgesic benefits in open liver surgery. However, the increased risk of postoperative coagulopathy after open liver surgery has promoted interest in alternate analgesic research. We aimed to explore whether ultrasound-guided anterior quadratus lumborum block at the lateral supra-arcuate ligament (LAL-QLB) with intravenous analgesia was noninferior to TEA under multimodal analgesia after open liver surgery. STUDY DESIGN: Seventy-four patients undergoing open liver surgery were randomized (1:1) to the LAL-QLB or TEA group in this open-label study. The primary outcome was the numeric rating scale during coughing at 24 hours postoperatively with a noninferiority limit of 1. RESULTS: The mean difference of numeric rating scale during coughing at 24 hours postoperatively was 0.32 (95% CI -0.03 to 0.68), showing noninferiority. The TEA group had better pain scores at 1 and 6 hours, and the early postoperative pain of the LAL-QLB group was within the clinically acceptable limit with no differences at other time points. The LAL-QLB group received more opioids within 24 hours postoperatively. There were no differences in analgesia-related adverse reactions or rescue analgesia. Postoperative coagulopathy was responsible with 19.4% of delayed epidural removal. TEA outperformed LAL-QLB in terms of ambulation and bowel recovery. There were no differences in hospital stay or 30-day postoperative complications. CONCLUSIONS: LAL-QLB provided noninferior analgesia at 24 hours postoperatively. Despite regarding coagulopathy and delayed epidural removal, TEA was found to be better than LAL-QLB for pain management after open liver surgery. Epidural removal required close coagulation test.

Comparison of Remimazolam-Flumazenil versus Propofol for Rigid Bronchoscopy: A Prospective Randomized Controlled Trial.

Background: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative−hypnotic that significantly reduces the times to sedation onset and recovery. This trial was conducted to confirm the recovery time from anesthesia of remimazolam-flumazenil versus propofol in patients undergoing endotracheal surgery under rigid bronchoscopy. Methods: Patients undergoing endotracheal tumor resection or stent implantation were randomly allocated into a remimazolam group (Group R) or a propofol group (Group P). The primary outcome was the recovery time from general anesthesia. The secondary outcomes were the time to loss of consciousness (LoC), hemodynamic fluctuations, and adverse events. Results: A total of 34 patients were screened, and 30 patients were enrolled in the study. The recovery time was significantly shorter for Group R (140 ± 52 s) than for Group P (374 ± 195 s) (p < 0.001). The times to LoC were 76 ± 40 s in Group R and 75 ± 25 s in Group P and were not significantly different. There were also no significant differences in hemodynamic fluctuations or adverse events between the two groups. Conclusions: The recovery time from general anesthesia in rigid bronchoscopy patients was shorter using remimazolam-flumazenil than with propofol, with no dramatic hemodynamic fluctuations and adverse events or differences between the agents. Remimazolam-flumazenil allows for faster recovery from anesthesia than propofol.

The Rostral Ventromedial and Lateral Medulla Are the Major Areas Responsive to Lung Cancer Progression among Brainstem Lung-Innervating Nuclei.

In recent years, the information crosstalk between the central nervous system and the periphery has been a hot topic, such as the brain-gut axis, brain-lung axis, etc. Among them, some studies have shown that brainstem nuclei activity can significantly affect the progression of peripheral tumor; however, regarding lung cancer, our understanding of the basic characteristics of the lung-innervating brain nuclei responsive to lung cancer progression remains deficient. Therefore, we used the pseudorabies virus for retrograde labeling of nerves to study the neural circuits between the lung and brain. We then established a mouse orthotopic lung cancer model and used the expression of the c-Fos gene in brain regions to characterize activated brain circuits and compared these results with those of the control group. We focused on c-Fos activity in nuclei associated with retrograde tracing regions of the brainstem. We found over 16 nuclei in the whole brain with direct or indirect lung innervation through neural retrograde labeling with the pseudorabies virus. We further revealed that the neuronal activity of the rostral ventrolateral reticular nucleus (RVL), caudal nucleus of Raphe (raphe obscurus nucleus, ROb), Raphe pallidus nucleus (RPa), and ventral gigantocellular reticular nucleus (GiV) in the rostral ventromedial and lateral medulla were significantly changed in an orthotopic lung cancer mouse model by the immunostaining of c-Fos early responsive protein. Thus, the distinctive rostroventral medulla area, functionally closely related to the vagus nerve, likely plays a role in central neural interaction with peripheral lung tumors and deserves future investigation.

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis.

Ropivacaine, a common local anesthetic in the clinic, has anti-proliferative and pro-apoptotic effects in numerous cancers, however, the underlying regulatory mechanism of ropivacaine in hepatocellular carcinoma remains unclear. In the current study, human HepG2 cells were stimulated with different ropivacaine concentrations. Cell Counting Kit-8 assay, cell colony formation, and cell cycle were used to monitor cell viability. Cell apoptosis, migration, and invasion were determined by flow cytometry and transwell assays. Tumor xenograft experiments were performed to prove the anti-cancer effect of ropivacaine in vivo. A high dose of ropivacaine inhibited proliferation and promoted apoptosis of HepG2 cells in a dose-dependent manner. Ropivacaine challenge also arrested cells in the G2 phase, followed by a decline in the protein expression of cyclin D1 and cyclin-dependent kinase 2, and an increase in p27 levels in HepG2 cells. Additionally, different ropivacaine doses suppressed cell migration and invasion by upregulating E-cadherin expression and downregulating N-cadherin expression. Mechanically, ropivacaine challenge gradually restrained insulin-like growth factor-1 receptor (IGF-1 R) expression and the activities of phosphorylated-PI3K, AKT, and mTOR in HepG2 cells with increased ropivacaine doses. In the tumor xenograft experiment, ropivacaine was confirmed to inhibit tumor growth, accompanied by inhibition of the IGF-1 R/PI3K/AKT/mTOR signaling axis. In conclusion, ropivacaine suppressed tumor biological characteristics and promoted apoptosis, resulting in the suppression of hepatocellular carcinoma progression by targeting the IGF-1 R/PI3K/AKT/mTOR signaling pathway. It is possible that ropivacaine-mediated local anesthesia may be developed as a novel surgical adjuvant drug for treating hepatocellular carcinoma.

Smoking is a risk factor for postoperative ileus after radical resection in male patients.

ABSTRACT: Most smokers are males, and smoking has been indicated as a risk factor for many cancers as well as postoperative complications after cancer surgery. However, little is known about whether smoking is a risk factor for postoperative ileus (POI) after radical rectal cancer resection in males. The aim of this study was to assess whether smoking is a risk factor for POI after radical resection in male rectal cancer patients.Data of 1486 patients who underwent radical resection for rectal cancer were extracted from the clinical medical system in our hospital and were statistically analyzed. POI was defined as nausea, vomiting or pain, failure to have bowel function for more than 4 days postoperatively, and absence of a mechanical bowel obstruction.The rate of POI was 12.79%. Univariate analysis showed that patients in the POI group were more likely to have a history of smoking and drinking and receive intraperitoneal chemotherapy and had a larger intraperitoneal chemotherapy dosage. In the multivariable analysis, smoking remained significantly associated with a higher incidence of POI (OR 2.238, 95% CI [1.545-3.240], P = .000). The results also showed that patients who received postoperative patient-controlled intravenous analgesia had a lower incidence of POI.Male patients with a history of smoking who undergo elective radical resection for rectal cancer have an increased risk for POI complications.

[The effect of neoadjuvant chemotherapy on patient controlled intravenous analgesia postoperatively in ovarian cancer patients].

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on patient controlled intravenous analgesia (PICA) postoperatively in ovarian cancer patients. METHODS: Sixty three patients with ovarian cancer (ASA I--III grade) were selected. They were divided into 2 groups according to with or without neoadjuvant chemotherapy: neoadjuvant chemotherapy group (N) 33 cases, direct operation group (D) 30 cases. Both of them were completed with tumor cell reduction-extinction operation under total intravenous general anesthesia. Patients' chemotherapy-induced peripheral neuropathy (CIPN) was assessed by the total neuropathy score exclusively clinically-based (TNSc) preoperatively, the assessment of analgesic effect and side-effect was performed postoperatively. RESULTS: No statistically significant difference between the two groups (P > 0.05) on ages, body mass index, ASA grades and Karnofsky scores. Patients in group N were significantly lower than that of group D (P < 0.05) on the VAS scores at 2, 4, 8 h postoperatively, the pressure times and effective times of Bolus and the total consumption amount of analgesic drug in the whole process of analgesia treatment But the scores on nausea and vomiting of group N were significantly higher than that of group D (P < 0.05). There were no significant differences on Bruggemann comfort scale at 2, 4, 8, 12 h postoperatively, dizziness scores, pruritus scores and Ramsay Sedation scores between this two groups (P > 0.05). There was negative linear correlation between the total consumption amount of analgesic drug in the whole process of analgesia treatment and TNSc scores (r = -0.881, P = 0.048), and there was positive linear correlation between nausea scores and TNSc scores (r = 0.920, P = 0.027). CONCLUSION: Patients with neoadjuvant chemotherapy have peripheral neuropathy at different degree before operation. The more serious of peripheral neuropathy, the less demand of PCIA analgesic drug postoperatively and with more side effects occur, such as nausea.

Efficacy of oxycodone in intravenous patient-controlled analgesia with different infusion modes after laparoscopic radical surgery of cervical cancer a prospective, randomized, double-blind study.

BACKGROUD: The aim of this study was to compare the analgesic and adverse effects of oxycodone with 3 different infusion modes on postoperative pain after laparoscopic radical surgery of cervical cancer. METHODS: Ninety patients undergoing laparoscopic radical surgery of cervical cancer were randomly divided into 3 groups: Group A (continuous infusion with 0.01 mg/kg/h and a bolus dose with 0.03 mg/kg), Group B (a bolus dose with 0.03 mg/kg) and Group C (PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass). A blinded observer recorded Visual Analogue Scale (VAS), Ramsay sedation score (RSS), infused cumulative dose of oxycodone and side effects at 1, 6, 12, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. RESULTS: There were significant differences in the VAS pain score when resting or coughing among 3 groups at 1, 6 and 48 hours postoperatively (P <.05). VAS was significantly higher in Group B than in Group A and C until postoperative 1, 6, and 48 hours (P <.05). There were significant differences in cumulative PCA dose among the 3 groups at 1 and 48 hours postoperatively (P <.05). Group C showed significantly less amount of cumulative PCA dose compared to other 2 groups at 1 hour, whereas cumulative PCA dose of Group A at 48 hours was significantly more than other 2 groups (P <.05). There were no significant differences in postoperative nausea and vomiting, FAS, muscle chilling score and RSS among 3 groups at 1, 6, 12, 24 and 48 hours postoperatively. In addition, there was no difference in overall satisfaction during 48 hours postoperatively among 3 groups. CONCLUSIONS: Oxycodone provides significant analgesic effect in 3 different infusion modes over 48 hours after laparoscopic radical surgery of cervical cancer, and a time-scheduled decremental continuous infusion of oxycodone can become a better choice for patients after surgery of cervical cancer.