The impact of Nrf2 knockout on the neuroprotective effects of dexmedetomidine in a mice model of cognitive impairment.

The nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway represents a crucial intrinsic protective system against oxidative stress and inflammation and plays a significant role in various neurological disorders. However, the effect of Nrf2 signalling on the regulation of cognitive impairment remains unknown. Dexmedetomidine (DEX) has neuroprotective effects and can ameliorate lipopolysaccharide (LPS)-induced cognitive dysfunction. Our objective was to observe whether Nrf2 knockout influences the efficacy of DEX in improving cognitive impairment and to attempt to understand its underlying mechanisms. An LPS-induced cognitive dysfunction model in wild-type and Nrf2 knockout mice (Institute of Cancer Research background; male; 8-12 weeks) was used to observe the impact of DEX on cognitive dysfunction. LPS was intraperitoneally injected, followed by novel object recognition and morris water maze experiments 24 h later. Hippocampal tissues were collected for histopathological and molecular analyses. Our research findings suggest that DEX enhances the expression of NQO1, HO-1, PSD95, and SYP proteins in hippocampal tissue, inhibits microglial proliferation, reduces pro-inflammatory cytokines IL-1ß and TNF-ɑ, increases anti-inflammatory cytokine IL-10, and improves dendritic spine density, thereby alleviating cognitive dysfunction induced by LPS. However, the knockout of the Nrf2 gene negated the aforementioned effects of DEX. In conclusion, DEX alleviates cognitive deficits induced by LPS through mechanisms of anti-oxidative stress and anti-inflammation, as well as by increasing synaptic protein expression and dendritic spine density. However, the knockout of the Nrf2 gene reversed the effects of DEX. The Nrf2 signaling pathway plays a crucial role in the mitigation of LPS-induced cognitive impairment by DEX.

Effects of butyrate on intestinal ischemia-reperfusion injury via the HMGB1-TLR4-MyD88 signaling pathway.

BACKGROUND: This study combined bioinformatics and experimental verification in a mouse model of intestinal ischemia-reperfusion injury (IRI) to explore the protection mechanism exerted by butyrate against IRI. METHODS: GeneCards, Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine and GSE190581 were used to explore the relationship between butyrate and IRI and aging. Protein-protein interaction networks involving butyrate and IRI were constructed via the STRING database, with hub gene analysis performed through Cytoscape. Functional enrichment analysis was conducted on intersection genes. A mouse model of IRI was established, followed by direct arterial injection of butyrate. The experiment comprised five groups: normal, sham, model, vehicle, low-dose butyrate, and high-dose butyrate. Intestinal tissue observation was done via transmission electron microscopy (TEM), histological examination via hematoxylin and eosin (H&E) staining, tight junction proteins detection via immunohistochemistry, and Western blot analysis of hub genes. Drug-target interactions were evaluated through molecular docking. RESULTS: Butyrate protected against IRI by targeting 458 genes, including HMGB1 and TLR4. Toll-like receptor pathway was implicated. Butyrate improved intestinal IRI by reducing mucosal damage, increasing tight junction proteins, and lowering levels of HMGB1, TLR4, and MyD88. Molecular docking showed strong binding energies between butyrate and HMGB1 (-3.7 kcal/mol) and TLR4 (-3.8 kcal/mol). CONCLUSIONS: According to bioinformatics predictions, butyrate mitigates IRI via multiple-target and multiple-channel mechanisms. The extent of IRI can be reduced by butyrate through the inhibition of the HMGB1-TLR4-MyD88 signaling pathway, which is related to senescence.

Protecting the non-operative lobe/s of the operative lung can reduce the pneumonia incidence after thoracoscopic lobectomy: a randomised controlled trial.

Lung isolation usually refers to the isolation of the operative from the non-operative lung without isolating the non-operative lobe(s) of the operative lung. We aimed to evaluate whether protecting the non-operative lobe of the operative lung using a double-bronchial blocker (DBB) with continuous positive airway pressure (CPAP) could reduce the incidence of postoperative pneumonia. Eighty patients were randomly divided into two groups (n = 40 each): the DBB with CPAP (Group DBB) and routine bronchial blocker (Group BB) groups. In Group DBB, a 7-Fr BB was placed in the middle bronchus of the right lung for right lung surgery and in the inferior lobar bronchus of the left lung for left lung surgery. Further, a 9-Fr BB was placed in the main bronchus of the operative lung. In Group BB, routine BB placement was performed on the main bronchus on the surgical side. The primary endpoint was the postoperative pneumonia incidence. Compared with Group BB, Group DBB had a significantly lower postoperative pneumonia incidence in the operative (27.5% vs 5%, P = 0.013) and non-operative lung (40% vs 15%) on postoperative day 1. Compared with routine BB use for thoracoscopic lobectomy, using the DBB technique to isolate the operative lobe from the non-operative lobe(s) of the operative lung and providing CPAP to the non-operative lobe(s) through a BB can reduce the incidence of postoperative pneumonia in the operative and non-operative lungs.

Continuous positive airway pressure for treating hypoxemia due to pulmonary vein injury: A case report.

BACKGROUND: Vascular injury during thoracoscopic surgery for esophageal cancer is a rare but life-threatening complication that can lead to severe hypotension and hypoxemia. Anesthesiologists need to provide rapid and effective treatment to save patients' lives. CASE SUMMARY: A 54-year-old male patient was scheduled to undergo a thoracoscopic-assisted radical resection of esophageal cancer through the upper abdomen and right chest. While dissociating the esophagus from the carina through the right chest, unexpected profuse bleeding occurred from a suspected pulmonary vascular hemorrhage. While the surgeon attempted to achieve hemostasis, the patient developed severe hypoxemia. The anesthesiologist implemented continuous positive airway pressure (CPAP) using a bronchial blocker (BB), which effectively improved the patient's oxygenation and the operation was completed successfully. CONCLUSION: CPAP using a BB can resolve severe hypoxemia caused by accidental injury of the left inferior pulmonary vein during surgery.

Effects of long-term exposure to sevoflurane on the proliferation, migration, invasion, and cisplatin sensitivity of esophageal cancer.

Background: Esophageal cancer has a high incidence and one of the highest mortality rates worldwide. There are few studies on the effects of sevoflurane on postoperative metastasis and recurrence of esophageal cancer. This study aimed to investigate the effect of sevoflurane on the progression of esophageal cancer and the underlying mechanism of the sensitivity to cisplatin. Methods: We used the esophageal squamous cell carcinoma (ESCC) line EC109 and esophageal adenocarcinoma (EADC) line SKGT-4. Cell proliferation and stemness potential were determined by MTT assay and sphere-forming assays, respectively. The protein expression of (sex determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4) was determined by western blot. Cell migration and invasion ability were separately determined by scratch assay and transwell assays, respectively. The distribution of cell cycle and apoptosis were detected by flow cytometry, and the levels of lactate dehydrogenase (LDH) were measured by the enzyme-linked immunosorbent assay (ELISA). Results: In the SKGT-4 cells, exposure to sevoflurane inhibited proliferation, increased the migration and invasion potential, increased the number of cells in S phase, promoted self-renewal ability, and up-regulated the expression of SOX2 and OCT4 compared with control cells. Compared with the cisplatin treated group, treatment with sevoflurane plus cisplatin reduced the level of LDH and inhibited apoptosis in the SKGT-4 cells. However, sevoflurane did not affect EC109 cells. Conclusions: Long-term exposure to sevoflurane inhibited the proliferation, increased migration and invasion capacity, and decreased the sensitivity to cisplatin in EADC by promoting stemness. However, sevoflurane had no effect on the behavior of ESCC.

Cardiac electrical storm induced by anesthesia was successfully managed during surgery: a case report.

BACKGROUND: At present, the overall number of cardiac storms is small, there is a paucity of published literature describing cardiac storms in patients undergoing superficial surgery under general anesthesia (GA). In recent years, cardiac storm has attracted much clinical attention due to its high mortality, difficult management and poor prognosis. CASE DESCRIPTION: This paper reports a 57-year-old male with cardiac electrical storm. He presented with clinical symptoms such as exudation, bad breath, restricted mouth opening, and mucous leukoplakia on local skin, without history of cardiac disease and cardiovascular disease, undergoing superficial face surgery under GA. At 2 hours after anesthesia induction, several premature ventricular beats were detected on monitoring. Hematocrit and plasma potassium were found to be markedly decreased. The patient subsequently experienced a cardiac electrical storm, with repeated episodes of polymorphic ventricular tachycardia (VT) not degenerating to ventricular fibrillation (VF). Combining these clinical symptoms and examinations, we made the diagnosis of cardiac electrical storm. At the first occurrence of bradycardia, we administered atropine, which resolved bradycardia. However, this was followed 10 minutes later by VT, which we treated with atropine and epinephrine. Epinephrine and amiodarone were given in the second episode; epinephrine and lidocaine were used to treat the third episode. Finally, he was treated successfully with pharmacologic therapy and chest compressions. No abnormal electrocardiograph events occurred in the patient after surgery. CONCLUSIONS: This case highlights the possibility of anesthesia-induced autotransfusion and cardiac electrical storm occurring in patients without known cardiac disease. For this kind of case needs as soon as possible electric defibrillation and electric cardioversion, timely intravenous application effective anti-arrhythmic drugs and other treatment measures. We expect that this case report adds to the existing literature on this subject.

HIF­1α protein SUMOylation is an important protective mechanism of action of hypothermia in hypoxic cardiomyocytes.

Different degrees of myocardial ischemia­reperfusion injury during open­heart surgery are inevitable. Therapeutic hypothermia is an important technique for reducing ischemia­reperfusion injury; however, there are numerous potential adverse effects. Furthermore, the underlying molecular mechanisms of action of therapeutic hypothermia remain unclear. In the present study, rat hearts were perfused for 30 min and subjected to 30 min of regional ischemia, followed by 120 min of reperfusion. Animals received intraperitoneal injection of spectomycin B1 at 30 min prior to the start of surgery. Total myocardial area, infarct area, myocardial injury, and apoptosis were assessed. H9C2 cells were incubated for 24  h at 34˚C with 5% CO2 to simulate therapeutic hypothermic stress, and cell viability and mitochondrial injury were evaluated. The levels of protein SUMOylation, hypoxia­inducible factor (HIF)­1α and vascular endothelial growth factor (VEGF) were determined by western blot analysis. It was demonstrated that hypoxia significantly increased the overall modification by the small ubiquitin­related modifier protein (SUMO) of various proteins in cardiomyocytes, both in vitro and ex vivo. In turn, this increased the protein levels of HIF­1α, continuously stimulated downstream VEGF expression. Therapeutic hypothermia further increased protein SUMOylation, whereas inhibiting the SUMOylation pathway reduced the protective effect of therapeutic hypothermia on hypoxic cardiomyocytes. Overall, these data suggested that increasing SUMOylation of HIF­1α may be an important molecular mechanism underlying the protective effects of therapeutic hypothermia following hypoxia in myocardial cells. These findings may aid in the use of therapeutic hypothermia for treatment of myocardial ischemia­reperfusion and help avoid excessive side effects.

Successful intraoperative management in patients with abdominal compartment syndrome induced by giant liposarcomas: Two case reports.

RATIONALE: Giant intra-abdominal liposarcomas weighing over 20 kg often increase the intra-abdominal pressure (IAP), which has severe effects on the cardiovascular and respiratory systems. Abdominal compartment syndrome is defined typically as the combination of a raised IAP of 20 mm Hg or higher and new onset of organ dysfunction or failure. The anesthetic management and perioperative management are very challenging. PATIENTS CONCERNS: We presented 2 patients with rare giant growing liposarcoma of the abdomen, weighing 21 kg and over 35 kg, respectively. Circulatory management was particularly difficult in the first case, while respiratory management and massive blood loss was very challenging in the second one. DIAGNOSIS: With a computed tomography scan and peritoneal-to-abdominal height ratio measurement, preoperatively the risk of developing intra-abdominal hypertension and abdominal compartment syndrome was recognized early in each patient. The inferior vena cava and right atrium of the first patient was compressed and malformed due to the uplifted diaphragm, while there was severe decreased lung volume and increased airway resistance, because of rare giant retroperitoneal liposarcomas in the second case. Histologic examination revealed dedifferentiated liposarcoma in both cases. INTERVENTIONS: Both of the patients underwent resection surgery with multiple monitoring; transesophageal echocardiography monitoring in the first case and pressure-controlled ventilation volume guaranteed mechanical ventilation mode in both cases. OUTCOMES: Intraoperatively and postoperatively no cardiopulmonary complications in both patients. The first patient was discharged without any complications on postoperative day 10, and the second patient underwent another surgery because of anastomotic leakage resulting from bowel resection. LESSONS: Multiple monitorings, in particular transesophageal echocardiography should be considered in patients with increased IAP due to a giant mass, while an appropriate lung protection ventilation strategy is crucial in these patients.

Novel Modification of Potassium Chloride Induced Cardiac Arrest Model for Aged Mice.

Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressions and intravenous epinephrine for resuscitation was modified by blood withdrawal prior to CA onset, so as to decrease the requisite KCl dose to induce CA by decreasing the circulating blood volume. The modification was then compared to the standard model in young adult mice subjected to 8 min CA. 22-month old mice were then subjected to 8 min CA, resuscitated, and compared to young adult mice. Post-CA functional recovery was evaluated by measuring spontaneous locomotor activity pre-injury, and on post-CA days 1, 2, and 3. Neurological score and brain histology were examined on day 3. Brain elF2α phosphorylation levels were measured at 1 h to verify tissue stress. Compared to the standard model, the modification decreased cardiopulmonary resuscitation duration and increased 3-day survival in young mice. For aged mice, survival was 100 % at 24 h and 54% at 72 h. Neurological deficit was present 3 days post-CA, although more severe versus young mice. Mild neuronal necrosis was present in the cortex and hippocampus. The modified model markedly induced elF2α phosphorylation in both age groups. This modified procedure makes the CA model feasible in aged mice and provides a practical platform for understanding injury mechanisms and developing therapeutics for elderly patients.