The Application Value of Esketamine and Dexmedetomidine in Preventing Postoperative Delirium and Hyperalgesia in Elderly Patients with Thoracic Anesthesia.

Objective: Our aim was to evauate the application value of esesketamine and dexmedetomidine in preventing postoperative hyperalgesia in elderly patients who received thoracic anesthesia. Methods: A total of 94 elderly patients who underwent thoracic anesthesia in Sanmen People's Hospital from January 2021 to October 2022 were selected and divided into a dexmedetomidine group (n = 47) and an esketamine group (n = 47) by the random number table method. All patients were continuously received intravenous (IV) remifentanil. In the dexmedetomidine group, dexmedetomidine 0.7 µg/kg was administered IV, followed by 0.2 to 0.5 µg/kg/h to maintain anesthesia, while in the esketamine group, esketamine 0.5 mg/kg was given IV 20 min after induction of anesthesia was completed. Results: Visual analogue scale (VAS) scores in the esketamine group were lower than in the dexmedetomidine group at 1, 6, 12 and 24 h postoperatively (P < .05), and Ramsay sedation scores were not statistically different from those in the dexmedetomidine group (P > .05). At 3 d postoperatively, the Mini-Mental State Examination (MMSE) scores in the dexmedetomidine group were lower than 1 d preoperatively; at 5 d postoperatively, the negative mood and Pittsburgh Sleep Quality Index (PSQI) scores were significantly higher in both groups than 1 d preoperatively; at 14 d postoperatively, the PSQI scores were higher in both groups than 1 d preoperatively, and there was no statistical difference between the negative mood scores at 1 d before surgery (P > .05). At 5 d postoperatively in the esketamine group, the negative mood scores were lower than in the dexmedetomidine group at 5 d postoperatively and the PSQI scores at 5 and 14 d postoperatively were lower than in the dexmedetomidine group (P < .05). Conclusion: Both esketamine and dexmedetomidine can be used to prevent postoperative delirium and nociceptive hypersensitivity after anesthesia in elderly patients with thoracic surgery. However, esketamine is superior to dexmedetomidine in analgesic effect, improvement of negative mood and sleep and stabilization of intraoperative hemodynamics, leading to better effect in preventing delirium and hyperalgesia after anesthesia.

PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B.

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

Circulation collapse caused by intracardiac thrombosis associated with tranexamic acid administration: A case report.

RATIONALE: Perioperative administration of tranexamic acid has been suggested to reduce bleeding and blood transfusion requirements in patients undergoing orthopedic surgery. Despite being sporadic, the potential risk for thrombotic complications cannot be ignored. However, intracardiac thrombosis associated with tranexamic acid administration is rare. We described a case of circulatory collapse caused by intracardiac thrombosis associated with tranexamic acid administration for a scheduled knee arthroplasty. PATIENT CONCERNS: A 62-year-old male patient was scheduled for a right knee arthroplasty. He had a history of hypertension and had undergone surgery for treatment of right femur fracture 30 years previously. Other than a high platelet count (498 × 109/L), results of laboratory investigations were within normal limits. The ultrasonic examination of both lower limbs showed no thrombosis. Upon sterilizing the surgical area, tranexamic acid (1.6 g) was intravenously administered after induction of anesthesia and intubation. Then the patient had a sudden circulatory collapse. Through cardiopulmonary resuscitation, the patient recovered spontaneous circulation. Transesophageal echocardiography revealed extensive thrombosis in the right atrium and ventricle. DIAGNOSIS: Circulation collapse caused by intracardiac thrombosis. INTERVENTIONS: Thrombolytic therapy was recommended after urgent multidisciplinary consultation. Thus, urokinase was administered intravenously. Fifty minutes after thrombolysis, the mass in ventricle disappeared. A shrunken mass was observed in the right atrium. After another half an hour, no abnormal echoes were seen in the right heart chambers. OUTCOMES: The patient was discharged after 43 days without any organ dysfunction. LESSONS: This case reminds clinicians that perioperative tranexamic acid administration may increase the risk of thrombosis, which needs focused attention from anesthesiologists. Prompt transesophageal echocardiography examination should be done to allow immediate diagnosis and effective thrombolysis therapy when unexplained cardiac arrest occurs during anesthesia.

NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling.

As a third-generation platinum drug, oxaliplatin has been widely applied in colorectal cancer (CRC); however, acquired resistance to oxaliplatin has become a major obstacle. In the present study, we found that the nuclear transcription factor Y subunit beta (NFYB) and E2F transcription factor 1 (E2F1) expression levels were significantly higher in oxaliplatin-resistant DLD1 and RKO CRC (OR-CRC) cells than in non-resistant cells. Additionally, highly expressed NFYB transactivated the E2F1 gene, which is important to maintain oxaliplatin resistance in OR-CRC cells. And Sirt1-dependent deacetylation suppresses the proapoptotic activity of E2F1 in OR-CRC cells. Through profiling the transcriptome of OR-CRC cells following E2F1 knockdown, CHK1 was identified as a target of E2F1. Deprivation of CHK1 sensitized OR-CRC cells to oxaliplatin. In vitro and in vivo phenotype experiments confirmed that an intact NFYB-E2F1-CHK1 axis was required to suppress oxaliplatin-induced apoptosis and maintain the tumorigenicity in OR-CRC cells. Knockdown of E2F1 in OR-CRC cells also decreased the expression of Pol κ, which was essential for CHK1 activation. Consistently, a high level of NFYB, E2F1, or CHK1 predicted poor survival in CRC patients, especially with oxaliplatin treatment. Collectively, the NFYB-E2F1 pathway displays a crucial role in the chemoresistance of OR-CRC by inducing the expression and activation of CHK1, providing a possible therapeutic target for oxaliplatin resistance in CRC.