Xinjin Chi

Background: Maintenance of cerebral perfusion during anesthetic induction is essential, particularly in patients vulnerable to hemodynamic instability. Transcranial Doppler (TCD) ultrasonography enables bedside assessment of cerebral blood flow (CBF) velocity and provides insight into cerebral hemodynamic changes during anesthesia. This study evaluated changes in CBF velocity during induction with Ciprofol and compared them with those of propofol and etomidate. Methods: This prospective quasi-experimental observational study included 72 adult patients (American Society of Anesthesiologists I–II) undergoing elective surgery with tracheal intubation. Patients received propofol (Group P), ciprofol (Group C), or etomidate (Group E) through non-randomized allocation based on routine clinical practice. Mean arterial pressure was maintained within ±20% of each patient’s baseline value using a standardized blood-pressure-guided management strategy. Bilateral middle cerebral artery (MCA) flow velocities were continuously monitored using TCD from baseline to 15 min after induction. Primary outcomes were mean flow velocities of the left and right MCA. Secondary outcomes included systolic velocity, diastolic velocity, pulsatility index, and resistance index. Between-group comparisons, area under the curve (AUC) analysis, and linear mixed-effects modeling were performed. Results: Although conventional hypothesis testing showed no significant differences in baseline characteristics (all P > 0.05), standardized mean difference analysis indicated potential baseline imbalances (Max standardized mean difference >0.2). AUC analysis of CBF parameters during the first 15 min after induction showed no significant differences among the three groups. Short-term fluctuation analysis revealed similar changes during the immediate and overall induction phases. During the stable phase, a significant difference was observed only in the right-sided resistance index. Linear mixed-effects models demonstrated significant group-by-time interactions for diastolic velocity, pulsatility index, and resistance index, indicating distinct temporal patterns among agents. Conclusions: In this prospective observational study, under a strict blood-pressure-guided management strategy, propofol, ciprofol, and etomidate were associated with broadly similar cerebral hemodynamic profiles during anesthetic induction, although subtle, parameter-specific differences in time-dependent cerebrovascular responses were observed. Given the non-randomized exploratory design, potential baseline imbalances, differences in phenylephrine requirements among groups, and the fact that the study was not designed or powered to establish equivalence, these findings should be interpreted cautiously as associative rather than causal and within the context of the standardized hemodynamic protocol. Confirmation in larger randomized controlled studies is warranted. Clinical trial number: This prospective observational study was registered and filed prior to participant enrollment in the Medical Research Registration and Filing Information System of the National Healthcare Security Information Platform (China) under registration number MR-44-23-036912. The registration information is provided for transparency.

Background Macrophages play the important roles in the diabetes and sepsis-related intestinal injury. Accumulating evidence suggests that transcription factors act as the fundamental link between macrophage polarization and tissue injury. However, the underlying mechanisms of transcription factors regulating macrophage polarization-related intestinal injury remain unclear under diabetes and sepsis conditions. Methods The cecal ligation and puncture (CLP)-induced sepsis models were established in both wild type (WT) and diabetic male mice. Clodronate liposome (Cls) was used to deplete macrophage. HE staining, inflammatory cytokines (TNF-α, IL-1β and IL-6) and intestinal mucosal barrier function markers (occludin, ZO-1, LPS and iFABP) were used to elevated intestinal damage. MicroRNA-array, RNA-seq and bioinformatic analysis were performed to detect the microRNA and mRNA expression and the potential regulation mechanism. In vitro, high glucose and LPS, miR-3061 mimics and Snail siRNA stimulation of RAW264.7 cells were cultured for further mechanism studies. Luciferase reporter assay was used to confirm the interplay between microRNA and its target genes. Results Compared to WT CLP mice, the diabetic CLP mice showed severe intestinal damage characterized by significantly increased Chui’s scores, expression of inflammatory cytokines (TNF-α, IL-1β and IL-6), serum LPS and iFABP concentration and reduced tight junction protein occluding and ZO-1 levels. Macrophage deplettion exhibited reverse the intestinal damage caused by CLP. The bioinformatic analysis identified that miR-3061/Snail1 might be a potential regulation axis of macrophage polarization. Furthermore, high glucose and LPS stimulation increased M1 macrophage and reduced levels of miR-3061, which was negatively associated with Snail1 in RAW264.7 cells. Mechanistic researches demonstrated that miR-3061 regulated macrophage polarization by targeting Snail1 mRNA 3′-untranslated region (3’‐UTR). Moreover, miR-3061 overexpression suppressed Snail1 expression, inhibited M1 macrophage and inflammatory cytokines. Conclusion This study elucidated that diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization, and further demonstrated that the miR-3061/Sani1 axis may be the potential target of macrophage polarization.

Postoperative pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome have contributed to mortality and morbidity of orthotopic liver transplantation (OLT) with unclear mechanisms. Mast cells (MCs) and polymorphonuclear neutrophils (PMNs) are the main inflammatory cells and participants in the process of ALI. The present study was designed to investigate the role of MCs and PMNs and their potential relation to ALI following OLT. Rat orthotopic autologous liver transplantation (OALT) model was designed to determine lung injury at different time points after liver reperfusion. We also evaluated the function of MCs and the effect of tumor necrosis factor-α (TNF-α) and tryptase on ALI and PMN apoptosis in rats subjected to OALT. Histological scores and inflammatory factor levels as well as PMN apoptosis were measured. Rats suffered from ALI after OALT, which was demonstrated by a collapse of the pulmonary architecture, pulmonary edema, and infiltration of inflammatory cells in alveolar and interstitial spaces, as well as increased levels of proinflammatory cytokines. ALI maximized at 8 h after OALT. However, PMN apoptosis lagged behind the pulmonary injury and maximized at 16 h after OALT, when the acute inflammation resolution initiated. MC stabilization, and tryptase and TNF-α inhibitors could significantly decrease the lung pathophysiologic scores accompanied by an increase in PMN apoptosis. ALI after OALT was associated with MC activation and PMN apoptosis. ALI progression might be affected by delayed PMN apoptosis, which was related to MC activation. Induction of PMN apoptosis might alleviate ALI after OALT.

Although tonsillectomy is a common and relatively safe procedure, postoperative pain after tonsillectomy is so severe that it impairs perioperative recovery disorder. Acute pain can also cause physical discomfort, anxiety, and even behaviour problems, and high-quality acute pain management can promote functional recovery and improve long-term functional outcomes. Despite recent efforts, it is still very difficult to provide sufficient analgesia for most patients due to the special operation site and the limitation of the existing analgesia program. Postoperative pain after tonsillectomy has two components: constant pain and swallow-evoked pain. Surgical intervention in the site of the tonsils might affect local muscles directly or indirectly through circulus tonsillaris nervous plexus. Although numerous drug comparison studies are being performed in this field, its postoperative analgesia programs remain controversial. The GPN is a mixed nerve that contains 3 components including the sensory, motor, and parasympathetic nerve fibres. Theoretically, the GPN block provides us with a direct way to block pain conduction. At present, post-tonsillectomy analgesia in most medical centers is based on analgesic agents, although there have been reports on the use of ultrasound-guided glossopharyngeal nerve (GPN) block. Post-tonsillectomy analgesia has attracted wide attention from multiple disciplines. This article systematically elucidates the various analgesics and methods used in post-tonsillectomy analgesia and explores the feasibility of ultrasound-GPN block, with an attempt to provide new insights for multimodal post-tonsillectomy analgesia.

Neuropathic pain is a kind of chronic pain that is triggered or caused primarily by damage to the nervous system and neurological dysfunction. It’s known that dexmedetomidine is a new type of highly selective alpha2-adrenoceptor agonist with sedation, anti-anxiety, analgesic and other effects. However, the function and mechanism of dexmedetomidine on neuropathic pain are not clear. Rat DRG neurons were isolated and identified using immunofluorescence assay. Following treatment with H₂O₂, dexmedetomidine or ROS inhibitor (NAC), the apoptosis and ROS levelswere examined by flow cytometery; apoptosis-related proteins and anaerobic glycolysis-related proteins were determined by western blot assay; glucose consumption, pyruvic acid, lactic acid and ATP/ADP ratios were also measured. The results revealed that dexmedetomidine inhibited H₂O₂-induced apoptosis and reactive oxygen species (ROS) in rat DRG neurons and in addition, dexmedetomidine downregulated the expression levels of anaerobic glycolysis-related proteins, significantly reduced glucose, pyruvic acid and lactic acid levels.It also increased the ATP/ADP ratio in H₂O₂-treated rat dorsal root ganglion (DRG) neurons. Moreover, we also demonstrated that ROS inhibitor (NAC) also inhibited H₂O₂-induced apoptosis and anaerobic glycolysis in rat DRG neurons. In conclusion, dexmedetomidine suppressed H₂O₂-induced apoptosis and anaerobic glycolysis activity by inhibiting ROS, in rat DRG neurons. Therefore, dexmedetomidine might play a pivotal role in neuropathic pain by the inhibition of ROS.

Patients with orthotopic liver transplantation (OLT) frequently develop acute gut injury (AGI), and dexmedetomidine (Dex) has been reported to exert a protective effect against AGI. We investigated whether Dex protects against AGI through antioxidative stress effects by the Nrf2/HO-1 antioxidative signaling pathway. Rats were randomly allocated into a sham group and six orthotopic autologous liver transplantation (OALT) groups receiving different doses of Dex together with/without α₂-adrenergic receptor (AR) blockers. Intestinal tissues were collected to visualize the barrier damage and to measure the indexes of oxidative stress. For in vitro studies, rat intestinal recess epithelial cells (IEC-6) underwent hypoxia/reoxygenation (H/R), and the protective role of Dex was evaluated after α_2A-AR siRNA silencing. OALT resulted in increased oxidative stress, significant intestinal injury, and barrier dysfunction. Dex attenuated OALT-induced oxidative stress and intestinal injury, which was abolished by the pretreatment with the nonspecific α_2A-AR siRNA blocker atipamezole and the specific α_2A-AR siRNA blocker BRL-44408, but not by the specific _2B/C-AR siRNA blocker ARC239. Silencing of α_2A-AR siRNA also attenuated the protective role of Dex on alleviating oxidative stress in IEC-6 cells subjected to H/R. Dex exerted its protective effects by activating Nrf2/HO-1 antioxidative signaling. Collectively, Dex attenuates OALT-induced AGI via α_2A-AR-dependent suppression of oxidative stress, which might be a novel potential therapeutic target for OALT-induced AGI.

The effect of liver dysfunction on target-controlled infusion (TCI) of propofol remains poorly documented. The pharmacodynamic performance of propofol TCI was evaluated in a cohort of Chinese patients with hepatic insufficiency. Fifty-three patients with hepatic insufficiency were enrolled in the current prospective, observational study. Anesthesia was induced with propofol via TCI to a plasma concentration of 3 µg/ml. Following loss of consciousness (LOC), fentanyl and cisatracurium were administered. Pharmacodynamic parameters were recorded during TCI, including time to LOC, bispectral index (BIS), heart rate (HR) and blood pressure. Patients were divided into two groups based on model of end stage liver disease (MELD) score: Those with a MELD score of ≤9 and those with a MELD score of ≥10. BIS, mean arterial pressure and HR were demonstrated to vary according to time, but were not affected by liver dysfunction. Hypotension was prominent in patients with a MELD score of ≥10 30 min after induction. The proportion of bradycardia and hypotension at the other time points was not significantly different between MELD scores of ≤9 and ≥10. Notably, no bradycardia was observed in MELD of ≥10. Thus, bradycardia and hypotension was observed in patients with hepatic insufficiency over time, although patients with different severities of hepatic insufficiency did not present with different depths of anesthesia. TCI of propofol to 3 µg/ml may be not suitable for patients with hepatic insufficiency, particularly those with severe liver dysfunction. Predictive concentrations (Cp) of TCI propofol requires further investigation and adjustment in patients with hepatic insufficiency (trial registration no. ChiCTR-OCH-12002255).

Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which influences patient survival rate obviously. However, its mechanisms are unclear and effective therapies are still lacking. The current study focused on effects of propofol on liver transplantation-induced ALI and whether its underlying mechanism was relative with connexin43 (Cx43) alternation. The authors postulated that endotoxin induced enhancement of Cx43 gap junction (GJ) plays a critical role in mediating post liver transplantation ALI and that pretreatment with the anesthetic propofol, known to inhibit gap junction, can confer effective protection. Male Sprague–Dawley rats underwent autologous orthotopic liver transplantation (AOLT) in the absence or presence of treatments with the selective Cx43 inhibitor, enanthol (0.1 mg/kg) and propofol (50 mg/kg), a commonly used anesthetic in clinical anesthesia. In vitro study, BEAS-2B cells, a kind of lung epithelial cell line expressing Cx43, exposed to lipopolysaccharide (LPS), which mainly contributed to ALI. Function of Cx43 GJ was regulated by Cx43 specific inhibitors, gap26 (300 μM) or enhancer, retinoic acid (10 μM) and two specific siRNAs. Compared with the sham group, AOLT results in ALI obviously with plasma endotoxin increase. Cx43 inhibition decreased ALI through inflammatory reaction reduction. In vitro studies, LPS-induced BEAS-2B cells damage was attenuated by Cx43 function inhibition, but amplified by enhancement. Another important finding was propofol reduced Cx43 function and protected against LPS-mediated BEAS-2B cells damage or AOLT-induced ALI, mechanisms of which were also associated with inflammatory reaction decrease. Cx43 plays a vital role in liver transplantation-induced ALI. Propofol decreased Cx43 function and protected against ALI in vivo and in vitro. This finding provide a new basis for targeted intervention of organ protection in liver transplantation, even in other kinds of operations.

Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling plays a dominant role in the pathogenesis of liver ischemia-reperfusion (IR) injury. Dexmedetomidine (Dex) protects the liver against IR injury via α₂-adrenoceptor activation, but the contribution of TLR4 signaling remains unknown. The authors aimed to examine whether pretreatment with Dex produces hepatic protection and investigate the influence of Dex on TLR4/NF-κB signaling. Dex was given via intraperitoneal injection 30 min prior to orthotopic autologous liver transplantation (OALT) in rats, and three α₂-adrenoceptor antagonists including atipamezole (a nonselective α₂ receptor blocker), ARC-239 (a specific α_2B/C blocker) and BRL-44408 (a specific α_2A blocker) were injected intraperitoneally 10 min before Dex administration. Histopathologic evaluation of the liver and the measurement of serum alanine aminotransferase activity, TLR4/NF-κB expression in the liver, and pro-inflammatory factors (serum tumor necrosis factor-α, interleukin-1β and hepatic myeloperoxidase) concentrations were performed 8 h after OALT. Dex ameliorated liver injury after OALT probably by suppressing the TLR4/NF-κB pathway and decreasing inflammatory mediator levels. The protective effects of Dex were reversed by atipamezole and BRL-44408, but not by ARC-239, suggesting that these effects were mediated in part by the α_2A subtype. In conclusion, Dex attenuates liver injury partly via the α_2A-adrenoceptor subtype, and the mechanism is due to the suppression of the TLR4/NF-κB pathway.