Developing a vanillin-derived imidazo-pyridin-containing fluorescent probe for imaging cysteine in living pulmonary cells under oxygen supply variation.

In this work, derived from vanillin and imidazo-pyridin backbone, a fluorescent probe IPV-Cys was developed for imaging the cysteine (Cys) level in living pulmonary cells under oxygen supply variation. By mimicking the oxygen supply variation in both the solution test and cellular imaging, the optical performance and imaging effect of IPV-Cys was investigated. In the solution system, the oxygen supply variation caused no impact on the reporting signals. The fluorescence reporting signal intensity at 490 nm suggested the enhancement along with the increase of the Cys concentration. The advantages of IPV-Cys included relatively high sensitivity, high stability, and high selectivity. On the basis of the low cyto-toxicity, IPV-Cys achieved the monitoring the endogenous Cys level in in living pulmonary cells and the impact of the oxygen supply variation by reporting fluorescence signals. The information here was meaningful for both the pre-clinical diagnosis and surgical techniques.

Remimazolam Alleviates Ventilator-Induced Lung Injury by Activating TSPO to Inhibit Macrophage Pyroptosis.

BACKGROUND: Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI. METHODS: A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments. RESULTS: Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1ß, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis. CONCLUSION: Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.

Nitroglycerin versus milrinone for low central venous pressure in patients undergoing laparoscopic hepatectomy: a double-blinded randomized controlled trial.

BACKGROUND: Conventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients' recovery. METHODS: In total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2-0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2-0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome. RESULTS: Blood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin. TRIAL REGISTRATION: ChiCTR2200056891,first registered on 22/02/2022.

Effects of targeted mild hypercapnia versus normocapnia on cerebral oxygen saturation in patients undergoing laparoscopic hepatectomy under low central venous pressure: a prospective, randomized controlled study.

BACKGROUND: Laparoscopic hepatectomy under low central venous pressure (LCVP) is associated with intraoperative organ hypoperfusion, including cerebral hypoperfusion. We hypothesized that a ventilation strategy designed to achieve targeted mild hypercapnia (TMH) (end-tidal carbon dioxide partial pressure [PetCO2] of 45 ± 5 mmHg) rather than targeted normocapnia (TN) (PetCO2 of 30 ± 5 mmHg) would increase regional cerebral oxygen saturation (rSO2) during laparoscopic hepatectomy under LCVP. METHODS: Eighty patients undergoing laparoscopic hepatectomy under LCVP were randomly divided into the TMH group (n = 40) and the TN group (n = 40). Mechanical ventilation was adjusted to maintain the PetCO2 within the relevant range. Cerebral oxygenation was monitored continuously using the FORE-SIGHT system before anesthetic induction until the patient left the operating room. Patient and surgical characteristics, rSO2, intraoperative hemodynamic parameters (CVP, mean artery blood pressure [MAP], and heart rate), PetCO2, intraoperative blood gas analysis results, and postoperative complications were recorded. RESULTS: No significant differences were observed in CVP, MAP, and heart rate between the two groups during surgery. The rSO2 was significantly lower in the TN group on both the left and right sides during the intraoperative period (P < 0.05), while the TMH group had a stable rSO2. In the TN group, the mean rSO2 decreased most during liver parenchymal transection when compared with the baseline value (P < 0.05). The mean (standard deviation) percentage change in rSO2 from baseline to parenchymal transection was - 7.5% (4.8%) on the left and - 7.1% (4.6%) on the right. The two groups had a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings demonstrate that rSO2 is better maintained during laparoscopic hepatectomy under LCVP when patients are ventilated to a PetCO2 of 45 ± 5 mmHg (TMH) than a PetCO2 of 30 ± 5 mmHg (TN). TRIAL REGISTRATION: ChiCTR2100051130(14/9/2021).

Comparison of adjuvant pharmaceuticals for caudal block in pediatric lower abdominal and urological surgeries: A network meta-analysis.

STUDY OBJECTIVE: Caudal block helps relieve pain after sub-umbilical surgery in pediatric patients; however, the duration for which it exerts its analgesic effect is limited. The addition of certain adjuvant agents to local anesthetics (LAs) that are used to administer caudal block can prolong postoperative analgesia. Therefore, we aimed to compare the efficiencies and side effects of caudal adjuvants in the settings of pediatric lower abdominal and urological surgeries. DESIGN: A network meta-analysis (NMA). PATIENTS: One hundred and twelve randomized controlled trials (RCTs) involving 6800 pediatric patients were included in the final analysis. INTERVENTIONS: Different adjuvant agents, namely clonidine, dexamethasone, dexmedetomidine, fentanyl, ketamine, magnesium, midazolam, morphine, neostigmine, and tramadol. MEASUREMENTS: The primary outcome was the duration of analgesia. The secondary outcomes included the requirement for additional analgesia, analgesic consumption, and postoperative complications. The effects and rankings were evaluated using NMA and the surface under the cumulative ranking curve scores, respectively. RESULTS: Neostigmine, dexmedetomidine, and dexamethasone were found to be the three most effective adjuvants that prolong the duration of analgesia for caudal block, and these adjuvants extended this duration by 8.9 h (95% confidence interval [CI], 7.1-10.7), 7.3 h (95% CI, 6.0-8.6), and 5.9 h (95% CI, 4.0-7.7), respectively. Caudal neostigmine was associated with an increase in the incidence of postoperative nausea and vomiting, whereas dexmedetomidine and dexamethasone showed no postoperative complications. CONCLUSIONS: This NMA provided evidence and suggested that dexmedetomidine and dexamethasone may be the most beneficial adjuvant pharmaceutics adding to LAs for caudal block in children. However, given the off-label status of caudal dexmedetomidine and dexamethasone, further high-quality RCTs are still warranted, especially to determine whether delayed neurological complications will occur.