ABSTRACT
Novel coronavirus pneumonia, also known as coronavirus disease 2019 (COVID-19), is caused by sub-severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2) infection. The spike (S) protein of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptors widely expressed on the surface of human cells leading to life-threatening respiratory infections. A serious hazard to human health is posed by the lack of particular treatment medications for this virus infection. We advocate the creation of high-affinity antibodies using the receptor binding domain (RBD) of S protein as a specific antigenic epitope to develop a drug that can precisely target therapy COVID-19 because SARS-CoV-2 infection of the host cells is dependent on S protein binding to ACE2. Finally, we obtained high-affinity antibodies 14F4HL and 14E3HL that have high affinity with RBD and well-drug-forming properties, suitable for further humanization studies. Thus, monoclonal antibodies that neutralize the S protein were identified in our study, which may provide new insights for the development of COVID-19 therapeutic drugs.
ABSTRACT
Objective: To evaluate the protective effect of target-directed fluid therapy on the lungs and postoperative rehabilitation in elderly patients with single-lung ventilation undergoing total endoscopic radical resection of esophageal cancer. Methods: Seventy elderly patients who underwent total endoscopic radical resection of esophageal cancer from January 2017 to December 2019 in our hospital were selected and divided into two groups by the random number table method: the goal-directed fluid treatment group (group G, n = 35) and the control group (group C, n = 35). Venous blood was extracted before surgery (T1), at the end of free esophagus (T2) by thoracoscopy, at the end of abdominal surgery (T3), and at the end of surgery (T4). IL-6 and IL-10 levels were detected by ELISA. The clinical pulmonary infection score (CIPS) was used to evaluate the pulmonary inflammation on the second day after surgery and the occurrence of complications. Duration of antibiotic use and length of hospital stay were recorded. Results: At T1, there were no significant differences in IL-6 and IL-10 levels between the two groups (P > 0.05). At T2, the IL-6 level in group G increased to 26.65 ± 1.80 pg/ml but was significantly lower than that in group C (32.28 ± 3.22 pg/ml) (P < 0.01). At T3 and T4, IL-6 and IL-10 levels in group G were significantly lower than those in group C (P < 0.01). The CIPS score of group G was lower than that of group C (1.5 ± 1.0 vs 2.7 ± 1.4), and the duration of antibiotic use in group G was shorter than that in group C (211.2 ± 15.4 vs 232.6 ± 18.7 h), with statistical significance (P < 0.01). The incidence of complications in group G was lower than that in group C (28.6% vs 40.0%), and the length of hospital stay in group G was shorter than that in group C (10.5 ± 1.7 vs 11.2 ± 1.9 days), but there was no significant difference between the two groups (P > 0.05). Conclusion: Target-directed fluid therapy inhibited inflammatory cytokine levels and had better lung protection, but no significant benefit in the complications or the length of hospital stay was observed.
ABSTRACT
In order to determine the role of the adrenergic system in bupivacaine-induced cardiotoxicity, a series of experiments were performed. In an animal experiment, male Sprague-Dawley (SD) rats under chloral hydrate anesthesia received intravenous bupivacaine, followed by an intravenous injection of adrenalin or isoprenalin, and the electrocardiogram (ECG), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of rise of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease (-dP/dtmax) were continually monitored. In a cellular experiment, freshly isolated adult SD rat ventricular myocytes were perfused with bupivacaine at different concentrations in the presence or absence of isoprenalin, with or without esmolol. The percentage of the sarcomere shortening (bl% peak h), departure velocity (dep v) of sarcomere shortening and time to 50% of the peak speed of myocyte contraction (Tp50) was assessed by a video-based edge-detection system. In an additional experiment, Swiss mice pretreated with saline, isoprenalin, esmolol or dexmedetomidine received bupivacaine to determine the 50% lethal dose (LD50) of bupivacaine. Electron microscopy of myocardial mitochondria was performed to assess damage of these structures. To test mitochondrial reactive oxygen species (ROS) production, freshly isolated SD rat ventricular myocytes were incubated with bupivacaine in the presence of isoprenalin, with or without esmolol. First, our results showed that bupivacaine significantly reduced the LVSP and +dP/dtmax, as well as enhanced the LVEDP and -dP/dtmax (P < 0.05, vs. control, and vs. baseline). Adrenalin and isoprenalin induced a further reduction of LVSP and +dP/dtmax (P < 0.05, vs. before adrenalin or isoprenalin delivery, and vs. control). Second, bupivacaine induced a dose-dependent cardiomyocyte contractile depression. While 5.9 µmol/L or 8.9 µmol/L of bupivacaine resulted in no change, 30.0 µmol/L of bupivacaine prolonged the Tp50 and reduced the bl% peak h and dep v (P < 0.05, vs. control and vs. baseline). Isoprenalin aggravated the bupivacaine-induced cardiomyocyte contractile depression, significantly prolonging the Tp50 (P < 0.05, vs. bupivacaine alone) and reducing the dep v (P < 0.05, vs. bupivacaine alone). Third, esmolol and dexmedetomidine significantly enhanced, while isoprenalin significantly reduced, the LD50 of bupivacaine in mice. Fourth, bupivacaine led to significant mitochondrial swelling, and the extent of myocardial mitochondrial swelling in isoprenalin-pretreated mice was significantly higher than that compared with mice pretreated with saline, as reflected by the higher mitochondrial damage score (P < 0.01). Meanwhile, esmolol pretreatment significantly reduced the mitochondrial damage score (P < 0.01). Fifth, bupivacaine significantly increased the ROS in freshly isolated cardiomyocytes, and added isoprenalin induced a further enhancement of ROS production (P < 0.05, vs. bupivacaine alone). Added esmolol significantly decreased ROS production (P < 0.05, vs. bupivacaine + isoprenalin). Our results suggest that bupivacaine depressed cardiac automaticity, conductivity and contractility, but the predominant effect was contractile dysfunction which resulted from the disruption of mitochondrial energy metabolism. ß-adrenergic activation aggravated the cellular metabolism disorder and therefore contractile dysfunction.
Subject(s)
Cardiotoxicity/physiopathology , Epinephrine/administration & dosage , Isoproterenol/administration & dosage , Myocardial Contraction/drug effects , Anesthesia/adverse effects , Animals , Blood Pressure/drug effects , Bupivacaine/administration & dosage , Bupivacaine/adverse effects , Cardiotoxicity/diagnostic imaging , Cardiotoxicity/etiology , Chloral Hydrate/administration & dosage , Disease Models, Animal , Electrocardiography , Heart Ventricles/drug effects , Heart Ventricles/physiopathology , Humans , Mice , Myocardial Contraction/physiology , Propanolamines/administration & dosage , Rats , Reactive Oxygen Species/metabolismABSTRACT
BACKGROUND: This meta-analysis aimed to assess the efficiency and safety of intravenous infusion of lidocaine for pain management after laparoscopic cholecystectomy (LC). METHODS: A systematic search was performed in PubMed (August 1966-2017), Medline (August 1966-2017), Embase (August 1980-2017), ScienceDirect (August 1985-2017), and the Cochrane Library. Only randomized controlled trials (RCTs) were included. Fixed/random effect model was used according to the heterogeneity tested by I2 statistic. Meta-analysis was performed using Stata.11.0 software. RESULTS: A total of 5 RCTs were retrieved involving 274 patients. The present meta-analysis indicated that there were significant differences between groups in terms of visual analog scale scores at 12hours (weighted mean difference [WMD]=-0.743, 95% CI: -1.246 to -0.240, Pâ=â.004), 24hours (WMD=-0.712, 95% CI: -1.239 to -0.184, Pâ=â.008), and 48hours (WMD=-0.600, 95% CI: -0.972 to -0.229, Pâ=â.002) after LC. Significant differences were found regarding opioid consumption at 12hours (WMD=-3.136, 95% CI: -5.591 to -0.680, Pâ=â.012), 24hours (WMD=-4.739, 95% CI: -8.291 to -1.188, Pâ=â.009), and 48hours (WMD=-3.408, 95% CI: -5.489 to -1.326, Pâ=â.001) after LC. CONCLUSION: Intravenous lidocaine infusion significantly reduced postoperative pain scores and opioid consumption after LC. In addition, there were fewer adverse effects in the lidocaine groups. Higher quality RCTs are still required for further research.