Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.

Effects of Ammonium Polyphosphate and Organic Modified Montmorillonite on Flame Retardancy of Polyethylene Glycol/Wood-Flour-Based Phase Change Composites.

With the depletion of fossil fuel energy and both the slow development and low utilization rate of new eco-friendly energy, finding new ways to efficiently store energy has become a research hotspot. Presently, polyethylene glycol (PEG) is an excellent heat storage material, but it is a typical solid-liquid phase change material (PCM) with a risk of leakage during phase transition. A combination of wood flour (WF) and PEG can effectively eliminate the risk of leakage after the melting of PEG. However, WF and PEG are both flammable materials, which impedes their application. Therefore, it is of great significance to expand their application by forming composites from among PEG, supporting mediums, and flame-retardant additives. This will improve both their flame retardancy and phase change energy storage performance, and will also lead to the preparation of excellent flame-retardant phase change composite materials with solid-solid phase change characteristics. To address this issue, ammonium polyphosphate (APP), organic modified montmorillonite (OMMT), and WF were blended into PEG in specific proportions to prepare a series of PEG/WF-based composites. Both thermal cycling tests and thermogravimetric analysis results demonstrated that the as-prepared composites had good thermal reliability and chemical stability. In addition, during differential scanning calorimetry tests, the PEG/WF/8.0APP@2.0OMMT composite presented the highest melting latent heat (176.6 J/g), and its enthalpy efficiency reached more than 98.3%. The PEG/WF/8.0APP@2.0OMMT composite also exhibited superior thermal insulation performance when compared to the pure PEG/WF composite. Furthermore, the PEG/WF/8.0APP@2.0OMMT composite exhibited a significant 50% reduction in peak heat release rate as a result of the synergistic effect between OMMT and APP in the gas and condensed phases. This work offers a useful strategy for the fabrication of multifunctional phase-change material, which is expected to broaden its industrial applications.

A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires.

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD.

OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.

Large-scale analysis of 2,152 Ig-seq datasets reveals key features of B cell biology and the antibody repertoire.

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual's repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.

[Effects of different nasotracheal intubations in obstructive sleep apnea hypopnea syndrome patients with uvulopalatopharyngoplasty].

OBJECTIVE: To explore the safe and effective way of nasotracheal intubations in obstructive sleep apnea hypopnea syndrome patients with uvulopalatopharyngoplasty. METHODS: Upon the approval of the Ethics Committee at Second Affiliated Hospital of Fujian Medical University, from August 2008 to November 2011, 90 sleep apnea hypopnea syndrome patients were randomly divided into 3 groups (n=30 each): GlideScope (G), fiberoptic bronchoscope (F) and combination of Glidescope with fiberoptic bronchoscope (G+F). The parameters of tracheal intubation time, placement of endotracheal intubation, tracheal injury and complications were recorded. Also systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were recorded at post-induction, the moment of tracheal intubation and post-intubation 1, 3, 5 min. Rate pressure product (RPP) was calculated at all time points as the product of heart rate and SBP during observation. RESULTS: All of them underwent successful endotracheal intubation. There were 24 successful cases of intubation during the first attempt in Group G with a success rate of 80%; 27 patients successful during the first attempt in group F with a success rate of 90%; all in group G+F successful during the first attempt with a success rate of 100%. The rates were significantly different in 3 groups (P<0.05). Groups G and F patients with failed intubation during the first attempt were of Mallampati III/IV. After induction, SBP, DBP, MAP and RPP were lower in 3 groups (P<0.05) while HR change was not obvious. Compared with the after induction, the moment of tracheal intubation and after intubation 1 min, 3 groups of patients with SBP, DBP, MAP, HR and RPP increased (P<0.05). Groups F and G+F after intubation in intubated patients and 1 min of SBP, DBP, MAP, HR, RPP were higher than G group (P<0.05). No difference existed between groups F and G+F. Three groups showed no serious tracheal injury, laryngeal edema, hoarseness or other complications. CONCLUSION: During nasotracheal intubation for Mallampati I/II patients, GlideScope offers better overall glottic views. For those of Mallampati III and IV, the combination of Glidescope with fiberoptic bronchoscope may achieve a higher success rate and shorter intubation time than the latter alone.

[Protective effect of breviscapine on cardiac function in children after cardiopulmonary bypass undergoing open heart surgery].

OBJECTIVE: To assess the condition of myocardial injury after cardiopulmonary bypass (CPB) and the effects of breviscapine (BVC) on cardiac function in children undergoing open heart surgery. METHODS: Thirty-six children (ASA II or III, aged 2-65 months) scheduled to receive ventricular septal defect repairing were randomly assigned to three groups, the control group treated with saline, and the BVC treated groups treated respectively with low dose (0.5 mg/kg) and high dose (1.0 mg/kg) BVC, 12 patients in each group. Saline or BVC (in volume of 15 mL) was administered intravenously after induction of anesthesia with micro-pump within 30 min. Blood levels of troponin I (cTn-I ) and malondialdehyde (MDA) were measured at different time points: pre-operation (T0), during aortic unclamping (T1), and 30 min, 1 h, 6 h, 24 h after aortic unclamping (T2, T3, T4, T5). And the time of operation, CPB, aortic unclamping, and the condition of drainage in 24 h after operation as well as the dosages of narcotics (midazolam, propofol and fentanyl) used were recorded. RESULTS: No significant difference among groups was found in terms of sex ratio, age, body weight, time of aortic unclamping, CPB and operation, as well as the dosages of narcotics used and the volume of post-operation drainage. Compared with baseline (T0), levels of cTn-I at T1, T4 and T5 increased significantly in all three groups (P<0.01), with the peak revealed at T4; cTn-I in the control group were higher than those in the low dose BVC treated group at T1 and T4 (P<0.01), and those in the high dose BVC group at T1, T4, and T5, while it was insignificantly different between the two BVC treated groups. Level of plasmal MDA began to rise in all groups at T1 with the peak revealed at T2, it lowered after then, and reached the baseline at T5; comparison between groups showed that it was lower in the BVC treated groups than in the control group at T1-T4. CONCLUSIONS: Different degree of cardiac injury always happens after open heart surgery and CPB, showing high level of cTn- I within 24 h with the peak revealed at 6 h after aortic unclamping. Intravenous perfusion BVC before CPB at the dose of 0.5 or 1 mg/kg could protect the cardiac function to some extent.