[Research progress on the application of non-nutritional effects of fat emulsion in the treatment of poisoning].

Fat emulsion is a drug commonly used clinically for parenteral nutrition support in critically ill patients.With the development of the pharmaceutical industry, fat emulsion has formed a variety of different formulations, among which different types of fat emulsion have their own metabolic and body energy supply characteristics, and the application indications are also different. In addition to providing the supply of nutrients, the role of fat emulsion in anti-toxicity, immune regulation, anti-inflammatory, anti-shock, cardiopulmonary resuscitation and other aspects has gradually been discovered. This article reviews the existing evidence-based medical evidence and expounds the mechanism and therapeutic role of fat emulsion in the treatment of critically ill patients with poisoning. Its value in the treatment of critically ill patients with poisoning was discussed, and some references were provided for the application of non-nutritional functions of fat emulsion in the future.

[Clinical analysis of 25 cases of acute oral 84 disinfectant poisoning].

Objective: To summarize the clinical characteristics and treatment effect of patients with acute oral 84 disinfectant poisoning, so as to improve the understanding, diagnosis and treatment of the disease. Methods: In January 2022, 25 hospitalized patients with acute oral 84 disinfectant poisoning admitted to our department from March 2016 to August 2021 were selected as the research objects, and their general conditions, poisoning reasons, poisoning time, dose of poisoning, clinical manifestations, blood routine and biochemical indicators, diagnosis, treatment and prognosis were selected. Results: A retrospective analysis was performed. Among the 25 patients, there were 4 males and 21 females, aged from 20 to 91 years, and M (Q(1), Q(3)) was 38.7 (27, 46) years; The poisoning time (from exposure to poison to treatment) was 1~72 h, and M (Q(1), Q(3)) was 10.5 (3, 11.5) h. The length of stay was 1~20 days, and M (Q(1), Q(3)) was 5.72 (2, 7) days.The dose was 40-500 ml, and the M (Q(1), Q(3)) was 219.6 (100, 330) ml. Chest CT showed exudative changes in both lungs in 4 patients, excessive decreased permeability in 1 case and pleural effusion in 1 case. Gastroscope showed 2 cases of erosive inflammation of gastric body and antrum, 1 case of esophageal ulcer and cardiac ulcer, 1 case of corrosive gastritis, gastric fundus ulcer and esophageal stenosis. Abdominal X-ray showed 1 case of abdominal intestinal dilatation and pneumatosis with multiple gas-liquid planes.There were 1 case of type I respiratory failure, 6 cases of gastrointestinal bleeding and 1 case of incomplete intestinal obstruction. There were 19 cases of nausea and vomiting, 9 cases of abdominal pain, 6 cases of pharyngeal pain and 6 cases of retrosternal burning pain, 1 case of cough and 2 cases of fatigue. Conclusion: Acute oral 84 disinfectant will cause varying degrees of damage to the human digestive tract and lungs. In severe cases, gastrointestinal bleeding, intestinal obstruction, hypoxemia, etc, and even life-threatening, should be paid attention to clinically. The treatment is mainly symptomatic support treatment, such as protecting gastrointestinal mucosa, controlling acute inflammatory reaction, protecting the functions of liver and kidney and other important organs.

[Expression of RAGE in asthmatic rats and the intervention of Roxithromycin].

Objective: To observe the expression of the Receptor of Advanced glycation end products (RAGE) in asthmatic rats, and explore the intervention of Roxithromycin. Methods: A total of 18 Specific Pathogen Free-class Brown Norway male rats were randomly divided into control group, asthma model group and Roxithromycin group, with 6 rats in each group. The asthmatic model was sensitized by intraperitoneal injection of Ovalbumin (OVA)+Al(OH)(3), and challenged with OVA. Rats in Roxithromycin group were given Roxithromycin 30 mg/kg 30 minutes before each challenge. Rats in control group and asthma model group were treated with equal volume of saline. The concentrations of RAGE and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent (ELISA); the pathological changes of lung tissues were observed by HE-staining; the thickness of airway wall and airway smooth muscle were measured by Image-Pro Plus; the relative expression of RAGE in lung tissues were detected by Western blot. Results: In asthma model group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously higher than those in control group [(494±32) vs (327±45) ng/L; (32.4±5.8) vs (13.1±2.9) ng/L; (553±38) vs (399±56) ng/L; (37.8±3.4) vs (19.4±2.5) ng/L] (all P<0.01); in Roxithromycin group, the concentrations of RAGE and IL-4 in the serum and BALF were obviously lower than those in asthma model group [(438±18) vs (494±32) ng/L; (22.8±6.0) vs (32.4±5.8) ng/L; (444±42) vs (553±38) ng/L; (25.6±4.5) vs (37.8±3.4) ng/L] (all P<0.05). In asthma model group, the bronchial wall was thickened, the lumen was narrow, the mucosal wrinkles were significantly increased, edema appeared under the mucosa, and a large number of inflammatory cells infiltrated and aggregated in the bronchi, perivascular and alveolar spaces; the thickness of airway wall and airway smooth muscle were significantly increased than those in control group (P<0.01); in Roxithromycin group, airway inflammation and remodeling were alleviated compared with those in asthma model group (P<0.05). In asthma model group, the expression of RAGE in lung tissues were significantly increased than those in control group (P<0.01); in Roxithromycin group, the expression of RAGE were significantly decreased than those in asthma model group (P<0.01). There were positive correlations between the expression of RAGE and IL-4 in BALF and serum (r=0.782, 0.804, all P<0.01); there were positive correlations between RAGE and total white cell counts, eosinophil counts, smooth muscle thickness (r=0.897, 0.927, 0.860, all P<0.01). Conclusions: The increasing of RAGE in asthmatic rats are positively correlated with airway inflammation and airway remodeling. Roxithromycin may inhibit the development of asthma by reducing the expression of RAGE.

[The role of S100A8/RAGE and Caveolin-1 and the effect of roxithromycin on their expression in a rat model of neutrophilic asthma].

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.

[Fabrication and evaluation of composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface].

Objective: To develope a titanium specimen with good osteogenic activity through fabrication of a composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface. Methods: An ordered micro-/nanotextured structure was prepared on the surface of titanium (the control), and then hydroxyapatite was deposited on the as-prepared ordered micro-/nanotextured structure by alternative loop immersion method. The ordered micro-/nanotextured structures before and after hydroxyapatite deposition were denoted as HA and MN, respectively. Surface morphology was observed using a scanning electron microscope. Bone marrow mesenchymal stem cells (BMMSC) were seeded on the surface of three different materials. Cell morphology was observed with a scanning electron microscope. Cell adhesion and cell proliferation were evaluated using 4', 6-diamidino-2-phenylindole staining and cell counting kit-8 assay, respectively. Extracellular matrix mineralization and the expression levels of osteogenesis-related genes were evaluated by alizarin red staining and real-time quantitative PCR, respectively. Each group has three samples in every experiment. Results: After alternative loop immersing, the MN's original microholes (20 µm in diameter) were retained, and the uniform petal-like hydroxyapatite was deposited on the MN's original titania nanotubes (70 nm in diameter). Compared with the control, BMMSC on MN and HA elongated further and intersected along the micron structure with noticeable pseudopodia and pseudoplates, and the trend was more pronounced especially on HA. The number of early adherent cells on HA was remarkably larger than that on the control and MN at each time point (P<0.05). On day 1, the A value of cell proliferation on HA was significantly higher than that on the control and MN (P<0.05). The A value of cell proliferation on HA was significantly lower than that on the control and MN on day 3 (P<0.05). On day 7, the A value of cell proliferation on HA was significantly lower than that on MN (P<0.05), but there was no statistically significant difference in the A value of cell proliferation between HA and the control on day 7 (P>0.05). The Avalue of extracellular matrix mineralization on HA (0.607±0.011) was significantly higher than that on the control and MN (0.268±0.025 and 0.522±0.022, respectively) (t=-0.25, P<0.001; t=-0.34, P<0.001). The expression levels of bone related genes on HA were significantly higher than those on the control and MN (P<0.05). Conclusions: HA could promote the BMMSC adhesion and osteogenic differentiation, support BMMSC proliferation, and demonstrate good osteogenic activity.

Protein tyrosine phosphatase SHP2 regulates TGF-ß1 production in airway epithelia and asthmatic airway remodeling in mice.

BACKGROUND: Transforming growth factor (TGF)-ß1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-ß1 production and thus a potential regulator of airway remodeling. OBJECTIVES: To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling. METHODS: The airways of Shp2(flox/flox) mice were infected with recombinant adenovirus vectors expressing a Cre recombinase-green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-ß1. RESULTS: Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-ß1 production by these cells correlated with the extent of shp2 gene expression. CONCLUSIONS: SHP2 activities in airway epithelial cells appear to modulate TGF-ß1 production and, in turn, regulate allergic airway remodeling following allergen provocation. CLINICAL IMPLICATIONS: Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung dysfunction associated with allergen challenge. As such, SHP2 represents a potentially novel therapeutic target for the treatment of asthmatics. CAPSULE SUMMARY: Airway epithelial protein tyrosine phosphatase SHP2 appears to modulate TGF-ß1 activities as part of one or more cellular pathways leading to regulating the airway remodeling and lung dysfunction occurring in mouse models of allergic respiratory inflammation.

Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.

SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergic mice. Blockade of SHP2 function by SHP2 inhibitor PHPS-1 or conditional shp2 knockdown by adenovirus-inhibited bone-marrow-derived eosinophil differentiation in vitro, with no detectable effects on the apoptosis of eosinophils. Furthermore, SHP2 induced eosinophil differentiation via regulation of the extracellular signal-regulated kinase pathway. Myeloid shp2 conditional knockout mice (LysM(cre)shp2(flox/flox)) failed to induce eosinophilia as well as airway hyper-responsiveness. The SHP2 inhibitor PHPS-1 also alleviated eosinophilic airway inflammation and airway hyper-responsiveness, accompanied by significantly reduced levels of systemic eosinophils and eosinophil lineage-committed progenitors in allergic mice. We demonstrate that inhibition of eosinophil development is SHP2-dependent and SHP2 is sufficient to promote eosinophil formation in vivo. Our data reveal SHP2 as a critical regulator of eosinophil differentiation, and inhibition of SHP2 specifically in myeloid cells alleviates allergic airway inflammation.

Therapeutic effect of magnesium isoglycyrrhizinate in rats on lung injury induced by paraquat poisoning.

OBJECTIVE: The aim of this study was to investigate the effect of Magnesium Isoglycyrrhizinate (MgIG) on intercellular adhesion moledule-1 (ICAM-1) and matrix metalloproteinase-9 (MMP-9) in rats with Paraquat (PQ) poisoning and its potential mechanism. MATERIALS AND METHODS: 30 male Sprague Dawley rats were randomly divided into five groups, including normal control group, poisoned control group, low-dose MgIG group, medium-dose MgIG group and high-dose MgIG group. Each group was treated with corresponding dose of MgIG once on daily basis by intraperitoneal injection 24 hours later, and the normal control group and poisoned control group were injected with physiological saline. All the animals were killed 14 days after poisoning, the contents of ICAM-1 and matrix MMP-9 were determined. HE staining and Masson staining were performed, the hydroxyproline (HYP) content in the lung tissue was also determined, and the expressions of ICAM-1 and MMP-9 were detected by immunohistochemical test. RESULTS: The contents of ICAM-1 and MMP-9 in the rat serum for all treatment groups were significantly decreased compared with those of the poisoned control group (p < 0.05, or < 0.01), and the expressions of the two proteins were significantly down-regulated, especially for the medium dose group. CONCLUSIONS: There is an improvement effect of ICAM-1 and MMP-9 in rats with Paraquat poisoning for the medium dose of MgIG, capable of slowing down the process of pulmonary fibrosis to certain extent.