Mediation effect of self-efficacy on the relationship between perceived social support and resilience in caregivers of patients with first-stroke in China: a cross-sectional survey.

BACKGROUND: Self-efficacy, perceived social support, and resilience in caregivers of first-stroke patients are closely related, while the interaction mechanism remains unclear. This research explores the mediation effect of self-efficacy in the relationship between perceived social support and resilience in caregivers of first-stroke patients in China. METHODS: Convenience sampling was designed and used to recruit participants from the General Hospital of Northern Theater in Shenyang, Liaoning Province, China, from February to October 2022, in which 207 self-reported participants completed the Connor-Davidson Resilience Scale (CD-RISC), Multidimensional Scale of Perceived Social Support (MSPSS) and General Self Efficacy Scale (GSES). In addition, the mediation effect of self-efficacy between perceived social support and resilience was determined by the PROCESS macro for SPSS. RESULT: Among the 207 caregivers of patients with first-stroke, the mean CD-RISC, MSPPS and GSES scores were (72.17 ± 11.28), (71.17 ± 8.99), and (29.64 ± 5.03) respectively. Caregivers' self-efficacy was positively correlated with perceived social support (r = 0.439, p < 0.01) and resilience (r = 0.730, p < 0.01). Self-efficacy served a mediation function partially between perceived social support and resilience, whose effect accounted for 52.90% of the total. CONCLUSION: Both simple and mediation roles of perceived social support and self-efficacy are established in the relationship of resilience among caregivers of first-stroke patients. Positive social support and self-efficacy are two important targets for future interventional studies, and interventions on them may synergistically improve resilience. Hence, the nurses and community workers should correctly evaluate social support and self-efficacy, confirm the health education requirements, and implement counseling intervention to protect and improve the health of first-stroke patients and their families.

Corrigendum: Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

[This corrects the article DOI: 10.3389/fnmol.2023.1182005.].

Association Between Bowel Wall Thickening and Long-Term Outcomes in Decompensated Liver Cirrhosis.

INTRODUCTION: Bowel wall thickening is commonly observed in liver cirrhosis, but few studies have explored its impact on the long-term outcomes of patients with cirrhosis. METHODS: Overall, 118 patients with decompensated cirrhosis were retrospectively enrolled, in whom maximum wall thickness of small bowel, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum could be measured in computed tomography (CT) images. X-tile software was employed to determine the best cut-off values of each segment of bowel wall thickness for predicting the risk of further decompensation and death. Cumulative rates of further decompensation and death were calculated by Nelson-Aalen cumulative risk curve analyses. Predictors of further decompensation and death were evaluated by competing risk analyses. Sub-distribution hazard ratios (sHRs) were calculated. RESULTS: Cumulative rates of further decompensation were significantly higher in patients with wall thickness of ascending colon ≥ 11.7 mm (P = 0.014), transverse colon ≥ 3.2 mm (P = 0.043), descending colon ≥ 9.8 mm (P = 0.035), and rectum ≥ 7.2 mm (P = 0.045), but not those with wall thickness of small bowel ≥ 8.5 mm (P = 0.312) or sigmoid colon ≥ 7.1 mm (P = 0.237). Wall thickness of ascending colon ≥ 11.7 mm (sHR = 1.70, P = 0.030), transverse colon ≥ 3.2 mm (sHR = 2.15, P = 0.038), descending colon ≥ 9.8 mm (sHR = 1.43, P = 0.046), and rectum ≥ 7.2 mm (sHR = 2.38, P = 0.045) were independent predictors of further decompensation, but not wall thickness of small bowel ≥ 8.5 mm (sHR = 1.19, P = 0.490) or sigmoid colon ≥ 7.1 mm (sHR = 0.63, P = 0.076). Small bowel, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum wall thickness were not significantly associated with death. CONCLUSIONS: Colorectal wall thickening, but not small bowel wall, may be considered for the prediction of further decompensation in cirrhosis.

Microstructurally and mechanically tunable acellular hydrogel scaffold using carboxymethyl cellulose for potential osteochondral tissue engineering.

In tissue engineering, scaffold microstructures and mechanical cues play a significant role in regulating stem cell differentiation, proliferation, and infiltration, offering a promising strategy for osteochondral tissue repair. In this present study, we aimed to develop a facile method to fabricate an acellular hydrogel scaffold (AHS) with tunable mechanical stiffness and microstructures using carboxymethyl cellulose (CMC). The impacts of the degree of crosslinking, crosslinker length, and matrix density on the AHS were investigated using different characterization methods, and the in vitro biocompatible of AHS was also examined. Our CMC-based AHS showed tunable mechanical stiffness ranging from 50 kPa to 300 kPa and adjustable microporous size between 50 µm and 200 µm. In addition, the AHS was also proven biocompatible and did not negatively affect rabbit bone marrow stem cells' dual-linage differentiation into osteoblasts and chondrocytes. In conclusion, our approach may present a promising method in osteochondral tissue engineering.

Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

Objective: This study aims to explore whether interferon-induced transmembrane protein 3 (IFITM3) is involved in recombinant human brain natriuretic peptide (rhBNP)-mediated effects on sepsis-induced cognitive dysfunction in mice. Methods: The cellular localization and expression level of IFITM3 in the hippocampus were detected. The IFITM3 overexpression was achieved using an intracranial stereotactic system to inject an adeno-associated virus into the hippocampal CA1 region of mice. Field experiments, an elevated plus maze, and conditioned fear memory tests assessed the cognitive impairment in rhBNP-treated septic mice. Finally, in the hippocampus of septic mice, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining and Immunoblot were used to detect changes in the protein expression of cleaved Caspase-8 and cleaved Caspase-3 in apoptosis-related pathways, and toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) p65 in inflammatory pathways. Results: Fourteen days after cecal ligation and puncture (CLP) surgery, IFITM3 localized in the plasma membrane and cytoplasm of the astrocytes in the hippocampus of septic mice, partially attached to the perivascular and neuronal surfaces, but not expressed in the microglia. The expression of IFITM3 was increased in the astrocytes and neurons in the hippocampus of septic mice, which was selectively inhibited by the administration of rhBNP. Overexpression of IFITM3 resulted in elevated anxiety levels and long-term learning and memory dysfunction, completely abolished the therapeutic effect of rhBNP on cognitive impairment in septic mice, and induced an increase in the number of neuronal apoptosis in the hippocampal CA1 region. The expression levels of cleaved Caspase-3 and cleaved Caspase-8 proteins were significantly increased in the hippocampus, but the expression levels of TLR4 and NF-κB p65 were not increased. Conclusion: The activation of IFITM3 may be a potential new target for treating sepsis-associated encephalopathy (SAE), and it may be one of the key anti-apoptotic mechanisms in rhBNP exerting its therapeutic effect, providing new insight into the clinical treatment of SAE patients.

Adipose-derived mesenchymal stem cell-loaded ß-chitin nanofiber hydrogel activates the AldoA/HIF-1α pathway to promote diabetic wound healing.

OBJECTIVES: To identify the effect of adipose-derived mesenchymal stem cell-loaded ß-chitin nanofiber (ADSC-loaded ß-ChNF) hydrogel on diabetic wound healing and clarify its mechanism of action. METHODS: We prepared the ADSC-loaded ß-ChNF hydrogel to repair wounds of db/db diabetic mice. Wound healing rate, histopathology, enzyme-linked immunosorbent assay, and western blot were used to confirm its role and mechanism in promoting diabetic wound healing. RESULTS: The ADSC-loaded ß-ChNF hydrogel accelerated wound healing in db/db diabetic mice, as indicated by increased cell proliferation, epithelization, and tissue granulation in the skin. Moreover, expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), matrix metalloproteinase 9 (MMP9), and TIMP metallopeptidase inhibitor 1 (TIMP1) were upregulated. These results demonstrate the beneficial effects of this ADSC-loaded ß-ChNF hydrogel on diabetic wound healing. Furthermore, we show that the ADSC-loaded ß-ChNF hydrogel activated aldolase A (AldoA)/hypoxia-inducible factor 1α (HIF-1α) signaling. An inhibitor of HIF-1α markedly decreased the promotive effects of the ADSC-loaded ß-ChNF hydrogel on wound healing and reduced expression of VEGF, VEGFR, MMP9, and TIMP1. CONCLUSIONS: Our findings suggest that the ADSC-loaded ß-ChNF hydrogel activated the HIF-1α/MMP9 axis through AldoA feedback to promote diabetic wound healing.

Proteomic global proteins analysis in blast lung injury reveals the altered characteristics of crucial proteins in response to oxidative stress, oxidation-reduction process and lipid metabolic process.

Background: Blast lung injury (BLI) is the most common fatal blast injury induced by overpressure wave in the events of terrorist attack, gas and underground explosion. Our previous work revealed the characteristics of inflammationrelated key proteins involved in BLI, including those regulating inflammatory response, leukocyte transendothelial migration, phagocytosis, and immune process. However, the molecular characteristics of oxidative-related proteins in BLI ar still lacking. Methods: In this study, protein expression profiling of the blast lungs obtained by tandem mass tag (TMT) spectrometry quantitative proteomics were re-analyzed to identify the characteristics of oxidative-related key proteins. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h and 1 w after blast exposure. The differential protein expression was identified by bioinformatics analysis and verified by western blotting. Results: The results demonstrated that thoracic blast exposure induced reactive oxygen species generation and lipid peroxidation in the lungs. Analysis of global proteins and oxidative-related proteomes showed that 62, 59, 73, 69, 27 proteins (accounted for 204 distinct proteins) were identified to be associated with oxidative stress at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. These 204 distinct proteins were mainly enriched in response to oxidative stress, oxidation-reduction process and lipid metabolic process. We also validated these results by western blotting. Conclusions: These findings provided new perspectives on blast-induced oxidative injury in lung, which may potentially benefit the development of future treatment of BLI.

Effects of Sevoflurane Laryngeal Mask Inhalation Combined with Intravenous Anesthesia on Perioperative Stress and Myocardial Injury in Elderly Patients with Acute Cholecystitis and Coronary Heart Disease.

Surgery is the first choice for the treatment of acute cholecystitis. To ensure the curative effect of surgery, laparoscopic anesthesia should be characterized by rapid induction, good analgesic effect, and rapid postoperative sobriety. With the aggravation of an aging population, acute cholecystitis combined with coronary heart disease is more common in the elderly. The selection of anesthesia protocols for these patients has become a hot topic in research. In this study, we selected 72 elderly patients with acute cholecystitis combined with coronary heart disease who were treated in our hospital from January 2019 to January 2022 to explore the effects of sevoflurane laryngeal mask inhalation combined with intravenous anesthesia on perioperative stress and myocardial injury in elderly patients with acute cholecystitis combined with coronary heart disease, in order to provide a scientific basis for the formulation of a surgical plan for elderly patients with acute cholecystitis combined with coronary heart disease.

Application of adipose mesenchymal stem cell-derived exosomes-loaded ß-chitin nanofiber hydrogel for wound healing.

INTRODUCTION: Clarifying the role and mechanism of exosome gel in wound repair can provide a new effective strategy for wound treatment. MATERIALS AND METHODS: The cellular responses of adipose mesenchymal stem cell-derived exosomes (AMSC-exos) and the wound healing ability of AMSC-exos-loaded ß-chitin nanofiber (ß-ChNF) hydrogel were studied in vitro in mouse fibroblasts cells (L929) and in vivo in rat skin injury model. The transcriptome and proteome of rat skin were studied with the use of sequenator and LC-MS/MS, respectively. RESULTS: 80 and 160 µg/mL AMSC-exos could promote the proliferation and migration of mouse fibroblastic cells. Furthermore, AMSC-exos-loaded ß-ChNF hydrogel resulted in a significant acceleration rate of wound closure, notably, acceleration of re-epithelialization, and increased collagen expression based on the rat full-thickness skin injury model. The transcriptomics and proteomics studies revealed the changes of the expression of 18 genes, 516 transcripts and 250 proteins. The metabolic pathways, tight junction, NF-κB signaling pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway. Complement factor D (CFD) and downstream Aldolase A (Aldoa) and Actn2 proteins in rats treated with AMSC-exos-loaded ß-ChNF hydrogel were noticed and further confirmed by ELISA and Western blot. CONCLUSION: These findings suggested that AMSC-exos-loaded ß-ChNF hydrogel could promote wound healing with the mechanism which is related to the effect of AMSC-exos on CFD and downstream proteins.

DDAH1 Promotes Lung Endothelial Barrier Repair by Decreasing Leukocyte Transendothelial Migration and Oxidative Stress in Explosion-Induced Lung Injury.

Explosion-induced injury is the most commonly encountered wound in modern warfare and incidents. The vascular inflammatory response and subsequent oxidative stress are considered the key causes of morbidity and mortality among those in blast lung injury. It has been reported dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays important roles in regulating vascular endothelial injury repair and angiogenesis, but its role in explosion-induced injury remains to be explained. To explore the mechanism of vascular injury in blast lung, 40 C57BL/6 wild type mice and 40 DDAH1 knockout mice were randomly equally divided into control group and blast group, respectively. Body weight, lung weight, and dry weight of the lungs were recorded. Diffuse vascular leakage was detected by Evans blue test. The serum inflammatory factors, nitric oxide (NO) contents, and ADMA level were determined through ELISA. Hematoxylin-eosin staining and ROS detection were performed for histopathological changes. Western blot was used to detect the proteins related to oxidative stress, cell adhesion molecules and leukocyte transendothelial migration, vascular injury, endothelial barrier dysfunction, and the DDAH1/ADMA/eNOS signaling pathway. We found that DDAH1 deficiency aggravated explosion-induced body weight reduction, lung weight promotion, diffuse vascular leakage histopathological changes, and the increased levels of inflammatory-related factors. Additionally, DDAH1 deficiency also increased ROS generation, MDA, and IRE-1α expression. Regarding vascular endothelial barrier dysfunction, DDAH1 deficiency increased the expression of ICAM-1, Itgal, Rac2, VEGF, MMP9, vimentin, and N-cadherin, while lowering the expression of occludin, CD31, and dystrophin. DDAH1 deficiency also exacerbated explosion-induced increase of ADMA and decrease of eNOS activity and NO contents. Our results indicated that explosion could induce severe lung injury and pulmonary vascular insufficiency, whereas DDAH1 could promote lung endothelial barrier repair and reduce inflammation and oxidative stress by inhibiting ADMA signaling which in turn increased eNOS activity.

Practice guidance for the use of terlipressin for liver cirrhosis-related complications.

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.

Adipose-derived mesenchymal stem cell-loaded ß-chitin nanofiber hydrogel promote wound healing in rats.

Because of stem cells are limited by the low efficiency of their cell homing and survival in vivo, cell delivery systems and scaffolds have attracted a great deal of attention for stem cells' successful clinical practice. ß-chitin nanofibers (ß-ChNF) were prepared from squid pens in this study. Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy proved that ß-ChNFs with the diameter of 5 to 10 nm were prepared. ß-ChNF dispersion became gelled upon the addition of cell culture medium. Cell culture experiments showed that ß-ChNFs exhibited negligible cytotoxicity towards ADSCs and L929 cells, and it was found that more exosomes were secreted by the globular ADSCs grown in the ß-ChNF hydrogel. The vivo experiments of rats showed that the ADSCs-loaded ß-ChNF hydrogel could directly cover the wound surface and significantly accelerate the wound healing and promote the generation of epithelization, granulation tissue and collagen. In addition, the ADSCs-loaded ß-ChNF hydrogel clearly regulated the expressions of VEGFR, α-SMA, collagen I and collagen III. Finally, we showed that ADSCs-loaded ß-ChNF hydrogel activated the TGFß/smad signaling. The neutralization of TGFß markedly reduced Smad phosphorylation and the expressions of TIMP1, VEGFR and α-SMA. Taken together, these findings suggest that ADSCs-loaded ß-ChNF hydrogel promises for treating wounds that are challenge to heal via conventional methods. Graphical abstract.

Ultrafiltration for patients with acute decompensated heart failure: A systematic review and meta-analysis.

BACKGROUND: Ultrafiltration plays an indispensable role in relieving congestion and fluid retention in patients with acute decompensated heart failure (ADHF) in recent years. So far, there is no consistent agreement about whether early ultrafiltration (UF) is a first-line treatment for patients with ADHF. We, therefore, conducted a meta-analysis to assess the efficacy and safety of UF. METHODS: PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that compared UF with diuretics in patients with ADHF and included our interested outcomes. The primary outcomes are heart failure rehospitalization, all-cause rehospitalization, and mortality. The second outcomes are fluid loss, weight loss, and adverse events. RevMan Version 5.4.1 was used to analyze the data of included studies. RESULTS: A total of 12 studies with 1197 patients were included. Our results showed a reduction in heart failure rehospitalization (risk ratio [RR] 0.67, 95% confidence interval [CI]: 0.52-0.87, P = .003) and all-cause rehospitalization (RR 0.62, 95% CI: 0.42-0.92; P = .02), an increase in fluid loss (1.47 L, 95% CI: 0.95-1.99 L, P < .001) and weight loss (1.65 kg, 95% CI: 0.90-2.41 kg; P < .001). There was no difference in mortality (RR 1.09, 95% CI: 0.78-1.51; P = .62). There were inconsistent agreements about which group have more total adverse events. Subgroup analysis showed that UF with larger mean fluid-remove rate (≥200 mL/h) could significantly remove more fluid, lose more weight, and decrease heart failure rehospitalization. Less weight loss for patients with ADHF may correlated to higher percent of ischemic etiology (ischemic etiology ≥50%). CONCLUSION: Although UF is more effective in removing fluid than diuretics and decrease rehospitalization of heart failure and all causes, there is not enough evidence to prove that UF is superior because of adverse events and mortality in the UF group. The mean fluid-removal rates should be set to ≥200 mL/h. Patient with different etiology may have different effects when treated with UF and it is a weak conclusion.Trial registration: The systematic review was registered with the International Prospective Registry of Systematic Reviews. (https://www.crd.york.ac.uk/prospero/, registration number CRD42021245049).

Resveratrol ameliorates thoracic blast exposure-induced inflammation, endoplasmic reticulum stress and apoptosis in the brain through the Nrf2/Keap1 and NF-κB signaling pathway.

Blast injuries include the various types of internal and external trauma caused by the impact force of high-speed blast waves with multiple mechanisms involved. Thoracic blast exposure could induce neurotrauma as well, but effective therapies are lacking. Resveratrol is a polyphenol flavonoid secreted by plants and has been shown to provide cardiovascular protection and play anti-inflammatory, anti-oxidation and anti-cancer roles. However, the effects of resveratrol on thoracic blast exposure-induced brain injury have not been investigated. To explore this, a mouse model of thoracic blast exposure-induced brain injury was established. Sixty C57BL/6 wild type mice were randomly divided equally into four groups (one control group, one model group, and model groups with 25 or 50 mg/kg resveratrol injected intraperitoneally). As traumatic brain injury often accompanied by mental symptoms, cognitive dysfunction and anxious behavior were evaluated by Y maze, elevated plus maze and open field test. We also examined the mice for histopathological changes by hematoxylin-eosin staining; the expressions of inflammatory-related factors by ELISA; endoplasmic reticulum stress in brain tissue via the generation of reactive oxygen species (ROS) and the expressions of inositol-requiring enzyme-α (IRE-α) and C/EBP homologous protein (CHOP); apoptosis by measuring levels of Bax, p53 and Bcl-2. In addition, proteins of related pathways were also studied by western blotting. We found that resveratrol significantly reduced the levels of inflammatory-related factors, including interleukin (IL)-1ß, IL-4, and high mobility group box protein 1(HMGB1), and increased the level of anti-inflammatory-related factor, IL-10, under thoracic blast exposure (P < 0.05). Cognitive dysfunction and anxious behavior were also ameliorated by resveratrol. In brain tissue, resveratrol significantly attenuated thoracic blast exposure-induced generation of ROS and expressions of IRE-α and CHOP, lowered the expressions of Bax and p53, and maintained Bcl-2 expression (P < 0.05). Additionally, resveratrol significantly ameliorated thoracic blast exposure-induced increases of Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor (NF)-κB and the decrease in nuclear factor erythroid 2-related factor 2(Nrf2) expression in the brain (P < 0.05). Our results indicate that resveratrol has a protective effect on thoracic blast exposure-induced brain injury that is likely mediated through the Nrf2/Keap1 and NF-κB signaling pathways.

Melatonin pretreatment alleviates blast-induced oxidative stress in the hypothalamic-pituitary-gonadal axis by activating the Nrf2/HO-1 signaling pathway.

Although melatonin has been demonstrated to exert a potent antioxidant effect, the ability of melatonin to alleviate blast-induced oxidative stress in the hypothalamic-pituitary-gonadal (HPG) axis remains unclear. This study aimed to elucidate the effects and underlying mechanism of melatonin pretreatment on the HPG axis disrupted by blast injury. Sixty C57BL/6 mice were randomly divided into control, blast, and blast + melatonin groups for behavioral experiments. The elevated maze experiment, open field experiment, and Morris Water Maze experiment were carried out on the 7th, 14th and 28th day after the blast injury. Fifty Sprague Dawley rats were randomly divided into control, blast, blast + melatonin, and blast + melatonin + luzindole groups for hormone assays and molecular and pathological experiments. Blood samples were used for HPG axis hormone detection and ELISA assays, and tissue samples were used to detect oxidative stress, inflammation, apoptosis, and stress-related protein levels. The results showed that melatonin pretreatment alleviated blast-induced behavioral abnormalities in mice and maintained the HPG axis hormone homeostasis in rats. Additionally, melatonin significantly reduced MDA5 expression and increased the expression of Nrf2/HO-1. Moreover, melatonin significantly inhibited NF-κB expression and upregulated IL-10 expression, and it reversed the blast-induced high expression of caspase-3 and Bax and the low expression of Bcl-2. Furthermore, luzindole counteracted melatonin inhibition of NF-κB and upregulated Nrf2/HO-1. Melatonin significantly alleviated blast-induced HPG axis hormone dyshomeostasis, behavioral abnormalities, oxidative stress, inflammation, and apoptosis, which may be achieved by upregulating the Nrf2/HO-1 signaling pathway. Our study suggested that melatonin pretreatment is a potential treatment for blast-induced HPG axis hormonal and behavioral abnormalities.

Proteomic Analysis Revealed the Characteristics of Key Proteins Involved in the Regulation of Inflammatory Response, Leukocyte Transendothelial Migration, Phagocytosis, and Immune Process during Early Lung Blast Injury.

Previous studies found that blast injury caused a significant increased expression of interleukin-1, IL-6, and tumor necrosis factor, a significant decrease in the expression of IL-10, an increase in Evans blue leakage, and a significant increase in inflammatory cell infiltration in the lungs. However, the molecular characteristics of lung injury at different time points after blast exposure have not yet been reported. Therefore, in this study, tandem mass spectrometry (TMT) quantitative proteomics and bioinformatics analysis were used for the first time to gain a deeper understanding of the molecular mechanism of lung blast injury at different time points. Forty-eight male C57BL/6 mice were randomly divided into six groups: control, 12 h, 24 h, 48 h, 72 h, and 1 w after low-intensity blast exposure. TMT quantitative proteomics and bioinformatics analysis were performed to analyze protein expression profiling in the lungs from control and blast-exposed mice, and differential protein expression was verified by Western blotting. The results demonstrated that blast exposure induced severe lung injury, leukocyte infiltration, and the production of inflammatory factors in mice. After analyzing the expression changes in global proteins and inflammation-related proteomes after blast exposure, the results showed that a total of 6861 global proteins and 608 differentially expressed proteins were identified, of which 215, 128, 187, 232, and 65 proteins were identified at 12 h, 24 h, 48 h, 72 h, and 1 week after blast exposure, respectively. Moreover, blast exposure-induced 177 differentially expressed proteins were associated with inflammatory responses, which were enriched in the inflammatory response regulation, leukocyte transendothelial migration, phagocytosis, and immune response. Therefore, blast exposure may induce early inflammatory response of lung tissue by regulating the expression of key proteins in the inflammatory process, suggesting that early inflammatory response may be the initiating factor of lung blast injury. These data can provide potential therapeutic candidates or approaches for the development of future treatment of lung blast injury.

Expert consensus on the prevention, diagnosis and treatment of cold injury in China, 2020.

Cold injury refers to local or systemic injury caused by a rapid, massive loss of body heat in a cold environment. The incidence of cold injury is high. However, the current situation regarding the diagnosis and treatment of cold injury in our country is not ideal. To standardize and improve the level of clinical diagnosis and treatment of cold injury in China, it is necessary to make a consensus that is practical and adapted to the conditions in China. We used the latest population-level epidemiological and clinical research data, combined with relevant literature from China and foreign countries. The consensus was developed by a joint committee of multidisciplinary experts. This expert consensus addresses the epidemiology, diagnosis, on-site emergency procedures, in-hospital treatment, and prevention of cold injury.

Quantitative analysis of the global proteome in lung from mice with blast injury.

AIM OF THE STUDY: The mechanism by which primary shock wave causes lung injury is unclear. The aim of this study is to find the changes of protein that can be helpful in understanding blast-induced lung injury. MATERIAL AND METHODS: A quantitative analysis of their global proteome was conducted in lung from mice with blast injury using LC-MS/MS. Protein annotation, unsupervised hierarchical clustering, functional classification, functional enrichment and cluster, and protein-protein interaction analyses were performed. Furthermore, western blotting was used to validate the changed protein levels. RESULTS: A total of 6498 proteins were identified, of which 5520 proteins were quantified. The fold-change cutoff was set at 1.2; 132 proteins were upregulated, and 104 proteins were downregulated. The bioinformatics analysis indicated that the differentially expressed proteins were involved in the cholesterol metabolism, asthma, nonalcoholic fatty liver disease. Remarkably, the processes related to the change of oxidative phosphorylation including the NADH dehydrogenase, Cytochrome C reductase, Cytochrome C oxidase and F-type ATPase were significantly upregulated, which were further verified by western blotting. CONCLUSION: These results confirmed that the oxidative phosphorylation is critical to blast-induced lung injury. LC/MS-based profiling presented candidate target/pathways that could be explored for future therapeutic development.

Tanshinone IIA alleviates blast-induced inflammation, oxidative stress and apoptosis in mice partly by inhibiting the PI3K/Akt/FoxO1 signaling pathway.

Although Tanshinone IIA (Tan IIA) has been associated with inflammation, oxidative stress and apoptosis, the effects of Tan IIA on lung blast injury remain uncertain. In this study, we explored the effects of Tan IIA on lung blast injury, studied its possible molecular mechanisms. Fifty C57BL/6 mice were randomly divided into the control, blast, blast + Tan IIA, blast + LY294002 (a PI3K inhibitor), or blast + Tan IIA + LY294002 groups. Serum and lung samples were collected 48 h after blast injury. The data showed that Tan IIA significantly inhibited blast-induced increases in the lung weight/body weight and wet/dry (W/D) weight ratios, decreased the CD44-and CD163-positive inflammatory cell infiltration in the lungs, reduced the IL-1ß, TNF-α and IL-6 expression, and enhanced IL-10 expression. Tan IIA also significantly alleviated the increases in MDA5 and IRE-a and the decrease in SOD-1 and reversed the low Bcl-2 expression and the high Bax and Caspase-3 expressions. Additionally, Tan IIA significantly decreased p-PI3K and p-Akt expression and increased p-FoxO1 expression. More importantly, both LY294002 and Tan IIA pretreatment markedly protected against blast-induced inflammation, oxidative stress and apoptosis in lung blast injury. These results suggest that Tan IIA protects against lung blast injury, which may be partly mediated by inhibiting the PI3K/Akt/FoxO1 signaling pathway.