Comparison of Bone Graft Preparations to Treat a Critical Bone Defect on a Rodent Animal Model.

Objective Although autologous bone grafting is the most widely used treatment for bone defects, the most effective preparation remains unclear. This animal study aimed to compare different autologous bone grafting preparation for the treatment of rat́s calvaria critical bone defect. Methods 122 rats were randomly allocated into three groups: Simulado, Macerated and Chopped. The specimens underwent craniotomies at the top center of their calvarias with a 7mm diameter circumferential cutter drill. The critical bone defect produced was treated or not according to the group the specimen wasallocated. The rats were euthanized at 3, 6 or 12 weeks post-op and its calvarias were analyzed by histomorphometry, bone densitometry, nanocomputed tomography (nCT), and biomechanical tests. Results The histomorphometry analysis showed the highest percentage of fulfillment of the critical bone defect in the chopped and macerated group when compared to simulado. The densitometry assessment evidenced higher bone mass at all endpoints analysis (p < 0.05) in the chopped group. The nCT data exhibited an expressive increase of bone in the chopped group when compared with the simulado and macerated groups. The biomechanical tests exhibited highest values of deformation, maximum force, and relative stiffness in the chopped group at any time of euthanasia (p < 0.05). Conclusions Our experimental work showed that chopped bone grafting preparation exhibited significant better outcomes than macerated in the treatment of a critical bone defect in rat́s calvaria.

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.

BACKGROUND: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. METHODS: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. RESULTS: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] µmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. CONCLUSIONS: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Sex Dimorphism in Pulmonary Arterial Hypertension Associated With Autoimmune Diseases.

Pulmonary hypertension is a rare, incurable, and progressive disease. Although there is increasing evidence that immune disorders, particularly those associated with connective tissue diseases, are a strong predisposing factor in the development of pulmonary arterial hypertension (PAH), there is currently a lack of knowledge about the detailed molecular mechanisms responsible for this phenomenon. Exploring this topic is crucial because patients with an immune disorder combined with PAH have a worse prognosis and higher mortality compared with patients with other PAH subtypes. Moreover, data recorded worldwide show that the prevalence of PAH in women is 2× to even 4× higher than in men, and the ratio of PAH associated with autoimmune diseases is even higher (9:1). Sexual dimorphism in the pathogenesis of cardiovascular disease was explained for many years by the action of female sex hormones. However, there are increasing reports of interactions between sex hormones and sex chromosomes, and differences in the pathogenesis of cardiovascular disease may be controlled not only by sex hormones but also by sex chromosome pathways that are not dependent on the gonads. This review discusses the role of estrogen and genetic factors including the role of genes located on the X chromosome, as well as the potential protective role of the Y chromosome in sexual dimorphism, which is prominent in the occurrence of PAH associated with autoimmune diseases. Moreover, an overview of animal models that could potentially play a role in further investigating the aforementioned link was also reviewed.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

Association between speckle tracking echocardiography and pressure-volume loops during cardiogenic shock development.

BACKGROUND: The relationship between speckle tracking assessed global longitudinal strain (GLS) and Doppler-based echocardiography with basic physiological markers of cardiac function derived from pressure-volume loops is poorly elucidated. OBJECTIVE: We aimed to describe the association between LS and Doppler-based echocardiography and direct measurements of central haemodynamic parameters from conductance catheter-based pressure-volume loops in an animal model with increasing left ventricular (LV) dysfunction. METHODS: 12 Danish landrace female pigs (75-80 kg) were used. All instrumentations were performed percutaneously, including the conductance catheter in the LV. Progressive LV dysfunction was induced by embolisation through the left main coronary artery with microspheres every 3 min until a >50% reduction in cardiac output (CO) or mixed venous saturation (SvO2), compared with baseline, or SvO2 <30%. Echocardiography was performed at baseline and 90 s after each injection. RESULTS: With progressive LV dysfunction, mean CO decreased from 5.6±0.9 L/min to 2.1±0.9 L/min, and mean SvO2 deteriorated from 61.1±7.9% to 35.3±6.1%. Mean LS and LV outflow tract velocity time integral (LVOT VTI) declined from -13.8±3.0% to -6.1±2.0% and 16.9±2.6 cm to 7.8±1.8 cm, respectively. LS and LVOT VTI showed the strongest correlation to stroke work in unadjusted linear regression (r2=0.53 and r2=0.49, respectively). LS correlated significantly with stroke volume, end-systolic elastance, systolic blood pressure, ventriculo-arterial coupling and arterial elastance. CONCLUSION: In an animal model of acute progressive LV dysfunction, echocardiographic and conductance catheter-based measurements changed significantly. LS and LVOT VTI displayed the earliest and the largest alterations with increased myocardial damage and both correlated strongest with stroke work.

Impact of Wildfires on Cardiovascular Health.

Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

Animal models of eosinophilic esophagitis, review and perspectives.

Eosinophilic oesophagitis (EoE) is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction. Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response, the exact pathogenesis is complex, and the efficacy of existing treatments is unsatisfactory. Therefore, the study of the pathophysiological process of EOE has received increasing attention. Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents. To maximize the use of existing animal models of EOE, it is important to understand the advantages or limitations of each modeling approach. This paper systematically describes the selection of experimental animals, types of allergens, and methods of sensitization and excitation during the preparation of animal models of EoE. It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Efficacy of Ganshuang granules on non-alcoholic fatty liver and underlying mechanism: a network pharmacology and experimental verification.

OBJECTIVE: To investigate the potential pharmacological mechanisms of Ganshuang granules (, GSG) in treating non-alcoholic fatty liver (NAFLD). METHODS: All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Protein-Protein interaction network, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD. Then, the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG. The levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot, respectively. RESULTS: Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD. Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD. Further experiments showed that the significantly decreased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment, as well as the expression levels of IL-6 and TNF-α in the liver. Furthermore, drug intervention increased the protein expression levels of phosphorylated-PI3K (P-PI3K) and P-AKT in the liver of the model group mice, and decreased the protein expression level of sterol regulatory element-binding protein 1. CONCLUSION: We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.

Potential Perturbations of Critical Cancer-regulatory Genes in Triple-Negative Breast Cancer Cells Within the Humanized Microenvironment of Patient-derived Xenograft Models.

PURPOSE: In this study, we aimed to establish humanized patient-derived xenograft (PDX) models for triple-negative breast cancer (TNBC) using cord blood (CB) hematopoietic stem cells (HSCs). Additionally, we attempted to characterize the immune microenvironment of the humanized PDX model to understand the potential implications of altered tumor-immune interactions in the humanized PDX model on the behavior of TNBC cells. METHODS: To establish a humanized mouse model, high-purity CD34+ HSCs from CB were transplanted into immunodeficient NOD scid γ mice. Peripheral and intratumoral immune cell compositions of humanized and non-humanized mice were compared. Additionally, RNA sequencing of the tumor tissues was performed to characterize the gene expression features associated with humanization. RESULTS: After transplanting the CD34+ HSCs, CD45+ human immune cells appeared within five weeks. A humanized mouse model showed viable human immune cells in the peripheral blood, lymphoid organs, and in the tumor microenvironment. Humanized TNBC PDX models showed varying rates of tumor growth compared to that of non-humanized mice. RNA sequencing of the tumor tissue showed significant alterations in tumor tissues from the humanized models. tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) is a shared downregulated gene in tumor tissues from humanized models. Silencing of TNFRSF11B in TNBC cell lines significantly reduced cell proliferation, migration, and invasion in vitro. Additionally, TNFRSF11B silenced cells showed decreased tumorigenicity and metastatic capacity in vivo. CONCLUSION: Humanized PDX models successfully recreated tumor-immune interactions in TNBC. TNFRSF11B, a commonly downregulated gene in humanized PDX models, may play a key role in tumor growth and metastasis. Differential tumor growth rates and gene expression patterns highlighted the complexities of the immune response in the tumor microenvironment of humanized PDX models.

Preclinical study of a novel ingestible bleeding sensor for upper gastrointestinal bleeding.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is a life-threatening condition that necessitates early identification and intervention and is associated with substantial morbidity, mortality, and socioeconomic burden. However, several diagnostic challenges remain regarding risk stratification and the optimal timing of endoscopy. The PillSense System is a noninvasive device developed to detect blood in patients with UGIB in real time. This study aimed to assess the safety and performance characteristics of PillSense using a simulated bleeding model. METHODS: A preclinical study was performed using an in vivo porcine model (14 animals). Fourteen PillSense capsules were endoscopically placed in the stomach and blood was injected into the stomach to simulate bleeding. The safety and sensitivity of blood detection and pill excretion were also investigated. RESULTS: All the sensors successfully detected the presence or absence of blood. The minimum threshold was 9% blood concentration, with additional detection of increasing concentrations of up to 22.5% blood. All the sensors passed naturally through the gastrointestinal tract. CONCLUSION: This study demonstrated the ability of the PillSense System sensor to detect UGIB across a wide range of blood concentrations. This ingestible device detects UGIB in real time and has the potential to be an effective tool to supplement the current standard of care. These favorable results will be further investigated in future clinical studies.

Establishment and application of animal models for portal vein thrombosis / 临床肝胆病杂志

Portal vein thrombosis （PVT） refers to thromboembolism that occurs in the extrahepatic main portal vein and/or intrahepatic portal vein branches. PVT is the result of the combined effect of multiple factors， but its pathogenesis remains unclear. Animal models are an important method for exploring the pathophysiological mechanism of PVT. Based on the different species of animals， this article reviews the existing animal models of PVT in terms of modeling methods， principles， advantages and disadvantages， and application.

Current research status of animal models for acute-on-chronic liver failure / 临床肝胆病杂志

Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models.

Effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma and its mechanism / 白血病·淋巴瘤

Objective:To explore the antitumor effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma (DLBCL) and its mechanism.Methods:The 6-week-old female BALB/c mice were selected, and the bilateral murine subcutaneous B-cell lymphoma model was established with murine B-cell lymphoma A20 cells. The subcutaneous tumor-bearing mice were randomly divided into untreated group (without treatment), ADU-S100 in situ vaccine treatment group (intratumoral injection of interferon gene stimulating factor agonist ADU-S100), doxorubicin in situ vaccine treatment group (intratumoral injection of doxorubicin), and ADU-S100/doxorubicin in situ vaccine treatment group (intratumoral injection of ADU-S100 and doxorubicin) by using random number table method, with 5 mice in each group. The right tumors of the bilateral subcutaneous tumor-bearing mice were defined as proximal tumors, and the left tumors of the bilateral subcutaneous tumor-bearing mice were defined as distal tumors. Only the proximal tumors were treated via the intratumoral route, and the distal tumors were not treated. On day 23 after tumor inoculation, the percentages of CD11c + dendritic cells (DC), CD8 + CD11c + DC and CD80 + CD11c + DC in the spleen of mice in each group were detected by flow cytometry. The splenocytes of mice in each group were stimulated with A20 tumor cell lysate in vitro, the percentages of 5'-ethynyl-2'-deoxyuridine-positive (EdU +) cells and tumor necrosis factor-α-positive (TNF-α +) cells in CD8 + T cells in each in situ vaccine treatment group were detected by flow cytometry, and the killing effect of cytotoxic T lymphocyte (CTL) in each group was measured by using the lactate dehydrogenase (LDH) cytotoxicity assay kit. The mice treated with ADU-S100/doxorubicin in situ vaccine were intraperitoneally injected with anti-mouse CD8α (clone 53-6.7) mAb or isotype control on days 7, 12 and 17 after tumor inoculation to eliminate CD8 + cells. On day 23 after tumor inoculation, the proximal and distal tumor volumes of mice in the ADU-S100/doxorubicin in situ vaccine combined with anti-mouse CD8α (clone 53-6.7) mAb or isotype control treatment group were measured, the percentages of CD8 + T cells and CD8 + CD11c + DC in the spleen of tumor-bearing mice in these two groups were detected by flow cytometry, and the infiltration of CD8 + T cells in the tumor tissues from these two groups was detected by immunohistochemistry (IHC) staining. Results:On days 11, 14, 17, 20 and 23 after tumor inoculation, the proximal and distal tumor volumes of mice in each treated group were lower than those in the untreated group (all P < 0.05). The proportions of CD11c + DC in the spleen of the untreated group, ADU-S100 in situ vaccine treatment group, doxorubicin in situ vaccine treatment group and ADU-S100/doxorubicin in situ vaccine treatment group were (4.92±0.63)%, (7.54±0.84)%, (7.45±0.86)% and (11.63±0.85)%, respectively, and the difference was statistically significant ( F = 72.30, P < 0.001); the proportions of CD8 + CD11c + DC were (1.36±0.34)%, (4.02±0.43)%, (4.22±0.61)% and (6.11±0.73)%, respectively, and the difference was statistically significant ( F = 76.09, P < 0.001); the proportions of CD80 + CD11c + DC were (0.51±0.24)%, (1.69±0.23)%, (1.82±0.25)% and (4.09±0.39)%, respectively, and the difference was statistically significant ( F = 167.40, P < 0.001). The CTL responses and the proportion of EdU + cells and TNF-α + cells in CD8 + T cells in each in situ vaccine treatment group were higher than those in the untreated group (all P < 0.05). Furthermore, the enhanced CTL responses and the increased proportion of EdU + cells and TNF-α + cells in CD8 + T cells were observed in the ADU-S100/doxorubicin in situ vaccine treatment group as compared to the ADU-S100 in situ vaccine treatment group and doxorubicin in situ vaccine treatment group (all P < 0.05). The proportions of CD8 + T cells and CD8 + CD11c + DC in the spleen of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were lower than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05) and both proximal and distal tumor volumes of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were larger than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05). Conclusions:ADU-S100/doxorubicin in situ vaccine can induce profound regression of proximal tumors in bilateral murine subcutaneous B-cell lymphoma model and generate systemic immune responses capable of partially inhibiting distant tumor growth, and the antitumor efficacy of ADU-S100/doxorubicin in situ vaccine may require CD8 + CD11c + DC-mediated CD8 + T cell immune responses.

The expression changes of TLR4/MyD88/NF-κB signaling pathway in a mouse model of olfactory dysfunction / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the expression changes of TLR4/MyD88/NF-κB signaling pathways in olfactory disorders.METHODS There were 40 healthy BALB/c mice who were divided into an observation group and a control group,with 20 mice in each group.Detection of Toll-like receptors(TLR4),myeloid differentiation primary response gene 88(MyD88)and nuclear factor kappa B(NF-κB)in mice using quantitative reverse transcription PCR level;Detection of TLR4,MyD88 and NF-κB by Western blot(WB)test protein content;Immunohistochemical detection of the expression of mouse olfactory marker protein(OMP).RESULTS There was no significant difference in foraging time between the two groups of mice before modeling(P>0.05),after modeling,the foraging time of the observation group mice was significantly longer than that of the control group(P<0.05);The relative mRNA expression level of TLR4,MyD88 and NF-κB in the nasal epithelium of mice in the observation group was significantly higher than that of the control group(P<0.05);The protein expression of TLR4,MyD88 and NF-κB in the nasal epithelium of mice in the observation group was significantly higher than that of the control group(P<0.05);The level of OMP protein in the nasal epithelium of the observation group was significantly lower than that of the control group(P<0.05).CONCLUSION Expression reinforcement of TLR4/MyD88/NF-κB signaling pathway in a mouse model of olfactory dysfunction.

Damage mechanisms of craniocerebral injury with seawater immersion: a review / 中华创伤杂志

Craniocerebral injury with seawater immersion is a special kind of compound injury, with low temperature, high permeability, high alkali, high salt content, and bacterial infection being the main causes. The injury is also characterized with complex damage mechanisms, difficulty to treat, and poor prognosis. At present, the damage mechanisms of craniocerebral injury with seawater immersion are mainly studied by establishing the experimental animal models at the levels of tissue, cell, organelle, molecule, etc. However, the craniocerebral injury with seawater immersion is more complex than the simple onshore craniocerebral injury, therefore, a stable disease model is not easy to construct. Most researches on the specific injury mechanisms are relatively single and one-sided, with many different views in existence, and the damage mechanisms of craniocerebral injury with seawater immersion have hitherto not been clear. The authors reviewed the research progress in the damage mechanisms of craniocerebral injury with seawater immersion, in order to promote the in-depth study of the mechanism of craniocerebral injury with seawater immersion and provide reference for its clinical treatment.