Objective: Main pancreatic duct (MPD) injury is rare but critical in abdominal trauma. Whether it accelerates skeletal muscle (SM) wasting and predicts poor outcomes remains unclear.Methods: This prospective cohort enrolled ICU-admitted closed abdominal trauma patients (Aug 2021–Jan 2024). SM and fat mass were assessed by CT and BIA at admission, 1 week, and 1 month. Primary endpoint was SM/fat change; secondary endpoints were chronic critical illness (CCI) and persistent inflammation, immunosuppression, and catabolism syndrome (PICS).Results: Of 212 patients (126 non‑pancreatic, 42 pancreatic without MPD injury, 44 with MPD injury), MPD injury patients had the greatest SM loss at 1 week: ΔSMA 14.9% and ΔSMI 14.2%, significantly higher than non‑pancreatic (ΔSMA 10.6%, P=0.016; ΔSMI 10.9%, P=0.024) and pancreatic without MPD injury (ΔSMA 8.2%, P=0.007; ΔSMI 8.1%, P=0.013). ΔSMA had the highest diagnostic value for PICS (AUC 0.83) and CCI (AUC 0.89), with cut‑offs of 11.9% and 12.7%. MPD injury was the strongest risk factor for excessive SM loss (OR 4.57 for ΔSMA>11.9%, OR 4.99 for ΔSMA>12.7%, both P<0.001).Conclusions: Abdominal trauma patients with MPD injury exhibit significantly accelerated skeletal muscle loss. The rate of SM loss within the first week is an effective predictor of CCI and PICS, highlighting its potential as an early prognostic marker.

Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are severe inflammatory conditions with high morbidity and mortality. Understanding the molecular mechanisms underlying these diseases is crucial for developing effective treatments. To investigate the molecular mechanisms underlying ALI, we established a lipopolysaccharide (LPS)-induced mouse model. Bioinformatics and machine learning techniques were utilized to identify key genes and construct gene co-expression networks. Single-cell RNA sequencing was performed to analyze Il1r2 expression specifically in neutrophils. CellChat and hdWGCNA were employed to explore gene co-expression modules and cell-cell communication networks, respectively. Experimental validations included qRT-PCR for gene expression quantification, and western blotting, immunohistochemistry, and immunofluorescence for protein-level confirmation. Four key genes—Cebpd, Hspa12b, Pim1, and Il1r2—were identified as potential biomarkers and therapeutic targets. Il1r2 was identified as a key regulator of inflammation, predominantly expressed in neutrophils. Immune cell infiltration analysis revealed increased neutrophils, monocytes, and dendritic cells in ALI samples. CellChat and hdWGCNA highlighted the significant role of Il1r2 in neutrophil-macrophage signaling in immune regulation. Furthermore, overexpression of Il1r2 in neutrophils reduced lung inflammation and promoted M2 macrophage polarization in vivo. This indicated that Il1r2 alleviates ALI by modulating the immune response, particularly through interactions with macrophages. Neutrophil-derived Il1r2 plays a critical role in modulating inflammation in ALI by promoting M2 macrophage polarization. These findings suggest that targeting Il1r2 may offer a novel therapeutic approach to control the immune response in ALI and other inflammatory diseases.

Managing uncontrolled and noncompressible bleeding presents a major challenge in emergency trauma care. Methods to halt bleeding quickly and efficiently, without applying direct pressure on the wound, have become a key focus of research. Herein, a novel fructose-modified chitosan/gelatin composite sponge has been developed, exhibiting high elasticity, low rebound pressure, and excellent cell compatibility. This material can rapidly return to its original form in around 1.5 s after being compressed by 80% upon contact with water. Additionally, experimental results from a rat liver wound model demonstrated that it exhibited a clear hemostatic effect. The hemostatic time was shortened from 204 ± 15.35 s to 53.3 ± 6.54 s, and the blood loss was reduced from 867 ± 153.15 mg to 187 ± 61.06 mg. Moreover, it can promote tissue healing by inhibiting the production of inflammatory factors including TNF-α, MCP-1, and IL-6. This material offers an effective solution for noncompressible tissue injuries.

The mechanism by which neutrophil extracellular traps (NETs) may cause intestinal barrier dysfunction in response to trauma/hemorrhagic shock (T/HS) remains unclear. In this study, the roles and mechanisms of NETs in macrophage polarization were examined to determine whether this process plays a role in tissue damage associated with T/HS. Rat models of T/HS and macrophage polarization were developed and the levels of NETs formation in the intestinal tissue of T/HS rats were assessed. NET formation was inhibited in models of T/HS to examine the effect on intestinal inflammation and barrier injury. The proportions of pro-inflammatory and anti-inflammatory macrophages in the damaged intestinal tissues were measured. Finally, high-throughput sequencing was performed to investigate the underlying mechanisms involved in this process. The study revealed that the level of NETs formation was increased and that inhibition of NETs formation alleviated the intestinal inflammation and barrier injury. Moreover, the number of pro-inflammatory macrophages increased and the number of anti-inflammatory macrophages decreased. RNA sequencing analysis indicated that NETs formation decreased the expression of transforming growth factor-beta receptor 2 (TGFBR2), bioinformatic analyses revealed that TGFBR2 was significantly enriched in the transforming growth factor-beta (TGF-β) signaling pathway. Verification experiments showed that NETs impeded macrophage differentiation into the anti-inflammatory/M2 phenotype and inhibited TGFBR2 and TGF-β expression in macrophages. However, treatment with DNase I and overexpression of TGFBR2, and inhibition of TGF-β promoted and prevented this process, respectively. NETs may regulate the macrophage polarization process by promoting intestinal barrier dysfunction in T/HS rats through the TGFBR2-mediated TGF-β signaling pathway.

The direct incorporation of alkanes and CO into value-added chiral products through alkane carbonylation is a desirable transformation; however, it remains inefficient. The carbonylation of alkanes via photoirradiated radical addition to CO requires mild reaction conditions but suffers from low conversion due to equilibrium constraints. Here an equilibrium-leveraging strategy that combines alkane carbonylation with various enantioselective transformations is reported. The combination of tetra- n -butylammonium decatungstate and chiral sodium phosphate catalysts enables alkane carbonylation/enantioselective Mannich reaction and alkane carbonylation/enantioselective radical addition cascade processes for the enantioselective synthesis of β-amino and α-amino ketones from alkanes, CO and anilines by breaking the equilibrium of reversible photocatalytic C–H carbonylation. While both reactions can tolerate a broad scope of cyclic alkanes and anilines, the synthetic method to synthesize β-amino ketones can use a range of aliphatic ketones as substrates. The synthetic process to form β-amino ketones can be readily scaled-up through use of an integrated continuous-flow and batch set-up, providing efficient gram-scale synthesis. Mechanistic studies reveal that the synthesis of α-amino ketones proceeds through the asymmetric addition of an acyl radical to an imine intermediate.

In the treatment of thrombosis, conventional nanocarriers inevitably have problems, such as adverse reactions and difficulties in synthesis. Inspired by the concept of 'medicine food homology,' we extracted and purified natural exosomes from mulberry leaves as carriers for the delivery of urokinase-type plasminogen activator (uPA) for targeted therapy. The obtained mulberry leaf exosomes (MLE) possessed a desirable hydrodynamic particle size (119.4 nm), a uniform size distribution (polydispersity index = 0.174), and a negative surface charge (-23.3 mv). Before loading with uPA, MLE were grafted with cyclic RGD (cRGD) to selectively bind activated platelets for thrombus targeting. The cytometry studies revealed that MLE@cRGD has a high thrombus targeting ability about 74.3 %. Animal tests demonstrated that the delivered uPA could dissolve clots almost completely in femoral vein thrombosis models. In addition, MLE could remodel venous microenvironments by effectively eliminating reactive oxygen species (ROS) and promoting the phenotypic transformation of macrophages from M1 to M2 for venous tissue repair.

Noninvasive treatment of inflammatory bowel disease with lower gastrointestinal bleeding is a major clinical challenge. In this study, we designed an orally targeted microsphere based on sunflower pollen microcapsules to localize the site of inflammatory injury and promote hemostasis and tissue repair. Due to the Eudragit and ascorbate palmitate coatings, EL/AP@PS(t+Dex) demonstrates pH- and enzyme-responsive release of loaded drugs and helps to resist the harsh environment of the gastrointestinal tract. Both in vitro and in vivo experiments show the characteristics of inflammation targeting and mucosal adhesion, which reduce the systematic exposure and increase the local drug concentration. In the DSS model, orally administered EL/AP@PS(t+Dex) significantly alleviates hematochezia, inhabits intestinal inflammation, and remarkably promotes the recovery of the intestinal epithelial barrier to reduce the exposure of intestinal microvessels. Furthermore, EL/AP@PS(t+Dex) optimized the composition of intestinal microbiota, which benefits intestinal homeostasis. This finding provides a fundamental solution for the treatment of intestinal bleeding caused by inflammatory bowel disease (IBD).

Microneedles (MNs) with unique three-dimensional stereochemical structures are suitable candidates for tissue fixation and drug delivery. However, existing hydrogel MNs exhibit poor mechanical properties after swelling and require complex preparation procedures, impeding their practical application. Hence, we engineered chitosan fiber-reinforced silk fibroin MN patches containing epigallocatechin gallate (SCEMN). A formic acid–calcium chloride system was introduced to fabricate hydrogel MNs with excellent inherent adhesion, and the incorporation of chitosan fiber as a reinforcing material enhanced mechanical strength and viscosity, thereby increasing the physical interlocking with tissue and the ability to maintain shape. The SCEMN with a lower insertion force firmly adhered to porcine skin, with a maximum detachment force of 11.98 N/cm2. Additionally, SCEMN has excellent antioxidant and antibacterial properties, facilitates macrophage polarization from M1 to M2, and demonstrates superior performance in vivo for diabetic wound repair compared with the commercial product Tegaderm™. This study represents the first trial of fiber-reinforced hydrogel MNs for robust tissue adhesion. Our findings underscore the significance of this innovative approach for advancing MN technology to enhance tissue adhesion and accelerate wound healing.

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

Management of noncompressible torso hemorrhage is an urgent clinical requirement, desiring biomaterials with rapid hemostasis, anti-infection and excellent resilient properties. In this research, we have prepared a highly resilient cryogel with both hemostatic and antibacterial effects by chemical crosslinking and electrostatic interaction. The network structure crosslinked by quaternized chitosan and genipin was interspersed with oxidized bacterial cellulose after lyophilization. The as-prepared cryogel can quickly return to the original volume when soaking in water or blood. The appropriately sized pores in the cryogel help to absorb blood cells and further activate coagulation, while the quaternary ammonium salt groups on quaternized chitosan inhibit bacterial infections. Both cell and animal experiments showed that the cryogel was hypotoxic and could promote the regeneration of wound tissue. This research provides a new pathway for the preparation of double crosslinking cryogels and offers effective and safe biomaterials for the emergent bleeding management of incompressible wounds.

Background This study aimed to develop and validate a model to predict the risk of prolonged weaning from mechanical ventilation in patients with abdominal trauma. Methods Patients with abdominal trauma were included and were divided into the training cohort and the validation cohort. The model was constructed using predictive factors identified by univariable and multivariable logistic regressions, and was validated by receiver operating characteristic curve, calibration curve, and decision curve analysis. Clinical outcomes were compared between model-stratified risk groups. Results In total,190 patients were included, with 133 in the training cohort and 57 in the validation cohort. Six predictive factors, the Acute Physiology and Chronic Health Evaluation II score, Injury Severity Score, Glasgow coma scale, total bilirubin, skeletal muscle index, and abdominal fat index, were identified and were included in the model. The model predicting prolonged weaning owned a good discrimination, had an excellent calibration, and exhibited a favorable net benefit within a reasonable range of threshold probabilities. Significant differences were shown in prolonged weaning and clinical outcomes between the high-risk and low-risk groups (P < .05). Multivariable Cox regression analysis showed that patients in the high-risk group had greater risk of 28-day mortality (P < .05). Conclusion This study established a model to predict the risk of prolonged weaning from mechanical ventilation and clinical outcomes in patients with abdominal trauma. Skeletal muscle index was identified as one of independent risk factors of prolonged weaning. The findings offer valuable insights for respiratory management in patients with abdominal trauma.

The direct carbonylation of alkanes with CO suffers from low conversion owing to equilibrium constraints. Now, a strategy is presented that combines reversible alkane carbonylation with an asymmetric transformation to overcome the equilibrium limitations, enabling the synthesis of chiral beta- and alpha-amino ketones from alkanes, CO and anilines.

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time ( > 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

Dysfunction of the intestinal barrier is a prevalent phenomenon observed across a spectrum of diseases, encompassing conditions such as mesenteric artery dissection, inflammatory bowel disease, cirrhosis, and sepsis. In these pathological states, the integrity of the intestinal barrier, which normally serves to regulate the selective passage of substances between the gut lumen and the bloodstream, becomes compromised. This compromised barrier function can lead to a range of adverse consequences, including increased permeability to harmful substances, the translocation of bacteria and their products into systemic circulation, and heightened inflammatory responses within the gut and beyond. Understanding the mechanisms underlying intestinal barrier dysfunction in these diverse disease contexts is crucial for the development of targeted therapeutic interventions aimed at restoring barrier integrity and ameliorating disease progression. Lipocalin-2 (LCN2) expression is significantly upregulated during episodes of intestinal inflammation, making it a pivotal indicator for gauging the extent of such inflammatory processes. Notably, however, LCN2 derived from distinct cellular sources, whether intestinal epithelial cells or immune cells, exhibits notably divergent functional characteristics. Furthermore, the multifaceted nature of LCN2 is underscored by its varying roles across different diseases, sometimes even demonstrating contradictory effects.

Neutrophil extracellular trap (NET) has been confirmed to be related to gut barrier injury during intestinal ischaemia-reperfusion (II/R). However, the specific molecular regulatory mechanism of NETs in II/R-induced intestinal barrier damage has yet to be fully elucidated. Here, we reported increased NETs infiltration accompanied by elevated inflammatory cytokines, cellular necroptosis and tight junction disruption in the intestine of human II/R patients. Meanwhile, NETs aggravated Caco-2 intestinal epithelial cell necroptosis, impairing the monolayer barrier in vitro. Moreover, Pad4-deficient mice were used further to validate the role of NETs in II/R-induced intestinal injury. In contrast, NET inhibition via Pad4 deficiency alleviated intestinal inflammation, attenuated cellular necroptosis, improved intestinal permeability, and enhanced tight junction protein expression. Notably, NETs prevented FUN14 domain-containing 1 (FUNDC1)-required mitophagy activation in intestinal epithelial cells, and stimulating mitophagy attenuated NET-associated mitochondrial dysfunction, cellular necroptosis, and intestinal damage. Mechanistically, silencing Toll-like receptor 4 (TLR4) or receptor-interacting protein kinase 3 (RIPK3) via shRNA relieved mitophagy limitation, restored mitochondrial function and reduced NET-induced necroptosis in Caco-2 cells, whereas this protective effect was reversed by TLR4 or RIPK3 overexpression. The regulation of TLR4/RIPK3/FUNDC1-required mitophagy by NETs can potentially induce intestinal epithelium necroptosis.

Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings. Thus, multiple hemostatic strategies are critical for treating large bleeding wounds. In this study, inspired by bombardier beetles to eject toxic spray for defense, a shape-memory aerogel with an aligned microchannel structure was proposed, employing thrombin-carrying microparticles loaded as a built-in engine to generate pulse ejections for enhanced drug permeation. Bioinspired aerogels, after contact with blood, can rapidly expand inside the wound, offering robust physical barrier blocking, sealing the bleeding wound, and generating a spontaneous local chemical reaction causing an explosive-like generation of CO2 microbubbles, which provide propulsion thrust to accelerate burst ejection from arrays of microchannels for deeper and faster drug diffusion. The ejection behavior, drug release kinetics, and permeation capacity were evaluated using a theoretical model and experimentally demonstrated. This novel aerogel showed remarkable hemostatic performance in severely bleeding wounds in a swine model and demonstrated good degradability and biocompatibility, displaying great potential for clinical application in humans.

BackgroundThe objective of this study was to explore whether longitudinal changes in skeletal muscle mass, from hospital admission to 3 weeks post-trauma, are associated with poor prognosis and nutritional intake in acutely hospitalized patients with abdominal trauma.MethodsA single-center retrospective observational review was conducted on 103 patients with abdominal trauma admitted to the Affiliated Jinling Hospital, Medical School of Nanjing University between January 2010 and April 2020. Skeletal muscle mass was assessed by abdominal computed tomography (CT) performed within 14 days before surgery and on post-trauma days 1–3 (week 0), 7–10 (week 1), 14–17 (week 2), and 21–24 (week 3). The skeletal muscle index (SMI) at L3, change in SMI per day (ΔSMI/day), and percent change in SMI per day (ΔSMI/day [%]) were calculated. The receiver-operating characteristic (ROC) curve was used to evaluate the discriminatory performance of ΔSMI/day (%) for mortality. Linear correlation analysis was used to evaluate the associations between ΔSMI/day (%) and daily caloric or protein intake.ResultsAmong the included patients, there were 91 males and 12 females (mean age ± standard deviation 43.74 ± 15.53 years). ΔSMI4-1/d (%) had a ROC-area under the curve of 0.747 (p = 0.048) and a cut-off value of −0.032 for overall mortality. There were significant positive correlations between ΔSMI4-1/d (%) and daily caloric intake and protein intake (Y = 0.0007501*X – 1.397, R2 = 0.282, R = 0.531, p < 0.001; Y = 0.008183*X - 0.9228, R2 = 0.194, R = 0.440, p < 0.001). Δ SMI/day (%) was positively correlated with daily caloric intake ≥80% of resting energy expenditure in weeks 2, 3, and 1–3 post-trauma and with protein intake >1.2 g/kg/d in weeks 3 and 1–3 post-trauma.ConclusionLoss of skeletal muscle mass is associated with poor prognosis and nutritional intake in patients admitted to hospital with abdominal trauma.

Objectives: Pancreatic trauma and subsequent pancreatic operation result in early pathophysiologic alterations. Understanding changes in energy expenditure and body composition is essential for optimal management. This study aims to observe changes in energy expenditure and body composition in patients during the early postoperative days (PODs) after pancreatic trauma.Methods: This is a retrospective review of patients who underwent surgery for blunt pancreatic trauma in a single trauma center. Data of body composition by bioimpedance spectroscopy and energy expenditure by indirect calorimetry were collected and analyzed in patients during the early PODs. The association of body composition parameters with major complications was analyzed.Results: Forty-one patients were included. Compared with POD-3, the total body water, extracellular water, fat-free mass, and skeletal muscle mass on POD-7 and -14 decreased significantly (all P < 0.05). The phase angle (PhA) increased significantly from POD-3 to -14 (P < 0.05). Resting energy expenditure was significantly higher than predicted and remained high throughout the study period. Over the 14-d study period, delivered energy was escalated to the level of resting energy expenditure. The PhA was significantly lower in patients with severe morbidity than in those without (3.6 [3.3-4.2] versus 4.5 [4.2-5.0]; P < 0.001). A multivariate analysis found that PhA was the independent variable for severe complications, with an odds ratio of 0.069 (95% CI, 0.011-0.427; P = 0.004). The predictive ability of PhA revealed an area under the receiver operating characteristic curve of 0.837, with an optimal threshold of 4.23.Conclusions: Changes in body composition and hypermetabolism state were observed from POD-3 to -14 after pancreatic trauma. A postoperative value of PhA < 4.23 is associated with severe complications. & COPY; 2023 Elsevier Inc. All rights reserved.