DEVELOPMENT AND VALIDATION OF A NOMOGRAM FOR PREDICTING 28-DAY IN-HOSPITAL MORTALITY IN SEPSIS PATIENTS BASED ON AN OPTIMIZED ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II SCORE.

ABSTRACT: Purpose : The objective of this study is to establish a nomogram that correlates optimized Acute Physiology and Chronic Health Evaluation II (APACHE II) score with sepsis-related indicators, aiming to provide a robust model for early prediction of sepsis prognosis in clinical practice and serve as a valuable reference for improved diagnosis and treatment strategies. Methods : This retrospective study extracted sepsis patients meeting the inclusion criteria from the MIMIC-IV database to form the training group. An optimized APACHE II score integrated with relevant indicators was developed using a nomogram for predicting the prognosis of sepsis patients. External validation was conducted using data from the intensive care unit at Lanzhou University Second Hospital. Results : The study enrolled 1805 patients in the training cohort and 203 patients in the validation cohort. A multifactor analysis was conducted to identify factors affecting patient mortality within 28 days, resulting in the development of an optimized score by simplifying evaluation indicators from APACHE II score. The results showed that the optimized score (area under the ROC curve [AUC] = 0.715) had a higher area under receiver operating characteristic curve than Sequential Organ Failure Assessment score (AUC = 0.637) but slightly lower than APACHE II score (AUC = 0.720). Significant indicators identified through multifactor analysis included platelet count, total bilirubin level, albumin level, prothrombin time, activated partial thromboplastin time, mechanical ventilation use and renal replacement therapy use. These seven indicators were combined with optimized score to construct a nomogram based on these seven indicators. The nomogram demonstrated good clinical predictive value in both training cohort (AUC = 0.803) and validation cohort (AUC = 0.750). Calibration curves and decision curve analyses also confirmed its good predictive ability, surpassing the APACHE II score and Sequential Organ Failure Assessment score in identifying high-risk patients. Conclusions : The nomogram was established in this study using the MIMIC-IV database and validated with external data, demonstrating its robust discriminability, calibration, and clinical practicability for predicting 28-day mortality in sepsis patients. These findings aim to provide substantial support for clinicians' decision making.

Salt Spray Resistance of Roller-Compacted Concrete with Surface Coatings.

In order to evaluate the feasibility of surface coatings in improving the performance of RCC under salt spray conditions, sodium silicate (SS), isooctyl triethoxy silane (IOTS), and polyurea (PUA) were used as surface coatings to prepare four types of roller-compacted concrete (RCC): reference RCC, RCC-SS, RCC-IOTS, and RCC-PUA. A 5% sodium sulfate solution was used to simulate a corrosive marine environment with high temperatures, high humidity, and high concentrations of salt spray. This study focuses on investigating various properties, including water absorption, abrasion loss, compressive strength, dynamic elastic modulus, and impact resistance. Compared to the reference RCC, the 24 h water absorption of RCC-SS, RCC-IOTS, and RCC-PUA without salt spray exposure decreased by 22.8%, 77.2%, and 89.8%, respectively. After 300 cycles of salt spray, the abrasion loss of RCC-SS, RCC-IOTS, and RCC-PUA reduced by 0.3%, 4.4%, and 34.3%, respectively. Additionally, their compressive strengths increased by 3.8%, 0.89%, and 0.22%, and the total absorbed energy at fracture increased by 64.8%, 53.2%, and 50.1%, respectively. The results of the study may provide a reference for the selection of coating materials under conditions similar to those in this study.

Precisely designed Fex (x = 1-2) cluster nanocatalysts for effective nanocatalytic tumor therapy.

Atomically dispersed metal clusters are considered as promising nanocatalysts due to their excellent physicochemical properties. Here, we report a novel strategy for precisely designing Fex (x = 1-2) cluster nanocatalysts (Fe1-N-C and Fe2-N-C) with dual catalytic activity, which can catalyze H2O2 into reactive oxygen species (ROS) and oxidize glutathione (GSH) into glutathione disulfide simultaneously. The adsorption energies of Fe-N sites in Fe2-N-C for GSH and H2O2 intermediates were well controlled due to the orbital modulation of adjacent Fe sites, contributing to the higher dual catalytic activity compared to Fe1-N-C. Additionally, tamoxifen (TAM) was loaded into Fe2-N-C (Fe2@TDF NEs) to down-regulate the intracellular pH for higher Fenton-like catalytic efficiency and ROS production. The generated ROS could induce apoptosis and lipid peroxidation, triggering ferroptosis. Meanwhile, upregulation of ROS and lipid peroxidation, along with GSH depletion and GPX4 downregulation could promote the apoptosis and ferroptosis of tumor cells. In addition, the lactic acid accumulation effect of TAM and the high photothermal conversion ability of Fe2@TDF NEs could further enhance the catalytic activity to achieve synergistic antitumor effects. As a result, this work highlights the critical role of adjacent metal sites at the atomic-level and provides a rational guidance for the design and application of nanocatalytic antitumor systems.

Precision therapy through breaking the intracellular redox balance with an MOF-based hydrogel intelligent nanobot for enhancing ferroptosis and activating immunotherapy.

With the advancement and development of nanomedicine, tumor precision therapy provides technical support for effective accumulation and targeted drug delivery, and reduces toxic side effects. In cancer cells, breaking the redox balance could induce cancer cell death. Herein, a novel iron-containing intelligent hydrogel nanobot (FeSe2-Ce6/MOF@HA/PEI/CpG@HHPA NPs, abbreviated as FSMH) is proposed to break the intracellular redox balance and trigger the immune response. The as-fabricated multifunctional FSMH could not only exert Fenton reactions in the acidic tumor microenvironment, converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH), but also effectively consume GSH to attenuate the intracellular oxidative stress. The negative charge of the FSMH nanohydrogel system guarantees its superexcellent stabilization in blood circulation and optimal tumor collection. Subsequently, the surface charge of the endocytosed FSMH was transformed to a positive charge after exposure to the acidic tumor environment, further improving its tumor collection and locally releasing Fe ions and immune adjuvants. Furthermore, Ce6 was released in a pH-responsive manner in the acidic microenvironment. In the presence of near-infrared light, singlet oxygen was produced by the FSMH nanohydrogel system, to ablate tumors and promote the maturation of dendritic cells, achieving the precision-combined strategies effect of CDT, PDT, and immunotherapy.

[Advances in the diagnosis and treatment of acute respiratory distress syndrome induced by pancreatitis].

Acute pancreatitis (AP) is one of the common diseases of the digestive system mainly characterized by acute inflammation of the pancreas and acinar cell destruction, and it can often develop into severe acute pancreatitis (SAP). Acute respiratory distress syndrome (ARDS) is one of the most common and serious complications of SAP and a common cause of death in patients with SAP. In recent years, there have gained new understanding of the pathogenesis, diagnosis, and treatment of SAP-related ARDS, however, a variety of drugs that have been shown to prevent ARDS in SAP animal models have not improved the prognosis of SAP-related ARDS patients in clinical researches. At present, the treatment of SAP-related ARDS still follows the general treatment principles of ARDS, such as treatment of primary disease, lung protective ventilation strategy, prone position ventilation, early short-term use of neuromuscular blockers and extracorporeal membrane oxygenation (ECMO), and so on. However, the influence of high intra-abdominal pressure, intestinal function failure, abdominal incision, and drainage tube on the treatment measures should also be considered for patients with SAP-related ARDS. This article reviews the recent progress in diagnosis and treatment of SAP-related ARDS.

Core-shell FePt-cube@covalent organic polymer nanocomposites: a multifunctional nanocatalytic agent for primary and metastatic tumor treatment.

Metastasis and spread are currently the main factors leading to high mortality of cancer, so developing a synergetic antitumor strategy with high specificity and hypotoxicity is in urgent demand. Based on the design concept of "nanocatalytic medicine", multifunctional nanotherapeutic agent FePt@COP-FA nanocomposites (FPCF NCs) are developed for cancer treatment. Specifically, in the tumor microenvironment (TME), FePt could catalyze intracellular over-expressed H2O2 to generate highly active hydroxyl radicals (˙OH), which could not only induce the apoptosis of tumor cells, but also activate the "ferroptosis" pathway resulting in the lipid peroxide accumulation and ferroptotic cell death. Moreover, owing to the excellent photothermal effect, the FPCF NCs could effectively ablate primary tumors under near-infrared (NIR) laser irradiation and produce numerous tumor-associated antigens in situ. With the assistance of a checkpoint blockade inhibitor, anti-CTLA4 antibody, the body's specific immune response would be initiated to inhibit the growth of metastatic tumors. In particular, such synergistic therapeutics could produce an effective immunological memory effect, which could prevent tumor metastasis and recurrence again. In summary, the FPCF NC is an effective multifunctional antitumor therapeutic agent for nanocatalytic/photothermal/checkpoint blockade combination therapy, which exhibits great potential in nanocatalytic anticancer therapeutic applications.

Overexpression of Nrf2 Protects Against Lipopolysaccharide and Cerulein-Induced Pancreatitis In Vitro and In Vivo.

OBJECTIVES: In this study, we focused on the function of nuclear factor E2-related factor 2 (Nrf2) in acute pancreatitis (AP), which has been shown to have protective effects in gliomas, hepatocytes, and astrocytes. METHODS: Acute pancreatitis cell line and animal model were induced by administration of lipopolysaccharide and cerulein into the cell supernatant or intraperitoneal injection. Oxidative stress status was evaluated by measuring the level of amylase, C-reactive protein, malondialdehyde, superoxide dismutase, and myeloperoxidase. Morphological alterations in the pancreas were evaluated by hematoxylin-eosin staining, the wet-to-dry weight ratio, and the pathology injury scores. Western blot, reverse transcription-polymerase chain reaction, and immunofluorescence staining were performed to analyze the expression of Nrf2, Heme oxygenase 1, and NAD(P)H: quinone oxidoreductase 1. RESULTS: Overexpression of Nrf2 inhibits oxidative stress and inflammatory responses by inducting the expression of superoxide dismutase as well as reducing the level of amylase, malondialdehyde, and myeloperoxidase in the AR42J rat pancreatic acinar cells in AP. Importantly, overexpression of Nrf2 displayed the same protective effect in vivo. Data from an AP rat model showed that Nrf2 could relieve pancreatic damage. CONCLUSIONS: These results indicated that Nrf2 has a protective role in lipopolysaccharide and cerulein-induced cytotoxicity, providing potential therapeutic strategies for the treatment of AP.