[Review and prospects of international clinical research in critical care medicine in 2023].

The main clinical research advances of critical care in 2023 includes: new trials of Chinese herbal medicine, hydroxocobalamin (vitamin B12), methylene blue as well glucocorticoids have shown the potential to improve outcomes of patients with sepsis and septic shock; international committees launched new global definition and managing recommendations for acute respiratory distress syndrome (ARDS). Besides, a cluster of new evidences has emerged in many aspects as following: fluid control strategy in sepsis (restrictive/liberative), antibiotic infusion strategy (continuous/intermittent), oxygen-saturation targets for mechanical ventilation (conservative/liberative), blood pressure targets after resuscitation from out-of-hospital cardiac arrest (hypotension/hypertension), blood pressure targets after successful stroke thrombectomy (intensive/conventional), and nutritional support strategies (low protein-calories/conventional protein-calories, fasting/persistent feeding before extubation). Thus, given above progress, carrying out high -quality domestic multi-center clinical registration researches, constructing shareable standardized databases, as well raising public awareness of sepsis, should be the essential steps to improve our level of intensive care medicine.

Relation between LRG1 and CD4+ T cells, cognitive impairment and neurological function in patients with acute ischemic stroke.

Objective: To assess the relationship between LRG1 and CD4+ T cells, cognitive impairment and neurological function in acute ischemic stroke (AIS). Methods: Plasma LRG1 was detected by ELISA in 175 patients with AIS at baseline, day (D) 1, D7, month (M) 1 and M3. Results: LRG1 was negatively related to Th2 and Treg cells and positively linked to Th17 (all p < 0.05). LRG1 increased from baseline to D1, then decreased until M3 (p < 0.001). LRG1 at each assessment point was increased in patients with cognitive impairment or poor neurological function at M3 versus those without (all p < 0.05). Conclusion: LRG1 is linked to decreased Th2 and Tregs, increased Th17, cognitive impairment and nonideal neurological function recovery in patients with AIS.

SpineHRformer: A Transformer-Based Deep Learning Model for Automatic Spine Deformity Assessment with Prospective Validation.

The Cobb angle (CA) serves as the principal method for assessing spinal deformity, but manual measurements of the CA are time-consuming and susceptible to inter- and intra-observer variability. While learning-based methods, such as SpineHRNet+, have demonstrated potential in automating CA measurement, their accuracy can be influenced by the severity of spinal deformity, image quality, relative position of rib and vertebrae, etc. Our aim is to create a reliable learning-based approach that provides consistent and highly accurate measurements of the CA from posteroanterior (PA) X-rays, surpassing the state-of-the-art method. To accomplish this, we introduce SpineHRformer, which identifies anatomical landmarks, including the vertices of endplates from the 7th cervical vertebra (C7) to the 5th lumbar vertebra (L5) and the end vertebrae with different output heads, enabling the calculation of CAs. Within our SpineHRformer, a backbone HRNet first extracts multi-scale features from the input X-ray, while transformer blocks extract local and global features from the HRNet outputs. Subsequently, an output head to generate heatmaps of the endplate landmarks or end vertebra landmarks facilitates the computation of CAs. We used a dataset of 1934 PA X-rays with diverse degrees of spinal deformity and image quality, following an 8:2 ratio to train and test the model. The experimental results indicate that SpineHRformer outperforms SpineHRNet+ in landmark detection (Mean Euclidean Distance: 2.47 pixels vs. 2.74 pixels), CA prediction (Pearson correlation coefficient: 0.86 vs. 0.83), and severity grading (sensitivity: normal-mild; 0.93 vs. 0.74, moderate; 0.74 vs. 0.77, severe; 0.74 vs. 0.7). Our approach demonstrates greater robustness and accuracy compared to SpineHRNet+, offering substantial potential for improving the efficiency and reliability of CA measurements in clinical settings.

Remarkably enhanced catalytic performance in CoOx/Bi4Ti3O12 heterostructures for methyl orange degradation via piezocatalysis and piezo-photocatalysis.

A novel heterojunction composite of CoOx/Bi4Ti3O12 was synthesized through a combination of molten salt and photodeposition methods. The optimal sample exhibited superior performance in the piezocatalytic degradation of methyl orange (MO) dye with a degradation rate of 1.09 h-1, which was 2.4 times higher than that of pristine Bi4Ti3O12. Various characterizations were conducted to reveal the fundamental nature accountable for the outstanding piezocatalytic performance of CoOx/Bi4Ti3O12. The investigation of the band structure indicated that the CoOx/Bi4Ti3O12 composite formed a type-I p-n heterojunction structure, with CoOx acting as a hole trapper to effectively separate and transfer piezogenerated carriers. Significantly, the MO degradation rate of the best CoOx/Bi4Ti3O12 sample further increased to 2.96 h-1 under combined ultrasonic vibration and simulated sunlight. The synergy between piezocatalysis and photocatalysis can be ascribed to the following factors. The photoexcitation process ensures the sufficient generation of charge carriers in the CoOx/Bi4Ti3O12, while the piezoelectric field within Bi4Ti3O12 promotes the separation of electron-hole pairs in the bulk phase. Furthermore, the heterojunction structure between Bi4Ti3O12 and CoOx significantly facilitates the surface separation of charge carriers. This increased involvement of free electrons and holes in the reaction leads to a remarkable enhancement in catalytic MO degradation. This work contributes to the understanding of the coupling mechanism between the piezoelectric effect and photocatalysis, and also provides a promising strategy for the development of efficient catalysts for wastewater treatment.

Uncovering the molecular mechanisms of Curcumae Rhizoma against myocardial fibrosis using network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis leads to cardiac remodeling and dysfunction. Curcumae Rhizoma has been utilized in clinical trials to treat a variety of cardiovascular illnesses, although its role in myocardial fibrosis is unknown. AIM OF THE STUDY: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with Curcumae Rhizoma. MATERIALS AND METHODS: The chemical components in the aqueous extract from Curcumae Rhizoma were identified using GC-MS analysis. A prediction network describing the relationship between Curcumae Rhizoma and MF was established based on information collected from multiple databases. Functional enrichment analysis was performed to investigate the specific functions and pathways involved in the candidate Curcumae Rhizoma targets acting on MF, which were further validated by vivo experiments. RESULTS: There were 444 targets obtained from the 39 active ingredients in Curcumae Rhizoma, and 5691 disease targets related to MF were identified. Then, 41 key targets were determined with the PPI interaction network, which was structured from 324 overlapping gene targets. GO and KEGG analyses revealed that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 signaling pathways might play crucial roles in the therapeutic mechanism of MF. According to the results of molecular docking, the binding activity between core components and targets was marvelous (affinity < -6 kcal/mol). Take it a step further, the experimental validation data affirmed that Curcumae Rhizoma substantially decreased myocardial fibrosis and recovered cardiac function in the ISO-induced rats. The associated proteins expression data implied that the p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways might be vital in the anti-fibrosis effect of Curcumae Rhizoma. CONCLUSION: The findings suggested that Curcumae Rhizoma diminished myocardial fibrosis by suppressing fibrosis multiplication and collagen deposition through inhibiting p38 MAPK/NF-κB and TGF-ß1/Smad2/3 pathways, which might be a promising therapeutic medicament for alleviating myocardial fibrosis.

Soft integration of a neural cells network and bionic interfaces.

Both glial cells and neurons can be considered basic computational units in neural networks, and the brain-computer interface (BCI) can play a role in awakening the latency portion and being sensitive to positive feedback through learning. However, high-quality information gained from BCI requires invasive approaches such as microelectrodes implanted under the endocranium. As a hard foreign object in the aqueous microenvironment, the soft cerebral cortex's chronic inflammation state and scar tissue appear subsequently. To avoid the obvious defects caused by hard electrodes, this review focuses on the bioinspired neural interface, guiding and optimizing the implant system for better biocompatibility and accuracy. At the same time, the bionic techniques of signal reception and transmission interfaces are summarized and the structural units with functions similar to nerve cells are introduced. Multiple electrical and electromagnetic transmissions, regulating the secretion of neuromodulators or neurotransmitters via nanofluidic channels, have been flexibly applied. The accurate regulation of neural networks from the nanoscale to the cellular reconstruction of protein pathways will make BCI the extension of the brain.

Functional mechanism of EGR3 in cerebral ischemia/reperfusion injury in rats by modulating transcription of pri-miR-146a/146b to miR-146 and suppressing SORT1 expression.

OBJECTIVE: EGR3 is implicated in angiogenesis in rats with cerebral ischemia/reperfusion injury (CIRI). This research aimed to explore the effect and in vivo and ex vivo mechanisms of EGR3 in CIRI. METHODS: CIRI rat models were established via middle cerebral artery occlusion. Cell models were established via oxygen-glucose deprivation/reoxygenation (OGD/R). Brain injury was assessed by neurological scoring, HE, and TTC staining. Inflammatory factors and oxidative stress markers were measured using corresponding kits. Mitochondrial membrane potential and mitochondrial respiration were examined by flow cytometry and respirometry. EGR3-miR-146 network was predicted on TransmiR v2.0 database. Target genes of miR-146 were screened on Starbase, Targetscan, and miRDB databases. miR-146 expression was determined by RT-qPCR. Levels of EGR3 and SORT1 were determined by Western blot. Binding relationships among EGR3, miR-146, and SORT1 were validated by dual-luciferase assay. EGR3, miR-146, and SORT1 levels were altered by injection or cell transfection to observe their functions. RESULTS: EGR3 was poorly-expressed in CIRI rats and OGD/R-induced neurons. EGR3 overexpression reduced inflammatory factor levels and attenuated oxidative stress and mitochondrial injury in CIRI rats and OGD/R-induced neurons. EGR3 bound to miR-146b promoter region. EGR3 promoted pri-miR-146a/146b processing and stimulated miR-146 transcription. miR-146 overexpression ameliorated oxidative stress and mitochondrial injury and miR-146 downregulation abolished the effect of EGR3 overexpression in vitro. miR-146 targeted SORT1. SORT1 overexpression invalidated the protective function of miR-146 overexpression on oxidative stress and mitochondrial injury in vitro. CONCLUSION: EGR3 protected against CIRI by mitigating oxidative stress and mitochondrial injury via the miR-146/SORT1 axis.

[International clinical research of critical care medicine in 2021].

The progress of critical care medicine in 2021 is still encouraging. The new international guideline for management of sepsis and septic shock came out after 4 years. Besides, a couple of preferable clinical evidences were released including restrictive blood transfusion strategy for patients with acute myocardial infarction, prevention of peripheral venous catheter infection, heparin inhalation and driving pressure setting in patients with acute respiratory distress syndrome (ARDS), lower oxygenation target for acute hypoxemic respiratory failure, low level positive end-expiratory pressure in non-ARDS patients with respiratory failure, light sedation or non-sedation strategy, biological phenotypes, as well machine learning in sepsis and ARDS. However, we also encounter negative results such as balanced solution during fluid resuscitation, hypothermia therapy after out-of-hospital cardiac arrest or traumatic brain injury, adrenomedullin-specific antibody adrecizumab therapy and coupled plasma filtration-adsorption (CPFA) therapy for patients with septic shock, extracorporeal carbon dioxide removal (ECCO2R) implementation in acute hypoxic respiratory failure, continuous infusion of hypertonic saline in patients with traumatic brain injury. Collectively, in the future, individualized diagnosis and management based on the principle of "wise choice" will become the daily practice scene for all intensivists.