Dendritic boron and nitrogen doped high-entropy alloy porous carbon fibers for high-efficiency hydrogen evolution reaction.

Among various electrocatalysts, high-entropy alloys (HEAs) have gained significant attention for their unique properties and excellent catalytic activity in the hydrogen evolution reaction (HER). However, the precise synthesis of HEA catalysts in small sizes remains challenging, which limits further improvement in their catalytic performance. In this study, boron- and nitrogen-doped HEA porous carbon nanofibers (HE-BN/PCNF) with an in situ-grown dendritic structure were successfully prepared, inspired by the germination and growth of tree branches. Furthermore, the dendritic fibers constrained the growth of HEA particles, leading to the synthesis of quantum dot-sized (1.67 nm) HEA particles, which also provide a pathway for designing HEA quantum dots in the future. This work provides design ideas and guiding suggestions for the preparation of borated HEA fibers with different elemental combinations and for the application of dendritic nanofibers in various fields.

Coupling High Hardness and Zn Affinity in Amorphous-Crystalline Diamond for Stable Zn Metal Anodes.

The highly reversible plating/stripping of Zn is plagued by dendrite growth and side reactions on metallic Zn anodes, retarding the commercial application of aqueous Zn-ion batteries. Herein, a distinctive nano dual-phase diamond (NDPD) comprised of an amorphous-crystalline heterostructure is developed to regulate Zn deposition and mechanically block dendrite growth. The rich amorphous-crystalline heterointerfaces in the NDPD endow modified Zn anodes with enhanced Zn affinity and result in homogeneous nucleation. In addition, the unparalleled hardness of the NDPD effectively overcomes the high growth stress of dendrites and mechanically impedes their proliferation. Moreover, the hydrophobic surfaces of the NDPD facilitate the desolvation of hydrate Zn2+ and prevent water-mediated side reactions. Consequently, the Zn@NDPD presents an ultrastable lifespan exceeding 3200 h at 5 mA cm-2 and 1 mAh cm-2. The practical application potential of Zn@NDPD is further demonstrated in full cells. This work exhibits the great significance of a chemical-mechanical synergistic anode modification strategy in constructing high-performance aqueous Zn-ion batteries.

Positive fluid balance and poor outcomes after initial intensive care unit admission in sepsis resuscitation: a retrospective study.

Introduction: Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU). Material and methods: A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model. Results: Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance. Conclusions: Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

Early bedside detection of pulmonary perfusion defect by electrical impedance tomography after pulmonary endarterectomy.

Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension. However, it poses risks of perioperative vascular complications, which can lead to serious clinical outcomes. This study introduces a novel noninvasive and radiation-free clinical imaging tool, electrical impedance tomography (EIT), for real-time bedside assessment of lung perfusion after PEA. It identifies ventilation-perfusion mismatches arising from postoperative complications, particularly valuable for patients with hemodynamic instability, thus eliminating risks tied to CT room transfers. The article reports a case where EIT was used to identify an in-situ thrombosis post-PEA, marking the first such application. The emphasis is on early detection using EIT, which offers a promising approach for therapeutic interventions and improved postoperative evaluations.

SOFA in sepsis: with or without GCS.

PURPOSE: Sepsis is a global public health burden. The sequential organ failure assessment (SOFA) is the most commonly used scoring system for diagnosing sepsis and assessing severity. Due to the widespread use of endotracheal intubation and sedative medications in sepsis, the accuracy of the Glasgow Coma Score (GCS) is the lowest in SOFA. We designed this multicenter, cross-sectional study to investigate the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis. METHODS: First, 3048 patients with sepsis admitted to Peking Union Medical College Hospital (PUMCH) were enrolled in this survey. The data were collected from June 8, 2013 to October 12, 2022. Second, 18,108 patients with sepsis in the eICU database were enrolled. Third, 2397 septic patients with respiratory system ≥ 3 points in SOFA in the eICU database were included. We investigated the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis in various ICUs of PUMCH, and then we validated the results in the eICU database. MAIN RESULTS: In data of ICUs in PUMCH, the predictive efficiency of SOFA without GCS (AUROC [95% CI], 24 h, 0.724 [0.688, 0.760], 48 h, 0.734 [0.699, 0.769], 72 h, 0.748 [0.713, 0.783], 168 h, 0.781 [0.747, 0.815]) was higher than that of SOFA with GCS (AUROC [95% CI], 24 h, 0.708 [0.672, 0.744], 48 h, 0.721 [0.685, 0.757], 72 h, 0.735 [0.700, 0.757], 168 h, 0.770 [0.736, 0.804]) on ICU mortality in patients with sepsis, and the difference was statistically significant (P value, 24 h, 0.001, 48 h, 0.003, 72 h, 0.004, 168 h, 0.005). In septic patients with respiratory system ≥ 3 points in SOFA in the eICU database, although the difference was not statistically significant (P value, 24 h, 0.148, 48 h, 0.178, 72 h, 0.132, 168 h, 0.790), SOFA without GCS (AUROC [95% CI], 24 h, 0.601 [0.576, 0.626], 48 h, 0.625 [0.601, 0.649], 72 h, 0.639 [0.615, 0.663], 168 h, 0.653 [0.629, 0.677]) had a higher predictive efficiency on ICU mortality than SOFA with GCS (AUROC [95% CI], 24 h, 0.591 [0.566, 0.616], 48 h, 0.616 [0.592, 0.640], 72 h, 0.628 [0.604, 0.652], 168 h, 0.651 [0.627, 0.675]). CONCLUSIONS: In severe sepsis, it is realistic and feasible to discontinue the routine GCS for SOFA in patients with a respiratory system ≥ 3 points, and even better predict ICU mortality.

Rationally designing of Co-WS2 catalysts with optimized electronic structure to enhance hydrogen evolution reaction.

Designing and developing cost-effective, high-performance catalysts for hydrogen evolution reaction (HER) is crucial for advancing hydrogen production technology. Tungsten-based sulfides (WSx) exhibit great potential as efficient HER catalysts, however, the activity is limited by the larger energy required for water dissociation under alkaline conditions. Herein, we adopt a top-down strategy to construct heterostructure Co-WS2 nanofiber catalysts. The experimental results and theoretical simulations unveil that the work functions-induced built-in electric field at the interface of Co-WS2 catalysts facilitates the electron transfer from Co to WS2, significantly reducing water dissociation energy and optimizing the Gibbs free energy of the entire reaction step for HER. Besides, the self-supported catalysts of Co-WS2 nanoparticles confining 1D nanofibers exhibit an increased number of active sites. As expected, the heterostructure Co-WS2 catalysts exhibit remarkable HER activity with an overpotential of 113 mV to reach 10 mA cm-2 and stability with 30 h catalyzing at 23 mA cm-2. This work can provide an avenue for designing highly efficient catalysts applicable to the field of energy storage and conversion.

Utility of paired plasma and drainage fluid mNGS in diagnosing acute intra-abdominal infections with sepsis.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs). METHODS: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed. RESULTS: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study. CONCLUSIONS: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use.

Incidence of chemotherapy-related cardiac dysfunction in cancer patients.

BACKGROUND: Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. HYPOTHESIS: A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. METHODS: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. RESULTS: A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). CONCLUSION: Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.

Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis / Correlación entre la expresión del antígeno carcinoembrionario (CEA) y las mutaciones de EGFR en el cáncer de pulmón de células no pequeñas: un metanálisis

Objectives: The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). Methods: Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. Results: Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48–2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18–2.15, P = 0.002) and stage I–IIIA (OR = 1.67, 95% CI: 1.01–2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25–3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07–2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31–2.57, P = 0.0004). Conclusions: This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.(AU)

The GFPT2-O-GlcNAcylation-YBX1 axis promotes IL-18 secretion to regulate the tumor immune microenvironment in pancreatic cancer.

The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.

Hydrogen alleviates impaired lung epithelial barrier in acute respiratory distress syndrome via inhibiting Drp1-mediated mitochondrial fission through the Trx1 pathway.

Acute respiratory distress syndrome (ARDS) is an acute and severe clinical complication lacking effective therapeutic interventions. The disruption of the lung epithelial barrier plays a crucial role in ARDS pathogenesis. Recent studies have proposed the involvement of abnormal mitochondrial dynamics mediated by dynamin-related protein 1 (Drp1) in the mechanism of impaired epithelial barrier in ARDS. Hydrogen is an anti-oxidative stress molecule that regulates mitochondrial function via multiple signaling pathways. Our previous study confirmed that hydrogen modulated oxidative stress and attenuated acute pulmonary edema in ARDS by upregulating thioredoxin 1 (Trx1) expression, but the exact mechanism remains unclear. This study aimed to investigate the effects of hydrogen on mitochondrial dynamics both in vivo and in vitro. Our study revealed that hydrogen inhibited lipopolysaccharide (LPS)-induced phosphorylation of Drp1 (at Ser616), suppressed Drp1-mediated mitochondrial fission, alleviated epithelial tight junction damage and cell apoptosis, and improved the integrity of the epithelial barrier. This process was associated with the upregulation of Trx1 in lung epithelial tissues of ARDS mice by hydrogen. In addition, hydrogen treatment reduced the production of reactive oxygen species in LPS-induced airway epithelial cells (AECs) and increased the mitochondrial membrane potential, indicating that the mitochondrial dysfunction was restored. Then, the expression of tight junction proteins occludin and zonula occludens 1 was upregulated, and apoptosis in AECs was alleviated. Remarkably, the protective effects of hydrogen on the mitochondrial and epithelial barrier were eliminated after applying the Trx1 inhibitor PX-12. The results showed that hydrogen significantly inhibited the cell apoptosis and the disruption of epithelial tight junctions, maintaining the integrity of the epithelial barrier in mice of ARDS. This might be related to the inhibition of Drp1-mediated mitochondrial fission through the Trx1 pathway. The findings of this study provided a new theoretical basis for the application of hydrogen in the clinical treatment of ARDS.

Phenotypes of esophageal pressure response to the change of positive end-expiratory pressure in patients with moderate acute respiratory distress syndrome.

Background: Esophageal pressure (Pes) has been used as a surrogate of pleural pressure (Ppl) to titrate positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. The relationship between Pes and PEEP remains undetermined. Methods: A gastric tube with a balloon catheter was inserted to monitor Pes in moderate to severe ARDS patients who underwent invasive mechanical ventilation. To assess the end-expiratory Pes response (ΔPes) to PEEP changes (ΔPEEP), the PEEP level was decreased and increased subsequently (with an average change of 3 cmH2O). The patients underwent the following two series of PEEP adjustment: (I) from PEEP-3 cmH2O to PEEPbaseline; and (II) from PEEPbaseline to PEEP+3 cmH2O. The patients were classified as "PEEP-dependent type" if they had ΔPes ≥30% ΔPEEP and were otherwise classified as "PEEP-independent type" (ΔPes <30% ΔPEEP in any series). Results: In total, 54 series of PEEP adjustments were performed in 18 ARDS patients. Of these patients, 12 were classified as PEEP-dependent type, and six were classified as PEEP-independent type. During the PEEP adjustment, end-expiratory Pes changed significantly in the PEEP-dependent patients, who had a Pes of 10.8 (7.9, 12.3), 12.5 (10.5, 14.9), and 14.5 (13.1, 18.3) cmH2O at PEEP-3 cmH2O, PEEPbaseline, and PEEP+3 cmH2O, respectively (median and quartiles; P<0.0001), while end-expiratory transpulmonary pressure (PL) was maintained at an optimal range [-0.1 (-0.7, 0.4), 0.1 (-0.6, 0.5), and 0.3 (-0.3, 0.7) cmH2O, respectively]. In the PEEP-independent patients, the Pes remained unchanged, with a Pes of 15.4 (11.4, 17.8), 15.5 (11.6, 17.8), and 15.4 (11.7, 18.30) cmH2O at each of the three PEEP levels, respectively. Meanwhile, end-expiratory PL significantly improved [from -5.5 (-8.5, -3.4) at PEEP-3 cmH2O to -2.5 (-5.0, -1.6) at PEEPbaseline to -0.5 (-1.8, 0.3) at PEEP+3 cmH2O; P<0.01]. Conclusions: Two types of Pes phenotypes were identified according to the ΔPes to ΔPEEP. The underlying mechanisms and implications for clinical practice require further exploration.

Hydrogen ameliorates endotoxin-induced acute lung injury through AMPK-mediated bidirectional regulation of Caspase3.

Septic lung injury is characterized by uncontrollable inflammatory infiltrations and acute onset bilateral hypoxemia. Evidence has emerged of the beneficial effect of hydrogen in acute lung injury (ALI), but the underlying mechanism is unclear. In this research, the recovery action of hydrogen on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells was investigated. The 7-day survival rate and body weight of mice were measured after intraperitoneal injection of LPS. Lung function was determined by a whole body plethysmography (WBP) system using the indicators respiratory rate and enhanced pause. Hematoxylin and eosin (HE) staining confirmed the signs of pulmonary edema and inflammatory ooze. Reverse transcription-polymerase chain reaction (RT-PCR) quantification was used to detect the expression of inflammatory factors. Western blotting analysis evaluated the expression levels of involved proteins in the AMP-activated protein kinase (AMPK) pathway. The experimental results confirmed that hydrogen provided an essential solution to the dissipative effects of LPS on survival rate, weight loss and lung function. The LPS-stimulated inflammatory factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also suppressed by hydrogen in A549 cells. Western blot analysis showed that hydrogen significantly upregulated the levels of phosphorylated AMPK (p-AMPK) and lowered the LPS-induced increased expression of dynamin-related protein 1 (Drp1) and Caspase3. These findings prove that hydrogen attenuated LPS-treated ALI by activating the AMPK pathway, supporting the feasibility of hydrogen treatment for sepsis.

Synergistic dual cell therapy for atherosclerosis regression: ROS-responsive Bio-liposomes co-loaded with Geniposide and Emodin.

The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.

Development of high-concentration labeled colloidal gold immunochromatographic test strips for detecting african swine fever virus p30 protein antibodies.

African Swine Fever (ASF), caused by the African swine fever virus (ASFV), has inflicted significant economic losses on the pig industry in China. The key to mitigating its impact lies in accurate screening and strict biosecurity measures. In this regard, the development of colloidal gold immunochromatographic test strips (CGITS) has proven to be an effective method for detecting ASFV antibodies. These test strips are based on the ASFV p30 recombinant protein and corresponding monoclonal antibodies. The design of the test strip incorporates a high-concentration colloidal gold-labeled p30 recombinant protein as the detection sensor, utilizing Staphylococcal Protein A (SPA) as the test line (T line), and p30 monoclonal antibody as the control line (C line). The sensitivity and specificity of the test strip were evaluated after optimizing the labeling concentration, pH, and protein dosage. The research findings revealed that the optimal colloidal gold labeling concentration was 0.05 %, the optimal pH was 8.4, and the optimal protein dosage was 10 µg/mL. Under these conditions, the CGITS demonstrated a detection limit of 1:512 dilution of ASFV standard positive serum, without exhibiting cross-reactivity with antibodies against other viral pathogens. Furthermore, the test strips remained stable for up to 20 days when stored at 50 °C and 4 °C. Comparatively, the CGITS outperformed commercial ELISA kits, displaying a sensitivity of 90.9 % and a specificity of 96.2 %. Subsequently, 108 clinical sera were tested to assess its performance. The data showed that the coincidence rate between the CGITS and ELISA was 93.5 %. In conclusion, the rapid colloidal gold test strip provides an efficient and reliable screening tool for on-site clinical detection of ASF in China. Its accuracy, stability, and simplicity make it a valuable asset in combating the spread of ASF and limiting its impact on the pig industry.

Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a degenerative pathology that affects both upper and lower extremity mobility and sensory function, causing significant pressure on patients and society. Prior research has suggested that ginsenosides may have neuroprotective properties in central nervous system diseases. However, the efficacy and mechanism of ginsenosides for CSM have yet to be investigated. PURPOSE: This study aims to analyze the composition of ginsenosides using UPLC-MS, identify the underlying mechanism of ginsenosides in treating CSM using network pharmacology, and subsequently confirm the efficacy and mechanism of ginsenosides in rats with chronic spinal cord compression. METHODS: UPLC-Q-TOF-MS was utilized to obtain mass spectrum data of ginsenoside samples. The chemical constituents of the samples were analyzed by consulting literature reports and relevant databases. Ginsenoside and CSM targets were obtained from the TCMSP, OMIM, and GeneCards databases. GO and KEGG analyses were conducted, and a visualization network of ginsenosides-compounds-key targets-pathways-CSM was constructed, along with molecular docking of key bioactive compounds and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenosides on CSM. Chronic spinal cord compression rats were intraperitoneally injected with ginsenosides (50 mg/kg and 150 mg/kg) and methylprednisolone for 28 days, and motor function was assessed to investigate the therapeutic efficacy of ginsenosides for CSM. The expression of proteins associated with TNF, IL-17, TLR4/MyD88/NF-κB, and NLRP3 signaling pathways was assessed by immunofluorescence staining and western blotting. RESULTS: Using UPLC-Q-TOF-MS, 37 compounds were identified from ginsenoside samples. Furthermore, ginsenosides-compounds-key targets-pathways-CSM visualization network indicated that ginsenosides may modulate the PI3K-Akt signaling pathway, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and Apoptosis by targeting AKT1, TNF, MAPK1, CASP3, IL6, and IL1B, exerting a therapeutic effect on CSM. By attenuating neuroinflammation through the TNF, IL-17, TLR4/MyD88/NF-κB, and MAPK signaling pathways, ginsenosides restored the motor function of rats with CSM, and ginsenosides 150 mg/kg showed better effect. This was achieved by reducing the phosphorylation of NF-κB and the activation of the NLRP3 inflammasome. CONCLUSIONS: The results of network pharmacology indicate that ginsenosides can inhibit neuroinflammation resulting from spinal cord compression through multiple pathways and targets. This finding was validated through in vivo tests, which demonstrated that ginsenosides can reduce neuroinflammation by inhibiting NLRP3 inflammasomes via multiple signaling pathways, additionally, it should be noted that 150 mg/kg was a relatively superior dose. This study is the first to verify the intrinsic molecular mechanism of ginsenosides in treating CSM by combining pharmacokinetics, network pharmacology, and animal experiments. The findings can provide evidence for subsequent clinical research and drug development.

Preparation and Peculiar Magnetic Properties at Low Temperatures of La1.85Sr0.15CuO4 Nanofibers.

Herein, the preparation process, morphology, structure, and magnetic properties of La1.85Sr0.15CuO4 (LSCO) cobweb-like nanofibers are reported. LSCO nanofibers with a regular grain size distribution are successfully prepared via electrospinning, followed by calcination. We conducted morphology analysis and elemental distribution using electron microscopy and energy-dispersive X-ray spectroscopy (EDS), respectively. Additionally, magnetic property testing was performed using a vibrating sample magnetometer (VSM) to confirm the superconducting properties of the samples. Interestingly, our samples exhibited a superconducting transition temperature, Tc, of 25.21 K, which showed some disparity compared to similar works. Furthermore, we observed a ferromagnetic response at low temperatures in the superconducting nanofibers. We attribute these phenomena to the effects generated by surface states of nanoscale superconducting materials.

SIMPLIFIED IMMUNE-DYSREGULATION INDEX: A NOVEL MARKER PREDICTS 28-DAY MORTALITY OF INTENSIVE CARE PATIENTS WITH SEPSIS.

ABSTRACT: Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. There is currently no simple immune-imbalance-driven indicator for patients with sepsis. Methods: This study was conducted in Peking Union Medical College Hospital. Patients with sepsis were identified according to Sepsis 3.0 after reviewing patient data from May 2018 through October 2022. Least absolute shrinkage and selection operator logistic regression was used for features selection. Receiver operating characteristic curves for 28-day mortality were used to compare the predictive performance of level of interleukin 6 (IL-6) and lymphocyte count (LY#) with that of the combined ratio, namely, the IL-6/LY# ratio. A Cox hazard model was also used to test the predictive performance of IL-6/LY# versus several other measurements. The dynamic trend of IL-6/LY# based on day 1 IL-6/LY# level was analyzed. Results: The mortality rate was 24.5% (220/898) in the study cohort. The LY#, IL-6 level, blood platelet count, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation II score, heart rate, age and Fi o2 level were identified as key factors for predicting 28-day mortality. IL-6/LY# was identified as a core indicator according to Least absolute shrinkage and selection operator logistic regression analysis. IL-6/LY# was significantly higher in nonsurvivors than in survivors (348 [154.6-1371.7] vs. 42.3 [15.4-117.1]). IL-6/LY# yielded a higher area under the curve (0.852 [95% CI = 0.820-0.879]) than the level of IL-6 (0.776 [95% CI = 0.738-0.809]) and LY# (0.719 [95% CI = 0.677-0.755]) separately. Survival analysis of mortality risk versus the IL-6/LY# ratio suggested that IL-6/LY# was significantly more predictive of patient risk than the Sequential Organ Failure Assessment score or the other factors ( P = 1.5 × 10 -33 ). In trend analysis, as the trend of D1-D3-D7 IL-6/LY# decreases, the morality rate is lower than increase or fluctuate group (42.1% vs. 58.3%, 37.9% vs. 43.8%, 37.5% vs. 38.5% in high, moderate, and low D1 IL-6/LY# group separately). Conclusion: IL-6/LY# examined on first day in intensive care unit can be used as an immune-imbalance alert to identify sepsis patients with higher risk of 28-day mortality. Decreasing trend of IL-6/LY# suggests a lower 28-day mortality rate of sepsis patients.