Optimize individualized energy delivery for septic patients using predictive deep learning models.

BACKGROUND AND OBJECTIVES: We aim to establish deep learning models to optimize the individualized energy delivery for septic patients. METHODS AND STUDY DESIGN: We conducted a study of adult septic patients in ICU, collecting 47 indicators for 14 days. We filtered out nutrition-related features and divided the data into datasets according to the three metabolic phases proposed by ESPEN: acute early, acute late, and rehabilitation. We then established optimal energy target models for each phase using deep learning and conducted external validation. RESULTS: A total of 179 patients in training dataset and 98 patients in external validation dataset were included in this study, and total data size was 3115 elements. The age, weight and BMI of the patients were 63.05 (95%CI 60.42-65.68), 61.31(95%CI 59.62-63.00) and 22.70 (95%CI 22.21-23.19), respectively. And 26.0% (72) of the patients were female. The models indicated that the optimal energy targets in the three phases were 900kcal/d, 2300kcal/d, and 2000kcal/d, respectively. Excessive energy intake increased mortality rapidly in the early period of the acute phase. Insufficient energy in the late period of the acute phase significantly raised the mortality as well. For the rehabilitation phase, too much or too little energy delivery were both associated with elevated death risk. CONCLUSIONS: Our study established time-series prediction models for septic patients to optimize energy delivery in the ICU. We recommended permissive underfeeding only in the early acute phase. Later, increased energy intake may improve survival and settle energy debts caused by underfeeding.

Ultrafast evanescently coupled waveguide MUTC-PDs with high responsivity.

Novel evanescently coupled waveguide modified uni-traveling carrier photodiodes (MUTC-PDs) employing a thick multi-layer coupling waveguide are reported. To improve the optical-to-electrical (O/E) conversion efficiency, a thick multi-layer coupling waveguide with a gradually increased refractive index from the bottom layer to the absorption layer is utilized. The refractive index profile facilitates the upward transmission of incident light into the absorption region, thereby enhancing the evanescent coupling efficiency. Meanwhile, the coupling waveguide, with a total thickness of 1.75 µm, expands the mode field diameter, thereby reducing the input coupling loss. Additionally, the top layer of the coupling waveguide also serves as the drift layer. This configuration facilitates efficient light absorption within a short PD length, thus ensuring ultrawide bandwidth and high O/E conversion efficiency simultaneously. Without an additional spot size coupler or anti-reflection coating, the measured responsivity is as high as 0.38 A/W for the PD with an active area of 5 × 6 µm2. Meanwhile, an ultrawide 3-dB bandwidth of 153 GHz has been demonstrated.

Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gαi/q and their ability to bind GDP-bound (inactive form) Gαi/q. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gαi/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gαi/q signaling from the plasma membrane. This is achieved by recruiting Gαi/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gαi/q signaling, thereby uncovering a novel mechanism for terminating Gαi/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gαi/q signaling beyond the plasma membrane.

A deep learning-powered diagnostic model for acute pancreatitis.

BACKGROUND: Acute pancreatitis is one of the most common diseases requiring emergency surgery. Rapid and accurate recognition of acute pancreatitis can help improve clinical outcomes. This study aimed to develop a deep learning-powered diagnostic model for acute pancreatitis. MATERIALS AND METHODS: In this investigation, we enrolled a cohort of 190 patients with acute pancreatitis who were admitted to Sichuan Provincial People's Hospital between January 2020 and December 2021. Abdominal computed tomography (CT) scans were obtained from both patients with acute pancreatitis and healthy individuals. Our model was constructed using two modules: (1) the acute pancreatitis classifier module; (2) the pancreatitis lesion segmentation module. Each model's performance was assessed based on precision, recall rate, F1-score, Area Under the Curve (AUC), loss rate, frequency-weighted accuracy (fwavacc), and Mean Intersection over Union (MIOU). RESULTS: Upon admission, significant variations were observed between patients with mild and severe acute pancreatitis in inflammatory indexes, liver, and kidney function indicators, as well as coagulation parameters. The acute pancreatitis classifier module exhibited commendable diagnostic efficacy, showing an impressive AUC of 0.993 (95%CI: 0.978-0.999) in the test set (comprising healthy examination patients vs. those with acute pancreatitis, P < 0.001) and an AUC of 0.850 (95%CI: 0.790-0.898) in the external validation set (healthy examination patients vs. patients with acute pancreatitis, P < 0.001). Furthermore, the acute pancreatitis lesion segmentation module demonstrated exceptional performance in the validation set. For pancreas segmentation, peripancreatic inflammatory exudation, peripancreatic effusion, and peripancreatic abscess necrosis, the MIOU values were 86.02 (84.52, 87.20), 61.81 (56.25, 64.83), 57.73 (49.90, 68.23), and 66.36 (55.08, 72.12), respectively. These findings underscore the robustness and reliability of the developed models in accurately characterizing and assessing acute pancreatitis. CONCLUSION: The diagnostic model for acute pancreatitis, driven by deep learning, exhibits excellent efficacy in accurately evaluating the severity of the condition. TRIAL REGISTRATION: This is a retrospective study.

Site-specific identification and quantitation of endogenous SUMOylation based on SUMO-specific protease and strong anion exchange chromatography.

Small ubiquitin-like modifier (SUMO) modification regulates various eukaryotic cellular processes and plays a pivotal role in interferon (IFN)-mediated antiviral defense. While immunoprecipitation enrichment method is widely used for proteome-wide analysis of endogenous SUMOylation, the inability to target all SUMO forms and high cost of antibodies limited its further application. Herein, we proposed an antibody-free enrichment method based on SUMO-specific protease and strong anion exchange chromatography (SPAX) to globally profile the endogenous SUMOylation. The SUMO1/2/3-modified peptides could be simultaneously enriched by SAX chromatography by utilizing its electrostatic interaction with SUMO1/2/3 remnants, which contained multiple aspartic acids (D) and glutamic acids (E). To remove the co-enriched D/E-containing peptides which might interfere with the detection of low-abundance SUMOylated peptides, SUMO-specific protease was used to cleave the SUMO1/2/3 remnants from enriched SUMOylated peptides. As the deSUMOylated peptides lost SUMO remnants, their interaction with SAX materials became weaker, and the D/E-containing peptides could thus be depleted through the second SAX separation. The SPAX method identified over twice the SUMOylated sites than using SAX method only, greatly improving the identification coverage of endogenous SUMOylated sites. Our strategy was then applied to the site-specific identification and quantification of endogenous SUMOylation in A549 cells stimulated by IFN-γ for the first time. A total of 226 SUMOylated sites on 146 proteins were confidently identified, among which multiple up-regulated sites were involved in IFN-mediated antiviral defense, demonstrating the great promise of SPAX to globally profile and discover endogenous SUMOylation with significant biological functions.

Perovskite CoSn(OH)6 nanocubes with tuned d-band states towards enhanced oxygen evolution reactions.

The CoSn(OH)6 perovskite hydroxide is a structure stable and inexpensive electrocatalyst for the oxygen evolution reaction (OER). However, the OER activity of CoSn(OH)6 is still unfavorable due to its limited active sites. In this work, an Fe3+ doping strategy is used to optimize the d-band state of the CoSn(OH)6 perovskite hydroxide. The CoSn(OH)6 catalyst with slightly Fe3+ doped nanocubes is synthesized by a facile hydrothermal method. Structure characterization shows that Fe3+ ions are incorporated into the crystal structure of CoSn(OH)6. Owing to the regulation of the electronic structure, CoSn(OH)6-Fe1.8% exhibits an OER overpotential of 289 mV at a current density of 10 mA cm-2 in OER electrochemical tests. In situ Raman spectroscopy shows that no obvious re-construction occurred during the OER for both CoSn(OH)6 and CoSn(OH)6-Fe1.8%. DFT calculations show that the introduction of Fe3+ into CoSn(OH)6 can shift the d-band center to a relatively high position, thus promoting the OER intermediates' adsorption ability. Further DFT calculations suggest that incorporation of an appropriate amount of Fe3+ into CoSn(OH)6 significantly reduces the rate-determining Gibbs free energy during the OER. This work offers valuable insights into tuning the d-band center of perovskite hydroxide materials for efficient OER applications.

Efficacy of taurine-enhanced enteral nutrition in improving the outcomes of critically ill patients: A systematic review and meta-analysis.

BACKGROUND: Taurine is considered an immunomodulatory agent. From current reports on clinical studies, we conducted a systematic review and meta-analysis to investigate the effects of taurine-enhanced enteral nutrition (EN) on the outcomes of critically ill patients to resolve conflicting evidence in literature. METHODS: Literature from PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, SINOMED, and WanFang databases were retrieved, and randomized controlled trials (RCTs) were identified. The time range spanned from January 1, 2000, to January 31, 2024. The Cochrane Collaboration Tool was used to evaluate the risk of bias. We used the GRADE approach to rate the quality of evidence and the I2 test to assess the statistical heterogeneity of the results. Risk ratio (RR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: Four trials involving 236 patients were finally included. The meta-analysis results indicated that taurine-enhanced EN did not reduce mortality (RR = 0.70, p = 0.45, 95% CI [0.28, 1.80], two trials, 176 participants, low quality). There was also no significant difference in length of stay in the intensive care unit (ICU) between the taurine-enhanced EN and control groups. Taurine-enhanced EN may reduce pro-inflammatory factor interleukin-6 (IL-6) levels in critically ill patients（the result about IL-6 cannot be pooled）. However, taurine-enhanced EN had no significant impact on high-sensitivity-C-reactive protein levels (MD = -0.41, p = 0.40, 95% CI [-1.35, 0.54], two trials, 60 participants, low quality). DISCUSSION: Taurine-enhanced EN may reduce IL-6 levels and is not associated with improved clinical outcomes in critically ill patients, which may have potential immunoregulatory effects in critically ill patients. Given that published studies have small samples, the above conclusions need to be verified by more rigorously designed large-sample clinical trials.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Artificial intelligence driven malnutrition diagnostic model for patients with acute abdomen based on GLIM criteria: a cross-sectional research protocol.

BACKGROUND: Patients with acute abdomen often experience reduced voluntary intake and a hypermetabolic process, leading to a high occurrence of malnutrition. The Global Leadership Initiative on Malnutrition (GLIM) criteria have rapidly developed into a principal methodological tool for nutritional diagnosis. Additionally, machine learning is emerging to establish artificial intelligent-enabled diagnostic models, but the accuracy and robustness need to be verified. We aimed to establish an intelligence-enabled malnutrition diagnosis model based on GLIM for patients with acute abdomen. METHOD: This study is a single-centre, cross-sectional observational investigation into the prevalence of malnutrition in patients with acute abdomen using the GLIM criteria. Data collection occurs on the day of admission, at 3 and 7 days post-admission, including biochemical analysis, body composition indicators, disease severity scoring, nutritional risk screening, malnutrition diagnosis and nutritional support information. The occurrence rate of malnutrition in patients with acute abdomen is analysed with the GLIM criteria based on the Nutritional Risk Screening 2002 and the Mini Nutritional Assessment Short-Form to investigate the sensitivity and accuracy of the GLIM criteria. After data cleansing and preprocessing, a machine learning approach is employed to establish a predictive model for malnutrition diagnosis in patients with acute abdomen based on the GLIM criteria. ETHICS AND DISSEMINATION: This study has obtained ethical approval from the Ethics Committee of the Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital on 28 November 2022 (Yan-2022-442). The results of this study will be disseminated in peer-reviewed journals, at scientific conferences and directly to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2200067044.

Capsaicin Enhanced the Efficacy of Photodynamic Therapy Against Osteosarcoma via a Pro-Death Strategy by Inducing Ferroptosis and Alleviating Hypoxia.

Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia-inducible factor-1α (HIF-1α) presents a considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor PDT by inducing ferroptosis and alleviating hypoxia is fabricated. Capsaicin (CAP) is widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger an increase in intracellular Ca2+ concentration, which is closely linked with ferroptosis, and participate in decreased oxygen consumption by inhibiting HIF-1α in tumor cells, potentiating PDT antitumor efficiency. Thus, CAP and the photosensitizer IR780 are coencapsulated into highly biocompatible human serum albumin (HSA) to construct a nanoplatform (CI@HSA NPs) for synergistic tumor treatment under near-infrared (NIR) irradiation. Furthermore, the potential underlying signaling pathways of the combination therapy are investigated. CI@HSA NPs achieve real-time dynamic distribution monitoring and exhibit excellent antitumor efficacy with superior biosafety in vivo. Overall, this work highlights a promising NIR imaging-guided "pro-death" strategy to overcome the limitations of PDT for OS by promoting ferroptosis and alleviating hypoxia, providing inspiration and support for future innovative tumor therapy approaches.

sTREM2 in the prognostic evaluation of acute lung injury after cardiac surgery in infants.

BACKGROUND: Previous studies have shown that TREM2 plays a protective role in acute lung injury (ALI). This prospective study aimed to investigate the role of sTREM2 as a forecasting factor for ALI in infants after pediatric cardiac surgery undergoing cardiopulmonary bypass (CPB). METHODS: Seventy-five consecutive patients younger than 1 year who underwent cardiac surgery were enrolled in this study. Sixty-one fulfilled the inclusion criteria and had been divided into ALI and non-ALI groups. Children's demographic characteristics and clinical data were collected. Perioperative sTREM2 levels were analyzed at five timepoints. RESULTS: In this study, children in the ALI group were younger, lighter, with higher RACHS-1 scores and underwent significantly longer CPB time. Post-CPB ALI had an impact on clinical outcomes, which contributed to a longer duration of mechanical ventilation, ICU and hospital stay than non-ALI group. Significant differences were manifested off-CPB, 1 h/6 h after CPB, and day 1 after surgery between the two groups. Binary logistic models revealed that off-CPB sTREM2 was significantly associated with the incidence of post-CPB ALI after adjustment. ROC analysis showed that the AUC of off-CPB sTREM2 level was 0.791, and the optimal cutoff value was 788.6 pg/ml. CONCLUSIONS: The off-CPB sTREM2 level was an independent prognostic factor for post-CPB ALI in infants. IMPACT: Plasma sTREM2 works together with downstream TREM2 to regulate inflammation response by binding the receptor to other cells. Previous studies have shown that TREM2 plays a protective role in ischemia-reperfusion and has anti-inflammatory effects on acute lung injury (ALI). This study analyzed the risk factors of post-cardiopulmonary bypass (CPB) ALI. We found that weight and off-CPB sTREM2 level were independent prognostic factors for post-CPB ALI. Plasma sTREM2 may serve as an early biomarker in the prognostic evaluation of acute lung injury after cardiac surgery in infants.

Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning.

MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

EMDL_m6Am: identifying N6,2'-O-dimethyladenosine sites based on stacking ensemble deep learning.

BACKGROUND: N6, 2'-O-dimethyladenosine (m6Am) is an abundant RNA methylation modification on vertebrate mRNAs and is present in the transcription initiation region of mRNAs. It has recently been experimentally shown to be associated with several human disorders, including obesity genes, and stomach cancer, among others. As a result, N6,2'-O-dimethyladenosine (m6Am) site will play a crucial part in the regulation of RNA if it can be correctly identified. RESULTS: This study proposes a novel deep learning-based m6Am prediction model, EMDL_m6Am, which employs one-hot encoding to expressthe feature map of the RNA sequence and recognizes m6Am sites by integrating different CNN models via stacking. Including DenseNet, Inflated Convolutional Network (DCNN) and Deep Multiscale Residual Network (MSRN), the sensitivity (Sn), specificity (Sp), accuracy (ACC), Mathews correlation coefficient (MCC) and area under the curve (AUC) of our model on the training data set reach 86.62%, 88.94%, 87.78%, 0.7590 and 0.8778, respectively, and the prediction results on the independent test set are as high as 82.25%, 79.72%, 80.98%, 0.6199, and 0.8211. CONCLUSIONS: In conclusion, the experimental results demonstrated that EMDL_m6Am greatly improved the predictive performance of the m6Am sites and could provide a valuable reference for the next part of the study. The source code and experimental data are available at: https://github.com/13133989982/EMDL-m6Am .

ACP-BC: A Model for Accurate Identification of Anticancer Peptides Based on Fusion Features of Bidirectional Long Short-Term Memory and Chemically Derived Information.

Anticancer peptides (ACPs) have been proven to possess potent anticancer activities. Although computational methods have emerged for rapid ACPs identification, their accuracy still needs improvement. In this study, we propose a model called ACP-BC, a three-channel end-to-end model that utilizes various combinations of data augmentation techniques. In the first channel, features are extracted from the raw sequence using a bidirectional long short-term memory network. In the second channel, the entire sequence is converted into a chemical molecular formula, which is further simplified using Simplified Molecular Input Line Entry System notation to obtain deep abstract features through a bidirectional encoder representation transformer (BERT). In the third channel, we manually selected four effective features according to dipeptide composition, binary profile feature, k-mer sparse matrix, and pseudo amino acid composition. Notably, the application of chemical BERT in predicting ACPs is novel and successfully integrated into our model. To validate the performance of our model, we selected two benchmark datasets, ACPs740 and ACPs240. ACP-BC achieved prediction accuracy with 87% and 90% on these two datasets, respectively, representing improvements of 1.3% and 7% compared to existing state-of-the-art methods on these datasets. Therefore, systematic comparative experiments have shown that the ACP-BC can effectively identify anticancer peptides.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

The Spectrum and Age-Sex Patterns Among Outpatients with Allergic Diseases - Yichang City, Hubei Province, China, 2018-2021.

What is already known about this topic?: Allergic diseases have affected an estimated 40% of the population in China. However, our understanding of the full spectrum of these diseases remains insufficient. What is added by this report?: Between 2018 and 2021, Yichang City documented 625,929 outpatient visits mainly related to skin and mucous membrane allergies (77.90%) and allergic respiratory conditions (19.64%). In 2021, the occurrence of outpatient visits for conditions such as allergic rhinitis, acute atopic conjunctivitis, and atopic dermatitis increased. The demographic analysis revealed that male patients comprised the majority of the under 18 age bracket (56.05%), while female patients were predominantly represented in the 18 to 65 age bracket (61.79%). What are the implications for public health practice?: This constitutes the first analysis of the spectrum of allergic diseases, utilizing regional outpatient data, which has substantial implications for understanding the disease burden.

Serum soluble triggering receptor levels expressed on myeloid cells2 identify early acute kidney injury in infants and young children after pediatric cardiopulmonary bypass.

Background: Acute kidney injury (AKI) is a potential complication after cardiopulmonary bypass (CPB) of pediatric cardiac surgery and contributes to a certain amount of perioperative mortality. Serum soluble triggering receptor expressed on myeloid cells2 (sTREM2) is an inflammation-associated cytokine in circulation. Alterations of sTREM2 level have been reported in Alzheimer's disease, sepsis, and some other pathologic conditions. This study aimed to investigate the role of sTREM2 as a forecasting factor for AKI in infants and young children and other factors associated with early renal injury after pediatric CPB. Methods: A prospective cohort study with consecutive infants and young children ≤ 3 years old undergoing CPB from September 2021 to August 2022 was conducted in an affiliated university children's hospital. These patients were divided into an AKI group (n = 10) and a non-AKI group (n = 60). Children's characteristics and clinical data were measured. Perioperative sTREM2 levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Results: In children developing AKI, the sTREM2 levels significantly decreased at the beginning of CPB compared to the non-AKI group. Based on binary logistic regression analysis and multivariable regression analysis, risk-adjusted classification for congenital heart surgery (RACHS-1), operation time, and the s-TREM2 level at the beginning of CPB (AUC = 0.839, p = 0.001, optimal cut-off value: 716.0 pg/ml) had predictive value for post-CPB AKI. When combining the sTREM2 level at the beginning of CPB and other indicators together, the area under the ROC curve enlarged. Conclusions: Operation time, RACHS-1 score, and sTREM2 level at the beginning of CPB were independent prognosis factors of post-CPB AKI in infants and young children ≤ 3 years old. Decreased sTREM2 identified post-CPB AKI, and ultimately hampered the outcomes. Our findings indicated that sTREM2 may be a protective factor for AKI after CPB in infants and young children ≤ 3 years old.

CRIP1 Reshapes the Gastric Cancer Microenvironment to Facilitate Development of Lymphatic Metastasis.

Lymphangiogenesis in tumors provides an auxiliary route for cancer cell invasion to drainage lymph nodes, facilitating the development of lymphatic metastasis (LM). However, the mechanisms governing tumor lymphangiogenesis and lymphatic permeability in gastric cancer (GC) remain largely unknown. Here, the unprecedented role and mechanism of cysteine-rich intestinal protein-1 (CRIP1) in mediating the development of GC LM is uncovered. A series of assays are performed to identify downstream targets of CRIP1, and rescue experiments are performed to confirm the effects of this regulatory axis on LM. CRIP1 overexpression facilitates LM in GC by promoting lymphangiogenesis and lymphatic vessel permeability. CRIP1 promotes phosphorylation of cAMP responsive element binding protein 1(CREB1), which then mediates vascular endothelial growth factor C (VEGFC) expression necessary for CRIP1-induced lymphangiogenesis and transcriptionally promotes C-C motif chemokine ligand 5 (CCL5) expression. CCL5 recruits macrophages to promote tumor necrosis factor alpha (TNF-α) secretion, eventually enhancing lymphatic permeability. The study highlights CRIP1 regulates the tumor microenvironment to promote lymphangiogenesis and LM in GC. Considering the current limited understanding of LM development in GC, these pathways provide potential targets for future therapeutics.

JNK1 activated pRb/E2F1 and inhibited p53/p21 signaling pathway is involved in hydroquinone-induced pathway malignant transformation of TK6 cells by accelerating the cell cycle progression.

Hydroquinone (HQ) is an important metabolites of benzene in the body, and it has been found to result in cellular DNA damage, mutation, cell cycle imbalance, and malignant transformation. The JNK1 signaling pathway plays an important role in DNA damage repair. In this study, we focused on whether the JNK1 signaling pathway is involved in the HQ-induced cell cycle abnormalities and the underlying mechanism. The results showed that HQ induced abnormal progression of the cell cycle and initiated the JNK1 signaling pathway. We further confirmed that JNK1 suppression decelerated the cell cycle progression through inhibiting pRb/E2F1 signaling pathway and triggering p53/p21 pathway. Therefore, we concluded that JNK1 might be involved in HQ-induced malignant transformation associated with activating pRb/E2F1 and inhibiting p53/p21 signaling pathway which resulting in accelerating the cell cycle progression.

Nucleated Red Blood Cells Are Predictive of In-Hospital Mortality for Pediatric Patients.

PURPOSE: We sought to establish whether nucleated red blood cells (NRBCs) are predictive of disposition, morbidity, and mortality for pediatric patients presenting to the emergency department (ED). METHODS: A single-center retrospective cohort study examining all ED encounters from patients aged younger than 19 years between January 2016 and March 2020, during which a complete blood count was obtained. Univariate analysis and multivariable logistic regression were used to test the presence of NRBCs as an independent predictor of patient-related outcomes. RESULTS: The prevalence of NRBCs was 8.9% (4195/46,991 patient encounters). Patient with NRBCs were younger (median age 4.58 vs 8.23 years; P < 0.001). Those with NRBCs had higher rates of in-hospital mortality (30/2465 [1.22%] vs 65/21,741 [0.30%]; P < 0.001), sepsis (19% vs 12%; P < 0.001), shock (7% vs 4%; P < 0.001), and cardiopulmonary resuscitation (CPR) (0.62% vs 0.09%; P < 0.001). They were more likely to be admitted (59% vs 51%; P < 0.001), have longer median hospital length of stay {1.3 (interquartile range [IQR], 0.22-4.14) vs 0.8 days (IQR, 0.23-2.64); P < 0.001}, and median intensive care unit (ICU) length of stay (3.9 [IQR, 1.87-8.72] vs 2.6 days [IQR, 1.27-5.83]; P < 0.001). Multivariable regression revealed presence of NRBCs as an independent predictor for in-hospital mortality (adjusted odds ratio [aOR], 2.21; 95% confidence interval [CI], 1.38-3.53; P < 0.001), ICU admission (aOR, 1.30; 95% CI, 1.11-1.51; P < 0.001), CPR (aOR, 3.83; 95% CI, 2.33-6.30; P < 0.001), and 30-day return to the ED (aOR, 1.15; 95% CI, 1.15-1.26; P < 0.001). CONCLUSIONS: The presence of NRBCs is an independent predictor for mortality, including in-hospital mortality, ICU admission, CPR, and readmission within 30 days for children presenting to the ED.