Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.

FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells.

Repetitive elements (REs) compose ∼50% of the human genome and are normally transcriptionally silenced, although the mechanism has remained elusive. Through an RNAi screen, we identified FBXO44 as an essential repressor of REs in cancer cells. FBXO44 bound H3K9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to transcriptionally silence REs post-DNA replication. FBXO44/SUV39H1 inhibition reactivated REs, leading to DNA replication stress and stimulation of MAVS/STING antiviral pathways and interferon (IFN) signaling in cancer cells to promote decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response. FBXO44 expression inversely correlated with replication stress, antiviral pathways, IFN signaling, and cytotoxic T cell infiltration in human cancers, while a FBXO44-immune gene signature correlated with improved immunotherapy response in cancer patients. FBXO44/SUV39H1 were dispensable in normal cells. Collectively, FBXO44/SUV39H1 are crucial repressors of RE transcription, and their inhibition selectively induces DNA replication stress and viral mimicry in cancer cells.

A FBXO7/EYA2-SCFFBXW7 axis promotes AXL-mediated maintenance of mesenchymal and immune evasion phenotypes of cancer cells.

A mesenchymal tumor phenotype associates with immunotherapy resistance, although the mechanism is unclear. Here, we identified FBXO7 as a maintenance regulator of mesenchymal and immune evasion phenotypes of cancer cells. FBXO7 bound and stabilized SIX1 co-transcriptional regulator EYA2, stimulating mesenchymal gene expression and suppressing IFNα/ß, chemokines CXCL9/10, and antigen presentation machinery, driven by AXL extracellular ligand GAS6. Ubiquitin ligase SCFFBXW7 antagonized this pathway by promoting EYA2 degradation. Targeting EYA2 Tyr phosphatase activity decreased mesenchymal phenotypes and enhanced cancer cell immunogenicity, resulting in attenuated tumor growth and metastasis, increased infiltration of cytotoxic T and NK cells, and enhanced anti-PD-1 therapy response in mouse tumor models. FBXO7 expression correlated with mesenchymal and immune-suppressive signatures in patients with cancer. An FBXO7-immune gene signature predicted immunotherapy responses. Collectively, the FBXO7/EYA2-SCFFBXW7 axis maintains mesenchymal and immune evasion phenotypes of cancer cells, providing rationale to evaluate FBXO7/EYA2 inhibitors in combination with immune-based therapies to enhance onco-immunotherapy responses.

Glucocorticoid Receptor:MegaTrans Switching Mediates the Repression of an ERα-Regulated Transcriptional Program.

The molecular mechanisms underlying the opposing functions of glucocorticoid receptors (GRs) and estrogen receptor α (ERα) in breast cancer development remain poorly understood. Here we report that, in breast cancer cells, liganded GR represses a large ERα-activated transcriptional program by binding, in trans, to ERα-occupied enhancers. This abolishes effective activation of these enhancers and their cognate target genes, and it leads to the inhibition of ERα-dependent binding of components of the MegaTrans complex. Consistent with the effects of SUMOylation on other classes of nuclear receptors, dexamethasone (Dex)-induced trans-repression of the estrogen E2 program appears to depend on GR SUMOylation, which leads to stable trans-recruitment of the GR-N-CoR/SMRT-HDAC3 corepressor complex on these enhancers. Together, these results uncover a mechanism by which competitive recruitment of DNA-binding nuclear receptors/transcription factors in trans to hot spot enhancers serves as an effective biological strategy for trans-repression, with clear implications for breast cancer and other diseases.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems.

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.

Posterior capsular radial sign: a novel method to confirm anterior vitreous cortex resection in phacovitrectomy.

BACKGROUND: The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. METHODS: A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. RESULTS: Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). CONCLUSION: In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.

Synergistic Visible Light Photocatalysis with Organocatalysis.

In recent years, the strategy of merging visible light photocatalysis and organocatalysis has been utilized and applied in a wide range of reactions. Taking advantage of synergistic visible light photocatalysis with organocatalysis, remarkable progress has recently been achieved in modern chemical synthesis. In these dual catalytic systems, photocatalysts or photosensitizers absorb visible light to induce their photo-excited states which can activate unreactive substrates via electron or energy transfer mechanisms, and organocatalysts are usually employed to control the chemical reactivities of the other substrates. This review mainly focuses on the recent development of cooperative catalysis by the combination of organocatalysis and photocatalysis in recent organic synthesis.

CEBPα/miR-101b-3p promotes meningoencephalitis in mice infected with Angiostrongylus cantonensis by promoting microglial pyroptosis.

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) infection can induce acute inflammation, which causes meningoencephalitis and tissue mechanical injury to the brain. Parasite infection-induced microRNAs play important roles in anti-parasite immunity in non-permissive hosts. miR-101b-3p is highly expressed after A. cantonensis infection; however, the role of miR-101b-3p and the transcription regulation of miR-101b-3p in A. cantonensis infection remain poorly characterized. RESULTS: In the present study, we found that miR-101b-3p inhibition alleviated inflammation infiltration and pyroptosis in A. cantonensis infection. In addition, we found that CCAAT/enhancer-binding protein alpha (CEBPα) directly bound to the - 6-k to - 3.5-k region upstream of miR-101b, and CEBPα activated miR-101b-3p expression in microglia. These data suggest the existence of a novel CEBPα/miR-101b-3p/pyroptosis pathway in A. cantonensis infection. Further investigation verified that CEBPα promotes pyroptosis by activating miR-101b-3p expression in microglia, and microglial pyroptosis further promoted inflammation. CONCLUSIONS: Our results suggest that a CEBPα/miR-101b-3p/pyroptosis pathway may contribute to A. cantonensis infection-induced inflammation and highlight the pro-inflammatory effect of miR-101b-3p. Video Abstract.

A case of TM infection with challenging differential diagnosis from lymphoma post-renal transplant.

BACKGROUND: Lymphomas involving the gastrointestinal tract may be manifested as anti-inflammatory tract bleeding, abdominal lymph node enlargement, or even perforation of the gastrointestinal tract. After organ transplantation, the likelihood of post-transplant lymphoproliferative disorders increases, and some rare infections may also appear. CASE PRESENTATION: Herein, we report a living transplant patient with talaromycosis marneffei (TSM) or Talaromyces marneffei (TM) infection with gastrointestinal hemorrhage and systemic lymph node enlargement, which presented clinically as lymphoma. CONCLUSION: This case is TSM in a kidney transplant patient, confirmed by lymph node biopsy and blood culture. The patient discharged from hospital successfully under the treatment of antifungal therapy and immunosuppressive therapy. Physicians should be aware that TSM can mimic lymphoma, and early diagnosis and treatment can benefit the outcomes.

The cost-effectiveness of a real-time seizure detection application for people with epilepsy.

OBJECTIVES: Automated seizure detection modalities can increase safety among people with epilepsy (PWE) and reduce seizure-related anxiety. We evaluated the potential cost-effectiveness of a seizure detection mobile application for PWE in Singapore. METHODS: We used a Markov cohort model to estimate the expected changes to total costs and health outcomes from a decision to adopt the seizure detection application versus the current standard of care from the health provider perspective. The time horizon is ten years and cycle duration is one month. Parameter values were updated from national databases and published literature. As we do not know the application efficacy in reducing seizure-related injuries, a conservative estimate of 1% reduction was used. Probabilistic sensitivity analysis, scenario analyses, and value of information analysis were performed. RESULTS: At a willingness-to-pay of $45,000/ quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio was $1,096/QALY, and the incremental net monetary benefit was $13,656. Probabilistic sensitivity analyses reported that the application had a 99.5% chance of being cost-effective. In a scenario analysis in which the reduction in risk of seizure-related injury was 20%, there was a 99.8% chance that the application was cost-effective. Value of information analysis revealed that health utilities was the most important parameter group contributing to model uncertainty. CONCLUSIONS: This early-stage modeling study reveals that the seizure detection application is likely to be cost-effective compared to current standard of care. Future prospective trials will be needed to demonstrate the real-world impact of the application. Changes in health-related quality of life should also be measured in future trials.

Theoretical study of protein adsorption on graphene/h-BN heterostructures.

The biological characteristics of planar heterojunction nanomaterials and their interactions with biomolecules are crucial for the potential application of these materials in the biomedical field. This study employed molecular dynamics (MD) simulations to investigate the interactions between proteins with distinct secondary structures (a single α-helix representing the minimal oligomeric domain protein, a single ß-sheet representing the WW structural domain of the Yap65 protein, and a mixed α/ß structure representing the BBA protein) and a planar two-dimensional heterojunction (a GRA/h-BN heterojunction consisting of a graphene nanoplate (GRA) and a hexagonal boron nitride nanoplate (h-BN)). The results indicate that all three kinds of protein can be quickly and stably adsorbed on the GRA/h-BN heterojunction due to the strong van der Waals interaction, regardless of their respective types, structures and initial orientations. Moreover, the proteins exhibit a pronounced binding preference for the hBN region of the GRA/h-BN heterojunction. Upon adsorption, the α-helix structure of the minimal oligomeric domain protein experiences partial or complete denaturation. Conversely, while the secondary structure of the single ß-sheet and mixed α/ß structure (BBA protein) undergoes slight changes (focus on the coil and turn regions), the main α-helix and ß-sheet structures remain intact. The initial orientation significantly impacts the degree of protein adsorption and its position on the GRA/h-BN heterojunction. However, regardless of the initial orientation, proteins can ultimately be adsorbed onto the GRA/h-BN heterojunction. Furthermore, the initial orientation has a minor influence on the structural changes of proteins. Significantly, the combination of different secondary structures helps mitigate the denaturation of a single α-helix structure to some extent. Overall, the adsorption of proteins on GRA/h-BN is primarily driven by van der Waals and hydrophobic interactions. Proteins with ß-sheet or mixed structures exhibit stronger biocompatibility on the GRA/h-BN heterojunction. Our research elucidated the biological characteristics of GRA/h-BN heterojunction nanomaterials and their interactions with proteins possessing diverse secondary structures. It offers a theoretical foundation for considering heterojunction nanomaterials as promising candidates for biomedical applications.

Adaptability of melanocytes post ultraviolet stimulation in patients with melasma.

BACKGROUND: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described. OBJECTIVES: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face. METHODS: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks. RESULTS: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers. CONCLUSIONS: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions.

The quantitative analysis of low-concentration (2%) ALA-PDT assisted with Q-switch 1064-nm Nd:YAG laser for acne vulgaris treatment.

Conventional 5-aminolevulinic acid-photodynamic (ALA-PDT) therapy (10-20%) has been widely applied for moderate-to-severe acne. The aim of this study is to investigate the effects of non-ablative Q-switched 1064-nm Nd:YAG laser-assisted ALA-PDT with low concentration (2%) on the treatment of acne vulgaris. Enrolled patients were randomly assigned to 2 groups. One group received combined therapy of 2% ALA-PDT and non-ablative Q-switched 1064-nm Nd:YAG laser, and the other received only 2% ALA-PDT. Patients in each group had received 3-session treatments with 4-week intervals (week 0, 4, and 8). Sebum secretion, melanin index, erythema index, and transepidermal water loss (TEWL) were assessed at week 2, 8, 12, and 24. VISIA® skin image system score and global esthetic improvement scale (GAIS) were also evaluated. Twenty-four participants were enrolled and evenly randomized to two groups. Significant improvement in sebum secretion was noted in combined therapy group compared to the monotherapy group at week 12 (37.5% versus 16.3%), and the improvement would still be noted until week 24 (18.3% versus 17.4%). Combined group also showed more severe melanin index and erythema index after treatment. For VISIA® skin analysis, patients in combined group had better percentile ranking in porphyrins and red-light images. There were no significant differences in GAIS at the end of the follow-up between each group, whereas higher proportion of satisfaction was noted in combined group at week 2. With the assistance of laser, low concentrations (2%) of 5-ALA can provide effective phototoxic reactions in treating acne vulgaris. The satisfaction of patients is high with acceptable adverse effects.

UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction.

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.

Artificial Urinary Biomarkers for Early Diagnosis of Acute Renal Allograft Rejection.

Acute renal allograft rejection (ARAR) after kidney transplantation associated with reduced graft survival and eventual graft failure is poorly diagnosed in hospitals. Here, we report the development of Artificial bioMarker Probes (AMPros) for sensitive urinalysis of ARAR in murine models. AMPros spontaneously go to the kidneys after systemic administration, specifically react with the prodromal immune biomarkers to activate their near-infrared fluorescence signals to report cell-mediated rejection, and efficiently undergo renal excretion into urine. Thus, AMPros enable convenient optical urinalysis that detects ARAR prior to histological manifestation of rejection, which is also earlier than current diagnostic methods measuring proinflammatory cytokines and peripheral blood lymphocyte mRNAs. Due to the high kidney specificity, AMPros-based urinalysis discriminates allograft rejection against other non-alloimmune specific diseases, which is unattainable by measurement of serological biomarkers. Such a noninvasive and sensitive urine test holds great promise in continuous monitoring of renal allograft conditions at low resource settings for timely clinical interventions.

In Vivo Kidney Allograft Endothelial Specific Scavengers for On-Site Inflammation Reduction under Antibody-Mediated Rejection.

Kidney transplantation is the most effective therapy for patients with end-stage renal disease. However, antibody-mediated rejection (ABMR) threatens long-term survival of renal grafts. Although ABMR can be controlled by donor-specific antibody clearance and B- or (and) plasma-cells inhibition, the treatment often causes severe side effects in patients. Therefore, there is need to explore site-specific scavengers. In this study, a nanovehicle carrying an anti-inflammatory drug is developed with complement component 4d targeting, a specific biomarker expressed on allograft endothelium under ABMR. Moreover, the nanovehicle is endowed with photothermal properties to control drug release. Analysis through systematic in vitro and in vivo toxicity, non-invasive targeted imaging, and in situ remote controlled drug release show the nanovehicle specifically targets allograft kidney endothelium, releases an anti-inflammatory drug, methylprednisolone, locally upon laser irradiation, and promotes recovery of injured endothelium, without affecting systemic inflammation or innate immune responses. This strategy has the potential for future clinical application in ABMR treatment.

Epidemiological and clinical characteristics of the chikungunya outbreak in Ruili City, Yunnan Province, China.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.

Molecular understanding of charge effect on desalination performance in lamellar MoS2 membranes.

Due to its advantages of superior oxidation resistance, excellent chemical stability and non-toxicity, molybdenum disulfide (MoS2) has shown prospects in seawater desalination applications. In this manuscript, molecular dynamics (MD) simulation has been employed to explore the effect of charge distribution in MoS2 nanosheets on the desalination performance of the lamellar MoS2 membrane. It is found that the model considering the atomic charge better describes the transport behavior of salt solution in the membranes. The water flux passing through the lamellar MoS2 membrane would be influenced little by the atomic charges in the MoS2 nanosheet. The lamellar MoS2 membrane considering the atomic charge distribution shows a screening effect between Na+ and Cl- ions.

Risk factors of pediatric venoarterial extracorporeal membrane oxygenation-related gastrointestinal bleeding after open-heart surgeries.

OBJECTIVE: To analyze the risk factors for gastrointestinal (GI) bleeding in congenital heart disease (CHD) patients supported with venoarterial extracorporeal membrane oxygenation (V-A ECMO) after open-heart surgery. METHODS: A retrospective analysis was performed on children with (GI group: 26 cases) and without (control group: 122 cases) GI bleeding during ECMO at Shanghai Children's Medical Center from 2017 to 2020. Clinical data were analyzed and compared between groups to search for risk factors for GI bleeding. RESULTS: A total of 148 cases were included in the study. The overall incidence of GI bleeding was 17.6% (26/148). The in-hospital mortality rate in the GI group was 61.5% (16/26) versus 45.9% (56/122) in the control group. Twenty-six patients suffered cardiac arrest before ECMO support. The GI bleeding incidence among extracorporeal cardiopulmonary resuscitation (ECPR) patients was 50.0% (13/26) versus 28.7 (35/122) among non-ECPR patients, p = 0.035. The activated clotting time (ACT) was 201.40 s (180.47 to 247.27) in the GI group versus 177.63 s (167.79 to 203.13) (p = 0.050) in the control group. The lowest antithrombin level (Min AT) was 27.00 ± 13.07% versus 37.62 ± 15.18 (p = 0.001). The pH and lactate levels before ECMO (Pre PH and Pre Lac) were lower in the GI group than in the control group. (7.31 ± 0.23 vs. 7.35 ± 0.17, p = 0.035 and 12.2 ± 6.11 vs. 7.78 ± 6.67, p = 0.003). Liver function during ECMO support was statistically worse in the GI group than in the control group. Multivariate analysis showed that Pre Lac (OR = 1.106 [1.018-1.202], p = 0.0016) was an independent risk factor for GI bleeding. ROC analysis of Pre Lac and GI bleeding showed an area under the curve (AUC) of 0.700 (95% CI: 0.600-0.800, p = 0.002) and a cutoff value of 9.30 mmol/L (sensitivity, 73.1%; specificity, 62.7%). CONCLUSIONS: As the first study in this field, the probability of GI bleeding and related mortality was found to be high in children supported with V-A ECMO after open-heart surgery. A higher lactate level before ECMO was an independent risk factor for GI bleeding.