The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*

This study aims to investigate the mechanism by which resveratrol(RES) alleviates cerebral vascular endothelial damage in sepsis-associated encephalopathy(SAE) through network pharmacology and animal experiments. By using network pharmacology, the study identified common targets and genes associated with RES and SAE and constructed a protein-protein interaction( PPI) network. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed to pinpoint key signaling pathways, followed by molecular docking validation. In the animal experiments, a cecum ligation and puncture(CLP) method was employed to induce SAE in mice. The mice were randomly assigned to the sham group, CLP group, and medium-dose and high-dose groups of RES. The sham group underwent open surgery without CLP, and the CLP group received an intraperitoneal injection of 0. 9% sodium chloride solution after surgery. The medium-dose and high-dose groups of RES were injected intraperitoneally with 40 mg·kg-1 and 60 mg·kg~(-1) of RES after modeling, respectively, and samples were collected 12 hours later. Neurological function scores were assessed, and the wet-dry weight ratio of brain tissue was detected. Serum superoxide dismutase(SOD), catalase( CAT) activity, and malondialdehyde( MDA) content were measured by oxidative stress kit. Histopathological changes in brain tissue were examined using hematoxylin-eosin(HE) staining. Transmission electron microscopy was employed to evaluate tight cell junctions and mitochondrial ultrastructure changes in cerebral vascular endothelium. Western blot analysis was performed to detect the expression of zonula occludens1( ZO-1), occludin, claudins-5, optic atrophy 1( OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), fission 1(Fis1), and hypoxia-inducible factor-1α(HIF-1α). Network pharmacology identified 76 intersecting targets for RES and SAE, with the top five core targets being EGFR, PTGS2, ESR1, HIF-1α, and APP. GO enrichment analysis showed that RES participated in the SAE mechanism through oxidative stress reaction. KEGG enrichment analysis indicated that RES participated in SAE therapy through HIF-1α, Rap1, and other signaling pathways. Molecular docking results showed favorable docking activity between RES and key targets such as HIF-1α. Animal experiment results demonstrated that compared to the sham group, the CLP group exhibited reduced nervous reflexes, decreased water content in brain tissue, as well as serum SOD and CAT activity, and increased MDA content. In addition, the CLP group exhibited disrupted tight junctions in cerebral vascular endothelium and abnormal mitochondrial morphology. The protein expression levels of Drp1, Fis1, and HIF-1α in brain tissue were increased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were decreased. In contrast, the medium-dose and high-dose groups of RES showed improved neurological function, increased water content in brain tissue and SOD and CAT activity, and decreased MDA content. Cell morphology in brain tissue, tight junctions between endothelial cells, and mitochondrial structure were improved. The protein expressions of Drp1, Fis1, and HIF-1α were decreased, while those of ZO-1, occludin, claudin-5, Mfn2, and OPA1 were increased. This study suggested that RES could ameliorate cerebrovascular endothelial barrier function and maintain mitochondrial homeostasis by inhibiting oxidative stress after SAE damage, potentially through modulation of the HIF-1α signaling pathway.
Animals ; Mice ; Network Pharmacology ; Resveratrol/administration & dosage* ; Male ; Sepsis-Associated Encephalopathy/genetics* ; Signal Transduction/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Endothelium, Vascular/metabolism* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Humans ; Sepsis/complications* ; Oxidative Stress/drug effects*

OBJECTIVES: To study the risk factors for hypoxemia in children with severe Mycoplasma pneumoniae pneumonia (SMPP). METHODS: A retrospective collection of clinical data from children diagnosed with SMPP at the Third Affiliated Hospital of Zhengzhou University from June to December 2023 was conducted. The patients were categorized into hypoxemia and non-hypoxemia groups. Logistic regression analysis was used to assess the risk factors for hypoxemia, and receiver operating characteristic (ROC) curve analysis was employed to analyze the diagnostic performance of various indicators. RESULTS: A total of 113 children with SMPP were included. Univariate logistic regression analysis showed that ferritin, aspartate aminotransferase, creatinine, creatine kinase isoenzyme, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, immunoglobulin G, complement C3, complement C4, age, extrapulmonary complications, and a chest computed tomography (CT) scan showing a bronchiolitis pattern were significant factors for hypoxemia in children with SMPP (P<0.05). Multivariate logistic regression analysis revealed that elevated ferritin levels, presence of extrapulmonary complications, and a bronchiolitis pattern on lung CT were independent risk factors for hypoxemia in these patients (P<0.05). The ROC curve analysis indicated that the combination of these three indicators for predicting hypoxemia had a sensitivity of 71.9%, a specificity of 95.1%, and an area under the curve of 0.888 (95%CI: 0.809-0.968). CONCLUSIONS In children with SMPP, when there are elevated ferritin levels, a bronchiolitis pattern on chest CT, and the presence of extrapulmonary complications, there should be a high level of vigilance for the potential development of hypoxemia.
Humans ; Pneumonia, Mycoplasma/complications* ; Male ; Female ; Risk Factors ; Child, Preschool ; Hypoxia/etiology* ; Retrospective Studies ; Child ; Logistic Models ; Infant ; ROC Curve ; Adolescent

OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

OBJECTIVE: To investigate whether Radix Sanguisorbae (RS, Diyu) could restore intestinal barrier function following sepsis using a cecal ligation and puncture (CLP)-induced septic rat model and lipopolysaccharide (LPS)-challenged IEC-6 cell model, respectively. METHODS: Totally 224 rats were divided into 4 groups including a control, sham, CLP and RS group according to a random number table. The rats in the control group were administrated with Ringer's lactate solution (30 mL/kg) with additional dopamine [10 µ g/(kg·min)] and given intramuscular injections of cefuroxime sodium (10 mg/kg) 12 h following CLP. The rats in the RS group were administrated with RS (10 mg/kg) through tail vein 1 h before CLP and treated with RS (10 mg/kg) 12 h following CLP. The rats in the sham group were only performed abdominal surgery without CLP. The rats in the CLP group were performed with CLP without any treatment. The other steps were same as control group. The effects of RS on intestinal barrier function, mesenteric microvessels barrier function, multi-organ function indicators, inflammatory response and 72 h survival window following sepsis were observed. In vitro, the effects of RS on LPS-challenged IEC-6 cell viability, the expressions of zona occludens-1 (ZO-1) and ferroptosis index were evaluated by cell counting kit-8, immunofluorescence and Western blot analysis. Bioinformatic tools were applied to investigate the pharmacological network of RS in sepsis to predict the active compounds and potential protein targets and pathways. RESULTS: The sepsis caused severe intestinal barrier dysfunction, multi-organ injury, lipid peroxidation accumulation, and ferroptosis in vivo. RS treatment significantly prolonged the survival time to 56 h and increased 72-h survival rate to 7/16 (43.75%). RS also improved intestinal barrier function and relieved intestinal inflammation. Moreover, RS significantly decreased lipid peroxidation and inhibited ferroptosis (P<0.05 or P<0.01). Administration of RS significantly worked better than Ringer's solution used alone. Using network pharmacology prediction, we found that ferroptosis and hypoxia inducible factor-1 (HIF-1 α) signaling pathways might be involved in RS effects on sepsis. Subsequent Western blot, ferrous iron measurements, and FerroOrange fluorescence of ferrous iron verified the network pharmacology predictions. CONCLUSION RS improved the intestinal barrier function and alleviated intestinal injury by inhibiting ferroptosis, which was related in part to HIF-1 α/heme oxygenase-1/Fe²⁺ axis.
Animals ; Sepsis/complications* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Rats ; Sanguisorba/chemistry* ; Intestinal Mucosa/metabolism* ; Iron/metabolism* ; Cell Line ; Disease Models, Animal ; Lipopolysaccharides

The need for mechanical ventilation due to severe hypoxemia and acute respiratory distress syndrome has increased dramatically in the global pandemic of severe respiratory infectious diseases. In clinical scenarios, it is sometimes necessary to briefly disconnect the ventilator pipeline from the artificial airway. Still, this operation can lead to a sharp drop in airway pressure, which is contrary to the protective lung ventilation strategy and increases the risk of environmental exposure to bioaerosol, posing a serious threat to patients and medical workers. At present, there is yet to be a practical solution. A new artificial airway device was designed by the medical staff from the department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University, based on many years of research experience in respiratory support therapy, and recently obtained the National Utility Model Patent of China (ZL 2019 2 0379605.4). The device comprises two connecting pipes, the sealing device body, and the globe valve represented by the iridescent optical ring. It has a simple structure, convenient operation, and low production cost. The device is installed between the artificial airway and the ventilator pipeline and realizes the instantaneous sealing of the artificial airway by adjusting the shut-off valve. Using this device to treat mechanically ventilated patients can minimize the ventilator-induced lung injury caused by the repeated disconnection of pipelines, avoid iatrogenic transmission of bioaerosols, and realize dual protection for patients and medical workers. It has extensive clinical application prospects and high health and economic value.
Humans ; Respiration, Artificial/adverse effects* ; Ventilators, Mechanical/adverse effects* ; Respiratory Distress Syndrome/therapy* ; Ventilator-Induced Lung Injury/prevention & control* ; Hypoxia/complications*

Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.
Humans ; Neoplasms/pathology* ; Lung Neoplasms/complications* ; Fibroblasts/pathology* ; Biomarkers ; Macrophages/pathology* ; Hypoxia ; Tumor Microenvironment

Obstructive sleep apnea syndrome (OSAS), a prevalent sleep disorder in children, is characterized by recurring upper airway obstruction during sleep. OSAS in children can cause intermittent hypoxia and sleep fragmentation, ultimately affect brain development and further lead to cognitive impairment if lack of timely effective intervention. In recent years, magnetic resonance imaging (MRI) and electroencephalogram (EEG) have been employed to investigate brain structure and function abnormalities in children with OSAS. Previous studies have indicated that children with OSAS showed extensive gray and white matter damage, abnormal brain function in regions such as the frontal lobe and hippocampus, as well as a significant decline in general cognitive function and executive function. However, the existing studies mainly focused on the regional activity, and the mechanism of pediatric OSAS affecting brain networks remains unknown. Moreover, it's unclear whether the alterations in brain structure and function are associated with their cognitive impairment. In this review article, we proposed two future research directions: 1) future studies should utilize the multimodal neuroimaging techniques to reveal the alterations of brain networks organization underlying pediatric OSAS; 2) further investigation is necessary to explore the relationship between brain network alteration and cognitive dysfunction in children with OSAS. With these efforts, it will be promising to identify the neuroimaging biomarkers for monitoring the brain development of children with OSAS as well as aiding its clinical diagnosis, and ultimately develop more effective strategies for intervention, diagnosis, and treatment.
Humans ; Child ; Sleep Apnea, Obstructive/complications* ; Cognition ; Hypoxia/complications* ; Hippocampus ; Frontal Lobe

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy ; Female ; Humans ; Placenta ; Fetal Growth Retardation/etiology* ; Pre-Eclampsia/pathology* ; Reactive Oxygen Species ; Hypoxia/pathology* ; Pregnancy Complications/pathology* ; Endoplasmic Reticulum Stress

Acute respiratory distress syndrome (ARDS) is a clinical syndrome defined by acute onset of hypoxemia and bilateral pulmonary opacities not fully explained by cardiac failure or volume overload. At present, there is no specific drug treatment for ARDS, and the mortality rate is high. The reason may be that ARDS has rapid onset, rapid progression, complex etiology, and great heterogeneity of clinical manifestations and treatment. Compared with traditional data analysis, machine learning algorithms can automatically analyze and obtain rules from complex data and interpret them to assist clinical decision making. This review aims to provide a brief overview of the machine learning progression in ARDS clinical phenotype, onset prediction, prognosis stratification, and interpretable machine learning in recent years, in order to provide reference for clinical.
Humans ; Hypoxia/complications* ; Respiratory Distress Syndrome/etiology* ; Prognosis ; Machine Learning