Comparison of oXiris and Conventional Continuous Renal Replacement Therapy in Managing Severe Abdominal Infections: Impact on Septic Shock Mortality.

OBJECTIVE: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. METHODS: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index (OI), lactate (Lac), platelet count (PLT), neutrophil ratio (N%), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), norepinephrine (NE) dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) were recorded prior to treatment initiation, at 24 hours, and 72 hours post-treatment for both the oXiris and conventional CRRT groups. Additionally, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, as well as mortality rates at 14 and 28 days for both groups were recorded. RESULTS: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 hours post-treatment compared to pre-treatment levels. Also, at 72 hours post-treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, OI, N%, and IL-6 at 24 hours post-treatment when compared to baseline values. Additionally, reductions were observed in APACHE II and SOFA scores. At 72 hours post-treatment, all parameters demonstrated enhancement except for PLT. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 hours post-treatment revealed variances in HR, MAP, Lac, NE dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 hours post-treatment indicated more significant improvements following oXiris treatment for both groups, except for PCT. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared to the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. CONCLUSION: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option.

Targeting TGR5 to mitigate liver fibrosis: Inhibition of hepatic stellate cell activation through modulation of mitochondrial fission.

Chronic hepatitis B virus (HBV) infection continues to be a prominent cause of liver fibrosis and end-stage liver disease in China, necessitating the development of effective therapeutic strategies. This study investigated the potential of targeting TGR5 to alleviate liver fibrosis by impeding the activation of hepatic stellate cells (HSCs), which play a pivotal role in fibrotic progression. Using the human hepatic stellate cell line LX-2 overexpressing hepatitis B virus X protein (HBX), this study revealed that TGR5 activation through INT-777 inhibits HBX-induced LX-2 cell activation, thereby ameliorating liver fibrosis, which is associated with the attenuation of mitochondrial fission and introduces a novel regulatory pathway in liver fibrosis. Additional experiments with mitochondrial fission inducers and inhibitors confirm the crucial role of mitochondrial dynamics in TGR5-mediated effects. In vivo studies using TGR5 knockout mice substantiate these findings, demonstrating exacerbated fibrosis in the absence of TGR5 and its alleviation with the mitochondrial fission inhibitor Mdivi-1. Overall, this study provides insights into TGR5-mediated regulation of liver fibrosis through the modulation of mitochondrial fission in HSCs, suggesting potential therapeutic strategies for liver fibrosis intervention.

Cardiac Arrest Due to Capecitabine Toxicosis Treated With ECMO and CRRT: A Case Report.

INTRODUCTION: This is the first report of a patient who developed cardiogenic shock after receiving oral chemotherapy with capecitabine and was treated with venoarterial extracorporeal membrane oxygenation combined with continuous renal replacement therapy. CLINICAL FINDINGS: A 58-year-old man developed an arrhythmia that rapidly progressed to cardiogenic shock and cardiac arrest after receiving oral capecitabine tablets to treat a rectal malignancy. INTERVENTIONS: The patient was treated with venoarterial extracorporeal membrane oxygenation in combination with continuous renal replacement therapy. OUTCOME: The patient made a full recovery and was discharged from the hospital. CONCLUSION: The use of comprehensive supportive treatments such as extracorporeal membrane oxygenation combined with continuous renal replacement therapy in patients with capecitabine-induced cardiac arrest can rapidly reduce drug concentrations, eliminate harmful substances, and improve the prognosis.

Neuromyelitis Optica spectrum disorder complicated with pure red cell aplasia: a case report.

BACKGROUND: Pure red cell aplasia (PRCA) in neuromyelitis optica spectrum disorder (NMOSD) has not been reported before. This study presents a patient with NMOSD who developed PRCA. CASE PRESENTATION: A 54-year-old female was admitted in January 2023 for dysuria and progressive numbness and weakness of lower limbs. She had difficulty standing and walking in a straight line. Both lower limbs were positive for the Babinski and Chaddock signs. MRI showed abnormal signals in the spinal cord. Aquaporin-4-IgG (AQP-4-IgG) was positive (1:320), and NMOSD was confirmed. Intravenous immunoglobulin and methylprednisolone were given, and the symptoms improved. She received maintenance treatment with methylprednisolone tablets, and the dosage was gradually reduced. She was readmitted for fatigue, palpitations, and shortness of breath in May 2023. Bone marrow aspiration and biopsy showed elevated erythroid precursors and erythroid hypoplasia, with normal megakaryocytes and myeloid precursors. Chest CT showed no mediastinal lymph node enlargement or thymoma. PRCA secondary to NMOSD was diagnosed. Recombinant human erythropoietin was given. Her condition improved after 1.5 months, as indicated by blood cell count and imaging. CONCLUSIONS: This case suggests that PRCA can be secondary to NMOSD. A comprehensive immune function and bone marrow evaluation might be necessary if abnormal blood cells are found while managing NMOSD.

The Novel Fusion Protein Melittin-MIL-2 Exhibits Strong Antitumor Immune Effect in Lung Adenocarcinoma Cell A549.

In previous studies, we developed a novel fusion protein named "melittin-MIL-2" which exhibited more anti-tumor activity. However, it remains unclear whether melittin-MIL-2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin-MIL-2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin-MIL-2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN-γ secretion in PBMCs. After melittin-MIL-2 stimulation, perforin expression and LAK/NK-like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin-MIL-2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM-1 and Fas expression in A549 cells exposed to melittin-MIL-2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin-MIL-2 stimulation. In vivo, melittin-MIL-2 substantially impeded the growth of lung adenocarcinoma and formed an immune-stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin-MIL-2 exhibits strong anti-tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA-1/ICAM-1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN-γ and perforin, and boosting LAK/NK-like killing activities. Immuno-effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.

Global research trends in regulating gut microbiome to improve type 2 diabetes mellitus: bibliometrics and visual analysis.

Background: Gut microbiome (GM) and type 2 diabetes mellitus (T2DM) have two-way effects. Improving T2DM by modulating GM in various ways, such as diet, exercise, and medication, is gradually becoming popular, and related studies have yielded positive results. However, there is still a lack of high-quality bibliometric analyses of research in this area. This study aims to systematize and comprehensively summarize the knowledge structure, research tropics, and research trends of GM and T2DM through bibliometric analysis. Methods: Publications related to GM and T2DM before January 9, 2024, in the Web of Science Core Collection (WOSCC) were searched in this study. Microsoft Excel 2019 was used to analyze publishing trends and CiteSpace (v.6.1.R6 Advanced) was used to analyze institutions, cited journals, references, and keywords.SCImago Graphica (v.1.0.39) was used to analyze countries/regions, institutions' collaborations, cited authors, and published journals. Results: We finally included 1004 articles published from 2008 to 2023. The number of published articles showed an upward trend and reached its peak in 2022. China is the country with the largest number of articles, Univ Copenhagen is the institution with the largest number of articles, Fukui, Michiaki, Hamaguchi, Masahide are the scholars with the largest number of articles, and Cani and Patrice D. are the scholars with the largest number of citations. NUTRIENTS(Q1/5.9) published the most publications, while Nature (Q1/64.8; Cited 804 times) is the most frequently cited journal. Gut microbiota, Obesity, and insulin resistance are the most frequently used keywords. This study found that current researches focus on the effects of diet, exercise, and pharmacological modification of GM to improve T2DM and explores specific mechanisms. Future researches will focus on three areas: complications of T2DM and specific physiological processes, methods and measures to regulate GM, and new experimental techniques and assays. Conclusion: The current researches confirmed the effects and specific mechanisms of modulating GM to improve T2DM. Further exploration of the effects of modulating GM on T2DM complications and specific physiologic processes is a future trend of research. Exploring specific methods for regulating GM and developing new experimental techniques and assays are important for future research.

Neuroprotective effect of marrubiin against MPTP-induced experimental Parkinson's disease in male wistar rats.

In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson's disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1ß, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (p < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (p < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (p < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1ß, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin's neuroprotective ability have to be studied in detail.

Genetic association and causal relationship between multiple modifiable risk factors and autoimmune liver disease: a two-sample mendelian randomization study.

BACKGROUND: The intricate etiology of autoimmune liver disease (AILD) involves genetic, environmental, and other factors that yet to be completely elucidated. This study comprehensively assessed the causal association between genetically predicted modifiable risk factors and AILD by employing Mendelian randomization. METHODS: Genetic variants associated with 29 exposure factors were obtained from genome-wide association studies (GWAS). Genetic association data with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) were also obtained from publicly available GWAS. Univariate and multivariate Mendelian randomization analyses were performed to identify potential risk factors for AILD. RESULTS: Genetically predicted rheumatoid arthritis (RA) (OR = 1.620, 95%CI 1.423-1.843, P = 2.506 × 10- 13) was significantly associated with an increased risk of AIH. Genetically predicted smoking initiation (OR = 1.637, 95%CI 1.055-2.540, P = 0.028), lower coffee intake (OR = 0.359, 95%CI 0.131-0.985, P = 0.047), cholelithiasis (OR = 1.134, 95%CI 1.023-1.257, P = 0.017) and higher C-reactive protein (CRP) (OR = 1.397, 95%CI 1.094-1.784, P = 0.007) were suggestively associated with an increased risk of AIH. Genetically predicted inflammatory bowel disease (IBD) (OR = 1.212, 95%CI 1.127-1.303, P = 2.015 × 10- 7) and RA (OR = 1.417, 95%CI 1.193-1.683, P = 7.193 × 10- 5) were significantly associated with increased risk of PBC. Genetically predicted smoking initiation (OR = 1.167, 95%CI 1.005-1.355, P = 0.043), systemic lupus erythematosus (SLE) (OR = 1.086, 95%CI 1.017-1.160, P = 0.014) and higher CRP (OR = 1.199, 95%CI 1.019-1.410, P = 0.028) were suggestively associated with an increased risk of PBC. Higher vitamin D3 (OR = 0.741, 95%CI 0.560-0.980, P = 0.036) and calcium (OR = 0.834, 95%CI 0.699-0.995, P = 0.044) levels were suggestive protective factors for PBC. Genetically predicted smoking initiation (OR = 0.630, 95%CI 0.462-0.860, P = 0.004) was suggestively associated with a decreased risk of PSC. Genetically predicted IBD (OR = 1.252, 95%CI 1.164-1.346, P = 1.394 × 10- 9), RA (OR = 1.543, 95%CI 1.279-1.861, P = 5.728 × 10- 6) and lower glycosylated hemoglobin (HbA1c) (OR = 0.268, 95%CI 0.141-0.510, P = 6.172 × 10- 5) were positively associated with an increased risk of PSC. CONCLUSIONS: Evidence on the causal relationship between 29 genetically predicted modifiable risk factors and the risk of AIH, PBC, and PSC is provided by this study. These findings provide fresh perspectives on the management and prevention strategies for AILD.

Focus on negatively regulated NLRs in inflammation and cancer.

Nucleotide-binding and oligomerization structural domain (NOD)-like receptors (NLRs) play an important role in innate immunity as cytoplasmic pattern recognition receptors (PRRs). Over the past decade, considerable progress has been made in understanding the mechanisms by which NLR family members regulate immune system function, particularly the formation of inflammasome and downstream inflammatory signals. However, recent studies have shown that some members of the NLRs, including Nlrp12, NLRX1, and NLRC3, are important in the negative regulation of inflammatory signaling and are involved in the development of various diseases, including inflammatory diseases and cancer. Based on this, in this review, we first summarize the interactions between canonical and non-canonical nuclear factor-κB (NF-κB) signaling pathways that are mainly involved in NLRs, then highlight the mechanisms by which the above NLRs negatively regulate inflammatory signaling responses as well as their roles in tumor progression, and finally summarize the synthetic and natural derivatives with therapeutic effects on these NLRs, which are considered as potential therapeutic agents for overcoming inflammatory diseases.

ECMO management for severe pulmonary embolism with concurrent cerebral hemorrhage: a case report.

Background: Acute pulmonary embolism (APE) is a common and potentially fatal cardiovascular disease that can lead to sudden cardiac arrest in severe cases. When conventional cardiopulmonary resuscitation measures fail to achieve the return of spontaneous circulation (ROSC) in patients with APE, venoarterial extracorporeal membrane oxygenation (ECMO) becomes a viable therapeutic option. As an advanced life support treatment, ECMO ensures the perfusion of critical organs, providing sufficient time for interventions necessary for ROSC. Case introduction: We report the case of a patient who experienced cardiac arrest due to pulmonary embolism. During the treatment, the patient received two sessions of external cardiopulmonary resuscitation (ECPR) as supportive care and experienced cerebral hemorrhage. Ultimately, the patient improved and was discharged following support from extracorporeal membrane oxygenation (ECMO), careful anticoagulation strategies, and intervention with balloon pulmonary angioplasty. Conclusion: ECMO can serve as an important life support technology for patients with severe APE. Through a cautious anticoagulation therapy, not only was the ECMO support successfully maintained but also was further deterioration of cerebral hemorrhage effectively prevented. For patients with concurrent main pulmonary artery embolism and bleeding, balloon pulmonary angioplasty may be an option.

The effect of therapeutic massage on patients with obesity: A systematic review and meta-analysis.

Background: Obesity is related to various diseases such as endocrine metabolism and cardiovascular diseases. We provide an evidence-based evaluation for the effect of massage on patients with obesity. Methods: Relevant literature published in PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI) and other databases were searched until October 2023. Meta-analysis was performed using RevMan 5.4. A p value less than 0.05 indicates a statistically significant difference. Results: Twelve studies were finally included. Compared with conventional therapy, massage therapy were more effective, mainly in terms of (1) weight [mean difference (MD) = -3.71, 95%CI = -6.51,-0.88]; (2) body mass index (BMI), [MD = -2.00, 95%CI = -3.38, -0.62]; (3) Waist circumference (WC), [MD = -6.24, 95%CI = -8.71, -3.77]; (4) total cholesterol (TC), [MD = -0.65, 95%CI = -1.08, -0.22]; (5) triglycerides (TG), [MD = -0.92, 95%CI = -1.37, -0.47]. Conclusion: Massage therapy may be more effective for patients with obesity than conventional treatment. Given the number of studies and potential heterogeneity, more high-quality randomized controlled trials are needed to confirm our conclusions.

Production Characteristics of Volatiles from Anthracite Cracking via Microwave-Induced Discharge.

The ignition of anthracite with arc plasma has not been applied due to its low chemical effect and volatile content in anthracite. The nonequilibrium plasma generated by a microwave-induced discharge has the ability to break branch chains and aromatic ring structures by kinetic effects, which has the potential for anthracite cracking and ignition. This work investigated anthracite cracking by microwave-induced discharges under an Ar/N2 atmosphere. Results showed that the maximum levels of CO production, total gas production, and total gas generation rate occur in 20% argon content due to an increase in the number of electrons and a decrease in the total electronic states excitation rate constant with an increase in the argon content. The total gas production in plasma cracking is larger than that by pyrolysis, indicating the crack of polycyclic aromatic hydrocarbon by plasma. In addition, we attempted anthracite combustion under an 80% N2 and 20% O2 atmosphere.

Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology.

This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.

Ratiometric electrochemical immunoassay based on 2D Co/Fe MOF decorated with toluidine blue and Fc-labeled Schiff base for accurate assay of alpha-fetoprotein in clinical serum.

The high level of alpha-fetoprotein (AFP) expression is closely related to hepatocellular carcinoma (HCC). Herein, a dual signal ratiometric electrochemical immunosensor based on chitosan-ferrocenecarboxaldehyde-spindle gold (Chit-Fc-SAu) and Co/Fe metal-organic framework-toluidine blue/polydopamine (Co/Fe MOF-TB/PDA) was proposed for quantitative analysis of AFP. Specifically, Chit-Fc-SAu worked as a substrate to trap more primary antibodies (Ab1) generating the first electrochemical signal from Fc. Thanks to the large specific surface area, the synergistic and electronic effects of Co/Fe MOF nanosheets, and the rich functional groups of PDA, Co/Fe MOF-TB/PDA could load more secondary antibodies (Ab2) and signal molecules (TB) providing another amplified electrochemical signal. In the presence of AFP, Ab1-AFP-Ab2 formed a sandwich structure, and as the AFP concentration increased, the peak current ratio of TB to Fc (ITB/IFc) also increased. The dual signal ratiometric strategy can avoid environmental signal interference and achieve signal self-calibration, thereby improving the accuracy and reproducibility of detection. After a series of exploration, this self-calibrated ratiometric immunosensor exhibited a wide linear range (0.001-200 ng mL-1), a low detection limit (0.34 pg mL-1), and good repeatability. When applied to the assay of clinical serum samples, the detection results of ratiometric sensor were consistent with that of commercial electrochemiluminescence (ECL) immunoassay, significantly superior to that of non-ratiometric sensor. The self-calibrated strategy based on ratiometric sensor helps to improve the accuracy of AFP in clinical diagnosis.

A 76-base pair duplication within the enhancer region of the HMX1 gene causes sheep microtia.

Sheep congenital microtia is characterized by underdeveloped ears and provides an ideal basis for studying human microtia. This study identified the causal mutation and regulatory mechanisms underlying this disorder. Whole-genome association analysis was conducted using 23 ear tissue samples from sheep with microtia and 28 samples from normal-eared sheep. A significant correlation was found between microtia and a 76-base pair duplication in the enhancer region of the HMX1 gene. Further analysis of offspring phenotypes confirmed an autosomal dominant inheritance pattern. Genotypic analysis showed that individuals that are homozygous for this duplication were earless, heterozygous individuals exhibited shortened ears, and wild-type individuals had normal ears. Moreover, luciferase assays confirmed that this duplication increased HMX1 gene expression, and duplication knock-in mice also exhibited shorter and narrower external ears compared to wild-type mice. Transcriptomic analysis further demonstrated that this duplication enhanced HMX1 gene expression in animal models. This study characterized the causal regulatory mutation underlying sheep microtia.

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)-dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α-dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)-specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

Visual analysis of obesity and hypothyroidism: A bibliometric analysis.

BACKGROUND: The prevalence of obesity is gradually increasing and is closely associated with hypothyroidism. It is of research interest to explore the association between obesity and hypothyroidism and the current status of research. METHODS: We chose the Web of Science Core Collection (WoSCC) database as the data source and searched to obtain relevant literature on obesity and hypothyroidism. And we used CiteSpace and VOSviewer to analyze the related literature. RESULTS: A total of 508 articles were included in the literature, with an overall increasing trend in the number of publications. There were 170 relevant countries or organizations, and the United States was the country with the most publications. There were 1742 related organizations, and the Egyptian Knowledge Bank (EKB) was the organization with the most publications. There are 3015 authors involved, and there is a clear collaboration between authors. There are 227 related journals and J CLIN ENDOCR METAB is the most cited journal. The most frequently occurring keywords were obesity and hypothyroidism, but also other related topics such as bariatric surgery, metabolic syndrome, insulin resistance, body mass index, and leptin. CONCLUSION: The research related to obesity and hypothyroidism is gradually gaining attention, and the research direction is gradually expanding to metabolic syndrome, insulin resistance, leptin, and other related topics.

Metabolomic signature between diabetic and non-diabetic obese patients: A protocol for systematic review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects. METHODS: The protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.

Clinical performance of AMA-M2, anti-gp210 and anti-sp100 antibody levels in primary biliary cholangitis: When detected by multiplex bead-based flow fluorescent immunoassay.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy, characterized by the presence of some autoantibodies in the serum. This study aimed to evaluate the clinical significance of AMA-M2, anti-gp210 and anti-sp100 antibody levels detected by multiplex bead-based flow fluorescent immunoassay (MBFFI) in PBC. METHODS: This study cohort included 238 PBC patients, 81 autoimmune hepatitis (AIH) patients, 62 systemic lupus erythematosus (SLE) patients, and 118 healthy controls. Serum AMA-M2, anti-gp210 and anti-sp100 antibody were detected by MBFFI and immunoblotting assay (IBT). The relationship between three antibody levels and cirrhosis, liver function, cholestasis markers and therapeutic effect to ursodesoxycholic acid (UDCA) was evaluated in PBC. RESULTS: MBFFI were presented good coincidence rate (87.39%-95.38%) with IBT. The level of AMA-M2, anti-gp210 and anti-sp100 antibodies in PBC patients were higher than other disease group and healthy controls (p ＜ .01). When compared with the healthy controls group, the AUC of AMA-M2, anti-gp210 and anti-sp100 antibodies were 0.9245, 0.7619, and 0.6789, respectively. In addition, gp210 antibody levels have diagnostic value in patients with liver cirrhosis (AUC: 0.7567). We found that when combine detect these three antibodies, the sensitivity was higher than individually detection. High level of serum anti-gp210 antibody could be related to worse liver function and more severe cholestasis in PBC patients. Moreover, serum antibody levels may decrease or remained flat in patients who responded well to UDCA. CONCLUSION: The detection of AMA-M2, anti-gp210 and anti-sp100 antibody levels by MBFFI showed good performance in the diagnosis of PBC. Serum anti-gp210 antibody level is related to cirrhosis, poor liver function and severe cholestasis in PBC.