Startseite Analysis of serum metabolomics in patients with different types of chronic heart failure
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Analysis of serum metabolomics in patients with different types of chronic heart failure

  • Bingzhang Jie EMAIL logo , Qiang Li , Ling Han , Liwei Chen und Ming Yang
Veröffentlicht/Copyright: 23. Juli 2025

Abstract

Background

Heart failure remains a major public health issue, and there are still no reliable biomarkers for left ventricular ejection fraction (LVEF).

Objective

To screen for differential metabolites in the blood of HFpEF, HFmrEF, and HFrEF patients based on metabolomics analysis of their blood samples.

Methods

Total 44 patients in HFpEF group, 30 patients in HFmrEF group, and 36 patients in HFrEF group were selected. The blood metabolites were analyzed by liquid chromatography high-resolution mass spectrometry and classified by principal component analysis, and then potential biomarker were screened. Partial least squares discriminant analysis was used to model and investigate the predictive ability of biomarkers for LVEF.

Results

Blood metabolite profiles of HFpEF, HFmrEF, and HFrEF groups could be well distinguished, and seven potential biomarkers were identified, such as phosphatidylcholine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylcholine, ceramide, sphingosine, and sphingomyelin. Four metabolic pathways, such as glycerol phospholipid metabolic pathway, linoleic acid metabolic pathway, purine pyrimidine metabolism pathway, and linolenic acid metabolism pathway were identified, among which glycerol phospholipid metabolism pathway was the most significant.

Conclusion

The changes in glycerol phospholipid metabolism pathway may help identify HFpEF, HFmrEF, and HFrEF.

1 Introduction

Heart failure (HF) is a complex syndrome that is the final stage of various cardiovascular diseases. According to left ventricular ejection fraction (LVEF), HF can be divided into HF with preserved ejection fraction (HFpEF, LVEF ≥ 50%), HF with mildly reduced ejection fraction (HFmrEF, LVEF 41–49%), and HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%). Despite significant progress in the diagnosis and treatment of HF, patients still have severe prognosis. Therefore, there is an urgent need to explore new biomarkers for HF.

The occurrence and development of HF involve multiple pathophysiological pathways such as metabolism, neurohormones, and the immune system. At present, many biomarker related to HF have been identified, such as brain natriuretic peptide (BNP), tumor factor TNF, interleukins IL-1β, IL-6, IL-18, IL-33, and Stromelysin-2 [1,2]. However, no laboratory indicators related to LVEF have been found. While BNP may be elevated in HF patients with preserved LVEF, it cannot distinguish HFpEF, HFmrEF, and HFrEF patients. The metabolic disorders in patients with HF are significant, and metabolomics help us understand the metabolic disorders associated with myocardial dysfunction.

Metabolomics refers to the use of systematic methods such as nuclear magnetic resonance, high-performance liquid chromatography, gas chromatography, and mass spectrometry to analyze the changes in endogenous metabolic product profiles in biological fluids and tissues caused by pathological physiological stimuli and genetic modifications. Among them, liquid chromatography-mass spectrometry technology has higher sensitivity and resolution, making it suitable for metabolomics research [3]. Despite many previous studies on the metabolomics of HF, we have very little knowledge on the differences in metabolomics among the patients with HFpEF, HFmrEF, and HFrEF.

Therefore, in this study we aimed to investigate characteristic metabolic spectrum of HF. We employed liquid chromatography-high-resolution mass spectrometry to obtain metabolite profiles of blood samples from patients with HFpEF, HFmrEF, and HFrEF, and conducted bioinformatics analysis of differential metabolites. Representative biomarkers were screened to provide new diagnostic strategies for HF.

2 Methods

2.1 Instruments and reagents

Following instruments and reagents were used in this study: Waters liquid chromatograph (Watsch, USA); Waters SYNAPT G2-Si mass spectrometer (Watsch, USA); high-speed freezing centrifuge (Sigma, USA), vacuum concentrator (Labconco, USA); methanol, water, acetonitrile, formic acid, and ammonium formate (mass spectrometry pure, Thermo Fisher, USA); and HSS T3 column (2.1 × 100 mm, 1.8 µm) (Watsch, USA).

2.2 Subjects

Blood samples were collected from HF patients at Fuxing Hospital affiliated with Capital Medical University, who were selected from 110 patients with congestive HF admitted to the Cardiovascular Department from September 2018 to December 2020. Inclusion criteria included: (1) all met the diagnostic criteria for central HF in the 2018 Chinese Heart Failure Diagnosis and Treatment Guidelines. (2) According to the 2021 ESC guidelines, HF was divided into HF with preserved ejection fraction (HFpEF, LVEF ≥ 50%), HF with mildly reduced ejection fraction (HFmrEF, LVEF 41%–49%), and HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), with 44 cases in the HFpEF group, 30 cases in the HFmrEF group, and 36 cases in the HFrEF group.

Exclusion criteria were (1) patients admitted without the main cause of HF; (2) those who die in the hospital; (3) patients with chronic HF caused by other reasons (such as blood system, chronic anemic heart disease, endocrine and metabolic factors such as hyperthyroidism heart disease), except for coronary heart disease, high heart disease, and dilated heart disease; (4) congenital heart disease patients with severe complications that require surgical treatment (such as valve disease); (5) patients with liver and kidney failure; (6) those who suffer from other serious systemic diseases such as malignant tumors, hemorrhagic diseases, severe acute infections or metabolic disorders; and (7) those who cannot clearly and accurately describe their medical history due to consciousness disorders, intellectual disabilities, or vague language. The general information of the samples is shown in Table 1. Blood samples were collected immediately upon admission, and centrifuged at 3,000 rpm for 10 min at 4°C. The supernatant was stored at −80°C for future use.

Table 1

Baseline characteristics of study patients in temperature groups

Characteristic LVEF ≥ 50% LVEF 41–49% LVEF ≤ 40% p-value
Number (n) 44 30 36
Age (years) 81.3 ± 9.9 77.0 ± 11.8 74.4 ± 15.6 0.100
Gender (male) 18 (40.9%) 18 (60.0%) 24 (66.7%) 0.055
Weight (kg) 65.9 ± 8.7 66.1 ± 9.3 67.7 ± 10.8 0.678
BMI (kg/m2) 24.5 ± 2.7 23.8 ± 2.8 24.1 ± 2.8 0.199
Heart rate (beats/min) 81.5 ± 17.1 81.7 ± 18.0 88.6 ± 22.1 0.130
Systolic pressure (mmHg) 140.3 ± 28.4 144.4 ± 24.2 131 ± 24.2 0.100
LVEF (%) 57.4 ± 3.9 45.5 ± 2.5 31.1 ± 5.9 <0.001
LVIDd (mm) 45.0 ± 6.3 50.3 ± 7.1 56.5 ± 8.2 <0.001
TC (mmol/L) 4.6 ± 0.7 4.5 ± 0.8 4.2 ± 0.5 0.873
TG (mmol/L) 1.88 ± 0.57 1.76 ± 0.65 1.54 ± 0.71 0.579
LDL-C (mmol/L) 2.89 ± 0.97 2.78 ± 0.85 2.54 ± 0.88 0.355
HDL (mmol/L) 1.36 ± 0.29 1.27 ± 0.38 1.14 ± 0.42 0.483
BNP (pg/mL) 1432.9 ± 1541.2 1963.5 ± 1468.8 2751.5 ± 1645.3 <0.001
Serum potassium (mmol/L) 4.0 ± 0.9 3.5 ± 0.7 3.7 ± 0.8 0.009
Serum sodium (mmol/L) 133.8 ± 6.1 133.2 ± 5.4 135.1 ± 6.9 0.329
BUN (mg/dL) 39.3 ± 22.5 36.7 ± 20.9 40.3 ± 25.7 0.835
Blood creatinine (μmol/L) 146.4 ± 81.3 162.7 ± 179.9 141.2 ± 75.8 0.975
eGFR (mL/min·1.73 m2) 44.6 ± 23.7 50.9 ± 29.6 50.6 ± 25.2 0.548
Blood glucose (mmol/L) 6.8 ± 0.9 6.5 ± 0.7 6.3 ± 0.7 0.729
Combined diseases
Coronary heart disease 37 (84.1%) 28 (93.3%) 33 (91.7%) 0.380
Hypertension 34 (77.3%) 22 (73.3%) 26 (72.2%) 0.862
Diabetes 17 (38.6%) 10 (33.3%) 11 (30.6%) 0.741
Hyperlipidemia 30 (68.2%) 19 (63.3%) 26 (72.2%) 0.742
Atrial fibrillation/atrial flutter 26 (59.1%) 15 (50.0%) 13 (36.1%) 0.123
Valvular disease 12 (27.3%) 9 (30.0%) 9 (25.0%) 0.902
Medications
β Receptor blockers 31 (70.5%) 23 (76.7%) 30 (83.3%) 0.402
ACEI/ARBs 22 (50.0%) 18 (60.0%) 16 (44.4%) 0.447
Spironolactone 16 (36.4%) 20 (66.7%) 25 (69.4%) 0.004
Digoxin 6 (13.6%) 2 (6.7%) 9 (25.0%) 0.111
Loop diuretic 28 (63.6%) 24 (80.0%) 32 (88.9%) 0.026

2.3 Sample processing

The samples were thawed at room temperature, and mixed with 400 μL pre-cooled mass spectrometry grade methanol solution (final concentration 80%), fully vortexed, and put on ice for 30 min. After centrifugation at 13,000 rpm for 15 min at 4°C, the supernatants (approximately 200 μL) were collected and centrifuged again at 13,000 rpm for 15 min. The supernatants were subjected to metabolomics analysis.

2.4 Metabolomics analysis

Chromatographic column: Waters Acquisition HSS T3 (2.1 × 100 mm, 1.8 µm), injection volume: 5 µL, flow rate: 0.4 mL/min, and column temperature: 40°C. Mass spectrometry conditions: capillary 1.5 kV, sample cone 30 V, desolvation gas temperature 500°C, desolvation gas flow 800 L/h, source temperature 120°C, and mobility carrier gas 32 mL/min. The ion scanning range 50–1,000m/z, and scanning time 0.2 s.

2.5 Data processing

Mass spectrometry contour map was imported into the Waters Nonlinear Progenesis (QI) software, with QC sample contour map as a reference sample alternative. The samples were divided into three groups: normal ejection fraction group, ejection fraction greater than 40% group, and ejection fraction less than 40% group. Principal component analysis (PCA) of unsupervised pattern recognition and partial least squares analysis (PLS-DA) of supervised pattern recognition were performed. Variable importance in the project was calculated based on the PLS-DA model. Differential compounds were identified based on p-value < 0.05 and fold change (Max/Min) > 1.2 values, and analyzed with Human Metabolome Database and Kyoto Encyclopedia of Genes and Genomes database. The differential metabolites were imported into MetaboAnalyst 4.0 (www.metaboanalysts.ca) for enrichment analysis, metabolic pathway analysis, and other related bioinformatics analysis.

  1. Informed consent: All patients provided written informed consent.

  2. Ethical approval: The study was approved by Ethics Committee of Fuxing Hospital and was carried out in accordance with ethical guidelines of Ethics Committee of Fuxing Hospital.

3 Results

3.1 PCA analysis of samples from different groups

As shown in Figure 1a, samples within the same group exhibited a good aggregation state, indicating good consistency in endogenous differential metabolites within the same group. There were significant differences in the contents of metabolites in different groups. The clustering circle of the group with normal ejection fraction (i.e., ejection fraction retention group) (EF Normal, EF ≥ 50%) was far from other groups, indicating significant difference in metabolites between the ejection fraction retention group and the group with mild reduction in ejection fraction (EF > 40%) and the group with reduced ejection fraction (EF < 40%). The difference in metabolites between patients with mild decrease in ejection fraction (EF > 40%) and those with reduced ejection fraction (EF < 40%) was relatively weak.

Figure 1 
                  PCA of heart failure patient groups with different ejection fractions. (a) PCA chart, where black represents the group with preserved ejection fraction, blue represents the group of heart failure patients with an ejection fraction greater than 40%, and red represents the group of heart failure patients with an ejection fraction less than 40%. (b) Goodness of fit test of PCA diagram. Under the sixth principal component, the cumulative value of R
                     2 and Q
                     2 was close to one thousand, indicating good goodness of PCA analysis model.
Figure 1

PCA of heart failure patient groups with different ejection fractions. (a) PCA chart, where black represents the group with preserved ejection fraction, blue represents the group of heart failure patients with an ejection fraction greater than 40%, and red represents the group of heart failure patients with an ejection fraction less than 40%. (b) Goodness of fit test of PCA diagram. Under the sixth principal component, the cumulative value of R 2 and Q 2 was close to one thousand, indicating good goodness of PCA analysis model.

Figure 1b shows the fitting score of PCA model. Under the sixth principal component, the cumulative value of R 2 and Q 2 was close to one thousand, indicating good goodness of PCA analysis model.

3.2 Identification and analysis of differential metabolites in different groups

The differential metabolites were identified using fragment ions from relevant databases, mainly including lipid substances such as phosphatidylcholine (PC), phosphatidylinositol (PI), lysophosphatidylcholine (LysoPC), lysophosphatidylphosphatidylcholine (LysoPE), ceramide, sphingosine, and sphingomyelin (SM).

Enrichment of metabolic pathways was carried out on three groups of differential metabolites. As shown in Figure 2a, the horizontal axis represented the important values of the metabolic pathway influence of differential metabolites, while the vertical axis represented the p-value size of the specialized metabolic pathway. The darker the color of the enriched metabolic pathway, the smaller p-value; the larger the circle, the more important the metabolic pathways affected. Under these conditions, the glycerol phospholipid metabolism pathway, linoleic acid metabolism pathway, purine pyrimidine metabolism pathway, and linolenic acid metabolism were all significantly regulated (Figure 2b).

Figure 2 
                  Metabolite enrichment analysis of three sets of differential metabolites. (a) Bubble diagram of metabolic enrichment. The larger the circle, the more important the metabolic pathways affected. (b) Importance value of metabolic pathway enrichment. The horizontal axis represented the important values of the metabolic pathway influence of differential metabolites, while the vertical axis represented the p-value size of the specialized metabolic pathway.
Figure 2

Metabolite enrichment analysis of three sets of differential metabolites. (a) Bubble diagram of metabolic enrichment. The larger the circle, the more important the metabolic pathways affected. (b) Importance value of metabolic pathway enrichment. The horizontal axis represented the important values of the metabolic pathway influence of differential metabolites, while the vertical axis represented the p-value size of the specialized metabolic pathway.

4 Discussion

HF is a serious and complex syndrome with high incidence rate and mortality, and no reliable indicators related to LVEF have been identified. Metabolomics is an innovative tool that can be used to detect new biomarkers of diseases [4,5]. Metabolomics has shown diagnostic value in evaluating metabolic disorders related to HF, and the distribution of metabolites provides better prognostic value compared to conventional biomarkers [68]. Therefore, metabolomics is expected to become a favorable tool for detecting biomarkers related to LVEF.

The liquid phase high-resolution mass spectrometry method used in this study has the characteristics of high sensitivity, high resolution, and good resolution, and has been widely used in basic and clinical metabolomics research in recent years. By using this method to detect the blood samples of patients with HFpEF, HFmrEF, and HFrEF, we identified seven potential biomarkers and several metabolic pathways related to the differences among HFpEF, HFmrEF, and HFrEF.

In this study, fragment ions from relevant databases were used to identify the differential metabolites. The differential metabolites in the three groups of patients with HFrEF, HFmrEF, and HFpEF mainly included lipid substances, such as PC, PI, LysoPC, LysoPE, ceramide, sphingosine, and SM. In terms of metabolic pathways, the glycerol phospholipid metabolic pathway, linoleic acid metabolic pathway, purine pyrimidine metabolic pathway, and linolenic acid metabolism were significantly regulated in the three groups of patients with HFrEF, HFmrEF, and HFpEF, with the glycerol phospholipid metabolic pathway being particularly important.

Glycerophospholipid metabolism is important for myocardial cells. LysoPCs, lysophosphatidylethanolamine (LysoPEs), lysophosphatidylserine, lysophosphatidic acid (LysoPEs), lysophosphatidylinositol, and lysophosphatidylglycerol can be produced after the hydrolysis of the side chain of glycerol phospholipid [9]. The metabolic abnormalities of lysophospholipids in the body are closely related to many diseases. As an important component of myocardial energy metabolism, glycerol phospholipids accelerate the degradation of myocardial cell membrane phospholipids when myocardial injury occurs, and may even be accompanied by severe mitochondrial function loss [10]. Cardiolipin (CL) is also synthesized during the metabolism of glycerol phospholipids. CL is one of the main phospholipids in inner mitochondrial membrane, which is related to the assembly and activity of various protein complexes in mitochondria. The respiratory chain complexes I to V and the proteins of the solute carrier family have shown tight binding with CL. CL not only binds to the surface of these proteins, but also promotes their assembly into supercomplexes and stabilizes their structure [11]. In HF, the loss of CL and tetralinolenic CL promotes the production of excessive reactive oxygen species, which are byproducts of inefficient mitochondrial electron transport chain complexes I and III, leading to cytochrome c catalyzed CL oxidation and myocardial cell apoptosis. Therefore, protecting CL and mitochondrial function may be key to preventing the development of HF [12].

Previous studies have shown close relationship between glycerophospholipid metabolism and HF. Miao et al. identified a total of 210 metabolites with significant differences between HF rats and normal rats. These metabolites mainly participate in tryptophan metabolism, branched chain amino acid metabolism, fatty acid metabolism, β oxidation, and glycerol phospholipid metabolism [13]. Wen et al. found that therapeutic effect of HF with hydrogenated amine combined with 6-gingerol was mainly related to the regulation of acetylphosphate, 3-carboxyl-1-hydroxypropylthiamine diphosphate, coenzyme A, palmitic acid, and oleic acid. Metabolic pathway analysis showed that the pathways affecting energy metabolism included glycerol phospholipid metabolism, fatty acid metabolism, pantothenic acid, coenzyme A biosynthesis, citric acid cycle (TCA cycle), pyruvate metabolism, and arachidonic acid metabolism [14]. The Linggui Zhugan Decoction could delay the pathological process of HF by regulating the disordered metabolic pathway and related enzymes, and the most crucial pathway is the metabolism of glycerol phospholipid and arachidonic acid [15]. However, none of the above studies have explored the metabolomic differences among HFrEF, HFmrEF, and HFpEF patients. In this study, blood samples from HFpEF, HFmrEF, and HFrEF patients were analyzed by metabonomics, and we identified seven potential biomarker and four metabolic pathways, but the underlying mechanisms still need to be further explored to develop novel biomarkers for chronic HF [16].

In conclusion, we analyzed blood metabonomics of 110 patients with congestive HF who were divided into three groups of HFpEF, HFmrEF, and HFrEF. The differential metabolites among them mainly include lipid substances, such as PC, PI, LysoPC, LysoPE, ceramide, sphingosine, and SM. The glycerol phospholipid metabolism pathway, linoleic acid metabolism pathway, purine pyrimidine metabolism pathway, and linolenic acid metabolism have all undergone significant regulation, among which the glycerol phospholipid metabolism pathway is particularly important. Changes in glycerol phospholipid metabolism pathway may help identify HFpEF, HFmrEF, and HFrEF.


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  1. Funding information: This study was supported by the scientific research and cultivation fund of Capital Medical University (No. pyz2018104).

  2. Author contributions: Q.L., L.H., L.C., and M.Y. collected and analyzed the data; B.J. designed and supervised the study. All authors read and approved the manuscript.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: All data generated or analyzed during this study are availabel upon request.

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Received: 2025-01-26
Revised: 2025-04-21
Accepted: 2025-05-05
Published Online: 2025-07-23

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  73. Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
  74. Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
  75. Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
  76. Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
  78. Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
  79. Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
  80. The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
  81. The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
  82. Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
  83. Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
  84. The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
  85. Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
  87. Correlation of serum calprotectin with outcome of acute cerebral infarction
  88. Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
  89. Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
  90. The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
  91. Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
  92. Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
  93. Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
  94. Analysis of serum metabolomics in patients with different types of chronic heart failure
  95. Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
  96. Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
  97. Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
  98. METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
  99. The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
  100. Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
  101. Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
  102. Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
  103. Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
  104. Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
  105. Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
  106. Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
  107. Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
  108. Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Review Articles
  156. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  157. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  158. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  159. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  160. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  161. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  162. The application of augmented reality in robotic general surgery: A mini-review
  163. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  164. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  165. Plant polyphenols, terpenes, and terpenoids in oral health
  166. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  167. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  168. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  169. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  170. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  171. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  172. Giant borderline ovarian tumours – review of the literature
  173. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  174. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  175. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  176. Supplement strategies for infertility in overweight women: Evidence and legal insights
  177. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  178. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  179. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  180. Strategies for hyperkalemia management in dialysis patients: A systematic review
  181. C-reactive protein-to-albumin ratio in peripheral artery disease
  182. Case Reports
  183. Delayed graft function after renal transplantation
  184. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  185. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  186. Giant right atrial hemangioma presenting with ascites: A case report
  187. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  188. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  189. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  190. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  191. Rapid Communication
  192. Biological properties of valve materials using RGD and EC
  193. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  194. Letter to the Editor
  195. Role of enhanced external counterpulsation in long COVID
  196. Expression of Concern
  197. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  198. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  199. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  200. Corrigendum
  201. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  202. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  203. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  204. Retraction
  205. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  206. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  207. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  208. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  209. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  210. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  211. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  212. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  213. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  214. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  215. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  216. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  217. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  218. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  219. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  220. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  221. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  222. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  223. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  224. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  225. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  226. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  227. A review of brain research on T2DM-related cognitive dysfunction
  228. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  229. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  230. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
Heruntergeladen am 25.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2025-1210/html?lang=de
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