Society of Medical Biochemists of Serbia
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Molecular and Biochemical Characterization of Peripheral Blood MMP-2 Upregulation and TIMP-2 Downregulation in In-Stent Restenosis
Background: The matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 (MMP-2/TIMP-2) axis is an important regulator of extracellular matrix turnover and vascular remodeling. Most previous studies have focused on either circulating protein levels or mRNA expression alone. Because PBMC mRNA expression and plasma protein concentration reflect different regulatory levels, paired cross-level analysis may provide a more complete characterization of peripheral blood MMP-2/TIMP-2 alterations in ISR. This study investigated the molecular and biochemical dysregulation of the peripheral blood MMP-2/TIMP-2 axis in patients with ISR. Methods: A total of 117 patients who underwent follow-up evaluation 6–12 months after coronary stent implantation were included, comprising 42 patients with ISR and 75 without ISR. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA, and MMP-2 and TIMP-2 mRNA expression levels in peripheral blood mononuclear cells were quantified by qPCR. Between-group differences, transcription–protein coupling, and associations with routine biochemical parameters were analyzed. Results: Patients with ISR showed increased MMP-2 expression and decreased TIMP-2 expression at both the mRNA and protein levels compared with patients without ISR. The altered MMP-2/TIMP-2 balance was consistent across transcriptional and protein measurements. TIMP-2 showed an inverse association with LDL-C at both levels, whereas the relationships between MMP-2-related measurements and hs-CRP, Hcy, and Lp(a) suggested heterogeneous biochemical regulation. Standardized qPCR- and ELISA-derived measurements showed consistent cross-level patterns, supporting the presence of parallel molecular and protein-level alterations of this axis. Conclusion: ISR is associated with a consistent peripheral blood MMP-2/TIMP-2 imbalance, involving increased MMP-2 expression and decreased TIMP-2 expression at both the mRNA and circulating protein levels. These findings provide pathobiochemical evidence that matrix-remodeling imbalance in ISR can be reflected in peripheral blood molecular and biochemical profiles.
Copyright (c) 2026 Xinghu Zhou, Hongbin Ma, Xuan Qiao, Ming Bai
Prognostic Value of Ferroptosis-Related Biomarkers ACSL4 and GPX4 in Critically Ill Patients: A Systematic Review and Meta-Analysis
Background: Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation and has been increasingly implicated in the pathogenesis of severe infections and critical illness. Acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) are key regulators of ferroptosis and may serve as clinically useful biomarkers for prognostic assessment. This systematic review and meta-analysis aimed to evaluate the prognostic significance of serum ACSL4 and GPX4 levels in critically ill patients with severe infections. Methods: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Biology Medicine Disc (CBM) was conducted from database inception to March 2026. Observational studies evaluating the association between serum ACSL4 and/or GPX4 levels and clinical outcomes in critically ill patients were included. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4 and Stata 16.0. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random-effects models. Diagnostic performance was evaluated using receiver operating characteristic (ROC) data where available. Heterogeneity, sensitivity analyses, and publication bias assessments were conducted according to standard methodological approaches. Results: A total of 42 records were identified, and two high-quality prospective cohort studies involving 437 critically ill patients were included. NOS scores ranged from 8 to 9 points. Meta-analysis demonstrated that ferroptosis-related biomarkers were significantly associated with short-term mortality. Reduced serum GPX4 (OR=1.076, 95% CI: 1.036–1.119), reduced GSH/GSSG ratio (OR=1.258, 95% CI: 1.161–1.364), and elevated serum ACSL4 (OR=4.00, 95% CI: 2.00–8.00) were independently associated with adverse outcomes. The pooled OR was 1.76 (95% CI: 1.03–3.01), indicating a significantly increased risk of short-term mortality in patients exhibiting ferroptosis pathway dysregulation. Regarding prognostic performance, ACSL4 alone yielded an area under the curve (AUC) of 0.713, whereas GPX4 alone showed limited predictive ability (AUC=0.573). Combined assessment of GPX4 and GSH/GSSG improved predictive performance substantially (AUC=0.841). Sensitivity analyses confirmed the robustness of the findings. Conclusion: Abnormal expression of ferroptosis-related biomarkers, particularly elevated ACSL4 and reduced GPX4 levels, is associated with poor short-term outcomes in critically ill patients with severe infections. Combined evaluation of ferroptosis-related markers may improve risk stratification and prognostic assessment. These findings support the potential clinical utility of the ACSL4/GPX4 axis as a biomarker system and highlight ferroptosis as a promising therapeutic target in critical illness.
Copyright (c) 2026 Yue Gao, Chengxiang Wang
Correlation analysis of serum CD354 and ANGPT2 levels with the prognosis of sepsis
[Objective] To explore the changes of procalcitonin (PCT), Angiopoietin-2 (ANGPT2), and serum Cluster of Differentiation 354 (CD354) concentrations in pediatric sepsis patients. [Methods] 190 children with sepsis who were hospitalized to our hospital between January 2024 and June 2025 had their clinical data analyzed retrospectively. Based on the severity of their conditions, the patients were divided into a severe group (n = 84) and a nonsevere group (n = 106). A survival group (n = 134) and a death group (n = 56) were created based on the prognosis of the two groups of children within 28 days after admission. Serum levels of CD354, ANGPT2, and PCT in the severe and nonsevere groups were compared, and the predictive efficacy of these indicators alone or in combination for assessing the severity of sepsis in children was determined using receiver operating characteristic (ROC) curves. The differences in serum CD354, ANGPT2 and PCT levels between the survival group and the death group were compared, and the predictive efficacy of these indicators alone or in combination for evaluating the prognosis of sepsis in children was determined using receiver operating characteristic (ROC) curves. [Results] The serum CD354, ANGPT2 and PCT levels were higher in the severe group than in the nonsevere group (P < 0.05). The sensitivity and specificity of serum CD354 for evaluating the severity of sepsis in children were 92.48% and 66.60%, respectively. The sensitivity and specificity of serum ANGPT2 for evaluating the severity of sepsis in children were 94.37% and 88.13%, respectively. The sensitivity and specificity of serum PCT for evaluating the severity of sepsis in children were 94.37% and 66.60%, respectively. The sensitivity and specificity of serum ANGPT2 for evaluating the severity of sepsis in children were 94.37% and 88.13%, respectively. The sensitivity and specificity of serum PCT for evaluating the prognosis of sepsis in children were 64.22% and 100.00%, respectively. Children who died had greater levels of serum CD354, ANGPT2, and PCT than children who survived (P < 0.05). For assessing the prognosis of sepsis in children, serum CD354 has sensitivity of 53.50% and specificity of 83.51%. Serum ANGPT2 has sensitivity and specificity of 82.17% and 98.54%, respectively, for assessing the prognosis of sepsis in children. The sensitivity and specificity of serum PCT for evaluating the prognosis of sepsis in children were 64.22% and 100.00%, respectively. [Conclusion] Serum CD354, ANGPT2 and PCT levels significantly guide the assessment of the severity of the condition in children with sepsis and provide important reference values for prognosis.
Copyright (c) 2026 Mingying Luo, Yun Hong, Junhao Chen, Cong Fu
The Diagnostic Accuracy of Novel Biomarkers Anti-ApoA-1, Anti-MDA-LDL, and Anti-Osteopontin IgG for Detecting Silent Myocardial Ischemia
Background: Silent myocardial ischemia (SMI) is a significant predictor of adverse cardiac events but remains underdiagnosed. We evaluated the diagnostic accuracy of three autoimmune-inflammation linked biomarkers—anti-apolipoprotein A-1 (anti-ApoA-1) IgG, anti-malondialdehyde-modified low-density lipoprotein (anti-MDA-LDL) IgG, and anti-osteopontin (anti-OPN) IgG—for detecting SMI. Methods: In this cross-sectional study, 210 participants were categorized into three groups: SMI (n=70), stable angina (SA, n=70), and healthy controls (n=70). SMI was defined by exercise-induced ST-segment depression on treadmill testing without symptoms. Serum levels of the three antibodies were measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis determined the area under the curve (AUC), sensitivity, and specificity. Results: All three biomarkers were significantly higher in the SMI group compared to SA and controls (p<0.001). For SMI vs. controls, anti-ApoA-1 IgG showed an AUC of 0.82 (95% CI 0.75-0.89), anti-MDA-LDL IgG an AUC of 0.78 (0.70-0.85), and anti-OPN IgG an AUC of 0.80 (0.73-0.87). A three-marker panel yielded an AUC of 0.91 (0.86-0.96) with a sensitivity of 87.1% and specificity of 84.3%. Anti-ApoA-1 IgG independently predicted SMI presence in multivariate analysis (OR 3.2, 95% CI 1.8-5.6, p<0.001). Conclusions: Anti-ApoA-1, anti-MDA-LDL, and anti-OPN IgG antibodies are promising biomarkers for SMI, with a combined panel demonstrating high diagnostic accuracy. These findings highlight the potential role of autoimmune-inflammatory pathways in painless myocardial ischemia.
Copyright (c) 2026 Zhongqing Wang, Bin Sun, Wei Wang, Tinglin Xiong, Gang Wei
The role of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in the efficacy evaluation of patients with membranous nephropathy
Objective: Monocyte chemoattractant protein-1 (MCP-1), serum B-cell activating factor (BAFF), complement B factor (CFB), and anti-M-type phospholipase A2 receptor (PLA2R) antibodies are investigated in connection with membranous nephropathy (MN) and their roles in evaluating the efficacy of treatment. Methods: 108 patients who were hospitalized to our hospital between January 2023 and June 2024 were chosen to serve as research participants. Patients were divided into remission and nonremission groups according to their clinical efficacy. The levels of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in patients with positive and negative anti-PLA2R and different pathological stages were compared, and the clinical data of the remission group and the nonremission group were compared. The association between serum levels of BAFF, CFB, and MCP-1 and anti-PLA2R antibody levels in patients who tested positive for anti-PLA2R antibody. The predictive efficacy of serum anti-PLA2R antibodies, BAFF, CFB, and MCP-1 for nonremission in MN patients after therapy was evaluated using receiver operating characteristic (ROC) curves. Results: There were 78 patients who were positive for anti-PLA2R antibodies and 30 patients who were negative for anti-PLA2R antibodies. The levels of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in patients positive for anti-PLA2R antibodies were significantly greater than those in patients negative for anti-PLA2R antibodies (P<0.05). The comparison of the serum BAFF, CFB and MCP-1 levels in MN patients at different stages were as follows: stage I < stage II < stage III < stage IV. Serum BAFF, CFB, and MCP-1 in patients positive for anti-PLA2R antibodies were positively correlated with the level of anti-PLA2R antibodies (r=0.792, 0.823, 0.832, P<0.001). Spearman correlation analysis revealed that the levels of serum BAFF, CFB, and MCP-1 in MN patients were positively correlated with pathological stage (rs=0.758, 0.752, 0.717, P<0.001). The pathological stage and anti-PLA2R antibody, BAFF, CFB and MCP-1 levels in the nonremission group were significantly greater than those in the remission group (P<0.05). After treatment, elevated serum levels of MCP-1, CFB, and BAFF were risk factors for nonremission in MN patients (P<0.05). The ROC curve analysis revealed that the area under the curve for the combined prediction of nonremission in MN patients after treatment with serum BAFF, CFB and MCP-1 was 0.948, which was greater than the area under the curve for the individual prediction of anti-PLA2R antibody and BAFF, CFB and MCP-1 (Z=4.116, 3.059, 4.122, 4.116, P<0.05). Conclusion: The levels of serum BAFF, CFB and MCP-1 in MN patients are related to the level of anti-PLA2R antibody, MN stage and therapeutic effect. Moreover, the combined detection of serum BAFF, CFB and MCP-1 has high predictive value for the nonremission of MN patients after treatment.
Copyright (c) 2025 Kaiyuan Zheng, Tongxin Qu, Lili Han, Yi Sun
Serum Keratin 1 and TMAP in cardiac function prognosis of acute heart failure (AHF)
[Objective] To explore the relationships between serum TMAP (Tumor metastasis-associated peptide) and KRT1(Keratin 1) levels and the cardiac function classification and prognosis of patients with acute heart failure (AHF). [Methods] From January 2022 to January 2025, 428 patients with acute heart failure (AHF) admitted to this hospital composed the AHF group. Among them, 162 patients had a NYHA cardiac function classification of grade II, 166 patients had a grade III, and 100 patients had a grade IV. The control group consisted of 100 more healthy volunteers who had physical examinations at the same hospital during the same time period. After the AHF patients received relevant treatments according to the guidelines and were discharged, a 6-month follow-up was conducted. Patients with a poor prognosis were those who were readmitted due to heart failure or cardiac death; patients with a positive prognosis were those who were not. Each study participant's serum levels of KRT1 and TMAP were determined using the enzyme-linked immunosorbent assay (ELISA). Patients with AHF were given baseline data. The relationship between the classification of cardiac function in AHF patients and serum TMAP and KRT1 levels was examined using Spearman correlation analysis. The factors determining a poor prognosis in individuals with AHF were examined using multivariate logistic regression analysis. The capacity of serum TMAP and KRT1 levels to predict a bad prognosis in AHF patients was examined using receiver operating characteristic (ROC) curves. Comparisons of the area under the curve (AUC) were conducted using the DeLong test. [Results] Serum TMAP levels were greater in the AHF group than in the control group (P < 0.05), and serum KRT1 levels were lower in the AHF group than in the control group (P < 0.05). The serum TMAP level increased with increasing cardiac function classification (F trend = 109.195, P trend < 0.001). Conversely, as heart function categorization increased, the serum KRT1 level dropped (F trend = 223.564, P trend < 0.001). According to Spearman correlation analysis, the cardiac function classification in AHF patients was positively connected with the serum TMAP level (r s = 0.711, P < 0.001) and inversely correlated with the serum KRT1 level (r s = -0.722, P < 0.001). TMAP, KRT1, and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels, along with the NYHA cardiac function classification, varied statistically significantly (P < 0.05) between the groups with bad and favorable prognoses. Elevated NT-pro BNP levels, elevated TMAP levels, and NYHA cardiac function classification grade IV were found to be independent risk factors for a poor prognosis in AHF patients (P < 0.05), while elevated KRT1 levels were found to be an independent protective factor against a poor outcome in AHF patients (P < 0.05), according to multivariate logistic regression analysis. The areas under the curve (AUCs) for serum TMAP and KRT1 alone and jointly were 0.782, 0.792, and 0.880, respectively, for predicting a poor prognosis in AHF patients, according to ROC curve analysis. The AUC of the combination of the two was greater than that of the single prediction of serum TMAP and KRT1 (Z = 3.956, 3.642; P < 0.001). [Conclusion] Serum TMAP levels are elevated in patients with AHF, whereas KRT1 levels are decreased. Both of these factors are related to the patients’ cardiac function classification and prognosis. Combined serum TMAP and KRT1 levels have relatively high predictive efficacy for poor prognosis in patients with AHF.
Copyright (c) 2026 Chengqun She, Juan Wu, Yaoguang Feng, Chaozhong Long, Zusong Tan
Correlation analysis of serum SERPINA3, CLEC2 and hs-CRP/ALB with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in STEMI
Objective To examine the main adverse cardiovascular events that occur in individuals who have had an acute ST-segment elevation myocardial infarction (STEMI) after receiving percutaneous coronary intervention (PCI), such as serum C-type lectin domain family member 2 (CLEC2), serine protease inhibitor family member A3 (SERPINA3), and high-sensitivity C-reactive protein/albumin (hs-CRP/ALB) levels. Methods The STEMI group included 132 patients who were observed for a year after being hospitalized to the hospital between January 2023 and September 2024. The patients were divided into two groups: the MACE group and the non-MACE group, based on whether MACE came after PCI. Additionally, The control group consisted of 68 healthy people who were examined physically at the hospital throughout the same time period. Using an enzyme-linked immunosorbent test, the levels of serum CLEC2, SERPINA3, hs-CRP, and ALB were measured in each research participant, and the hs-CRP to ALB ratio was computed. After PCI, multivariate logistic regression was utilized to examine the variables affecting MACEs in STEMI patients. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of single and combined detection of serum CLEC2, SERPINA3, and hs-CRP/ALB for MACEs in STEMI patients after PCI. Results The incidence of MACE after PCI in 132 STEMI patients was 31.06% (41/132). The levels of serum CLEC2, SERPINA3 and hs-CRP/ALB in the STEMI group were significantly greater than those in the control group (P<0.05). Independent risk factors for MACEs following PCI in STEMI patients included age ≥62 years, Killip grade ≥ grade III, cardiac troponin I level ≥1.7 ng/mL, CLEC2 level ≥155 pg/mL, SERPINA3 level ≥350 ng/L, and hs-CRP/ALB≥0.50 (P<0.05), while left ventricular ejection fraction ≥50% was an independent protective factor. The area under the ROC curve (0.856) of the combined detection of serum CLEC2, SERPINA3, and hs-CRP/ALB for the prediction of MACEs in STEMI patients after PCI was greater than that of the individual detection of each index. Conclusion Serum CLEC2 levels ≥155 pg/mL, SERPINA3 levels ≥350 ng/L, and hs-CRP/ALB≥0.50 are closely related to the occurrence of MACEs in STEMI patients after PCI and can be used as auxiliary predictive indicators for the occurrence of MACEs in STEMI patients after PCI.
Copyright (c) 2025 Yuncong Ma, Suxia Fang, Shasha Liu, Zhencong Jiang
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Copyright (c) 2026 Jiahao Chen, Wenwu Liu, Xinci Zhang, Chenchen Zhu
Neutrophil Redox Imbalance in Acute Coronary Syndrome
Summary Background: Oxidative stress contributes significantly to the pathogenesis of acute coronary syndrome (ACS), with neutrophils playing a pivotal role in mediating vascular injury through reactive oxygen species and myeloperoxidase (MPO)-derived oxidants. We aimed to assess the oxidative stress markers and antioxidant enzyme activities in neutrophils from ACS patients. Methods: Neutrophils were isolated from 77 ACS patients and 33 control subjects. Oxidative stress was evaluated by measuring conjugated dienes, hydroperoxides, and chloramines. Antioxidant status was assessed via non-protein and total thiol levels, and enzymatic activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx-1), and glutathione reductase (GR). MPO peroxidase and chlorinating activities were also quantified. Results: ACS patients exhibited significantly elevated levels of conjugated dienes (p < 0.005), chloramines (p < 0.005), thiols (p < 0.05), SOD activity (p = 0.01), and MPO chlorinating activity (p < 0.05). No significant differences were observed in catalase, GPx-1, GR, or MPO peroxidase activity. Significant correlations were found between lipid peroxidation markers and antioxidant parameters, particularly SOD and MPO chlorinating activity. Multiple regression identified SOD and chloramines as independent predictors of lipid peroxidation. Conclusion: Neutrophils from ACS patients display a disrupted redox balance characterized by enhanced lipid peroxidation, increased thiol content, and selective activation of MPO chlorination. These results underscore the relevance of neutrophil-derived redox markers as potential diagnostic tools and treatment targets in ACS. Keywords: acute coronary syndrome, neutrophils, oxidative stress
Copyright (c) 2025 Ilija M Dragojevic, Dijana Miric, Bojana Kisic, Dragana Puhalo Sladoje, Ljiljana Popovic, Dragisa Rasic
Correlation analysis of the serum CCR5 and LXA4 levels with airway remodeling in bronchial asthma patients and nursing summary
[Objective] To analyze the expression levels of serum chemokine receptor 5 (CCR5) and lipoxin A4 (LXA4) in patients with bronchial asthma and their correlations with immune dysfunction and airway remodeling. [Methods] According to the severity of the disease, 240 patients with bronchial asthma admitted to our hospital from January 2023 to May 2025 were divided into mild to moderate asthma groups (n=180) and severe asthma groups (n=60). As the control group, 150 more healthy people who were admitted for a physical examination during that time were chosen. The serum CCR5 and LXA4 levels and immune function indicators (CD3+, CD4+, CD8+, and CD4+/CD8+) of each group were detected, and the airway remodeling indicators [airway lumen area (LA), airway wall area (WA) and total airway area (TA)] of the right upper lobe tip segment were examined via CT. The correlations between the serum CCR5 and LXA4 levels and immune dysfunction as well as airway remodeling were analyzed via a bivariate Spearman correlation test, and a multivariate logistic model was established to analyze the independent risk factors influencing the serum CCR5 and LXA4 levels in patients with bronchial asthma. [Results] Compared to the mild to moderate group, the severe group had greater serum levels of LXA4 and CCR5. Serum CCR5 was higher in the severe group than in the mild to moderate group, and LXA4 was lower in the severe group than in the mild to moderate group. There were statistically significant differences (P<0.05). Serum CD8+ T cell levels were higher than in the control group, whereas CD3+, CD4+, and CD4+/CD8+ T cell levels were lower in the mild to moderate and severe groups. Furthermore, the severe group had lower levels of CD3+, CD4+, and CD4+/CD8+ T cells than the mild to moderate group, whereas the mild to moderate group had greater levels of CD8+ T cells. The mild to moderate group of patients and the severe group of patients had lower levels of LA, WA, and TA in the right superior lobe apex segment than the control group, and patients in the severe group had lower levels of these three parameters than those in the mild to moderate group. There was a negative connection between serum CCR5 and LXA4 and CD3+, CD4+, and CD4+/CD8+ (P<0.05) and a positive correlation with CD8+, LA, WA, and TA. Multivariate logistic regression analysis revealed that disease severity, CD3+, CD4+, CD8+, CD4+/CD8+, LA, WA, and TA were independent risk factors for increased serum CCR5 and LXA4 in patients with bronchial asthma (P<0.05). [Conclusion] Serum CCR5 and LXA4 are closely related to the severity of bronchial asthma, immune dysfunction and airway remodeling.
Copyright (c) 2026 Haiyue Huang, Ruirui Luo, Xuan Yang, Zhigang Wu, Zhongxi Ding
The Serum Damine oxidase (DAO), serum bacterial endotoxin (BT) and D-lactic acid (D-Lac) TNF-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in patients sepsis combined with acute kidney injury after Bexira administration
Objective: The present investigations were designed to investigate the clinical effectiveness of Bexira in acute kidney injury patients complicated by a septic condition, and further analyze its potential effects on Serum Damine oxidase (DAO), serum bacterial endotoxin (BT) and D-lactic acid (D-Lac) TNF-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in patients, so as to enhance the scientific basis for clinical treatments. Methods: Between January 2024 and December 2024, 200 patients with sepsis associated with acute kidney injury were admitted to our hospital. These individuals were incorporated into our research cohort. In order to ensure the scientificity and comparability of the study, we used A random number table method to randomly divide these 200 patients into panels A and B, with 100 patients in per group. Group A patients received standard conventional care, including but not limited to anti-infective therapy, nutritional support, and symptomatic management. Group B received additional treatment with Bexira on the basis of group A. All patients enrolled in the study underwent detailed clinical assessments and appropriate medical examinations to ensure the safety and efficacy of the treatment. Prior to treatment, all patients underwent a comprehensive assessment to understand their baseline health status. 7 days after the start of treatment, the changes of intestinal mucosal barrier function, immune function and their prognosis were monitored in both groups. By comparing the two populations before and after treatment, we aim to better understand what factors may affect a patient's recovery process and long-term prognosis. Results: After 7 days of treatment, we observed significant reductions in diamine oxidase (DAO) levels, bacterial endotoxin (BT) content, and D-lactic acid (D-Lac) concentration in both experimental groups. Especially in group B, the changes of these three biomarkers were more significant, and their values were lower than those of control group A, indicating that the treatment effect of group B was better than that of group A. This variation is of major concern in terms of statistically validity, that is, P<0.05, meaning that the test results could not be regarded as due to chance or error, but could be confirmed as changes in biological indicators caused by effective treatment strategies. These data not only demonstrate the short-term effect of the treatment, but also hint at possible long-term benefits, and warrant further research to explore more about the pharmacological mechanism of effect and clinical application of this agent. Conclusions: Among the many options for treating sepsis associated with acute kidney injury, the application of Bexira proved to be a significant advance. also enhance the level of the body's immune response, thereby helping to improve the overall health status and prognosis of patients.
The Novel Serum Biomarkers for Real-Time Treatment Monitoring and Prognostication in Hepatocellular Carcinoma Patients
Background: Alpha-fetoprotein (AFP) has limited utility for real-time monitoring of hepatocellular carcinoma (HCC) during locoregional and systemic therapies. We evaluated six novel serum biomarkers—circulating tumor DNA (ctDNA), des-gamma-carboxy prothrombin (DCP), Golgi protein 73 (GP73), osteopontin (OPN), heat shock protein 70 (HSP70), and neutrophil-to-lymphocyte ratio (NLR)—against AFP for post-treatment response assessment and prognostication following transarterial chemoembolization (TACE) and sorafenib. Methods: A prospective cohort of 148 patients with intermediate-stage HCC undergoing TACE (n=86) or sorafenib (n=62) was enrolled. Serum samples were collected at baseline, week 4, week 8, and at radiologic progression. Biomarker kinetics were correlated with mRECIST response and overall survival (OS). Area under the receiver operating characteristic curve (AUC) was calculated for residual disease detection and progression prediction. Results: For post-TACE residual disease detection, HSP70 showed the highest sensitivity (88%), followed by GP73 (84%). For sorafenib monitoring, DCP and OPN independently predicted progression (AUC 0.86 and 0.83 respectively). A composite panel (DCP + GP73 + OPN + HSP70) achieved 92% specificity for early progression detection (AUC 0.93). Patients with persistent elevation of ≥3 markers at week 8 had significantly worse median OS (6.2 vs. 16.8 months, p<0.001). Conclusion: Novel serum biomarkers—particularly DCP for sorafenib monitoring, HSP70 and GP73 for post-TACE residual disease detection, and OPN for tumor burden tracking—enable effective real-time treatment monitoring and prognostication in HCC, outperforming AFP across multiple therapeutic contexts.
Copyright (c) 2026 Jing Wang, Qing Yang, Lei Zhao, Yiming Feng
Digital Biomarkers and Medical Algorithms in the Serbian Healthcare Ecosystem: A Comparative Analysis of Knowledge, Attitudes, Practice and Economic Valuation Among Key Healthcare Stakeholders
Background: Digital healthcare transformation, characterized by digital biomarkers and medical algorithms emergence promises to redefine healthcare system. However, successful implementation relies on acceptance, readiness and economic valuation of key stakeholders as biochemists and clinicians. This study provides first analysis of attitudes, practices, knowledge and economic valuation around digital health diagnostics with specific focus on two sub-cohorts - Biochemists (Medical/Clinical) and Clinicians (Pathologists/Gastroenterologists) as implementation frontrunners. Methods: A cross-sectional survey was conducted with a cohort of 105 healthcare professionals from 53 prominent healthcare institutions. The study used a structured instrument for analysis of digital competencies, perceived benefits and potential risks. A Contingent Valuation Method was employed to determine Willingness to Pay for digital medical solutions. Results: The cohort exhibited high digital literacy level (4.6 out of 5). Biochemists, grounded in analytical validation, expressed greater caution regarding clinical relevance and data privacy. Conversely, Clinicians, driven by the need for diagnostic decision support, demonstrated caution towards finance topics. The analysis revealed optimal price point at €65.9 ± 75.56 (95% CI: €41.2 – €90.6). There is no significant difference between sub-cohorts (p = 0.89). While more than 75% of participants believed digital biomarkers would yield systemic financial savings, 74% were unaware of the existing regulatory frameworks. Conclusions: Serbian healthcare community possesses robust digital foundation. Biochemists view digital medical solutions as analytical solutions requiring validation, while clinicians view them as solutions for diagnostic ambiguity. Establishing national working group on "Digital Diagnostics" to develop guidelines for the validation and to develop reimbursement codes is crucially needed.
Copyright (c) 2026 Dragiša Obradović, Đorđe Kralj, Andrijana Milošević Georgiev, Dragana Lakić
Diagnostic Value of Integrated Serum Protein Carbonyl, 8-Hydroxy-2'-Deoxyguanosine, and PGC-1α Profiling for Myocardial Energy Metabolism Disorder in Ischemic Cardiomyopathy
Background: Patients with ischemic cardiomyopathy (ICM) often have abnormalities in myocardial energy metabolism, whereas conventional cardiac function indices may not capture metabolic injury in a timely manner. This study aimed to evaluate the diagnostic value of combined serum protein carbonyl (PC), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) detection for myocardial energy metabolism disorder in patients with ICM. Methods: A total of 167 patients with ICM hospitalized between June 2024 and October 2025 were retrospectively enrolled. According to myocardial energy metabolism status, they were divided into an energy metabolism disorder group (n=78) and a non-disorder group (n=89). Serum PC, 8-OHdG, and PGC-1α levels were measured. Clinical data, cardiac function indices, and serum biomarker levels were compared between the two groups. A combined diagnostic model was then constructed using logistic regression, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of single indicators and combined detection. Results: Compared with the non-disorder group, the energy metabolism disorder group showed increased PC and 8-OHdG levels and decreased PGC-1α levels, with statistically significant differences (P<0.001). Multivariate logistic regression showed that PC, 8-OHdG, and PGC-1α were independently associated with myocardial energy metabolism disorder. ROC analysis showed that the areas under the curve (AUCs) of PC, 8-OHdG, and PGC-1α alone were 0.806, 0.791, and 0.772, respectively. The AUC of the combined diagnostic score increased to 0.884, with a sensitivity of 87.18% and a specificity of 79.78%, and the AUC of the combined model was higher than that of each single indicator. Conclusion: Increased serum PC and 8-OHdG levels and decreased PGC-1α levels are closely related to myocardial energy metabolism disorder in patients with ICM. Combined detection of the three indicators shows good diagnostic performance and may provide laboratory evidence for the auxiliary identification and risk stratification of myocardial energy metabolism disorder.
Circulating tumor-associated biomarkers and pulmonary function in lung cancer patients with comorbid COPD: A retrospective prognostic analysis
Background: Chronic obstructive pulmonary disease (COPD) is closely associated with lung cancer development and progression through persistent systemic inflammation and immune-biochemical alterations. Circulating tumor-associated biochemical biomarkers may reflect disease severity and provide valuable prognostic information. This study aimed to explore the potential association between circulating tumor markers and prognosis in lung cancer patients with comorbid COPD, acknowledging the exploratory nature of this retrospective analysis. Methods: Clinicopathological characteristics and circulating biochemical biomarkers, including carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), cytokeratin-19 fragment (CYFRA21-1), and vascular endothelial growth factor (VEGF), were analyzed. Multivariate logistic regression was performed to identify independent prognostic biochemical predictors. Receiver operating characteristic (ROC) curve analysis was used to evaluate prognostic performance. Results: Patients with COPD demonstrated significantly elevated circulating levels of tumor-associated biochemical biomarkers compared with those without COPD (P<0.05). Multivariate analysis identified advanced TNM stage, lymph node metastasis, and increased serum concentrations of CYFRA21-1, CEA, CA125, CA153, CA199, and VEGF as independent biochemical predictors of poor prognosis (P<0.05). ROC curve analysis showed that CA199 (AUC>0.75), CA153 (AUC>0.75), and CA125 (AUC>0.75) exhibited strong prognostic performance, indicating their clinical utility for laboratory-based risk stratification. Conclusions: In this retrospective analysis, circulating tumor-associated biochemical biomarkers showed potential associations with prognosis in lung cancer patients with COPD. However, these findings are hypothesis-generating and require prospective validation before clinical implementation. The observed associations should not be interpreted as established prognostic markers for clinical decision-making without further multi-center, prospective studies. Current evidence supports continued reliance on established staging systems and comprehensive clinical assessment rather than biomarker-based risk stratification alone.
Copyright (c) 2026 Hongxia Ma, Qian Zhang, Junnan Yue, Jun Su, Xingrui Meng, Fangyuan Ren, Zheng Li
The Effect of Treatment on Serum C3, C4, IL-10, IL1-β, IL-6, TNF-α in Patients with Systemic Lupus Erythematosus
Objective: This study aimed to evaluate the effects of structured lifestyle optimization, including nutritional intake and exercise training, on serum levels of Complement C3, C4, IL-10, IL1-β, IL-6, and TNF-α in patients with systemic lupus erythematosus (SLE) and Libman-Sacks endocarditis (LSE). Methods: A total of 122 SLE patients with LSE, treated at our hospital from May 2022 to May 2024, were randomized into a control group (CG, n=61) receiving conventional medical interventions and an intervention group (IG, n=61) receiving additional personalized exercise and nutritional interventions for 24 weeks. Serum levels of Complement C3, C4, IL-10, IL1-β, IL-6, and TNF-α were measured at baseline, 3 months, and 6 months. Secondary endpoints included nutritional status (albumin, hemoglobin) and patient compliance. Results: Of 113 patients completing the study, the intervention group (IG) showed significant improvement in serum Complement C3 (0.84 ± 0.18 g/L vs. 0.75 ± 0.16 g/L in control group [CG], P=0.006) and albumin levels (37.12 ± 5.37 g/L vs. 35.00 ± 4.89 g/L, P=0.03) at 6 months. Complement C4 levels increased in the IG (0.20 ± 0.09 g/L vs. 0.17 ± 0.12 g/L, P=0.136, not significant). IL-1β (3.9 ± 3.77 pg/mL vs. 4.6 ± 4.1 pg/mL, P=0.468) and TNF-α (12.6 ± 4.1 pg/mL vs. 14.1 ± 5.2 pg/mL, P=0.092) showed non-significant reductions in the IG compared to the CG. No significant changes were observed in IL-10 or IL-6 levels. Compliance was significantly higher in the IG (92.86% vs. 78.95%, P=0.038). Conclusion: Structured lifestyle optimization significantly improved serum Complement C3 and albumin levels and showed non-significant trends toward reductions in IL-1β and TNF-α in SLE patients with LSE, suggesting a potential adjunctive role in managing immune and nutritional status.
Copyright (c) 2025 Nadira Reyimu, Yueyue Jing
Correlation analysis of serum SIR2L4, C1QTNF5 and CBP-35 levels with the prognosis of diabetic retinopathy patients
Objective: To explore the relationships between serum Silent Mating Type Information Regulation 2 Homolog 4 (SIR2L4), C1q and tumor necrosis factor related protein 5 (C1QTNF5), Carbohydrate-binding protein 35 (CBP-35) and glycolipid metabolism and prognosis in patients with diabetic retinopathy (DR). Methods: The DR group was selected from among 230 hospitalised DR patients admitted between January 2023 and January 2024, including 122 non-proliferative DR patients (Non-proliferative DR group) and 108 proliferative DR patients (Proliferative DR group). Additionally, 100 subjects who underwent health check-ups in the hospital during the same period were selected as the control group. Indicators of SIR2L4, C1QTNF5, CBP-35, blood glucose [Fasting plasma glucose (FPG)], and the levels of blood lipids in the DR group and the control group were measured and compared. Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) were among them. Moreover, the correlations between serum SIR2L4, C1QTNF5, and CBP-35 levels and blood glucose and lipid indicators in DR patients were analysed. The DR patients were monitored and followed up with for six months after treatment. Depending on their level of visual impairment, the patients were split into groups with excellent and poor prognoses. The levels of serum SIR2L4, C1QTNF5 and CBP-35 in the two groups were compared. Multivariate logistic regression was used to analyse the risk factors for poor prognosis in DR patients. A receiver operating characteristic (ROC) curve was used to analyse the predictive value of single or combined detection of SIR2L4, C1QTNF5, and CBP-35 for poor prognosis in patients with DR. Results: Pearson correlation analysis revealed that the levels of SIR2L4, C1QTNF5, and CBP-35 in DR patients were positively correlated with FPG, TG, TC, and LDL-C (P<0.05) and negatively correlated with HDL-C (P<0.05). The poor-prognosis group had higher serum levels of SIR2L4, C1QTNF5, and CBP-35 than the good-prognosis group (P<0.05). The poor prognosis group’s DR course was longer than the excellent prognosis group’s (P<0.05), and the proportion of proliferative DR was greater than that in the good prognosis group (P<0.05). DR course ≥6 months, SIR2L4 ≥24 ng/mL, C1QTNF5 ≥8 ng/mL, CBP-35> 1,400 ng/mL, and DR stage of the proliferative type were all independent risk factors for poor prognosis in DR patients. The ROC curve analysis showed that the AUCs of each index for predicting a poor prognosis in DR patients were 0.799, 0.746, and 0.711, respectively, when the ideal cutoff values for the individual detection of serum SIR2L4, C1QTNF5, and CBP-35 were 24 ng/mL, 8 ng/mL, and 400 pg/mL, respectively. Based on the results of the multivariate logistic regression analysis, a model with Ln(P/1-P)=0.573×XSIR2L4+0.809×XC1QTNF5+0.424×XCBP-35 was established for the combined detection of the three indicators. The AUC of this model for predicting poor prognosis in DR patients was 0.836 (95% CI: 0.709–0.964), indicating a relatively high predictive value. Conclusion: The levels of SIR2L4, C1QTNF5 and CBP-35 in the serum of DR patients are increased and are correlated with glycolipid metabolism. Moreover, a SIR2L4 concentration ≥24 ng/mL, a C1QTNF5 concentration ≥8 ng/mL, a CBP-35 concentration ≥1,400 ng/mL, a DR course ≥6 months, and a proliferative stage of DR are risk factors for an unfavourable prognosis in DR patients. The poor prognosis of DR patients can be predicted more accurately by the combination detection of SIR2L4, C1QTNF5, and CBP-35 than by their individual detection.
Copyright (c) 2025 Wenming Cheng, Hua Lu, Ting Song, Wei Liu
The diagnostic value of serum 25-Hydroxyvitamin D, MIS and Insulin-like Growth Factor 1 for polycystic ovary syndrome (PCOS)
Objective To investigate blood levels and the importance of Müllerian Inhibiting Substance (MIS), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), and 25-hydroxyvitamin D [25(OH)D] in patients with polycystic ovarian syndrome (PCOS). Methods The observation group consisted of 212 PCOS patients who received treatment at this institution between May 2022 and May 2024, while the control group consisted of 212 healthy women who were examined physically at same hospital within the same time frame. The two groups' general information, serum 25(OH)D, MIS, IGF-1, and IGFBP-3 levels, as well as their sex hormones and glucose metabolism markers, were compared. PCOS patients were divided into the IR group and the non-IR group according to whether insulin resistance (IR) occurred. The two groups' levels of serum 25(OH)D, MIS, IGF-1, and IGFBP-3 were compared. The study examined the associations among the four markers and the homeostasis model of insulin resistance index (HOMA-IR), as well as their supplementary diagnostic utility for PCOS. Results The level of 25(OH)D in the observation group was lower than that in the control group (P<0.05). Total testosterone (TT), luteinizing hormone (LH), estradiol (E2), fasting insulin (FINS), fasting blood glucose (FBG), serum MIS, IGF-1, IGFBP-3, HOMA-IR, and the average body mass index were all greater in the observation group than in the control group (P<0.05). The IR group's 25(OH)D level was lower than the non-IR group's (P<0.05). Serum MIS, IGF-1, and IGFBP-3 levels were higher in the IR group than in the non-IR group (P<0.05). The levels of serum MIS, IGF-1 and IGFBP-3 in the observation group were positively correlated with HOMA-IR (r=0.659, 0.586, 0.565, P<0.05), and 25(OH)D was negatively correlated with HOMA-IR (r=-0.548, P<0.05). The combined auxiliary diagnosis of PCOS by serum 25(OH)D, MIS, IGF-1, and IGFBP-3 had an area under the curve of 0.963, according to the results of receiver operating characteristic curve analysis, which was greater than that of the single detection of each index (0.819, 0.864, 0.814, 0.799). Conclusion MIS, IGF-1, IGFBP-3, and serum 25(OH)D levels are associated with the development and occurrence of PCOS. The combined detection of these four indicators has high auxiliary diagnostic value for PCOS and is conducive to clinical prevention and treatment.
Copyright (c) 2025 Shaomeng Sun, Jianrui Zheng, Ziying Xie
Effects of Thrombospondin-1 (THBS1) and Toll-like Receptor 4 (TLR-4) levels in the serum and synovial fluid of patients with knee osteoarthritis
Objective To explore the changes in and significance of Thrombospondin-1 (THBS1) and Toll-like receptor 4 (TLR-4) levels in the serum and joint fluid of patients with knee osteoarthritis (KOA). Methods 184 KOA patients who were admitted to our hospital between May 2022 and February 2025 were chosen to serve as the observation group, and another 64 healthy adults who underwent physical examinations at the same hospital during the same period composed the control group. Tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, THBS1, and TLR-4 levels in the two groups' serum and joint fluid were compared. The correlations between the levels of TNF-α, IL-1β, THBS1 and TLR-4 in the serum and synovial fluid of the two groups and the severity of KOA were evaluated, and the clinical value of THBS1 and TLR-4 in the diagnosis of KOA was analyzed. Results TNF-α, IL-1β, THBS1, and TLR-4 levels in the observation group's serum and joint fluid were considerably higher than those in the control group (P<0.05). With an increase in Kellgren-Lawrence (K-L) grade, the observation group's serum and joint fluid had higher amounts of TNF-α, IL-1β, THBS1, and TLR-4. When TNF-α, IL-1β, THBS1, and TLR-4 levels were compared among K-L grades, statistically significant differences were found (P<0.05). The K-L grade of the patients was positively correlated with TNF-α, IL-1β, THBS1, and TLR-4 in the blood and joint fluid (P<0.05), and the factors of TNF-α, IL-1β, THBS1, and TLR-4 in the observation group's serum and joint fluid were positively correlated with each other (P<0.05). The sensitivity and specificity of serum THBS1 and TLR-4 for the diagnosis of KOA were 0.916 and 0.889 and 0.825 and 0.865, respectively, and the optimal cutoff values were 247.262 and 5.084 ng/mL, respectively. The sensitivity and specificity of THBS1 and TLR-4 in the joint fluid for diagnosing KOA were 0.945 and 0.932 and 0.985 and 0.916, respectively, and the optimal cutoff values were 239.745 and 4.620 ng/mL, respectively. Conclusion THBS1 and TLR-4 in serum and synovial fluid can be used as potential markers for the clinical diagnosis and assessment of KOA conditions, both of which have high diagnostic efficacy. Moreover, the detection of serum THBS1 and TLR-4 is less invasive, has a lower cost, and is more acceptable to patients.
Copyright (c) 2025 Yingjie Xu, Zhen Tian, Mingjin Liang, Xiaoyun Li
The Effect of auto-verification on turnaround time for clinical chemistry and immunoassay tests
Background: Auto-verification is increasingly recognized as a key tool for improving quality and efficiency in clinical laboratories. This study aimed to investigate the impact of an auto-verification system implemented for clinical chemistry and immunoassay tests on turnaround time (TAT) in a tertiary-care medical biochemistry laboratory. Methods: This study was conducted in the Medical Biochemistry Laboratory of XXX Hospital, a tertiary healthcare institution. Clinical chemistry and immunoassay tests were subjected to auto-verification using the navify® Lab Operations middleware (Roche Diagnostics, Germany) integrated with the MIA-MED Laboratory Information System (MIA Technology, Turkey). Algorithms were developed in accordance with CLSI AUTO10-A and AUTO15 guidelines, incorporating rules for quality control, serum indices, analyzer flags, delta checks, critical values, consistency checks, and analytical measurement intervals, as well as recommendations from the national health authorities. Validation of the algorithms was carried out using both simulated and patient data. The proportion of results exceeding predefined TAT targets was compared before and after auto-verification implementation with using the chi-square test. p<0.05 was considered statistically significant. Results Overall, 71% of test results and 21% of tube-based results were verified automatically. Median TAT was reduced by 6 minutes for emergency tests and 12 minutes for routine tests. The proportion of results exceeding the TAT threshold decreased significantly from 6.4% before auto-verification to 5.8% after auto-verification implementation (p < 0.001). Conclusions Auto-verification, with clearly defined and validated rules, enhances both the reliability and timeliness of laboratory results, thereby supporting quality improvement initiatives in clinical laboratories
Copyright (c) 2026 Havva Yasemin Çinpolat
APPLICABILITY OF LDL-CHOLESTEROL CALCULATION FORMULAS IN HYPERTRIGLYCERIDEMIA: INSIGHTS FROM THE VOJVODINA
Background: LDL-cholesterol is a key parameter for assessing the risk of atherosclerotic cardiovascular disease. Direct measurement of LDL-cholesterol is not always possible due to practical or financial reasons, making the use of calculation formulas essential for its evaluation. The aim of this study was to examine the applicability of four different formulas for calculating LDL-cholesterol compared to direct method in patients with serum triglyceride levels from 4.5 to 9.0 mmol/L in the population of Vojvodina. Methods: The retrospective study included 272 subjects whose lipid status parameters were measured using standard laboratory methods between June 2022 and June 2023. The participants had serum triglyceride levels ranging from 4.5 and 9.0 mmol/L. LDL-cholesterol was determined by direct method (d-LDL-C) on Alinity c analyser (Abbott). Additionally, LDL-cholesterol levels were calculated for this population using the formulas proposed by Friedewald, Sampson, Anandaraja and Martin. Results: In the studied population, the average age was 52 years and the median concentration of triglycerides was 5.48 (4.94-6.58) mmol/L. A statistically significant positive correlation was found between d-LDL-C and all calculated parameters (P<0.001). The lowest mean difference was observed between d-LDL-C and the Sampson formula (MD=-0.032). When comparing d-LDL-C and LDL-cholesterol values obtained by calculation, only the formula of Sampson et al. did not show a statistically significant difference (P=0.240). Conclusion: In the studied population of patients with hypertriglyceridemia, the formula by Sampson et al. showed the best performance in comparison to the others tested and its application could be considered for the Vojvodina population.
Copyright (c) 2026 Dragana Žuvić, Stanislava Nikolić, Romana Mijović, Branislava Ilinčić, Aneta Ranđelović Živković, Dušan Sedlarević, Velibor Čabarkapa
Correlation analysis of the expression levels of serum Endothelial Cell Adhesion Molecule-1 and Sirtuin 1 Protein in acute respiratory distress syndrome
Objective: To investigate the relationships among serum silencing information regulator 2-related enzyme 1 (SIRT1) expression levels, endothelial cell-specific molecule-1 (ESM-1), and fibroblast growth factor-21 (FGF21) and treatment results in patients with acute respiratory distress syndrome (ARDS) associated with sepsis. Methods: A total of 140 patients with sepsis-related ARDS were selected and divided into a good outcome group of 96 patients and a poor outcome group of 44 patients according to the treatment outcome. The levels of serum SIRT1, ESM-1 and FGF21 were compared between the two groups; the correlations between serum SIRT1, ESM-1, and FGF21 and the severity of the disease as well as the treatment outcome were analyzed; and the predictive value of serum SIRT1, ESM-1 and FGF21 for treatment outcomes was evaluated. Results: Compared to the group with a favorable outcome, the bad outcome group's serum SIRT1 level was lower, while the ESM-1 and FGF21 levels were significantly greater than those in the good outcome group (P<0.05). Serum SIRT1 levels steadily declined in patients with mild, moderate, and severe illness, while ESM-1 and FGF21 levels steadily rose (P<0.05). ESM-1 and FGF21 showed a positive association with illness severity (P<0.05), while serum SIRT1 showed a negative correlation (P<0.05) with disease severity, according to Spearman correlation analysis. Partial correlation analysis revealed that the serum SIRT1, ESM-1, and FGF21 levels were significantly correlated with the treatment outcomes of patients with sepsis-related ARDS (P<0.05). Serum SIRT1, ESM-1, and FGF21 levels and treatment outcomes were strongly correlated (P<0.05) in patients with sepsis-related ARDS. Serum SIRT1, ESM-1, and FGF21 areas under the curve (AUCs) for predicting the course of treatment for patients with ARDS associated with sepsis were 0.742, 0.838, and 0.796, respectively. The sensitivity was 77.27%, 77.27%, and 70.45%, and the specificity was 64.58%, 81.25%, and 87.50%, respectively. For patients with sepsis-related ARDS, the combined prediction of the three markers' AUC for treatment outcome was 0.939, with a sensitivity of 88.64% and a specificity of 83.33%, which was significantly greater than the individual predictive value of the three indicators alone (P< 0.05). Conclusion: The levels of serum SIRT1, ESM-1 and FGF21 in patients with sepsis-related ARDS are strongly connected with both the efficacy of treatment and the severity of the illness, have the ability to independently predict treatment outcomes, and have a greater combined predictive value.
Copyright (c) 2025 Can Peng, Zhigang Sun, Yanyan Liu, Hao Zhao
Clinical significance of miR-3178 in non-small cell lung cancer patients
Background & objectives：Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality, with low survival rate and poor prognosis This study aims to explore the diagnostic and prognostic value of miR-3178 in NSCLC. Methods: Study included 118 NSCLC patients and 97 healthy subjects. RT-qPCR measured miR-3178 and MIB2 in serum or cell lines. χ2 tests linked miR-3178 to clinicopathological features. ROC, Kaplan-Meier, and Cox analyses evaluated diagnostic and prognostic significance of miR-3178 and MIB2. Results: Compared to the control group, the expression level of miR-3178 was significantly reduced, while MIB2 expression was notably elevated in NSCLC patients. The expression of miR-3178 is significantly correlated with the TNM stage and LNM in NSCLC patients. NSCLC patients with higher miR-3178 expression levels exhibit significantly higher 5-year overall survival rates. Furthermore, TNM stage, miR-3178 expression, and MIB2 expression are independent risk factors that influence the prognosis of NSCLC. MIB2 serves as a target gene of miR-3178, and their expression levels display a significant negative correlation. When diagnosing NSCLC solely based on miR-3178, the AUC is 0.838; for MIB2 alone, the AUC is 0.818; however, when miR-3178 and MIB2 are combined for diagnosis, the AUC increases to 0.903. Conclusion: The downregulation of miR-3178 and upregulation of MIB2 are associated with the progression and deterioration of NSCLC patients, indicating poor prognosis. miR-3178 targets MIB2, and their combined diagnosis can enhance the diagnostic value for NSCLC, potentially reducing the risk of adverse outcomes.
Copyright (c) 2026 Haizhen Yu, Shizhen Li
Serum OX40 Ligand as a Biochemical Regulator of Th2-Dominant Immune Activation in Asthma: An Integrated Cytokine Network Analysis
Background: Asthma is characterized by complex immune dysregulation involving coordinated cytokine and chemokine networks. OX40 ligand (OX40L), a key T-cell co-stimulatory molecule, has been implicated in Th2-mediated inflammation; however, its serum-level biochemical interactions with immune activation pathways in asthma remain incompletely defined. Methods: In this cross-sectional study, serum OX40L and immune activation-related factors were quantified in 82 patients with asthma and 40 healthy controls. Multiplex cytokine analysis was performed to measure Th2-, Th17-, pro- and anti-inflammatory mediators, along with chemokines and total IgE. Lung function indices were assessed by spirometry. Correlation analysis and multivariable linear regression were applied to identify immune factors independently associated with serum OX40L levels. Results: Serum OX40L concentrations were significantly elevated in asthma patients compared with controls and increased progressively with disease severity (all P<0.001). OX40L exhibited strong positive correlations with Th2-associated cytokines, particularly interleukin-5 (IL-5; r=0.75, P<0.001), and chemokines, while showing a significant inverse association with the anti-inflammatory cytokine IL-10. OX40L levels were also negatively correlated with forced expiratory volume in one second (FEV1%pred; r=-0.72, P<0.001). Multivariable regression identified IL-5 (β=0.35), FEV1%pred (β=-0.28), and annual exacerbation frequency (β=0.22) as independent biochemical determinants of serum OX40L, collectively explaining 68.3% of its variance. Conclusion: Serum OX40L is closely integrated within the Th2-dominant immune activation network in asthma and reflects both immune imbalance and functional airway impairment. These findings support OX40L as a biochemically relevant indicator of immune activation intensity and highlight its potential role within cytokine-driven regulatory pathways in asthma.
Evaluation of Plasma Alpha Klotho Levels in Obese Cases
Background: Klotho is an anti-aging gene that lengthens life when excessively expressed and accelerates aging when disrupted. In our study, we will research the correlations between plasma α-Klotho (α-KL) protein levels with body mass index (BMI), carotid intima media thickness (CIMT), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), high-sensitivity c-reactive protein (hsCRP) and cholesterol values in obese patients. Methods: This study was conducted in a single-centered and cross-sectional manner. Results: The study was performed with a total of 90 participants, 35 women (38.9%) and 55 men (61.1%). Of participants included in the study, 30 were normal weight (33.3%) (Group 1), 30 were overweight (33.3%) (Group 2) and 30 were obese (33.3%) (Group 3). There were statistically significant differences in the α-KL protein (p=0.010), hsCRP (p<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.022), values of the study groups. There is no significant difference between the study groups in terms of CIMT (p=0.380), TOS (p=0.613), TAS (p=0.056) and, OSI (p=0.943) values. Conclusions: In conclusion, in this study, the overweight group had α-KL protein values that were significantly higher than the obese group, while hsCRP values were significantly higher in the obese group compared to the overweight and normal weight groups. There were no significant differences for CIMT, TAS, TOS and, OSI values in the study groups. There were no significant correlations between α-KL protein values with BMI, hsCRP, CIMT, TAS, TOS and OSI values of participants in the study.
Copyright (c) 2026 Ibrahim Solak, Ibrahim Guney, Nevin Sekmenli, Huseyin Kurku, Mehmet Ali Eryilmaz
Serum Biochemical and Inflammatory Biomarker Profiles in Severe Preeclampsia and Their Clinical Predictive Value
Background: Preeclampsia is a pregnancy-specific hypertensive disorder characterized by systemic endothelial dysfunction, metabolic disturbances, and inflammatory activation. However, comprehensive biochemical and inflammatory biomarker profiles associated with disease severity, particularly severe preeclampsia, remain insufficiently defined. This study aimed to investigate serum biochemical and inflammatory markers in preeclampsia and to evaluate their clinical predictive value for severe disease. Methods: In this retrospective case–control study, pregnant women were classified into severe preeclampsia (n=30), mild preeclampsia (n=30), and normal pregnancy control groups (n=30). Serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), uric acid, creatinine, albumin, total bilirubin, triglycerides, and total cholesterol, were measured. Inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8, tumor necrosis factor-α, procalcitonin, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio, were analyzed. Group comparisons, Spearman correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses were performed. Results: Both biochemical and inflammatory markers showed significant stepwise alterations across the three groups, with the most pronounced abnormalities observed in severe preeclampsia (P < 0.05). LDH, uric acid, CRP, IL-6, and albumin were significantly associated with disease severity. Multivariable logistic regression identified elevated LDH, uric acid, CRP, IL-6, and reduced albumin as independent predictors of severe preeclampsia. ROC analysis demonstrated that the combined biomarker model achieved good discriminative performance, with an area under the curve of 0.89 (95% CI: 0.81–0.96). Conclusions: Severe preeclampsia is characterized by distinct serum biochemical and inflammatory biomarker profiles. An integrated biomarker-based model may serve as a practical tool for early identification and risk stratification of severe preeclampsia.
Copyright (c) 2026 Fan Yang, Yanping Liu, Yanyan Liu
Correlation analysis of serum FGLP1, UACR and the risk of heart failure in patients with type 2 diabetes
Objective To explore the correlations between serum FGLP1 (Fibrinogen-like protein 1 C-terminal peptide) levels, the urine albumin-to-creatinine ratio (UACR) and left ventricular diastolic dysfunction (LVDD) in elderly patients with type 2 diabetes mellitus (T2DM). Methods From August 2023 to August 2025, 256 elderly patients with T2DM who were admitted to our hospital were selected as the case group, and 120 healthy individuals who underwent physical examinations were selected as the control group. In accordance with the diagnostic criteria for LVDD, T2DM patients were divided into a disorder group (n=70) and a nondisorder group (n=186), and single-factor analysis, multivariate logistic regression analysis, and Spearman correlation analysis were performed to explore the correlation between serum FGLP1 levels, UACRs and LVDD in T2DM patients, and receiver operating characteristic curves were used to evaluate the ability of serum FGLP1 levels and urine UACR to predict LVDD. Results The serum FGLP1 concentration and urine UACR were higher in the case group than in the healthy group (P<0.05). There were statistically significant differences in age, disease duration, serum FGLP1 concentration and UACR between the LVDD group and the non-LVDD group (P<0.05). Multivariate logistic regression analysis revealed that age ≥ 75 years, long disease duration, elevated UACR, and elevated serum FGLP1 concentration were independent risk factors for LVDD in patients with T2DM (P<0.05). Spearman correlation analysis indicated a positive association between LVDD and serum FGLP1 levels as well as UACR (r = 0.551, 0.559; both P<0.05). The areas under the curve for predicting LVDD by serum FGLP1 concentration, urine UACR and the prediction model were 0.848, 0.896 and 0.956, respectively. Conclusion Serum FGLP1 levels and urinary UACR in elderly patients with type 2 diabetes mellitus are closely related to LVDD. The combined detection of these two indicators is helpful for the early diagnosis of LVDD.
Copyright (c) 2026 Lianheng Xia, Yingshuo Guo, Jiaxin Wang, Tingxuan Wang, Chunhui Xu, Meiyu Song, Chang Du, Qingjie Wang, Jie Gao
Correlation analysis of serum CCL3, TRACP-5b and Sclerostin with the prognosis of multiple myeloma patients
[Objective] To investigate the clinical use of Sclerostin, tartrate-resistant acid phosphatase 5b (TRACP-5b), and serum C-C motif chemokine ligand 3 (CCL3) levels in assessing the health and prognosis of patients with multiple myeloma. [Methods] 250 patients with multiple myeloma who visited the hospital between January 2023 and December 2024 were selected as the observation group, whereas 150 healthy individuals who were evaluated there during that time made up the control group. The levels of serum CCL3, TRACP-5b and Sclerostin in the observation group before and after treatment were compared, as were the levels of serum CCL3, TRACP-5b and Sclerostin. The levels of serum CCL3, TRACP-5b and Sclerostin in MM patients with different tumor stages and different degrees of bone destruction were compared, and the univariate and multivariate factors of death within one year in MM patients were analyzed. To compare the predictive efficacy of single and combined detection of serum CCL3, TRACP-5b and Sclerostin for death within one year in patients with multiple myeloma. [Results] The levels of serum CCL3, TRACP-5b and Sclerostin in the observation group before and after treatment were significantly greater than those in the control group, and the differences were statistically significant (P<0.05). After treatment, the levels of serum CCL3, TRACP-5b and Sclerostin in the observation group were significantly lower than those before treatment, and the differences were statistically significant (P<0.05). There were statistically significant differences in tumor stage, classification of degree of bone destruction, CCL3 level, TRACP-5b level and Sclerostin level (P<0.05). Multivariate analysis revealed that tumor stage, the degree of bone destruction, the CCL3level, the TRACP-5b level and the Sclerostin level were the factors influencing death within one year in patients with multiple myeloma (P<0.05). The levels of serum CCL3, TRACP-5b and Sclerostin have relatively high predictive efficacy for death within one year in patients with multiple myeloma. The sensitivity of the combined detection of the three indicators was 90.3%, the specificity was 87.4%, and the area under the receiver operating characteristic curve (AUC) was 0.937, which was significantly greater than that of CCL3 (Z=3.061, P=0.002), TRACP-5b (Z=3.625, P<0.001), and Sclerostin (Z=2.579). When tested separately (P =0.010), there was no statistically significant difference in the AUC among the three indicators (P>0.05). [Conclusion] CCL3, TRACP-5b and Sclerostin are involved in the occurrence and development of multiple myeloma and have high value in predicting death within one year.
Copyright (c) 2025 Cuimei Jiang, ManMan Sun, Dashan Gao, Xiaoli Zhang, Jianan Pan
PREDICTION OF CHANGES IN VAGUS NERVE MORPHOLOGY BASED ON BIOCHEMICAL MARKERS OF INFLAMMATION IN COVID 19 INFECTION
Background. Prediction of cross-sectional area n. vagus on the sonogram, based on the values ​​of some inflammation biomarkers in the blood Methods. In 68 patients with a PCR test (+) for SARS-COV 2, the cross-sectional area of the nerve (CSA) was measured by ultrasound, as an average of three measurements. The values of CRP, fibrinogen and ferritin were determined. CSA values from both sides and all biomarkers were classified as (0)- within normal limits and (1)- all other values. Logistic linear regression was performed and a strong linear relationship between predictors was excluded. A neural network and binary logistic regression model was formed for the CSA values on the right side, on the left side the connection between the selected predictors and the CSA of the left vagus was not established. Results. On the right side, CSA is 1.32±0.3; on the left 1.2±0.28. In the study, 11.8%, 22.1% and 8.82% had normal values of CRP, fibrinogen and ferritin respectively. A strong linear association of predictors was ruled out by linear logistic regression. A neural network with two hidden layers and 6 number of units in either hidden layer was formed in 2 seconds. The accuracy percentage of the model in training is 91.5% and in testing it is 90.5%. The AUC of this model is 0.76 (p=0.018, p<0.05). Logistic binary regression model: logitX2D= 18.018+ (20.752x CRP values)+ (-38.77x fibrinogen values)+(2.175x ferritin values), where X2D- is the cross-sectional area of the right n. vagus, given by the model. Exp(B) of the model is 7.5, Psample = 0.88, OR=56.25, accuracy of the model is 91.2%, Omnibus test: χ2=14.193, p=0.003(p<0.05). Model reliability coefficient -2LogLH=35.068 and AUC =0.76, p=0.018. Overall model quality 0.61 (limit is 0.5). On the left side, the value of CSA n.vagus cannot be predicted using selected predictors.
Laboratory diagnostics of chronic kidney disease in Serbia: current practice and priorities for harmonisation
Abstract Background To assess current laboratory practices in chronic kidney disease (CKD) diagnostics in Serbia and identify areas requiring harmonization in line with national and international guidelines. Methods A cross-sectional, questionnaire-based survey was conducted between June and August 2025 with the support of the Serbian Society of Medical Biochemists, which distributed invitations to its members working in medical laboratories across Serbia. Eighty-three laboratories participated (response rate 84.7%), representing primary, secondary, tertiary, and private healthcare sectors. Data were analyzed descriptively. Results All laboratories measured serum creatinine, but other essential components of CKD diagnostics were not consistently implemented. Creatinine-based estimated glomerular filtration rate (eGFR) was calculated in 63.9% of laboratories, and only 34.9% reported eGFR automatically with every creatinine result. Albuminuria testing was available in 55.4% of laboratories; quantitative albumin measurement was performed in 31.3%, and albumin-to-creatinine ratio (ACR) was reported in 7.2%. Serum cystatin C was available in 7.2% of laboratories. Fewer than half (43.4%) implemented both eGFR reporting and albuminuria testing. Practices differed in analytical methods, reference intervals, urine sample types, and reporting models. Integration of eGFR and ACR was most frequent in private laboratories and least frequent at the primary healthcare level. Conclusions CKD laboratory diagnostics in Serbia remain largely creatinine-based, with limited integration of albuminuria assessment and automatic eGFR reporting. Broader implementation of ACR and improved reporting standardization are needed to support earlier detection and risk stratification of CKD.
Copyright (c) 2026 Vera Lukić, Dušica Mrdaković, Neda Milinković