Home Medicine Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
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Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment

  • Qing-Nian Wu ORCID logo , Zhi-Ying Deng ORCID logo , Rui-hang Huang ORCID logo , Wei-Da Liang ORCID logo , Ping Chen ORCID logo , Chun-Lin Liu ORCID logo EMAIL logo and Liu Liu ORCID logo EMAIL logo
Published/Copyright: December 19, 2025

Abstract

Objectives

Rapid pathogen identification in peritoneal dialysis effluent (PDE) is crucial for managing peritoneal dialysis-related peritonitis (PDRP). This study evaluated a modified Sepsityper Kit protocol with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for direct identification from positive PDE cultures.

Methods

A total of 143 positive PDE culture bottles were prospectively analyzed between August 2022 and November 2023. The standard Sepsityper Kit protocol was modified by incorporating additional centrifugation and washing steps. Following processing with the modified kit, the samples were directly identified by MALDI-TOF MS. The performance of this method was then compared with the reference identification method.

Results

Among the samples, 139 (97.2 %) were monomicrobial and 4 (2.8 %) polymicrobial. Compared to the reference method, the modified Sepsityper Kit achieved an overall agreement of 89.9 % (score≥1.60) and 77.7 % (score≥1.80). At the ≥1.60 cutoff, agreement rates were 95.2 % for Gram-negative bacteria, 87.8 % for Gram-positive bacteria, and 85.7 % for fungi.

Conclusions

MALDI-TOF MS is a reliable and rapid tool for the identification of pathogens in positive PDE blood culture bottles.

Introduction

Peritoneal dialysis serves as a vital renal replacement therapy for end-stage renal disease [1]. However, the efficacy and longevity of this treatment are frequently compromised by the occurrence of peritoneal dialysis-related peritonitis (PDRP), a prevalent and serious complication that remains a major cause of technique failure and patient morbidity [2]. The rapid and accurate identification of causative pathogens in peritoneal dialysis effluent (PDE) is therefore critical for guiding targeted antimicrobial therapy and improving clinical outcomes [3].

The diagnosis of PDRP currently relies on clinical features and laboratory tests [4]. Conventional PDE culture can identify the organisms causing peritonitis, but this process takes at least 48 h [5]. Although, polymerase chain reaction-based assays can require less time, these assays are often labor-intensive and expensive [6]. Previous studies have demonstrated that matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a reliable and accurate tool for identifying bacteria [7]. It has been widely used for the direct identification of colonies on solid plates and clinical specimens, such as blood, urine, and cerebrospinal fluid [8], [9], [10]. However, direct identification employing MALDI-TOF MS from positive PDE blood culture bottles is scarce.

In the literature, several MALDI-TOF MS-based preprocessing methods, such as differential centrifugation and washings, selective lysis of blood cells, the use of serum separator tubes, transient incubation, and commercial processing with the Sepsityper Kit, have been employed to accelerate pathogen identification [11]. Among these, the Sepsityper Kit has shown particular promise [12]. Therefore, the aim of this study was to compare the performance of the Sepsityper Kit-assisted MALDI-TOF MS with the reference identification method for identifying pathogens in PDE.

Materials and methods

Sample collection

A total of 143 positive PDE vials were prospectively collected between August 2022 and November 2023. All PDE samples were inoculated at the bedside into aerobic (BacT/Alert FA Plus) and anaerobic (BacT/Alert FN Plus) culture vials (bioMérieux, France) and promptly transported to the laboratory. The vials were incubated using the BacT/ALERT 3D automated system (bioMérieux, France). All bottles were cultured for up to five days or until flagged as positive by the system. Positive samples underwent Gram staining and were subcultured onto blood agar, chocolate agar, and MacConkey agar plates (Jiangmen Kailin, China). Simultaneously, each positive sample was processed in parallel using the Sepsityper Kit (Bruker Daltonik, Germany) for rapid microbial identification. This research protocol was approved by our hospital’s Ethics Committee in compliance with the Declaration of Helsinki principles.

Reference identification method

All solid media were incubated at 35 °C under 5 % CO2 for 18–24 h in a Thermo Fisher Scientific incubator. Following incubation, bacterial colonies were harvested and subjected to identification through either (1) MALDI-TOF MS (Bruker Daltonics, Germany) or (2) biochemical profiling using the VITEK 2 system (bioMérieux, France). Discordant results between these two methods were resolved by molecular sequence-based identification targeting the partial 16S rRNA gene, gyrBgene, and the ITS region [13].

Sepsityper Kit protocol

The Sepsityper Kit was used following the manufacturer’s instructions with some modifications. Prior to the Sepsityper protocol, 2 mL of broth was transferred into a 3 mL sterile tube and centrifuged at 8,000 rpm for 2 min. The supernatant was discarded, and 1 mL of deionized water was added. The mixture was vortexed thoroughly, centrifuged at 13,000 rpm for 2 min, and the supernatant was discarded again. Another 1 mL of deionized water was added, followed by 200 μL of the Sepsityper lysis reagent. The mixture was vortexed for 10 s and incubated at room temperature for 5 min before centrifugation at 13,000 rpm for 1 min. After discarding the supernatant, the pellet was resuspended in 1 mL of Sepsityper Washing Buffer and centrifuged again at 13,000 rpm for 1 min. The supernatant was discarded, and the pellet was resuspended in 1 mL of deionized water, followed by centrifugation at 13,000 rpm for 2 min. The pellet was then resuspended in 30 µL of 70 % formic acid (Sigma-Aldrich), vortexed for 5 s to ensure complete dispersion, and incubated at room temperature for 2 min. Next, 30 µL of acetonitrile (Sigma-Aldrich) was added, and the sample was centrifuged at 13,000 rpm for 2 min. Finally, 1 µL of the supernatant was spotted in duplicate onto a 96-spot polished steel target plate (Bruker Daltonics, Germany). Each spot was overlaid with 1 µL of α-cyano-4-hydroxycinnamic acid (HCCA) matrix solution and air-dried prior to MALDI-TOF analysis. Figure 1 summarized the modified Sepsityper Kit protocol employed in this study.

Figure 1: 
Overview of the modified Sepsityper Kit protocol for rapid identification from positive blood cultures.
Figure 1:

Overview of the modified Sepsityper Kit protocol for rapid identification from positive blood cultures.

Analysis with MALDI-TOF MS

Mass spectra were automatically acquired and analyzed using the Bruker MALDI Biotyper Microflex LT/SH system (Bruker Daltonics, Bremen, Germany) equipped with the MBT-Sepsityper-RUO module. In accordance with the manufacturer’s recommendations, identification thresholds were set at scores of ≥1.60 for reliable genus-level identification and ≥1.80 for species-level identification.

Results

Comparison of the identification results between the reference identification method and the Sepsityper Kit method

Among 143 positive PDE culture bottles analyzed, 139 (97.2 %) were monomicrobial and 4 (2.8 %) were polymicrobial, as determined by the reference identification method. The monomicrobial isolates comprised 90 (64.7 %) Gram-positive bacteria, 42 (30.2 %) Gram-negative bacteria, and 7 (5.0 %) fungi. The distribution of these 139 microbial species and their corresponding identification scores were summarized in Table 1. Compared to the reference method, the Sepsityper Kit method demonstrated an overall agreement rate of 89.9 % for isolates with a score≥1.60 and 77.7 % for those with a score≥1.80. When stratified by microbial group (Table 2), the agreement rates for Gram-negative bacteria were 95.2 % (score ≥1.60) and 88.1 % (score ≥1.80). The corresponding rates for Gram-positive bacteria were 87.8 and 73.3 %, while those for fungi were 85.7 and 71.4 %.

Table 1:

MALDI Biotyper bacterial identification scores obtained from monomicrobial dialysis effluent blood cultures with the Sepsityper Kit.

Reference method (no. of isolates) Sepsityper Kit method (score)
<1.60 ≥1.60 ≥1.80
Gram-positive bacteria (90) 11 79 66
Staphylococcus aureus (10) 0 10 10
Staphylococcus epidermidis (16) 4 12 8
Staphylococcus haemolyticus (11) 2 9 7
Staphylococcus warneri (6) 0 6 5
Staphylococcus caprae (3) 0 3 3
Staphylococcus capitis (3) 0 3 3
Staphylococcus hominis (2) 0 2 2
Staphylococcus cohnii (2) 0 2 2
Enterococcus faecalis (6) 0 6 5
Enterococcus faecium (4) 0 4 3
Streptococcus oralis (4) 2 2 1
Streptococcus gordonii (8) 0 8 7
Streptococcus anginosus (2) 1 1 1
Streptococcus salivarius (6) 1 5 4
Streptococcus vestibularis (1) 0 1 1
Streptococcus mitis (3) 1 2 1
Corynebacterium striatum (2) 0 2 2
Corynebacterium jeikeium (1) 0 1 1
Gram-negative bacteria (42) 2 40 37
Escherichia coli (14) 0 14 14
Klebsiella pneumoniae (12) 2 10 8
Klebsiella oxytoca (2) 0 2 2
Pseudomonas aeruginosa (4) 0 4 4
Acinetobacter baumannii (4) 0 4 3
Enterobacter cloacae (1) 0 1 1
Alcaligenes faecalis (1) 0 1 1
Morganella morganii (1) 0 1 1
Proteus mirabilis (2) 0 2 2
Citrobacter freundii (1) 0 1 1
Fungi (7) 1 6 5
Candida parapsilosis (3) 1 2 1
Candida albicans (2) 0 2 2
Candida glabrata (1) 0 1 1
Candida tropicalis (1) 0 1 1
Total (139) 14 125 108
Table 2:

Numbers and percentages of concordant results by two methods.

Group of microorganism Reference method(no. of isolates) Sepsityper Kit method (score)
≥1.60 ≥1.80
Gram-positive bacteria 90 79(87.8) 66(73.3)
Gram-negative bacteria 42 40(95.2) 37(88.1)
Fungi 7 6(85.7) 5(71.4)
Total 139 125(89.9) 108(77.7)

Discordant microorganism identification by the reference method and the Sepsityper Kit method

As summarized in Table 3, five discordant identification results were observed between the two methods. These discrepancies primarily involved species discrimination within the genera of Staphylococcus, Streptococcus, and Acinetobacter.

Table 3:

Discordant microorganism between two methods in identification results.

Sepsityper Kit method (score) Reference method
S. aureus 1.82 S. epidermidis
S. haemolyticus 1.65 S. epidermidis
A. baumannii/Acinetobacter calcoaceticus 1.67 A. baumannii
S. mitis/S. oralis 1.62 S. oralis
Streptococcus pneumoniae 1.75 S. mitis

Identification scores of four mixed microorganisms by the Sepsityper Kit method

In this study, only four polymicrobial samples were identified. Among them, three samples were correctly identified for only one microbial species, while the remaining sample was accurately identified for both bacterial species, as detailed in Table 4.

Table 4:

MALDI Biotyper scores for identifying mixed infections in four positive dialysis effluent blood culture bottles.

Reference method Sepsityper Kit method (score)
E. coli + S. aureus E. coli (2.32)

S. aureus (1.96)
E. coli + E. faecalis E. coli (2.08)
E. coli + E. faecalis E. coli (1.92)
E. faecalis + S. haemolyticus S. haemolyticus (2.12)

Discussion

Early identification of pathogens in PDRP is crucial for clinicians to initiate targeted antibiotic therapy. In this study, after enrichment with a blood culture system, the PDE samples were centrifuged and washed to reduce host protein interference before being processed with the Sepsityper Kit for direct identification by MALDI-TOF MS. Compared to the reference method, the Sepsityper Kit demonstrated high concordance, with an overall agreement rate of 89.9 % for isolates with a score ≥1.60 and 77.7 % for those with a score≥1.80.

Current sample preparation methods for direct microbial identification from body fluids via MALDI-TOF MS include various in-house protocols and commercial systems, such as the Sepsityper® Kit (Bruker Daltonics, Bremen, Germany), VITEK® MS blood culture kit (bioMérieux), and the rapid BACpro® II kit (Nittobo Medical Co., Tokyo, Japan) [14]. Among these, the Sepsityper Kit has emerged as the predominant commercial solution for processing positive blood culture samples [12]. A meta-analysis indicated that the Sepsityper Kit enabled reliable species-level identification in 80 % of 3,320 positive blood culture bottles, with Gram-negative bacteria consistently showing higher identification rates (90 %) compared to Gram-positive bacteria (76 %) or yeast (66 %) [15]. In this study, we modified the standard Sepsityper protocol by incorporating additional centrifugation and washing steps to address challenges specific to PDE, including high protein concentration, elevated salt and glucose levels, and interference from high-abundance host proteins (e.g., albumin and IgG) that can obscure microbial protein signatures in mass spectrometry [16], 17]. Compared to the reference identification method, our modified Sepsityper Kit protocol demonstrated significantly improved performance. The overall agreement rates for Gram-negative bacteria were 95.2 % (score ≥1.60) and 88.1 % (score ≥1.80). The corresponding rates for Gram-positive bacteria were 87.8 and 73.3 %, and those for fungi were 85.7 and 71.4 %. These metrics are notably superior to those reported in prior studies. For instance, identification rates for Gram-negative bacilli and Gram-positive cocci in CSF samples were documented at 81.0 and 9.1 %, respectively, using a washing/centrifugation protocol [18]. Another study utilizing an in-house extraction method for ascitic fluid cultures reported rates of 86.0 % for Gram-negative and 73.0 % for Gram-positive organisms [19]. Furthermore, Noll et al. reported 81 % species-level identification concordance with conventional culture when applying the Sepsityper Kit to 37 synovial fluid samples enriched in the BacT/Alert system [20]. Although factors such as geographical origin, pathogen distribution, and sample size can influence the efficacy of the Sepsityper Kit protocol [21], the enhanced performance of our method can be attributed to three key modifications: (1) broth subculture to increase bacterial load, (2) the incorporation of additional centrifugation and washing steps, and (3) optimization of spectral cutoff thresholds.

This study identified five discordant identification results between the reference method and the Sepsityper Kit method. Specifically, two isolates confirmed as Staphylococcus epidermidis by the reference method were misidentified by the Sepsityper Kit as Staphylococcus aureus and Staphylococcus haemolyticus, respectively. Although our laboratory strictly adhered to the manufacturer’s protocol, including the use of trifluoroacetic acid (TFA) protocol and maintained rigorous microplate cleanliness, these misidentifications may be attributed to multiple factors. Potential reasons include target plates contamination, insufficient bacterial load, background spectral interference, high similarity of ribosomal proteins among closely related species, and limitations inherent in the current reference database, which is consistent with reports from previous studies [6], 22]. It is crucial to note that such misidentification in clinical practice may lead to erroneous pathogen reporting and subsequent inappropriate antimicrobial therapy, posing potential risks for treatment failure and the amplification of antimicrobial resistance. However, the direct MALDI-TOF MS identification from positive PDE samples employed in this study has not been clinically validated and should be considered for research purposes only. In this context, Gram staining morphology provides essential preliminary guidance, as the microscopic morphology of S. aureus differs noticeably from that of coagulase-negative staphylococci [23]. Furthermore, our findings align with known challenges in MALDI-TOF MS identification, particularly for closely related species/groups such as the Acinetobacter baumannii/Acinetobacter calcoaceticus complex, the Streptococcus mitis/Streptococcus oralis group, and Streptococcus pneumoniae. These difficulties primarily stem from high 16S rRNA gene sequence homology among these organisms [24]. Recent investigations into the low identification rates and suboptimal spectral quality for S. pneumoniae using the Sepsityper Kit suggest that the efficacy of the lysis buffer may be a critical factor, potentially compounded by intrinsic characteristics of different serotypes [25]; however, this conclusion warrants further validation with larger datasets.

Consistent with previous reports highlighting the challenge of polymicrobial infection identification for MALDI-TOF MS systems [26], 27], our study observed that among four polymicrobial samples, only one was accurately identified for both bacterial species, while the other three were correctly identified for a single species. This limited identification efficiency may be attributed to several factors, including unequal bacterial loads, background protein interference, and inherent limitations in the algorithmic discrimination of overlapping spectral profiles [14]. Although recent methodological advancements, such as the MALDI Biotyper MSP identification MIXED method, have shown promise in improving the identification of polymicrobial samples by enhancing the deconvolution of complex spectral data [28], its application in this study under specific experimental conditions did not yield satisfactory results, thereby suggesting that its efficacy may be influenced by sample-specific factors or require further protocol optimization.

This study has several limitations. First, the relatively small sample size, particularly the limited number of polymicrobial infections (only 4 cases) and fungal isolates (n=7), may affect the generalizability of the findings to broader clinical settings [29]. Second, the single-center design could limit the applicability of our results across regions with differing microbial epidemiology. Therefore, validation through future multicenter studies is necessary. Third, although the method demonstrates a significant advantage in rapid pathogen identification, our study lacks direct evidence linking the reduced time-to-identification to tangible improvements in clinical outcomes, such as optimized antibiotic stewardship or reduced hospitalization duration. Consequently, the practical clinical utility of this approach warrants further investigation in studies that incorporate analyses of clinical endpoints. Finally, the absence of standardized protocols for sample processing in direct bacterial identification complicates cross-study comparisons of method performance, as the efficacy of such in-house methods is often highly operator-dependent [30].

In summary, our study demonstrated that MALDI-TOF MS provides a convenient, rapid, and accurate approach for the direct identification of positive PDE samples.


Corresponding authors: Chun-Lin Liu, Department of Clinical Microbiology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, No. 120 Guidan Road, Foshan, 528222, China, E-mail: ; and Liu Liu, Department of Gastroenterology, The Six Affiliated Hospital of South China University of Technology, No. 120 Guidan Road, Foshan, 528222, Foshan, China, E-mail:

  1. Funding information: The authors declared that this study has received no financial support.

  2. Author contributions: Qing-Nian Wu: obtained ethics approval, collected the data, and wrote the original draft of the manuscript. Zhi-Ying Deng, Rui-hang Huang, Wei-Da Liang, and Ping Chen: developed the original study protocol and supervised the investigation and data collection. Chun-Lin Liu and Liu Liu: reviewed and edited the manuscript. All authors have read and approved the final 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 available upon request.

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Received: 2025-04-27
Accepted: 2025-11-27
Published Online: 2025-12-19

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

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

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  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
  21. Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
  22. The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
  23. Health literacy and health-related quality of life: The mediating role of irrational happiness
  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
  28. Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
  29. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
  30. Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
  31. Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
  32. Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
  33. The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
  34. The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
  35. Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
  36. Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
  40. A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
  42. Identifying early screening factors for depression in middle-aged and older adults: A cohort study
  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
  47. Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
  48. Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
  49. The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
  50. Expression and clinical significance of ITGA3 in breast cancer
  51. Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
  52. rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
  53. Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
  54. Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
  55. Gender beliefs and legitimization of dating violence in adolescents
  56. Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
  57. Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
  58. Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
  59. Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
  60. Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
  61. Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
  62. GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
  63. Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
  64. MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
  65. Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
  66. Trends in research on preterm birth in twin pregnancy based on bibliometrics
  67. Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
  68. Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
  69. Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
  70. Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
  71. Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
  72. CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
  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. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
  158. 10.1515/med-2025-1313
  159. 10.1515/med-2025-1316
  160. Health education pathway for individuals with temporary enterostomies using patient journey mapping
  161. 10.1515/med-2025-1321
  162. 10.1515/med-2025-1324
  163. 10.1515/med-2025-1325
  164. 10.1515/med-2025-1327
  165. 10.1515/med-2025-1331
  166. Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
  167. 10.1515/med-2025-1337
  168. 10.1515/med-2025-1347
  169. 10.1515/med-2025-1360
  170. Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
  171. Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
  172. Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
  173. Review Articles
  174. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  175. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  176. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  177. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  178. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  179. 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
  180. The application of augmented reality in robotic general surgery: A mini-review
  181. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  182. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  183. Plant polyphenols, terpenes, and terpenoids in oral health
  184. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  185. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  186. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  187. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  188. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  189. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  190. Giant borderline ovarian tumours – review of the literature
  191. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  192. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  193. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  194. Supplement strategies for infertility in overweight women: Evidence and legal insights
  195. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  196. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  197. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  198. Strategies for hyperkalemia management in dialysis patients: A systematic review
  199. C-reactive protein-to-albumin ratio in peripheral artery disease
  200. 10.1515/med-2025-1251
  201. 10.1515/med-2025-1330
  202. 10.1515/med-2025-1332
  203. Antibiotic prescribing patterns in general dental practice- a scoping review
  204. Clinical and medico-legal reflections on non-invasive prenatal testing
  205. Case Reports
  206. Delayed graft function after renal transplantation
  207. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  208. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  209. Giant right atrial hemangioma presenting with ascites: A case report
  210. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  211. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  212. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  213. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  214. Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
  215. 10.1515/med-2025-1362
  216. Rapid Communication
  217. Biological properties of valve materials using RGD and EC
  218. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  219. Letter to the Editor
  220. Role of enhanced external counterpulsation in long COVID
  221. Expression of Concern
  222. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  223. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  224. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  225. Corrigendum
  226. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  227. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  228. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  229. Retraction
  230. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  231. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  232. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  233. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  234. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  235. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  236. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  237. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  238. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  239. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  240. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  241. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  242. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  243. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  244. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  245. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  246. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  247. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  248. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  249. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  250. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  251. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  252. A review of brain research on T2DM-related cognitive dysfunction
  253. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  254. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  255. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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