Home Medicine Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
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Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system

  • Małgorzata Szostakowska-Rodzoś EMAIL logo , Anna Fabisiewicz , Izabella Myśliwy , Agnieszka Jagiełło-Gruszfeld , Aleksandra Konieczna and Ewa A. Grzybowska
Published/Copyright: August 22, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Background

Recent studies have highlighted that one of the main drivers for metastatic formation and resistance to the therapy are circulating tumor cells (CTCs) and cancer stem-like cells (CSCs). Measuring the CTCs has emerged as a non-invasive procedure for selecting the patients with higher risk of progression/relapse. However, still there are no methods enabling the identification of stem-like phenotype of the CTCs.

Methods

The image-based method was used for the identification of the circulating cancer stem-like cells (CCSCs) in metastatic breast cancer patients. The method was optimized using the CSCs established in the mammosphere culture of MCF-7 cells. Next the protocol was implemented to identify the CCSCs in samples collected from 60 patients.

Results

The recovery ratio for CCSCs identification using the established method was ∼60%. The CCSCs were identified as rare events accruing only in 2 patients out of 60, who participated in the study. Interestingly, the CCSCs were found only in CTC clusters. The analysis of SOX2 expression in formalin-fixed, paraffin-embedded material, revealed that the SOX2 expression was present in primary tumor samples.

Conclusion

The CCSCs presence was found to be a very rare event. The obtained results suggest that the CCSCs are mainly present in CTC clusters and stem-like reprograming of the cancer cells might occur early, in the primary tumor.

Keywords: circulating tumor cells; SOX2; cancer stem cells; breast cancer; CytoTrack; liquid biopsy

1 Introduction

Breast cancer (BC) is one of the most common female tumors diagnosed worldwide. In the US, BC represents 29% of all new cancer cases in women [1]. Biological subtypes of BC are classified according to the expression of steroid receptors (estrogen [ER) and progesterone [PR]) and human epidermal growth factor receptor 2 (HER2). Cancers that are positive for ER receptor (ER+) and/or PR receptor (PR+) are classified as luminal [2]. Luminal BC (ERα+) is known to have a more favorable prognosis in terms of 10-year survival than other subtypes. However, 10-year survival does not fully reflect the long-term survival and mortality of these cancers. Therefore, identifying the most effective diagnostic markers for the long-term prognosis is crucial in these malignancies.

Current predictive oncology research works are focused on non-invasive biomarkers for cancer recurrence and survival perdition. Most studies concentrate on analyzing blood markers like inflammation-based markers, albumin-to-globulin ratio or carbohydrate antigens [3,4] that had shown independent prediction value for various cancers, like colorectal cancer. However, as BCs, especially luminal BCs are considered “cold” inflammation malignancies, the utility of inflammation based-markers remains limited for specific subtypes of BC [5]. Other classical markers like cancer carcinoembryonic antigen and CA15-3, shown to be often associated with disease recurrence and metastasis [6] in BC, they have their limitations [7]. Another approach, represented by modified Glasgow prognostic score designed to assess the systemic inflammatory response, may further improve prognostic efficiency and has been shown to have an independent prognostic value in BC patients [8]. Comparing such classic serum-based indices with novel biomarkers like circulating tumor cells (CTCs)/circulating cancer stem-like cells (CCSCs) may further refine risk stratification strategies and guide personalized treatment approaches.

Precise prognosis for the patients with luminal BCs is difficult, because late relapses are common. Late relapse in a woman with ERα+ BCs is associated with the activation of dormant tumor cells at metastatic sites [9]. Dormant tumor cells display growth arrest that precludes proliferation, which lowers their sensitivity to the cytotoxic treatment. The presence of dormant, disseminated tumor cells (DTCs) has been shown to be associated with poorer prognosis, with 40–60% of patients with DTCs detected in bone marrow suffering from metastatic disease [10,11]. Thus, the detection of DTCs may be important for prognosis. However, the main challenge is the ability to correctly assess probability of DTCs reactivation, leading to metastatic progression.

One of the potential triggers of this process might be the cells’ reprogramming associated with the generation of cancer stem-like cells (CSCs). CSCs are a small population of tumor cells that are capable of self-renewal, producing heterogeneous lineages of cancer cells that comprise the tumor. CSCs are a unique biological subpopulation of cancer cells that could survive indefinitely [12]. One of the hallmarks of CSCs is the expression of stemness markers: SOX2, OCT4, and NANOG. From these markers, SOX2 is one of the most well-known for its association with the progression of cancers. It is known that SOX2 is a regulator of the pathways that regulate epithelial to mesenchymal transition, such as NF-κB, WNT, NOTCH, HEDGEHOG [13,14,15]. Despite growing knowledge about CSCs’ importance in cancer, it is still unclear at what stage of cancer progression these cells arise. However, it is suspected that because of the ability for self-renewal and high epithelial-mesenchymal plasticity, the stem-like phenotype might be present more in CTCs. Most of CTCs occur as circulating single cells; however, they might also appear as multicellular (>3 cells) groups, called clusters. CTC clusters have been shown to be even ten times rarer events than single CTCs, but most probably they have higher metastatic potential [16]. The detailed mechanism of CTC clusters origin and their cellular component is still unknown. Some studies have shown that CTC clusters might be somewhat a reservoir for CSCs as CD44 expression [17] and hypomethylation of stemness markers [18] have been observed in CTC clusters.

As the cancer-stem like cells are also known from their properties to form new metastases and drug resistance, it is believed that some fraction of CTCs might harbor the stemness properties and be classified as the CCSCs. However, the details of CCSCs’ metastasis potential and clinical value are still unknown. One of the most challenging issues in CCSCs characterization and studies is lack of validated methods for CCSCs identification. Despite the growing knowledge and the advancement in CTCs research, the methods for CSCs identification are still missing. Currently only few methods describing CCSCs were described: nanoparticle-mediated Raman imaging method for CCSC characterization [19], separation enrichment [20], and flow cytometry [21].

Here we report the new results on CCSCs identification in advanced BC patients, based on the SOX2 expression. We modified previously described protocol for CTCs detection [22] for identification of the SOX2-positive CTCs, as representatives of CCSCs. In this work, we present optimization of this method with the use of MCF-7-derived CSCs using CytoTrack system, as well as the pilot studies on patients’ samples.

2 Materials and methods

2.1 Cell culture

The MCF-7 cell line was chosen for this model as it is well-established luminal BC model with known tendency to from mammospheres with SOX2+ cells. MCF-7 cells (ATCC, passage 20–30) were cultured in DMEM Complete medium (Merck) with 10% heat-inactivated FBS, 100 µg/mL penicillin, and 100 µg/mL streptomycin. For spheroid culture of MCF-7 cell line, the single cell suspensions were seeded in density 4 × 104 cells/well into 6-well Corning Costar Ultra-Low attachment plates in 3dGRO Spheroid Medium (Merck) with 100 µg/mL penicillin and 100 µg/mL streptomycin. The single cell suspensions were made by filtering the cell culture with cell strainer of 40 µm. Spheroid culture was set in a starting volume of 2 mL of the medium. The half culture volume of fresh medium was added every 3 days. Sphere formation and stemness markers were evaluated after 7 days of sphere culture.

2.2 Reverse transcription qPCR (RT-qPCR)

The expression of the stemness marker SOX2 in mammosphere culture was confirmed by the RT-qPCR. After 7 days of sphere culture cells from mammosphere, 2D cell culture was harvested in the same time-points at the confluency of ∼70%. The RNA was isolated with the use of Universal RNA Purification Kit (EURx) according to the manufacturer’s protocol. 1 µg RNA was reverse transcribed with the use of NG dART RT kit (EURx) according to the manufacturer’s protocol. The success of the RT-PCR reaction was confirmed with the PCR reaction for GAPDH with the use of starters: forward 5′-GAAGGTGAAGGTCGGAGTC-3′; reverse 5′-GAAGATGGTGATGGGATTTC-3′. The reaction conditions were set as: 95oC for 5 min, followed by 25× cycles: 95°C for 30 s, 60°C for 30 s, 72°C for 30 s, ending with 72°C for 5 min and 4°C incubation. The qPCR reaction was performed in Applied Biosystems™ 7500 Fast (Applied Biosystems) thermocycler. The PCR reaction was set in 20 µL containing 100 ng cDNA, 2× TaqMan™ Gene Expression Master Mix (Applied Biosystems), ddH2O, 20× TaqMan Gene Expression assays: SOX2 (ThermoFisher, Hs04234836_s1) and GAPDH (ThermoFisher, Hs02786624_g1). The reaction conditions were: 95oC for 10 min followed by 45× cycles of 95°C for 30 s, 60°C for 60 s. All data with Ct value lower than 25 for GAPDH reference gene were excluded from the analysis. All samples were run in triplicates. Wells with high SD (>0.3) were excluded from the analysis. The change in SOX2 expression was calculated using ΔΔCt.

2.3 Biological sample collection

Sixty patients diagnosed with luminal metastatic BC (MBC) were selected for the study. The inclusion criteria for patients were: age >18, ongoing hormonal treatment, and identification of distant metastases. All participants signed the informed consent.

For spike-in experiments blood was collected from healthy volunteers. Formalin-fixed, paraffin-embedded (FFPE) primary cancer samples were collected from the archive of the Pathology Department in National Research Institute of Oncology. The study protocol was approved by the National Research Institute of Oncology Ethics Committee (84/2020).

2.4 Spike-in experiments

For optimization of the detection of the SOX2 positive cells, we calibrated the sample processing protocol using MCF-7 cells from 2D and mammosphere culture. The cells were counted and 100 cells were suspended in blood sample from healthy donor. The recovery ratio for identification of spiked cells was calculated as: identified cells spiked − in cells × 100 % . The spike-in experiments were done in duplicates. The previously optimized protocol for CTCs identification [22] was used as the basis for the further modification and optimization of the final conditions. The conditions pre- and post- optimization are listed in Table S2.

2.5 Sample processing

Blood samples were collected in the 9 mL EDTA tubes and processed within 2 h after collection. Samples were centrifuged at 2,500 × g for 10 min. The buffy coat containing nuclear cells, including tumor cells, were transferred to a new 15 mL tube. The residual erythrocytes were lysed with the use of FACS Lysing solution (BD Biosciences) and with incubation time 15 min in the room temperature. Then, the samples were centrifuged at 3,000 × g for 5 min. The lysis step was repeated, with the incubation time 10 min in room temperature and centrifugation at 3,000 × g for 5 min. Thereafter, cells were permeabilized with the saponin-based permeabilization buffer (0.5% saponin + 0.5% BSA + 0.01% sodium azide in 1× PBS), with incubation time 15 min in the room temperature followed by centrifugation at 3,000 × g for 5 min. Permeabilized cells were stained with the use of Alexa Fluor 488-conjugated pancytokeratin (pan-CK) antibody (final dilution 1:25), AlexFluor700 conjugated CD45 antibody (final dilution 1:50), PE conjugated E-Cadherin antibody (final dilution 1:50), eFluor660-conjugated SOX2 (final dilution 1:12), and 4,6-diamidino-2-phenylindole (DAPI) (final dilution 1:1,000). The antibodies stain was diluted using the perm/wash buffer (0.25% saponin + 1% BSA in 1× PBS). Samples were left in the antibodies over-night in the dark, at 4°C. Next stained cells were washed two times with perm/wash buffer, containing 1% BSA and centrifugated at 3,000 × g for 5 min. Washed and stained cells were resuspended in 1 mL of ultra-pure H2O and smeared on the glass disc in sterile conditions. The discs were left to dry overnight. Dried samples were mounted with glycerol-based mount medium (80% glycerol in Tris-HCl, pH = 8.5 with 0.5% N-propyl gallate) and fixed with the use of fixogum. Prepared samples were stored in −80°C until CytoTrack analysis. Detailed materials, including buffer solutions and antibodies source are listed in Table S1.

2.6 CTCs identification

All samples were processed as described above and analyzed on CytoTrack system. For analysis the glass disc containing stained cells was mounted in the mounting arm with a spring-lock mechanism. Focus plan was obtained based on the DAPI channel, at eight places on the disc. Scanning was performed with 488 nm Argon-Neon laser, in a spiral pattern with a bandwidth of 10μm, a process taking ∼5 min. All signals from the Alexa Fluor 488 emission channel were recorded and listed in the hotspot table. Recorded events were visually inspected by the operator. The criteria for CTC identification were set as: nearly round size with ≥6 µm diameter, visible nucleus, pan-CK signal, and negative surface stain for CD45. Detected cells with the above criteria were identified as CTCs. Clusters were defined as group of ≥3 cells, with at least three visible nuclei in DAPI channel, with at least three cells identified as CTCs. For SOX2+ CTCs identification, we established the following criteria: nearly round size with ≥6 µm diameter, visible nucleus, pan-CK signal, positive surface stain for E-cadherin, and positive nuclei for SOX2. Cells matching these criteria were defined as SOX2+ CTCs.

2.7 Immunohistochemistry (IHC)

IHC staining was performed on 3-μm FFPE tissue sections using Envision Detection System (DAKO, Glostrup, Denmark). Tissue sections were deparaffinized with xylene and rehydrated in a series of ethanol solutions of decreasing concentration. Heat-induced epitope retrieval was applied by incubating the samples in Target Retrieval Solution pH 6 (DAKO) in a 96°C water bath, for 30 min. Cooled slides were treated with a Blocker of Endogenous Peroxidase (DAKO) for 5 min and then incubated with the primary rabbit monoclonal antibody SOX2 (C70B1, Cell Signaling Technology) in dilution 1:100 for 1 h in room temperature. The color reaction was developed with 3,3′-diaminobenzidine tetrahydrochloride (Dako) as a substrate. Nuclear contrast was achieved by using hematoxylin counterstaining.

2.8 Statistical analysis

The categorical data generated in the study were analyzed via U-Mann Whitney or Kruskal–Wallis non-parametric tests. The primary end point was overall survival (OS) in relation to CTCs presence. The OS was defined as the time from the date of blood collection to death from any cause. If an outcome was not reached during the observation time, the variables were censored. Kaplan–Meier plots and the log-rank tests were used to illustrate and compare survival between subgroups.

  1. Ethics statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Maria Sklodowska-Curie National Research Institute of Oncology (84/2020). All participants read and signed the informed consent.

3 Results

3.1 Identification of the SOX2+ tumor cells

The spheres were evaluated every 2 days to check for the overgrowth of the sphere (>200 µm diameter). The spheroids were passaged every 14 days. The mean sphere diameter on the 7th day of culture was ∼173 µm (Figure 1a). The SOX2 expression was measured on the 7th day of the spheroid culture, as previously we identified this time-point as the most optimal for SOX2 evaluation [23]. The elevated SOX2 expression in cells was confirmed via qPCR (Figure 1b). Next, the cells with confirmed SOX2 expression were used for the CCSCs identification optimization.

Figure 1 The results from sphere formation assay and recovery ratio for identification of SOX2+ cells in blood sample. (a) The microscopic images of MCF-7-derived spheres in different time-points of the mammosphere formation assay. (b) The expression of SOX2 measured via qPCR on 7th day of sphere formation; **p-value <0.01. (c) The recovery ratio of panCK + cells (tumor cells) and SOX2+ tumor cells determined during the spike-in experiments. (d) The images from CytoTrack system with identified SOX2+ cells in spike-in experiments.
Figure 1

The results from sphere formation assay and recovery ratio for identification of SOX2+ cells in blood sample. (a) The microscopic images of MCF-7-derived spheres in different time-points of the mammosphere formation assay. (b) The expression of SOX2 measured via qPCR on 7th day of sphere formation; **p-value <0.01. (c) The recovery ratio of panCK + cells (tumor cells) and SOX2+ tumor cells determined during the spike-in experiments. (d) The images from CytoTrack system with identified SOX2+ cells in spike-in experiments.

The cells from cell cultures: SOX2-culture (2D) and SOX2 + culture (mammosphere) were used in the spike-in experiments and optimization of the protocol. During the optimization process the most challenging was identification of the SOX2 staining as antibodies tend to not penetrate the nucleus. Therefore, the proper parameters of the permeabilization buffer and permeabilization time were optimized. Further optimizations included antibodies dilution, incubation time, and conditions. The final protocol described in the methods section was chosen as the one with the best performance. Using this protocol the recovery ratio for spike in experiments was as follows:

81% for MCF-7 2D cells and 84% for MCF-7 mammosphere cells. The mean recovery ratio for SOX2+ cells identification was: 4% for MCF-7 2D cells and 60% for MCF-7 mammosphere cells (Figure 1c and d). The low recovery ratio of the SOX2+ cells might be associated with the necessity of determining the stain location (nuclear).

3.2 Patients characteristics

Overall, 60 patients were enrolled in the study; however, samples from 5 patients were discarded due to the technical issues. Therefore, in the final analysis, data from 55 patients were used. The median age of patients was 66 (range 35–84), all patients were previously treated with antiestrogen therapy, 69% of patients received radiotherapy and >80% of patients were treated with the CDK4/6 inhibitors and chemotherapy as adjuvant therapy. The detailed patients group characterization is presented in Table 1.

Table 1

Clinical characteristics of the patients group

Age
<66 27
≥66 28
HER2 status
HER2+ 4
HER− 49
N/D 2
No. of meta sites
1 30
2 16
≥3 9
Meta sites
Bones 37
Liver 15
Lung 14
Other 17
Histological subtype
NST 41
Lobular 5
Other 9
Treatment
HTH 4
HTH + CHTH 7
HTH + CDK4/6 7
HTH + CHTH + CDK4/6 37
Radiotherapy
RTH+ 38
RTH− 17

3.3 CTC identification and SOX2 detection in patient samples

The CTCs were detected in ∼33% of advanced BC patients. The CCSCs, defined as CTCs with detectable SOX2 expression, were detected in samples from two patients (Figure 2b). These CCSCs were only detected in CTC clusters, suggesting the importance of CTC clusters in CSCs generation. The CTC clusters were detected in four patients.

Figure 2 The consolidated data from CTCs detection, where (a) The frequency of CTCs+ patients with detailed CTC clusters positive patients (left panel) and detailed SOX2+ CTCs patients (right panel). (b) The number of patients with SOX2+ CTCs detected; (c) The SOX2+ detected cells in patients; the patient number is stated on the left: #1 and #2. (d) The SOX2 expression detected in the FFPE samples of patients: patient #4 SOX2 negative sample; patient #2 SOX2 positive with low SOX2 expression (red arrows); patient #3 SOX2 positive patient (red arrows). (e) The prognostic value of the detected CTCs for the OS.
Figure 2

The consolidated data from CTCs detection, where (a) The frequency of CTCs+ patients with detailed CTC clusters positive patients (left panel) and detailed SOX2+ CTCs patients (right panel). (b) The number of patients with SOX2+ CTCs detected; (c) The SOX2+ detected cells in patients; the patient number is stated on the left: #1 and #2. (d) The SOX2 expression detected in the FFPE samples of patients: patient #4 SOX2 negative sample; patient #2 SOX2 positive with low SOX2 expression (red arrows); patient #3 SOX2 positive patient (red arrows). (e) The prognostic value of the detected CTCs for the OS.

The primary tumor samples FFPEs were collected for 40 patients included in the studies. For 15 samples without CTCs in blood sample, the FFPE samples were not available. The SOX2 protein expression was found to be a very rare event. Overall, we detected very low nucleus expression of SOX2 in samples derived from two patients. Interestingly, these patients were also identified with the SOX2+ CTCs and clusters. This might suggest that CSCs transformation occurs early in the cancer progression and this phenotype might be maintained during progression.

As the potential CCSCs were detected only in two patients, the data are not suitable for survival analysis considering the CCSCs value in the BC prognosis. The CTCs presence was identified as a significant prognostic marker for OS (Figure 2e), which complies with the majority of research.

4 Discussion

Since the current tools for long-term prognosis in luminal BC patients lack the required precision, there is a need for more universal approach and the identification of the new non-invasive biomarkers.

In this report, we presented a novel method for CCSCs identification based on previously described CytoTrack system [22,24]. This EpCAM independent system for CTCs identification proved to be a useful tool in liquid biopsy research [22]. It has two advantages over the other systems based on immune detection: it does not eliminate any cells and it allows for the additional recognition of the markers other than standard CTC detection. In the approach presented here, this possibility was utilized to recognize stem cell marker SOX2, which represents an alternative for the surface markers used so far (CD133, CD24, and CD44) [25,26,27].

The recovery ratio for the SOX2+ cells detection in this study was low (∼60%). This might be associated with the specific mechanisms behind CSCs generation in mammosphere culture. Despite the overall upregulation of the SOX2 expression, it is possible that in the mammosphere model, only a fraction of cells transforms into CSCs. The other reason for relatively low recovery ratio of CCSCs via this method might be the technical difficulty associated with nuclear staining for SOX2. Thus, further optimization of the staining presents the opportunity for detecting larger population of SOX2+ cells.

In our study, we observed CCSCs identified as SOX2+ as the rare events occurring only in two patients (3.64%). In contrary, some previous studies describe CCSCs as more frequent for advanced BC patients, e.g., in ∼44% [25] of MBC patients. However, the other study was using different stem marker (CD133) for CCSCs identification. It was described before that while SOX2 and CD133 are both considered stemness markers, their expression is independent, and their clinical relevance might differ. SOX2 expression was found to be positively correlated with the regional lymph nodes metastasis, while the same was not found for CD133 expression [28]. Interestingly, while analyzing samples from patients, we detected SOX2 expression only in CTC clusters. Our data reporting SOX2 expression exclusively in CTC clusters confirm some previous findings concerning CTC clusters, reported by Gkountela et al. [18], who analyzed the methylation profiles of single and cluster CTCs. They observed that binding sites for stemness- and proliferation-associated transcription factors are specifically hypomethylated in CTC clusters, including binding sites for SOX2 [18]. This change in methylation should result in activation and expression of SOX2 specifically in CTC clusters. Other studies also reported that population of CSCs is found in CTC clusters [17]. These studies, as well as our data might suggest that the CTC clusters are the main reservoir of CSCs in cancer progression. It is also worth to point out that when cells are grown in non-adherent conditions, forming mammospheres, which bear some resemblance to CTC clusters, they display elevated expression of stem cell markers. These properties may be important for the survival of tumor cells in the harsh conditions of the bloodstream. Further studies addressing this issue with large group of patients should be done for better understanding of clusters’ role in CSCs maintenance.

Interestingly, IHC studies of the matching primary tumor samples revealed SOX2 presence only in the samples from patients who also had SOX2 + CTC clusters, suggesting that CSCs marker expression occurred early in cancer progression.

Overall, our studies highlight the difficulty of identification of the CCSCs in blood samples from advanced BC patients using SOX2 as a marker. Nevertheless, we determined that probable reservoir for CSCs are CTC clusters, highlighting the importance of further studies associated with the clinical value of CTC clusters on large cohort of patients.

We identified small group of patients and low recovery ratio for CCSCs as the main limitations of our studies.

In conclusion, novel biomarkers like CTCs/CCSCs offer a promise for better prognosis, but need further development. Additionally, their combined use with other markers, like inflammation-based score determination may further improve prognosis [29].

  1. Funding information: This research was funded by Polish National Science Center (Grant Number 2019/33/N/NZ5/00758).

  2. Author contributions: Study design and conceptualization: M.Sz.-R. and E.A.G.; selection of patients for the study and collection of clinical data: A.J.-G. and A.K.; CTCs detection, data analysis, and statistical analysis: M.Sz.-R.; FFPE analysis: I.M.; writing, redaction, and figures preparation: M.Sz.-R., A.F., E.A.G., and I.M. All authors have read and agreed to the published version of the manuscript.

  3. Conflict of interest: Małgorzata Szostakowska-Rodzoś is an Assistant Editor in Open Medicine. This did not interfere with the peer-review process. The rest of the authors declare no conflict of interests.

  4. Data availability statement: The data supporting the findings of this study are available within the article and its supplementary materials. Additional data related to the study can be requested from the corresponding author upon reasonable request.

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Received: 2025-05-13
Revised: 2025-06-25
Accepted: 2025-07-18
Published Online: 2025-08-22

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

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

Articles in the same Issue

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  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
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  77. Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
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  110. Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
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  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
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  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
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  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
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  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
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  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
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  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. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. 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
  164. The application of augmented reality in robotic general surgery: A mini-review
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  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
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  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
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  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
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  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
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  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
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  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
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  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
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  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
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  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
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  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
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  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
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  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2025-1265
Keywords for this article
circulating tumor cells; SOX2; cancer stem cells; breast cancer; CytoTrack; liquid biopsy
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
  5. Risk factors for severe adverse drug reactions in hospitalized patients
  6. Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
  7. Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
  8. CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
  11. Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
  15. Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
  17. Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  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. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. 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
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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