Abstract
Background
Macrophage accumulation found in biopsy specimens of patients with dilated cardiomyopathy (DCM) has been thought to reflect chronic myocarditis. However, it is unsettled whether they are responsible for the active or persistent phase of the disease.
Objective
The aim of this study was to count the number of macrophages in relation to plasma concentrations of cardiac troponin T (cTnT).
Methods
We studied the biopsies of 181 patients with DCM by immunohistochemistry using anti-CD68(+) antibodies. The total number of CD68(+) and the number of CD68(+) cells attached to injured cardiomyocytes were counted and presented as the number of cells/mm2.
Results
Two expression patterns of CD68(+) macrophages were observed: those localized freely in the interstitial space only, and the cells attached to injured cardiomyocytes. As regards macrophages adhered to injured cardiomyocytes, 72 out of 181 (39.8%) patients presented these cells in the biopsy sections. Both the total number of CD68(+) macrophages and the number of CD68(+) cells directly adhered correlated negatively with cTnT in the serum of DCM patients (Spearman’s rho, r = −0.45, P < 0.001 and r = −0.31, P = 0.009, respectively).
Conclusion
Macrophages attached to injured cardiomyocytes may reflect chronic (ongoing) inflammation in the myocardium.
1 Introduction
Dilated cardiomyopathy (DCM) is related to a broad range of progressive disorders characterized by pathological myocardial remodeling in a diffuse or multifocal manner manifested clinically by impaired cardiac contractility [1]. The end stage of the disease leads to symptomatic heart failure (HF) in most patients and is related to high morbidity and mortality rates [2,3].
It has generally been assumed that chronic immune response may play an important role in the development and disease progression [2,4]. Accordingly, we recently reported that a higher number of CD68-positive macrophages in biopsy specimens significantly predicted the clinical progression of HF due to DCM in patients after a 1-year follow-up [5]. These observations confirmed the previously reported impact of macrophages on the prognosis in DCM [6].
Cardiac tissue contains large numbers of resident and infiltrative macrophages, which play a major role in immune response and post-inflammatory tissue remodeling [7,8]. Macrophage family cells have marked phenotypic heterogeneity, which is related to their inflammatory responses [9]. In addition, macrophages are not “permanently differentiated.” They are characterized by plasticity and are able to shift their transcriptional profile depending on the local environment [10,11,12].
So far, all data on macrophages in the myocardium of DCM patients have been based on counting the total number of these cells. However, considering the fact that histological detection of myocarditis (MCI) requires the presence of cell infiltration with myocyte cell necrosis, the detection of CD68(+) macrophages that are in direct contact with injured cardiac myocytes may be another important feature suggesting ongoing inflammation. However, the definition of universal histological criteria for ongoing MCI is still open to debate.
In the context of the above-mentioned cell necrosis, cardiac troponin T (cTnT) is a specific serum marker of myocardial injury, suggesting ongoing myocardial injury [13]. The increased cTnT level may be related to neurohormonal activation, cytotoxic effect of inflammatory cytokines, cell stretch, and the effect of oxidative stress, which may lead to chronic low-level troponin elevation [14]. In addition, it may serve as a marker for HF progression [15]. The prevalence of elevated troponin T is associated with adverse outcomes in chronic HF [16,17].
Considering the above, the aim of this study was to determine the number of CD68(+) macrophages (total number vs those that were in direct contact with injured cardiac myocytes) in biopsy sections in relation to plasma concentrations of cTnT in patients with DCM with a clinical suspicion of MCI.
2 Materials and methods
2.1 Patients
We studied right ventricular biopsy specimens of 181 consecutive patients with DCM and a clinical suspicion of MCI (159M, 22F). The mean duration of symptoms was 1.8 years. All biopsied patients presented with functional class II and III HF symptoms (New York Heart Association; NYHA) and decreased left ventricular ejection fraction (<40%) in the echo study. Each patient underwent standard clinical assessment, including a detailed history and physical examination, routine blood studies, thyroid function testing, echocardiography, coronary angiography, and an endomyocardial biopsy. cTnT was measured using the EDTA-plasma samples by electrochemiluminescence (Elecsys 2010 analyzer, Roche Diagnostics, Germany). The lowest detection limit for cTnT was <0.01 ng/mL. All patients were on typical therapeutic regimens for HF prior to the biopsy.
2.2 Endomyocardial biopsy procedure
Endomyocardial biopsy was performed using a Cordis bioptome (Cordis Corp., Miami, US). The minimum number of five specimens was obtained from the right side of the ventricular septum. The specimens were promptly immersed in sterile saline and transported on ice to the laboratory. All specimens were fixed for 20 min in cold acetone, immersed in embedding medium (OCT compound, Miles Inc, Elkhart, IN), and stored in liquid nitrogen until tested. Cryostat specimens were cut serially into sections of 5 m thickness, air-dried at room temperature, and assayed.
2.3 Immunohistochemistry
Immunohistochemistry on cryostat sections was performed using a Leica Bond Max autostainer (Leica Biosystems). The protocol was based on antibody detection, and the samples were stained using the hematoxylin kit (BOND Polymer Refine Red Detection; DS9390; Leica Biosystems). The frozen sections were incubated with murine monoclonal antihuman antibodies anti-CD68(+) macrophages (cloneEBM11) from DAKO, Glostrup, Denmark. The dilution of the antibody was verified in a series of pilot experiments and was 1:200. As a negative control, clone M0PC-21 from Leica Biosystems was used. As a positive control, liver biopsy specimens from patients with chronic active hepatitis were used. All sections from each patient were scanned using the GRUNDIUM Ocus ®microscope scanner. The total number of CD68(+) macrophages and the number of CD68 macrophages attached to injured cardiomyocytes were counted and presented as the number of cells per mm2. All counts were made using NIS Elements software from Nikon.
2.4 Statistical analysis
All parametric data were expressed as mean ± SD. Non-normally distributed data were analyzed by non-parametric descriptive statistics and presented as median (1st–3rd quartile). To assess the relationship between quantitative data, the Spearman’s rank coefficient was used. Differences were considered statistically significant when P < 0.05. Statistical analyses were performed using PS IMAGO 4.0 (IBM SPSS Statistics 24 software package).
-
Ethical approval: The protocol was approved by the institutional Bioethics Committee.
-
Informed consent: All patients gave their informed consent.
3 Results
Baseline patient characteristics are given in Table 1. None of the patients presented with hypertension, valvular disease except for relative mitral and/or tricuspid regurgitation, ischemic or systemic heart disease. In this immunohistochemistry study on cryostat sections, we observed two expression patterns of CD68(+) macrophages, i.e., localized freely in the interstitial space (Figure 1a and b) only, and macrophages attached to cardiomyocytes (Figure 2a and b). The mean number of total CD68(+) macrophages and the number of those adhered to injured cardiomyocytes were 26.8 ± 12.9 and 2.67 ± 4.71/mm2, respectively. In addition, we revealed an average of total CD68(+) cell number >14 cells/mm2 in 100 out of 181 (55.2%) patients. As far as the CD68(+) macrophages adhered to injured cardiac myocytes are concerned, 72 out of 181 (39.8%) samples presented these cells on cryostat sections. Importantly, in 7 positive cases for the presence of adhered macrophages (7 out of 81, 8.64%), the average of total CD68(+) cells was <14 cells/mm2.
Clinical and patient demographic details
| Sex, male/female | 159/22 |
| Age, years | 41.3 ± 9.9 |
| Male | 39.7 ± 7.9 |
| Female | 42.4 ± 8.8 |
| Atrial fibrillation, n (%) | 26 (14.3) |
| BMI (kg/m2) | 25.6 ± 3.9 |
| Male | 24.8 ± 2.8 |
| Female | 26.9 ± 6.1 |
| NYHA, n (II/III) | 161/20 |
| LVEF (%) | 30.1 ± 9.5 |
| LVDD (mm) | 65.8 ± 8.8 |
| LVSD (mm) | 49.1 ± 8.8 |
| MR (score), median (1st–3rd quartile) | 1.2 (1.0–2.2) |
| C-reactive protein (mg/L), median (1st–3rd quartile) | 2.2 (1.2–4.2) |
| cTnT (ng/mL), median (1st–3rd quartile) | 0.005 (0.005–0.10) |
| NT-proBNP (pmol/L), median (1st–3rd quartile) | 497.7 (142.7–1156.5) |
Values are expressed as mean ± SD or as indicated. BMI, body mass index; cTnT, cardiac troponin T; MR, mitral regurgitation; NT-proBNP, amino-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; LVDD, left ventricular diastolic dimension; LVSD, left ventricular systolic dimension.

Representative images of CD68(+) macrophages from the frozen samples. (a) Diffusely distributed CD68(+) cells (red color/arrows) localized in the interstitial space (arrows) of the nearly normal myocardium. (b) Another case with free CD68(+) macrophages (red color/arrows).

Representative images of CD68(+) macrophages from the frozen samples. (a) CD68(+) macrophages adhered to injured cardiomyocytes (red color/arrows). (b) Another case with activated macrophages (red color/arrows) in tight contact with injured cardiomyocytes with an average of 19.8/mm2 cells in this case.
Based on the immunohistological criteria for MCI published previously [18], only 49 out of 181 (27%) cases presented with MCI in this cohort of patients. Spearman’s rank coefficient showed a significant correlation between the total number of CD68(+) macrophages and CD68(+) cells directly adhered to injured cardiac myocytes (r = 0.53, P < 0.001). Importantly, both the total number of CD68(+) macrophages and the number of CD68 cells directly adhered correlated negatively with cTnT in the serum of DCM patients (Spearman’s rho, r = −0.45, P < 0.001, and r = −0.31, P = 0.009, respectively) (Table 2).
Association between the total number of CD68(+) macrophages and the number of adhered CD68(+) cells by Spearman’s rank coefficient test
| cTnT | |||
|---|---|---|---|
| Spearman’s rho | Total CD68(+) | Correlation coefficient | −0.455** |
| Sig. (2-tailed) | 0.000 | ||
| N | 181 | ||
| Adhered CD68(+) | Correlation coefficient | −0.314** | |
| Sig. (2-tailed) | 0.009 | ||
| N | 181 | ||
**Correlation is significant at the 0.01 level (2-tailed).
4 Discussion
The results of the present study contribute to the available data regarding the use of macrophage infiltration in endomyocardial biopsy as a marker of MCI, especially in the context of chronic (ongoing) form of the disease. Accordingly, this study demonstrated that CD68(+) macrophages could adopt two forms, i.e., the first was characterized by their presence in the interstitial space, without direct contact with the surrounding cardiomyocytes, and the second showed macrophages attached to injured cardiomyocytes using immunohistochemistry. Both of these forms were inversely proportional to cTnT serum levels, which suggested an impaired phagocytic activity of these cells in DCM patients [5].
Currently, there is no doubt that inflammation plays a pivotal role in the pathogenesis of DCM [4]. The longstanding debate on the histological criteria of MCI allowed for setting the quantitative threshold of >14 mononuclear leukocytes per mm2 on endomyocardial biopsy samples with the presence of >7 T lymphocytes per mm2 for the diagnosis of MCI [18]. However, despite the evolving understanding and diagnostic criteria of myocardial inflammation, universal histological criteria for a chronic form of MCI using endomyocardial biopsy have not been established yet [4,19,20]. Partially, it stems from the fact that histological detection of inflammation requires the presence of a high index of inflammatory cell infiltrations combined with the signs of myocyte injury, which can be hampered by the focal nature of the disease, especially in its chronic form [21]. On the other hand, myocyte injury per se is a pathophysiological heterogeneous mechanism, including local ischemia as a major cause [22,23,24].
Based on the immunohistological criteria for MCI published previously [25], only 27% of patients with cut-off values for CD68(+) >14 cells/mm2 can be considered positive for having macrophage infiltrations, which indicated MCI in our cohort of patients. These findings are consistent with the results of previous studies by Baccouche et al., where active MCI in endomyocardial biopsy was found in 26% of patients with troponin-I positive acute chest pain in the absence of significant coronary artery disease [26].
Other studies and our previous article recently reported that a higher number of CD68-positive macrophages in biopsy specimens significantly predicted clinical progression of HF due to DCM in patients after a 1-year follow-up [5,6]. Moreover, accumulated clinical and experimental data suggest that chronic inflammation may be responsible for the development and disease progression in at least some of them [4].
5 Conclusions
In conclusion, counting CD68(+) macrophages, which are attached to injured cardiomyocytes, may be useful for detecting chronic (ongoing) inflammation in the biopsy specimens of patients with DCM, particularly in those who did not meet the immunohistological criteria for MCI. Further studies are warranted to assess the cut-off value for detecting adhered macrophages that could best reflect chronic inflammation in biopsy sections.
-
Funding information: This research was funded by grants from the Medical University of Silesia (KNW-1-113/K/8/0, KNW-1-053/K/9/0, PCN-1-156/N/0/0).
-
Author contributions: Conceptualization, writing-review, and editing, O.W./E.R.-W./R.W.; formal analysis, A.B.; methodology, D.D.
-
Conflict of interest: The authors state that there are no conflicts of interest to disclose.
-
Data availability statement: All data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
References
[1] Schultheiss HP, Fairweather DL, Caforio ALP, Escher F, Hershberger RE, Lipshultz SE, et al. Dilated cardiomyopathy. Nat Rev Dis Primers. 2019;5:32. 10.1038/s41572-019-0084-1.Suche in Google Scholar PubMed PubMed Central
[2] Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T, et al. Predictors of outcome in patients with suspected myocarditis. Circulation. 2008;118:639–48. 10.1161/CIRCULATIONAHA.108.769489.Suche in Google Scholar PubMed
[3] Devaux B, Scholz D, Hirche A, Klovekorn WP, Schaper J. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. Eur Heart J. 1997;18:470–9. 10.1093/oxfordjournals.eurheartj.a015268.Suche in Google Scholar PubMed
[4] Trachtenberg BH, Hare JM. Inflammatory cardiomyopathic syndromes. Circ Res. 2017;121:803–18. 10.1161/CIRCRESAHA.117.310221.Suche in Google Scholar PubMed
[5] Reichman-Warmusz E, Nowak J, Kaczmarek K, Nowalany-Kozielska E, Wojnicz R. Impact of cellular myocardial infiltration on clinical outcome in non-ischemic heart failure. J Clin Pathol. 2022;75:30–3. 10.1136/jclinpath-2020-206964.Suche in Google Scholar PubMed
[6] Nakayama T, Sugano Y, Yokokawa T, Nagai T, Matsuyama T, Ohta-Ogo K, et al. Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy. Eur J Hear Fail. 2017;19:490–8. 10.1002/ejhf.767.Suche in Google Scholar PubMed
[7] Mues B, Brisse B, Zwadlo G, Themann H, Bender F, Sorg C. Phenotyping of macrophages in endomyocardial biopsies as a new approach to diagnosis of myocarditis. Eur Heart J. 1990;11:1–5. 10.1093/oxfordjournals.eurheartj.a059767.Suche in Google Scholar PubMed
[8] Lafuse WP, Wozniak DJ, Rajaram MVS. Role of cardiac macrophages on cardiac inflammation, fibrosis and tissue repair. Cells. 2021;10:51. 10.3390/cells10010051.Suche in Google Scholar PubMed PubMed Central
[9] Gordon S. Alternatively activation of macrophages. Nat Rev Immunol. 2003;3:23–35. 10.1038/nri978.Suche in Google Scholar PubMed
[10] Nahrendorf M, Swirski FK. Abandoning M1/M2 for a network model of macrophage function. Circ Res. 2016;119:414–7. 10.1161/CIRCRESAHA.116.309194.Suche in Google Scholar PubMed PubMed Central
[11] Matysiak N, Mielanczyk L, Kaczmarek K, Zaba M, Reichman-Warmusz E, Wojnicz R. New insights into the pathogenesis of cardiac papillary fibroelastomas. Folia Histochem Cytobiol. 2021;59:212–25. 10.5603/FHC.a2021.0027.Suche in Google Scholar PubMed
[12] Stevens TW, Khalaf FK, Soehnlen S, Hegde P, Storm K, Chandramohan Meenakshisundaram CH, et al. Dirty jobs: macrophages at the heart of cardiovascular disease. Biomedicines. 2022;10:1579. 10.3390/biomedicines10071579.Suche in Google Scholar PubMed PubMed Central
[13] Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. N Engl J Med. 2000;343:1139–47. 10.1056/NEJM200010193431602.Suche in Google Scholar PubMed
[14] Setsuta K, Seino Y, Takahashi T, Sasaki K, Harada A, Takano T, et al. Clinical significance of elevated levels of cardiac troponin T in patients with chronic heart failure. Am J Cardiol. 1999;84:608–11. 10.1016/s0002-9149(99)00391-4.Suche in Google Scholar PubMed
[15] Missov E, Mair J. A novel biochemical approach in congestive heart failure: cardiac troponin T. Am Heart J. 1999;138:95–9. 10.1016/s0002-8703(99)70252-8.Suche in Google Scholar PubMed
[16] Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, et al. Val-HeFT Investigators Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation. 2007;116:1242–9. 10.1161/CIRCULATIONAHA.106.655076.Suche in Google Scholar PubMed
[17] Sato Y, Yamada T, Taniguchi R, Nagai K, Makiyama T, Okada H, et al. Persistently increased serum concentrations of cardiac troponin T in patients with idiopathic dilated cardiomyopathy are predictive of adverse outcomes. Circulation. 2001;103:369–74. 10.1161/01.cir.103.3.369.Suche in Google Scholar PubMed
[18] Basso C, Calabrese F, Angelini A, Carturan E, Thiene G. Classification and histological, immunohistological, and molecular diagnosis of inflammatory myocardial disease. Heart Fail Rev. 2013;18:673–81. 10.1007/s10741-012-9355-6.Suche in Google Scholar PubMed
[19] Noutsias M, Seeberg B, Schultheiss HP, Kuhl U. Expression of cell adhesion molecules in dilated cardiomyopathy. Evidence for endothelial activation in inflammatory cardiomyopathy. Circulation. 1999;99:2124–31. 10.1161/01.cir.99.16.2124.Suche in Google Scholar PubMed
[20] Ammirat E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, et al. Management of acute myocarditis and chronic inflammatory cardiomyopathy. An expert consensus document. Circ Heart Fail. 2020;13:e007405. 10.1161/CIRCHEARTFAILURE.120.007405.Suche in Google Scholar PubMed PubMed Central
[21] Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena CH, Athanasiadis A, et al. Comparative evaluation of left and right ventricular endomyocardial biopsy. Differences in complication rate and diagnostic performance. Circulation. 2010;122:900–9. 10.1161/CIRCULATIONNAHA.109.924167.Suche in Google Scholar
[22] Heuvel AFM, Veldhuisen DJ, Wall EE, Blanksma PK, Siebelink HM, Vaalburg WM, et al. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2000;35:19–28. 10.1016/s0735-1097(99)00499-4.Suche in Google Scholar PubMed
[23] Neglia D, Michelassi C, Trivieri MG, Sambuceti G, Giorgetti A, Pratali L, et al. Prognostic role of myocardial blood flow impairment in idiopathic left ventricular dysfunction. Circulation. 2002;105:186–93. 10.1161/hc0202.102119.Suche in Google Scholar PubMed
[24] Haywood GA, Tsao P, von der Leyen HE, Mann MJ, Keeling PJ, Trindade PT, et al. Expression of inducible nitric oxide synthase in human heart failure. Circulation. 1996;93:1087–94. 10.1161/01.cir.93.6.1087.Suche in Google Scholar PubMed
[25] Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013;34:2636–48. 10.1093/eurheartj/eht210.Suche in Google Scholar PubMed
[26] Baccouche H, Mahrholdt H, Meinhardt G, Merher R, Voehringer M, Hill S, et al. Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease. Eur Heart J. 2009;30:2869–79. 10.1093/eurheartj/ehp328.Suche in Google Scholar PubMed
© 2025 the author(s), published by De Gruyter
This work is licensed under the Creative Commons Attribution 4.0 International License.
Artikel in diesem Heft
- Research Articles
- Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
- Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
- Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
- Risk factors for severe adverse drug reactions in hospitalized patients
- Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
- Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
- CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
- Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
- Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
- Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
- Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
- Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
- Association between statin administration and outcome in patients with sepsis: A retrospective study
- 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
- A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
- Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
- Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
- Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
- Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
- Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
- The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
- Health literacy and health-related quality of life: The mediating role of irrational happiness
- Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
- Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
- Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
- Clinical analysis of ten cases of HIV infection combined with acute leukemia
- Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
- Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
- Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
- Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
- Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
- The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
- The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
- Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
- Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
- Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
- The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
- 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
- A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
- A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
- Identifying early screening factors for depression in middle-aged and older adults: A cohort study
- Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
- Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
- High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
- RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
- Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
- Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
- The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
- Expression and clinical significance of ITGA3 in breast cancer
- Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
- rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
- Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
- Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
- Gender beliefs and legitimization of dating violence in adolescents
- Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
- Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
- Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
- Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
- Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
- Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
- GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
- Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
- MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
- Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
- Trends in research on preterm birth in twin pregnancy based on bibliometrics
- Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
- Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
- Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
- Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
- Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
- CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
- Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
- Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
- Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
- Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
- Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
- Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
- Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
- The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
- The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
- Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
- Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
- The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
- Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
- Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
- Correlation of serum calprotectin with outcome of acute cerebral infarction
- Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
- Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
- The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
- Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
- Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
- Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
- Analysis of serum metabolomics in patients with different types of chronic heart failure
- Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
- Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
- Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
- METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
- The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
- Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
- Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
- Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
- Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
- Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
- Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
- Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
- Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
- Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
- Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
- Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
- HALP score in Demodex blepharitis: A case–control study
- Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
- Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
- Comparison of the two intestinal anastomosis methods in pediatric patients
- Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
- Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
- Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
- Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
- Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
- Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
- Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
- Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
- A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
- Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
- FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
- Association of placenta weight and morphology with term low birth weight: A case–control study
- Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
- Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
- TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
- Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
- Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
- Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
- Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
- H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
- Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
- Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
- Motivational interviewing for alcohol use reduction in Thai patients
- Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
- Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
- Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
- CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
- Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
- The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
- OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
- The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
- Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
- Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
- Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
- Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
- The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
- Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
- Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
- Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
- Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
- Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
- Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
- Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
- Efficacy and safety of PD-1/PD-L1 inhibitors in pancreatic ductal adenocarcinoma: a systematic review and Meta-analysis of randomized controlled trials
- The value of diagnostic experience in O-RADS MRI score for ovarian-adnexal lesions
- Health education pathway for individuals with temporary enterostomies using patient journey mapping
- Serum TLR8 as a potential diagnostic biomarker of coronary heart disease
- Intraoperative temperature management and its effect on surgical outcomes in elderly patients undergoing lichtenstein unilateral inguinal hernia repair
- Immunohistochemical profiling and neuroepithelial heterogeneity in immature ovarian teratomas: a retrospective digital pathology-based study
- Associated risk factors and prevalence of human papillomavirus infection among females visiting tertiary care hospital: a cross-sectional study from Nepal
- Comparative evaluation of various disc elution methods for the detection of colistin-resistant gram-negative bacteria
- Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
- Causal association between ceramide levels and central precocious puberty: a mendelian randomization study
- Novel predictive model for colorectal liver metastases recurrence: a radiomics and clinical data approach
- Relationship between resident physicians’ perceived professional value and exposure to violence
- Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
- Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
- Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
- Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
- Development and internal validation of a nomogram for predicting short-term prognosis in ICU patients with acute pyelonephritis
- The association between hypoxic burden and blood pressure in patients with obstructive sleep apnea
- Promotion of asthenozoospermia by C9orf72 through suppression of spermatogonia activity via fructose metabolism and mitophagy
- Review Articles
- The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
- Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
- Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
- Review of mechanisms and frontier applications in IL-17A-induced hypertension
- Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
- 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
- The application of augmented reality in robotic general surgery: A mini-review
- The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
- Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
- Plant polyphenols, terpenes, and terpenoids in oral health
- Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
- End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
- The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
- Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
- PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
- Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
- Giant borderline ovarian tumours – review of the literature
- Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
- Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
- Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
- Supplement strategies for infertility in overweight women: Evidence and legal insights
- Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
- A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
- Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
- Strategies for hyperkalemia management in dialysis patients: A systematic review
- C-reactive protein-to-albumin ratio in peripheral artery disease
- Research progress on autophagy and its roles in sepsis induced organ injury
- Neuronutrition in autism spectrum disorders
- Pumilio 2 in neural development, function, and specific neurological disorders
- Antibiotic prescribing patterns in general dental practice- a scoping review
- Clinical and medico-legal reflections on non-invasive prenatal testing
- Smartphone use and back pain: a narrative review of postural pathologies
- Targeting endothelial oxidative stress in hypertension
- Exploring links between acne and metabolic syndrome: a narrative review
- Case Reports
- Delayed graft function after renal transplantation
- Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
- Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
- Giant right atrial hemangioma presenting with ascites: A case report
- Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
- EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
- Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
- Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
- Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
- A rare case of Opalski syndrome with a suspected multiple sclerosis etiology
- Newly diagnosed B-cell acute lymphoblastic leukemia demonstrating localized bone marrow infiltration exclusively in the lower extremities
- Rapid Communication
- Biological properties of valve materials using RGD and EC
-
A single oral administration of flavanols enhances short
-term memory in mice along with increased brain-derived neurotrophic factor - Repeat influenza incidence across two consecutive influenza seasons
- Letter to the Editor
- Role of enhanced external counterpulsation in long COVID
- Expression of Concern
- Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
- Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
- Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
- Corrigendum
- Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
- Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
- Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
- Retraction
- Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
- Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
- Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
- Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
- Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
- Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
- The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
- Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
- Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
- Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
- Special Issue The evolving saga of RNAs from bench to bedside - Part III
- Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
- The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
- Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
- Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
- A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
- Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
- Special Issue Diabetes mellitus: pathophysiology, complications & treatment
- Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
- Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
- A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
- A review of brain research on T2DM-related cognitive dysfunction
- Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
- Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
- CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
Artikel in diesem Heft
- Research Articles
- Network pharmacological analysis and in vitro testing of the rutin effects on triple-negative breast cancer
- Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
- Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
- Risk factors for severe adverse drug reactions in hospitalized patients
- Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with Fonsecaea monophora based on single-cell sequencing
- Development and validation of headspace gas chromatography with a flame ionization detector method for the determination of ethanol in the vitreous humor
- CMSP exerts anti-tumor effects on small cell lung cancer cells by inducing mitochondrial dysfunction and ferroptosis
- Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
- Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
- Comparison of the effectiveness of nurse-led preoperative counseling and postoperative follow-up care vs standard care for patients with gastric cancer
- Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
- Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
- Association between statin administration and outcome in patients with sepsis: A retrospective study
- 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
- A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
- Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function
- Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
- Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
- Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
- Vitamin D replacement therapy may regulate sleep habits in patients with restless leg syndrome
- The first-line antihypertensive nitrendipine potentiated the therapeutic effect of oxaliplatin by downregulating CACNA1D in colorectal cancer
- Health literacy and health-related quality of life: The mediating role of irrational happiness
- Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
- Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
- Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
- Clinical analysis of ten cases of HIV infection combined with acute leukemia
- Investigating the cardioprotective potential of quercetin against tacrolimus-induced cardiotoxicity in Wistar rats: A mechanistic insights
- Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis
- Diagnostic value of ratio of blood inflammation to coagulation markers in periprosthetic joint infection
- Sex-specific associations of sex hormone binding globulin and risk of bladder cancer
- Core muscle strength and stability-oriented breathing training reduces inter-recti distance in postpartum women
- The ERAS nursing care strategy for patients undergoing transsphenoidal endoscopic pituitary tumor resection: A randomized blinded controlled trial
- The serum IL-17A levels in patients with traumatic bowel rupture post-surgery and its predictive value for patient prognosis
- Impact of Kolb’s experiential learning theory-based nursing on caregiver burden and psychological state of caregivers of dementia patients
- Analysis of serum NLR combined with intraoperative margin condition to predict the prognosis of cervical HSIL patients undergoing LEEP surgery
- Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
- The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
- 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
- A cross-sectional study: Relationship between serum oxidative stress levels and arteriovenous fistula maturation in maintenance dialysis patients
- A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
- Identifying early screening factors for depression in middle-aged and older adults: A cohort study
- Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
- Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
- High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
- RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
- Impact of peripheral conditioning on reperfusion injury following primary percutaneous coronary intervention in diabetic and non-diabetic STEMI patients
- Clinical efficacy of azacitidine in the treatment of middle- and high-risk myelodysplastic syndrome in middle-aged and elderly patients: A retrospective study
- The effect of ambulatory blood pressure load on mitral regurgitation in continuous ambulatory peritoneal dialysis patients
- Expression and clinical significance of ITGA3 in breast cancer
- Single-nucleus RNA sequencing reveals ARHGAP28 expression of podocytes as a biomarker in human diabetic nephropathy
- rSIG combined with NLR in the prognostic assessment of patients with multiple injuries
- Toxic metals and metalloids in collagen supplements of fish and jellyfish origin: Risk assessment for daily intake
- Exploring causal relationship between 41 inflammatory cytokines and marginal zone lymphoma: A bidirectional Mendelian randomization study
- Gender beliefs and legitimization of dating violence in adolescents
- Effect of serum IL-6, CRP, and MMP-9 levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia
- Effect of smoking and smoking cessation on hematological parameters in polycythemic patients
- Pathogen surveillance and risk factors for pulmonary infection in patients with lung cancer: A retrospective single-center study
- Necroptosis of hippocampal neurons in paclitaxel chemotherapy-induced cognitive impairment mediates microglial activation via TLR4/MyD88 signaling pathway
- Celastrol suppresses neovascularization in rat aortic vascular endothelial cells stimulated by inflammatory tenocytes via modulating the NLRP3 pathway
- Cord-lamina angle and foraminal diameter as key predictors of C5 palsy after anterior cervical decompression and fusion surgery
- GATA1: A key biomarker for predicting the prognosis of patients with diffuse large B-cell lymphoma
- Influencing factors of false lumen thrombosis in type B aortic dissection: A single-center retrospective study
- MZB1 regulates the immune microenvironment and inhibits ovarian cancer cell migration
- Integrating experimental and network pharmacology to explore the pharmacological mechanisms of Dioscin against glioblastoma
- Trends in research on preterm birth in twin pregnancy based on bibliometrics
- Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma
- Single-cell transcriptomic analysis identifies a stress response Schwann cell subtype
- Acute pancreatitis risk in the diagnosis and management of inflammatory bowel disease: A critical focus
- Effect of subclinical esketamine on NLRP3 and cognitive dysfunction in elderly ischemic stroke patients
- Interleukin-37 mediates the anti-oral tumor activity in oral cancer through STAT3
- CA199 and CEA expression levels, and minimally invasive postoperative prognosis analysis in esophageal squamous carcinoma patients
- Efficacy of a novel drainage catheter in the treatment of CSF leak after posterior spine surgery: A retrospective cohort study
- Comprehensive biomedicine assessment of Apteranthes tuberculata extracts: Phytochemical analysis and multifaceted pharmacological evaluation in animal models
- Relation of time in range to severity of coronary artery disease in patients with type 2 diabetes: A cross-sectional study
- Dopamine attenuates ethanol-induced neuronal apoptosis by stimulating electrical activity in the developing rat retina
- Correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture
- Factors associated with maternal attention and distraction during breastfeeding and childcare: A cross-sectional study in the west of Iran
- Mechanisms of hesperetin in treating metabolic dysfunction-associated steatosis liver disease via network pharmacology and in vitro experiments
- The law on oncological oblivion in the Italian and European context: How to best uphold the cancer patients’ rights to privacy and self-determination?
- The prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index for survival in patients with colorectal cancer
- Factors affecting the measurements of peripheral oxygen saturation values in healthy young adults
- Comparison and correlations between findings of hysteroscopy and vaginal color Doppler ultrasonography for detection of uterine abnormalities in patients with recurrent implantation failure
- The effects of different types of RAGT on balance function in stroke patients with low levels of independent walking in a convalescent rehabilitation hospital
- Causal relationship between asthma and ankylosing spondylitis: A bidirectional two-sample univariable and multivariable Mendelian randomization study
- Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
- Correlation of serum calprotectin with outcome of acute cerebral infarction
- Comparison of computed tomography and guided bronchoscopy in the diagnosis of pulmonary nodules: A systematic review and meta-analysis
- Curdione protects vascular endothelial cells and atherosclerosis via the regulation of DNMT1-mediated ERBB4 promoter methylation
- The identification of novel missense variant in ChAT gene in a patient with gestational diabetes denotes plausible genetic association
- Molecular genotyping of multi-system rare blood types in foreign blood donors based on DNA sequencing and its clinical significance
- Exploring the role of succinyl carnitine in the association between CD39⁺ CD4⁺ T cell and ulcerative colitis: A Mendelian randomization study
- Dexmedetomidine suppresses microglial activation in postoperative cognitive dysfunction via the mmu-miRNA-125/TRAF6 signaling axis
- Analysis of serum metabolomics in patients with different types of chronic heart failure
- Diagnostic value of hematological parameters in the early diagnosis of acute cholecystitis
- Pachymaran alleviates fat accumulation, hepatocyte degeneration, and injury in mice with nonalcoholic fatty liver disease
- Decrease in CD4 and CD8 lymphocytes are predictors of severe clinical picture and unfavorable outcome of the disease in patients with COVID-19
- METTL3 blocked the progression of diabetic retinopathy through m6A-modified SOX2
- The predictive significance of anti-RO-52 antibody in patients with interstitial pneumonia after treatment of malignant tumors
- Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian randomization
- Development and validation of potential molecular subtypes and signatures of ocular sarcoidosis based on autophagy-related gene analysis
- Widespread venous thrombosis: Unveiling a complex case of Behçet’s disease with a literature perspective
- Uterine fibroid embolization: An analysis of clinical outcomes and impact on patients’ quality of life
- Discovery of lipid metabolism-related diagnostic biomarkers and construction of diagnostic model in steroid-induced osteonecrosis of femoral head
- Serum-derived exomiR-188-3p is a promising novel biomarker for early-stage ovarian cancer
- Enhancing chronic back pain management: A comparative study of ultrasound–MRI fusion guidance for paravertebral nerve block
- Peptide CCAT1-70aa promotes hepatocellular carcinoma proliferation and invasion via the MAPK/ERK pathway
- Electroacupuncture-induced reduction of myocardial ischemia–reperfusion injury via FTO-dependent m6A methylation modulation
- Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
- Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis
- HALP score in Demodex blepharitis: A case–control study
- Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
- Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
- Comparison of the two intestinal anastomosis methods in pediatric patients
- Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
- Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
- Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
- Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
- Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
- Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
- Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
- Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
- A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
- Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
- FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
- Association of placenta weight and morphology with term low birth weight: A case–control study
- Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
- Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
- TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
- Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
- Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
- Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
- Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
- H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
- Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
- Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
- Motivational interviewing for alcohol use reduction in Thai patients
- Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
- Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
- Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
- CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
- Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
- The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
- OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
- The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
- Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
- Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
- Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
- Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
- The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
- Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
- Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
- Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
- Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
- Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
- Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
- Identification of hub genes related to acute kidney injury caused by sevoflurane anesthesia and endoplasmic reticulum stress
- Efficacy and safety of PD-1/PD-L1 inhibitors in pancreatic ductal adenocarcinoma: a systematic review and Meta-analysis of randomized controlled trials
- The value of diagnostic experience in O-RADS MRI score for ovarian-adnexal lesions
- Health education pathway for individuals with temporary enterostomies using patient journey mapping
- Serum TLR8 as a potential diagnostic biomarker of coronary heart disease
- Intraoperative temperature management and its effect on surgical outcomes in elderly patients undergoing lichtenstein unilateral inguinal hernia repair
- Immunohistochemical profiling and neuroepithelial heterogeneity in immature ovarian teratomas: a retrospective digital pathology-based study
- Associated risk factors and prevalence of human papillomavirus infection among females visiting tertiary care hospital: a cross-sectional study from Nepal
- Comparative evaluation of various disc elution methods for the detection of colistin-resistant gram-negative bacteria
- Effect of timing of cholecystectomy on weight loss after sleeve gastrectomy in morbidly obese individuals with cholelithiasis: a retrospective cohort study
- Causal association between ceramide levels and central precocious puberty: a mendelian randomization study
- Novel predictive model for colorectal liver metastases recurrence: a radiomics and clinical data approach
- Relationship between resident physicians’ perceived professional value and exposure to violence
- Multiple sclerosis and type 1 diabetes: a Mendelian randomization study of European ancestry
- Rapid pathogen identification in peritoneal dialysis effluent by MALDI-TOF MS following blood culture enrichment
- Comparison of open and percutaneous A1 pulley release in pediatric trigger thumb: a retrospective cohort study
- Impact of combined diaphragm-lung ultrasound assessment on postoperative respiratory function in patients under general anesthesia recovery
- Development and internal validation of a nomogram for predicting short-term prognosis in ICU patients with acute pyelonephritis
- The association between hypoxic burden and blood pressure in patients with obstructive sleep apnea
- Promotion of asthenozoospermia by C9orf72 through suppression of spermatogonia activity via fructose metabolism and mitophagy
- Review Articles
- The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
- Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
- Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
- Review of mechanisms and frontier applications in IL-17A-induced hypertension
- Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
- 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
- The application of augmented reality in robotic general surgery: A mini-review
- The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
- Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
- Plant polyphenols, terpenes, and terpenoids in oral health
- Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
- End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
- The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
- Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
- PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
- Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
- Giant borderline ovarian tumours – review of the literature
- Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
- Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
- Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
- Supplement strategies for infertility in overweight women: Evidence and legal insights
- Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
- A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
- Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
- Strategies for hyperkalemia management in dialysis patients: A systematic review
- C-reactive protein-to-albumin ratio in peripheral artery disease
- Research progress on autophagy and its roles in sepsis induced organ injury
- Neuronutrition in autism spectrum disorders
- Pumilio 2 in neural development, function, and specific neurological disorders
- Antibiotic prescribing patterns in general dental practice- a scoping review
- Clinical and medico-legal reflections on non-invasive prenatal testing
- Smartphone use and back pain: a narrative review of postural pathologies
- Targeting endothelial oxidative stress in hypertension
- Exploring links between acne and metabolic syndrome: a narrative review
- Case Reports
- Delayed graft function after renal transplantation
- Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
- Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
- Giant right atrial hemangioma presenting with ascites: A case report
- Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
- EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
- Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
- Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
- Combined VAT and retroperitoneoscopy for pleural empyema due to nephro-pleuric fistula in xanthogranulomatous pyelonephritis
- A rare case of Opalski syndrome with a suspected multiple sclerosis etiology
- Newly diagnosed B-cell acute lymphoblastic leukemia demonstrating localized bone marrow infiltration exclusively in the lower extremities
- Rapid Communication
- Biological properties of valve materials using RGD and EC
-
A single oral administration of flavanols enhances short
-term memory in mice along with increased brain-derived neurotrophic factor - Repeat influenza incidence across two consecutive influenza seasons
- Letter to the Editor
- Role of enhanced external counterpulsation in long COVID
- Expression of Concern
- Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
- Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
- Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
- Corrigendum
- Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
- Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
- Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
- Retraction
- Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
- Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
- Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
- Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
- Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
- Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
- The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
- Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
- Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
- Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
- Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
- Special Issue The evolving saga of RNAs from bench to bedside - Part III
- Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
- The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
- Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
- Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
- A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
- Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
- Special Issue Diabetes mellitus: pathophysiology, complications & treatment
- Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
- Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
- A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
- A review of brain research on T2DM-related cognitive dysfunction
- Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
- Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
- CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms